<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03258762</url>
  </required_header>
  <id_info>
    <org_study_id>204678</org_study_id>
    <nct_id>NCT03258762</nct_id>
  </id_info>
  <brief_title>Phase I Study of Pyrimethamine in Healthy Japanese and Caucasian Subjects</brief_title>
  <official_title>A Single Centre, Open-label, Parallel-group, Single Oral Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Pyrimethamine in Healthy Japanese and Caucasian Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pyrimethamine in combination with a sulphonamide is known to be effective in the treatment of&#xD;
      toxoplasmosis. However, Pyrimethamine has not been approved by the Japanese regulatory body&#xD;
      (Pharmaceutical and Medical Devices Agency [PMDA]/ Ministry of Health, Labor and Welfare&#xD;
      [MHLW]). The pharmacokinetics (PK) of Pyrimethamine has been investigated following&#xD;
      administration of Sulfadoxine/Pyrimethamine tablet in healthy Japanese subjects. However, the&#xD;
      study did not provide sufficient information for approval of Pyrimethamine in Japan; hence,&#xD;
      PMDA has requested confirmation of the PK of Pyrimethamine in another PK study in Japanese&#xD;
      and Caucasian healthy subjects. This study will be a single centre, open-label,&#xD;
      parallel-group, single oral dose study to evaluate the PK, safety and tolerability of&#xD;
      Pyrimethamine in healthy Japanese and Caucasian male subjects. Subjects will undergo a&#xD;
      screening visit within 30 days prior to first dose of the study drug. On Day 1, subjects will&#xD;
      be administered a single oral dose of pyrimethamine 50 milligrams (mg) along with calcium&#xD;
      folinate 15 mg after an overnight fast of at least 10 hours. Subjects will continue to&#xD;
      receive calcium folinate once daily until Day 8 of the treatment period. Blood sampling for&#xD;
      PK analysis and safety assessments will be performed prior to dosing and over 22 days after&#xD;
      dosing. Each subject will participate in the study for approximately 2 months from screening&#xD;
      to follow-up.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 25, 2017</start_date>
  <completion_date type="Actual">November 19, 2017</completion_date>
  <primary_completion_date type="Actual">November 19, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population is defined as all participants who administered at least one dose of study treatment and who have PK sample taken and analyzed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vd/F of Pyrimethamine in Healthy Caucasian Male Participants</measure>
    <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)</measure>
    <time_frame>Up to Day 23</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who take at least one dose of study treatment were included in Safety Population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea.</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of clinical chemistry parameters including glucose, sodium, calcium, potassium, and urea at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphatase, ALT and AST at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine.</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, bilirubin and creatinine at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Clinical Chemistry Parameters: Protein</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of clinical chemistry parameter including protein at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value. Data was not available as all basophil values were below the detection limit. Hence, the change from baseline in basophil values were not calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Reticulocytes</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameter including reticulocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Hematocrit</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Hemoglobin</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameter including mean corpuscular hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Mean Corpuscular Volume</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameter including mean corpuscular volume at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Erythrocytes</measure>
    <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Blood samples were collected for the analysis of hematology parameter including erythrocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Urinalysis Parameter</measure>
    <time_frame>Day -1, 24, 96, 168, 336 and follow up (504 hours)</time_frame>
    <description>The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of can be read as Trace, + and ++ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Specific Gravity at Indicated Time Points</measure>
    <time_frame>Day -1, 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine Potential of Hydrogen (pH) at Indicated Time Points</measure>
    <time_frame>Day -1, 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
    <description>Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)</measure>
    <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours</time_frame>
    <description>Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pulse Rate</measure>
    <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours</time_frame>
    <description>Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Temperature</measure>
    <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours</time_frame>
    <description>Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, and QT Interval Corrected for Heart Rate by Fredericia's Formula (QTcF) Interval</measure>
    <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours</time_frame>
    <description>A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically measures PR, QRS, QT, and QTcF intervals. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of ECG Parameter: ECG Mean Heart Rate</measure>
    <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours</time_frame>
    <description>A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically calculates mean ECG heart rate. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Toxoplasmosis</condition>
  <arm_group>
    <arm_group_label>Healthy Japanese male subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Caucasian male subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Caucasian male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pyrimethamine</intervention_name>
    <description>Pyrimethamine will be available as 25 mg tablets. Subjects will be orally administered two pyrimethamine tablets on Day 1 in a fasted condition with 240 mL of water.</description>
    <arm_group_label>Healthy Caucasian male subjects</arm_group_label>
    <arm_group_label>Healthy Japanese male subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcium folinate</intervention_name>
    <description>Calcium folinate will be available as 5 mg tablets. Subjects will be orally administered three calcium folinate tablets on Day 1 along with pyrimethamine followed by once daily administration of calcium folinate until Day 8. Each administration will be with 240 mL water.</description>
    <arm_group_label>Healthy Caucasian male subjects</arm_group_label>
    <arm_group_label>Healthy Japanese male subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects should be between 20 and 64 years of age inclusive, at the time of signing&#xD;
             the informed consent.&#xD;
&#xD;
          -  Subjects who are overtly healthy as determined by medical evaluation including medical&#xD;
             history, physical examination, laboratory tests and cardiac monitoring.&#xD;
&#xD;
          -  Body weight &gt;= 50 kilograms (kg) and body mass index (BMI) within the range 18.5 to&#xD;
             30.0 kilogram per square meters (kg/m^2) (inclusive).&#xD;
&#xD;
          -  Japanese or Caucasian male.&#xD;
&#xD;
          -  A male subject must agree to use contraception during the treatment period and until&#xD;
             follow-up.&#xD;
&#xD;
          -  Japanese ethnic origin defined as having been born in Japan, having four ethnic&#xD;
             Japanese grandparents, holding a Japanese passport or identity papers and being able&#xD;
             to speak Japanese. Subjects should also have lived outside Japan for less than 10&#xD;
             years at the time of screening.&#xD;
&#xD;
          -  Caucasian subject will be defined as an individual having four grandparents who are&#xD;
             all descendants of the original people of Europe.&#xD;
&#xD;
          -  Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) &gt; 1.5 times upper limit of normal (ULN).&#xD;
&#xD;
          -  Bilirubin &gt; 1.5 times ULN (isolated bilirubin &gt; 1.5 times ULN is acceptable if&#xD;
             bilirubin is fractionated and direct bilirubin &lt; 35 percent).&#xD;
&#xD;
          -  QT interval corrected for heart rate according to Fridericia's formula (QTcF) &gt; 450&#xD;
             milliseconds (msec).&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  History of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine,&#xD;
             hematological, or neurological disorders capable of significantly altering the&#xD;
             absorption, metabolism, or elimination of drugs; constituting a risk when taking the&#xD;
             study treatment; or interfering with the interpretation of data.&#xD;
&#xD;
          -  Abnormal blood pressure as determined by the investigator.&#xD;
&#xD;
          -  Hematological values: outside normal range at screening.&#xD;
&#xD;
          -  Serum creatinine level: outside normal range at screening visit.&#xD;
&#xD;
          -  Past or intended use of over-the-counter or prescription medication including herbal&#xD;
             medications within 14 days prior to dosing.&#xD;
&#xD;
          -  Participation in the study would result in loss of blood or blood products in excess&#xD;
             of 500 milliliters (mL) within 3 months.&#xD;
&#xD;
          -  Exposure to more than 4 new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Current enrollment or past participation within the last 30 days before signing of&#xD;
             consent in this clinical study involving an investigational study treatment or any&#xD;
             other type of medical research.&#xD;
&#xD;
          -  Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C&#xD;
             antibody test result at screening. Subjects with positive Hepatitis C antibody due to&#xD;
             prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C&#xD;
             RNA test is obtained.&#xD;
&#xD;
          -  Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3&#xD;
             months prior to first dose of study treatment. Test is optional and subjects with&#xD;
             negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA&#xD;
             testing.&#xD;
&#xD;
          -  Positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  Positive human immunodeficiency virus (HIV) antibody test.&#xD;
&#xD;
          -  Regular use of known drugs of abuse.&#xD;
&#xD;
          -  Regular alcohol consumption within 6 months prior to the study defined as: For an&#xD;
             average weekly intake of &gt; 14 units for males. One unit is equivalent to 10 grams (g)&#xD;
             of alcohol: a can of mid-strength (equivalent to 375 mL) beer, 1 glass (100 mL) of&#xD;
             table wine or 1 measure (30 mL) of spirits (including rice wine).&#xD;
&#xD;
          -  History or regular use of tobacco- or nicotine-containing products within 6 months&#xD;
             prior to screening.&#xD;
&#xD;
          -  Sensitivity to any of the study treatments, or components thereof, or drug or other&#xD;
             allergy that, in the opinion of the investigator or medical monitor, contraindicates&#xD;
             participation in the study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <reference>
    <citation>Iida T, Nand RA, Ino H, Ogura H, Itoh H, Igarashi H, Numachi Y, Gross AS. Evaluation of the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Pyrimethamine in Healthy Male Subjects of Japanese and European Ancestry. Clin Pharmacol Drug Dev. 2020 Aug;9(6):768-773. doi: 10.1002/cpdd.771. Epub 2020 Jan 16.</citation>
    <PMID>31950646</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <results_first_submitted>November 16, 2018</results_first_submitted>
  <results_first_submitted_qc>March 26, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 27, 2019</results_first_posted>
  <last_update_submitted>March 17, 2020</last_update_submitted>
  <last_update_submitted_qc>March 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Japanese</keyword>
  <keyword>Caucasian</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>pyrimethamine</keyword>
  <keyword>toxoplasmosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Toxoplasmosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Pyrimethamine</mesh_term>
    <mesh_term>Calcium</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD is available via the Clinical Study Data Request site (click on the link provided below)</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>https://clinicalstudydatarequest.com/Posting.aspx?ID=20305</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 19, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03258762/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03258762/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted in healthy Japanese and Caucasian male participants to evaluate safety, tolerability and pharmacokinetic (PK) parameters of Pyrimethamine. This study was conducted at a single center in Australia.</recruitment_details>
      <pre_assignment_details>A total of 14 healthy participants were enrolled in this study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Healthy Japanese Participants</title>
          <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 milligram (mg) tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 milliliters (mL) of water.</description>
        </group>
        <group group_id="P2">
          <title>Healthy Caucasian Participants</title>
          <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy Japanese Participants</title>
          <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
        </group>
        <group group_id="B2">
          <title>Healthy Caucasian Participants</title>
          <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.0" spread="3.27"/>
                    <measurement group_id="B2" value="30.7" spread="6.02"/>
                    <measurement group_id="B3" value="29.9" spread="4.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Asian: Japanese Heritage/East Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White/Caucasian/European heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population is defined as all participants who administered at least one dose of study treatment and who have PK sample taken and analyzed.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population is defined as all participants who administered at least one dose of study treatment and who have PK sample taken and analyzed.</description>
          <population>Pharmacokinetic Population</population>
          <units>Nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="430.5" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours* nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59013.1" spread="15.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours* nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64670.3" spread="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours* nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8756.3" spread="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122.75" spread="21.499"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.000" lower_limit="1.00" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Milliliter per hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="773.2" spread="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="135330.9" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="371.1" spread="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours* nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41582.0" spread="26.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours* nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44869.1" spread="27.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours* nanogram per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6930.8" spread="19.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.000" lower_limit="1.000" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1/2 of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>T1/2 of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.46" spread="20.745"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL/F of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>CL/F of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Milliliters per hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1114.4" spread="27.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vd/F of Pyrimethamine in Healthy Caucasian Male Participants</title>
        <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
        <time_frame>Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
        <population>Pharmacokinetic Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Vd/F of Pyrimethamine in Healthy Caucasian Male Participants</title>
          <description>Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.</description>
          <population>Pharmacokinetic Population</population>
          <units>Milliliters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="157125.8" spread="16.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)</title>
        <description>An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who take at least one dose of study treatment were included in Safety Population.</description>
        <time_frame>Up to Day 23</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)</title>
          <description>An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who take at least one dose of study treatment were included in Safety Population.</description>
          <population>Safety Population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea.</title>
        <description>Blood samples were collected for the analysis of clinical chemistry parameters including glucose, sodium, calcium, potassium, and urea at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea.</title>
          <description>Blood samples were collected for the analysis of clinical chemistry parameters including glucose, sodium, calcium, potassium, and urea at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Millimoles per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Glucose, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.33" spread="0.403"/>
                    <measurement group_id="O2" value="-0.26" spread="0.310"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.43" spread="0.281"/>
                    <measurement group_id="O2" value="-0.10" spread="0.200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.60" spread="0.424"/>
                    <measurement group_id="O2" value="-0.37" spread="0.214"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Category title 4. : Glucose, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.43" spread="0.335"/>
                    <measurement group_id="O2" value="-0.09" spread="0.241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose, Follow-up (504 hours), n= 7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.24" spread="0.395"/>
                    <measurement group_id="O2" value="0.00" spread="0.276"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.116" spread="0.0608"/>
                    <measurement group_id="O2" value="-0.054" spread="0.0862"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.006" spread="0.0947"/>
                    <measurement group_id="O2" value="-0.033" spread="0.0670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.006" spread="0.0730"/>
                    <measurement group_id="O2" value="-0.033" spread="0.0739"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.083" spread="0.1224"/>
                    <measurement group_id="O2" value="-0.040" spread="0.0432"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.100" spread="0.0781"/>
                    <measurement group_id="O2" value="-0.042" spread="0.0637"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.427"/>
                    <measurement group_id="O2" value="0.00" spread="0.580"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.356"/>
                    <measurement group_id="O2" value="-0.11" spread="0.515"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.463"/>
                    <measurement group_id="O2" value="-0.21" spread="0.241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.216"/>
                    <measurement group_id="O2" value="-0.21" spread="0.515"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" spread="0.402"/>
                    <measurement group_id="O2" value="-0.22" spread="0.488"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="3.55"/>
                    <measurement group_id="O2" value="0.0" spread="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="3.05"/>
                    <measurement group_id="O2" value="1.0" spread="1.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="2.63"/>
                    <measurement group_id="O2" value="1.7" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="1.38"/>
                    <measurement group_id="O2" value="-0.3" spread="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="1.86"/>
                    <measurement group_id="O2" value="-0.5" spread="1.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" spread="0.772"/>
                    <measurement group_id="O2" value="1.01" spread="1.110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.26" spread="1.190"/>
                    <measurement group_id="O2" value="-0.03" spread="0.660"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" spread="1.053"/>
                    <measurement group_id="O2" value="-0.26" spread="0.885"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="0.896"/>
                    <measurement group_id="O2" value="1.06" spread="1.726"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea, Follow up,(504 hours) n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.99" spread="1.995"/>
                    <measurement group_id="O2" value="1.27" spread="1.317"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)</title>
        <description>Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphatase, ALT and AST at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)</title>
          <description>Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphatase, ALT and AST at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>International units per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Alkaline Phosphatase, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.0" spread="11.60"/>
                    <measurement group_id="O2" value="-3.3" spread="5.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.7" spread="10.67"/>
                    <measurement group_id="O2" value="-3.1" spread="2.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.0" spread="11.56"/>
                    <measurement group_id="O2" value="-4.1" spread="3.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.0" spread="12.00"/>
                    <measurement group_id="O2" value="-2.9" spread="5.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase, Follow-up (504 hours), n=7,6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.6" spread="11.18"/>
                    <measurement group_id="O2" value="-9.3" spread="5.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="5.03"/>
                    <measurement group_id="O2" value="-3.3" spread="2.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="6.23"/>
                    <measurement group_id="O2" value="-5.1" spread="4.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="5.53"/>
                    <measurement group_id="O2" value="-4.4" spread="8.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="9.84"/>
                    <measurement group_id="O2" value="-3.9" spread="2.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="11.25"/>
                    <measurement group_id="O2" value="-5.3" spread="4.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.4" spread="4.61"/>
                    <measurement group_id="O2" value="-1.9" spread="4.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.7" spread="5.12"/>
                    <measurement group_id="O2" value="-4.3" spread="6.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="5.32"/>
                    <measurement group_id="O2" value="-3.0" spread="7.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="9.81"/>
                    <measurement group_id="O2" value="-2.4" spread="5.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="4.16"/>
                    <measurement group_id="O2" value="-1.5" spread="6.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine.</title>
        <description>Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, bilirubin and creatinine at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine.</title>
          <description>Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, bilirubin and creatinine at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Micromoles per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Direct bilirubin, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="1.98"/>
                    <measurement group_id="O2" value="0.6" spread="0.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="1.27"/>
                    <measurement group_id="O2" value="0.7" spread="1.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="2.30"/>
                    <measurement group_id="O2" value="0.9" spread="1.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.60"/>
                    <measurement group_id="O2" value="0.9" spread="1.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin, Follow-up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.50"/>
                    <measurement group_id="O2" value="0.3" spread="1.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="5.16"/>
                    <measurement group_id="O2" value="3.1" spread="4.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="5.83"/>
                    <measurement group_id="O2" value="2.4" spread="5.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="8.10"/>
                    <measurement group_id="O2" value="1.0" spread="5.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" spread="5.83"/>
                    <measurement group_id="O2" value="-0.3" spread="5.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.4" spread="5.56"/>
                    <measurement group_id="O2" value="-1.7" spread="7.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.7" spread="8.16"/>
                    <measurement group_id="O2" value="26.6" spread="6.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.4" spread="5.06"/>
                    <measurement group_id="O2" value="30.1" spread="7.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.9" spread="5.08"/>
                    <measurement group_id="O2" value="24.6" spread="4.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.1" spread="6.18"/>
                    <measurement group_id="O2" value="14.9" spread="4.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="6.16"/>
                    <measurement group_id="O2" value="9.5" spread="7.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Clinical Chemistry Parameters: Protein</title>
        <description>Blood samples were collected for the analysis of clinical chemistry parameter including protein at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Clinical Chemistry Parameters: Protein</title>
          <description>Blood samples were collected for the analysis of clinical chemistry parameter including protein at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Gram per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.9" spread="4.06"/>
                    <measurement group_id="O2" value="-2.3" spread="4.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.6" spread="6.80"/>
                    <measurement group_id="O2" value="-2.9" spread="1.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.6" spread="7.32"/>
                    <measurement group_id="O2" value="-4.1" spread="2.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.4" spread="6.29"/>
                    <measurement group_id="O2" value="-2.4" spread="1.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.4" spread="4.69"/>
                    <measurement group_id="O2" value="-4.2" spread="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes</title>
        <description>Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value. Data was not available as all basophil values were below the detection limit. Hence, the change from baseline in basophil values were not calculated.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes</title>
          <description>Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value. Data was not available as all basophil values were below the detection limit. Hence, the change from baseline in basophil values were not calculated.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>10^9 cells per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Basophils, 24 hours, n=0, 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Basophils, 96 hours, n=0, 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Basophils, 168 hours, n=0, 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Basophils, 336 hours, n=0, 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Basophils, Follow up (504 hours), n=0, 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Eosinophils, 24 hours, n=4, 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.096"/>
                    <measurement group_id="O2" value="0.07" spread="0.058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophils, 96 hours, n=4, 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.150"/>
                    <measurement group_id="O2" value="0.00" spread="0.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophils, 168 hours, n=4, 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.115"/>
                    <measurement group_id="O2" value="0.00" spread="0.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophils, 336 hours, n=3, 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.100"/>
                    <measurement group_id="O2" value="0.00" spread="0.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophils, Follow up (504 hours), n=4, 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="0.058"/>
                    <measurement group_id="O2" value="-0.05" spread="0.071"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.27" spread="0.528"/>
                    <measurement group_id="O2" value="0.36" spread="0.251"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.11" spread="0.508"/>
                    <measurement group_id="O2" value="0.30" spread="0.277"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.574"/>
                    <measurement group_id="O2" value="0.26" spread="0.276"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.50" spread="0.616"/>
                    <measurement group_id="O2" value="0.09" spread="0.363"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.41" spread="0.441"/>
                    <measurement group_id="O2" value="0.00" spread="0.514"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.11" spread="0.107"/>
                    <measurement group_id="O2" value="0.04" spread="0.113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.190"/>
                    <measurement group_id="O2" value="-0.01" spread="0.227"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.186"/>
                    <measurement group_id="O2" value="0.00" spread="0.153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.09" spread="0.177"/>
                    <measurement group_id="O2" value="0.00" spread="0.115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="0.172"/>
                    <measurement group_id="O2" value="-0.03" spread="0.216"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.63" spread="0.939"/>
                    <measurement group_id="O2" value="-0.54" spread="0.702"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.76" spread="1.066"/>
                    <measurement group_id="O2" value="-0.79" spread="0.799"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.61" spread="1.128"/>
                    <measurement group_id="O2" value="-0.69" spread="0.546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.93" spread="1.181"/>
                    <measurement group_id="O2" value="-0.96" spread="0.516"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.09" spread="1.299"/>
                    <measurement group_id="O2" value="-0.97" spread="0.612"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.3" spread="18.82"/>
                    <measurement group_id="O2" value="-11.6" spread="27.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.1" spread="20.82"/>
                    <measurement group_id="O2" value="-6.3" spread="22.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.0" spread="26.58"/>
                    <measurement group_id="O2" value="-13.3" spread="38.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.4" spread="35.09"/>
                    <measurement group_id="O2" value="-27.3" spread="38.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.9" spread="31.49"/>
                    <measurement group_id="O2" value="-24.3" spread="44.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.00" spread="1.441"/>
                    <measurement group_id="O2" value="-0.09" spread="0.912"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.89" spread="1.624"/>
                    <measurement group_id="O2" value="-0.46" spread="1.149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.67" spread="1.738"/>
                    <measurement group_id="O2" value="-0.36" spread="0.735"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.50" spread="1.649"/>
                    <measurement group_id="O2" value="-0.77" spread="0.911"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes, Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.59" spread="1.757"/>
                    <measurement group_id="O2" value="-0.97" spread="1.159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Reticulocytes</title>
        <description>Blood samples were collected for the analysis of hematology parameter including reticulocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Reticulocytes</title>
          <description>Blood samples were collected for the analysis of hematology parameter including reticulocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Proportion of reticulocytes in blood</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0016" spread="0.00172"/>
                    <measurement group_id="O2" value="0.0003" spread="0.00125"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0017" spread="0.00544"/>
                    <measurement group_id="O2" value="-0.0006" spread="0.00162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0013" spread="0.00577"/>
                    <measurement group_id="O2" value="0.0009" spread="0.00212"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0011" spread="0.00430"/>
                    <measurement group_id="O2" value="0.0003" spread="0.00335"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0013" spread="0.00368"/>
                    <measurement group_id="O2" value="0.0017" spread="0.00308"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Hematocrit</title>
        <description>Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Hematocrit</title>
          <description>Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Proportion of red blood cells in blood</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.001" spread="0.0135"/>
                    <measurement group_id="O2" value="0.007" spread="0.0198"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.009" spread="0.0186"/>
                    <measurement group_id="O2" value="-0.006" spread="0.0127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.004" spread="0.0181"/>
                    <measurement group_id="O2" value="-0.006" spread="0.0162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.014" spread="0.0190"/>
                    <measurement group_id="O2" value="-0.016" spread="0.0215"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.036" spread="0.0230"/>
                    <measurement group_id="O2" value="-0.025" spread="0.0152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Hemoglobin</title>
        <description>Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Hemoglobin</title>
          <description>Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Gram per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="2.45"/>
                    <measurement group_id="O2" value="3.0" spread="5.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="5.71"/>
                    <measurement group_id="O2" value="0.0" spread="2.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="5.32"/>
                    <measurement group_id="O2" value="-1.7" spread="5.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.9" spread="4.95"/>
                    <measurement group_id="O2" value="-3.6" spread="4.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.1" spread="6.47"/>
                    <measurement group_id="O2" value="-6.0" spread="3.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin</title>
        <description>Blood samples were collected for the analysis of hematology parameter including mean corpuscular hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin</title>
          <description>Blood samples were collected for the analysis of hematology parameter including mean corpuscular hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Picogram</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.00"/>
                    <measurement group_id="O2" value="0.0" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.53"/>
                    <measurement group_id="O2" value="0.0" spread="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.82"/>
                    <measurement group_id="O2" value="-0.1" spread="0.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.90"/>
                    <measurement group_id="O2" value="-0.3" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.58"/>
                    <measurement group_id="O2" value="-0.2" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Volume</title>
        <description>Blood samples were collected for the analysis of hematology parameter including mean corpuscular volume at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Volume</title>
          <description>Blood samples were collected for the analysis of hematology parameter including mean corpuscular volume at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Femtoliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="0.98"/>
                    <measurement group_id="O2" value="-0.7" spread="2.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.90"/>
                    <measurement group_id="O2" value="-1.4" spread="1.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.11"/>
                    <measurement group_id="O2" value="-1.1" spread="1.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="0.98"/>
                    <measurement group_id="O2" value="-1.9" spread="1.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="1.27"/>
                    <measurement group_id="O2" value="-1.7" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Erythrocytes</title>
        <description>Blood samples were collected for the analysis of hematology parameter including erythrocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Erythrocytes</title>
          <description>Blood samples were collected for the analysis of hematology parameter including erythrocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>10^12 cells per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.026" spread="0.0820"/>
                    <measurement group_id="O2" value="0.100" spread="0.1943"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.101" spread="0.1642"/>
                    <measurement group_id="O2" value="0.006" spread="0.0680"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.024" spread="0.2204"/>
                    <measurement group_id="O2" value="-0.021" spread="0.1906"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n= 7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.187" spread="0.2051"/>
                    <measurement group_id="O2" value="-0.079" spread="0.1901"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.411" spread="0.2032"/>
                    <measurement group_id="O2" value="-0.183" spread="0.1229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Urinalysis Parameter</title>
        <description>The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of can be read as Trace, + and ++ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.</description>
        <time_frame>Day -1, 24, 96, 168, 336 and follow up (504 hours)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Urinalysis Parameter</title>
          <description>The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of can be read as Trace, + and ++ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.</description>
          <population>Safety Population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ketones, 336 hours, ++</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ketones, 336 hours, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ketones, follow up (504 hours), +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Occult blood, 336 hours, +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Occult blood, follow up, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein, Day -1, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein, 24 hours, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein, 96 hours, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein, 168 hours, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein, 336 hours, trace</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Specific Gravity at Indicated Time Points</title>
        <description>Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.</description>
        <time_frame>Day -1, 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Specific Gravity at Indicated Time Points</title>
          <description>Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day -1, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0127" spread="0.00856"/>
                    <measurement group_id="O2" value="1.0177" spread="0.00720"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0214" spread="0.00621"/>
                    <measurement group_id="O2" value="1.0256" spread="0.00665"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0211" spread="0.00832"/>
                    <measurement group_id="O2" value="1.0236" spread="0.00550"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0211" spread="0.00821"/>
                    <measurement group_id="O2" value="1.0207" spread="0.00562"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0193" spread="0.00871"/>
                    <measurement group_id="O2" value="1.0246" spread="0.00945"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0183" spread="0.00720"/>
                    <measurement group_id="O2" value="1.0222" spread="0.00728"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Urine Potential of Hydrogen (pH) at Indicated Time Points</title>
        <description>Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).</description>
        <time_frame>Day -1, 24, 96, 168, 336 hours and follow up (504 hours)</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Potential of Hydrogen (pH) at Indicated Time Points</title>
          <description>Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>pH</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day -1, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.21" spread="0.699"/>
                    <measurement group_id="O2" value="6.86" spread="1.144"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.86" spread="0.244"/>
                    <measurement group_id="O2" value="5.79" spread="0.567"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.79" spread="0.393"/>
                    <measurement group_id="O2" value="6.07" spread="0.345"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.93" spread="0.535"/>
                    <measurement group_id="O2" value="6.07" spread="0.450"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.00" spread="0.577"/>
                    <measurement group_id="O2" value="6.00" spread="0.408"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow up (504 hours), n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.43" spread="0.673"/>
                    <measurement group_id="O2" value="6.08" spread="0.492"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)</title>
        <description>Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)</title>
          <description>Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Millimeter of mercury (mmHg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DBP, 4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.0" spread="6.98"/>
                    <measurement group_id="O2" value="-0.7" spread="6.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.4" spread="6.02"/>
                    <measurement group_id="O2" value="-0.3" spread="8.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.9" spread="5.24"/>
                    <measurement group_id="O2" value="-2.9" spread="4.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.4" spread="6.50"/>
                    <measurement group_id="O2" value="2.0" spread="2.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 72 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" spread="9.11"/>
                    <measurement group_id="O2" value="-4.6" spread="5.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.9" spread="10.14"/>
                    <measurement group_id="O2" value="-2.7" spread="9.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 120 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.1" spread="10.02"/>
                    <measurement group_id="O2" value="-3.4" spread="11.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 144 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.6" spread="8.81"/>
                    <measurement group_id="O2" value="-5.4" spread="7.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.1" spread="10.25"/>
                    <measurement group_id="O2" value="-1.0" spread="6.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.7" spread="9.66"/>
                    <measurement group_id="O2" value="-5.3" spread="4.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, 504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.3" spread="8.73"/>
                    <measurement group_id="O2" value="-0.7" spread="10.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="5.93"/>
                    <measurement group_id="O2" value="1.3" spread="7.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="3.41"/>
                    <measurement group_id="O2" value="1.0" spread="9.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="6.32"/>
                    <measurement group_id="O2" value="-3.4" spread="11.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="6.20"/>
                    <measurement group_id="O2" value="-1.1" spread="8.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 72 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="6.78"/>
                    <measurement group_id="O2" value="-4.6" spread="11.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="9.96"/>
                    <measurement group_id="O2" value="2.6" spread="8.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 120 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.3" spread="5.53"/>
                    <measurement group_id="O2" value="0.9" spread="7.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP,144 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.6" spread="7.30"/>
                    <measurement group_id="O2" value="-3.3" spread="6.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="8.18"/>
                    <measurement group_id="O2" value="0.9" spread="6.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.9" spread="11.05"/>
                    <measurement group_id="O2" value="-2.6" spread="8.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, 504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.0" spread="7.92"/>
                    <measurement group_id="O2" value="-1.5" spread="5.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pulse Rate</title>
        <description>Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pulse Rate</title>
          <description>Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="5.19"/>
                    <measurement group_id="O2" value="4.7" spread="6.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="11.45"/>
                    <measurement group_id="O2" value="10.1" spread="6.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" spread="8.38"/>
                    <measurement group_id="O2" value="-5.0" spread="4.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" spread="18.12"/>
                    <measurement group_id="O2" value="-0.3" spread="4.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="11.26"/>
                    <measurement group_id="O2" value="-0.3" spread="4.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="13.44"/>
                    <measurement group_id="O2" value="0.6" spread="3.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="9.58"/>
                    <measurement group_id="O2" value="2.0" spread="6.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>144 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="16.74"/>
                    <measurement group_id="O2" value="-0.1" spread="3.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="17.62"/>
                    <measurement group_id="O2" value="7.1" spread="7.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="17.61"/>
                    <measurement group_id="O2" value="1.6" spread="7.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="18.52"/>
                    <measurement group_id="O2" value="2.2" spread="6.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Temperature</title>
        <description>Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Temperature</title>
          <description>Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Celsius</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.195"/>
                    <measurement group_id="O2" value="0.27" spread="0.095"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" spread="0.172"/>
                    <measurement group_id="O2" value="0.26" spread="0.230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.07" spread="0.150"/>
                    <measurement group_id="O2" value="-0.01" spread="0.241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="0.190"/>
                    <measurement group_id="O2" value="-0.04" spread="0.113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.271"/>
                    <measurement group_id="O2" value="-0.10" spread="0.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.11" spread="0.212"/>
                    <measurement group_id="O2" value="-0.04" spread="0.098"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.191"/>
                    <measurement group_id="O2" value="-0.17" spread="0.189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>144 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.14" spread="0.223"/>
                    <measurement group_id="O2" value="-0.09" spread="0.107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>168 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.09" spread="0.186"/>
                    <measurement group_id="O2" value="0.01" spread="0.135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>336 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.27" spread="0.315"/>
                    <measurement group_id="O2" value="-0.13" spread="0.170"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.26" spread="0.479"/>
                    <measurement group_id="O2" value="-0.07" spread="0.242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, and QT Interval Corrected for Heart Rate by Fredericia's Formula (QTcF) Interval</title>
        <description>A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically measures PR, QRS, QT, and QTcF intervals. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, and QT Interval Corrected for Heart Rate by Fredericia's Formula (QTcF) Interval</title>
          <description>A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically measures PR, QRS, QT, and QTcF intervals. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Millisecond</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PR Interval, 4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.3" spread="4.07"/>
                    <measurement group_id="O2" value="-4.6" spread="5.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR Interval, 12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.7" spread="10.52"/>
                    <measurement group_id="O2" value="-5.9" spread="3.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR Interval, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.1" spread="8.67"/>
                    <measurement group_id="O2" value="-0.1" spread="5.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR Interval, 48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.0" spread="33.80"/>
                    <measurement group_id="O2" value="0.3" spread="5.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR Interval, 504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.3" spread="10.05"/>
                    <measurement group_id="O2" value="2.2" spread="9.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS duration, 4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="1.40"/>
                    <measurement group_id="O2" value="-2.1" spread="3.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS duration, 12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="3.86"/>
                    <measurement group_id="O2" value="-0.6" spread="4.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS duration, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="2.50"/>
                    <measurement group_id="O2" value="-2.0" spread="3.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS duration, 48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="11.16"/>
                    <measurement group_id="O2" value="0.4" spread="7.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS duration, 504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="3.59"/>
                    <measurement group_id="O2" value="-0.8" spread="8.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT interval, 4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" spread="15.59"/>
                    <measurement group_id="O2" value="-20.4" spread="14.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT interval, 12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.9" spread="29.17"/>
                    <measurement group_id="O2" value="-21.7" spread="20.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT interval, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" spread="25.79"/>
                    <measurement group_id="O2" value="-7.3" spread="7.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT interval, 48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="21.55"/>
                    <measurement group_id="O2" value="-14.7" spread="13.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT interval, 504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.7" spread="32.07"/>
                    <measurement group_id="O2" value="-9.2" spread="22.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval, 4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.9" spread="10.42"/>
                    <measurement group_id="O2" value="-6.6" spread="12.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval, 12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.7" spread="8.94"/>
                    <measurement group_id="O2" value="-5.7" spread="12.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval, 24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="7.71"/>
                    <measurement group_id="O2" value="-0.1" spread="12.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval, 48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="40.64"/>
                    <measurement group_id="O2" value="-2.9" spread="12.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval, 504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="12.84"/>
                    <measurement group_id="O2" value="-2.2" spread="9.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of ECG Parameter: ECG Mean Heart Rate</title>
        <description>A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically calculates mean ECG heart rate. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
        <time_frame>Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours</time_frame>
        <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Japanese Participants</title>
            <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
          <group group_id="O2">
            <title>Healthy Caucasian Participants</title>
            <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of ECG Parameter: ECG Mean Heart Rate</title>
          <description>A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically calculates mean ECG heart rate. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.</description>
          <population>Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).</population>
          <units>Beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="11.37"/>
                    <measurement group_id="O2" value="6.0" spread="6.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="19.91"/>
                    <measurement group_id="O2" value="7.1" spread="5.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.3" spread="19.67"/>
                    <measurement group_id="O2" value="3.1" spread="6.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours, n=7, 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="15.64"/>
                    <measurement group_id="O2" value="5.0" spread="5.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>504 hours, n=7, 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.1" spread="25.71"/>
                    <measurement group_id="O2" value="3.2" spread="7.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23</time_frame>
      <desc>Non-serious AEs and SAEs for Safety Population was reported</desc>
      <group_list>
        <group group_id="E1">
          <title>Healthy Japanese Participants</title>
          <description>Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
        </group>
        <group group_id="E2">
          <title>Healthy Caucasian Participants</title>
          <description>Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
      <email>GSKClinicalSupportHD@gsk.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03258762
org study id: 204678
nct id: NCT03258762
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pyrimethamine in combination with a sulphonamide is known to be effective in the treatment of
      toxoplasmosis. However, Pyrimethamine has not been approved by the Japanese regulatory body
      (Pharmaceutical and Medical Devices Agency [PMDA]/ Ministry of Health, Labor and Welfare
      [MHLW]). The pharmacokinetics (PK) of Pyrimethamine has been investigated following
      administration of Sulfadoxine/Pyrimethamine tablet in healthy Japanese subjects. However, the
      study did not provide sufficient information for approval of Pyrimethamine in Japan; hence,
      PMDA has requested confirmation of the PK of Pyrimethamine in another PK study in Japanese
      and Caucasian healthy subjects. This study will be a single centre, open-label,
      parallel-group, single oral dose study to evaluate the PK, safety and tolerability of
      Pyrimethamine in healthy Japanese and Caucasian male subjects. Subjects will undergo a
      screening visit within 30 days prior to first dose of the study drug. On Day 1, subjects will
      be administered a single oral dose of pyrimethamine 50 milligrams (mg) along with calcium
      folinate 15 mg after an overnight fast of at least 10 hours. Subjects will continue to
      receive calcium folinate once daily until Day 8 of the treatment period. Blood sampling for
      PK analysis and safety assessments will be performed prior to dosing and over 22 days after
      dosing. Each subject will participate in the study for approximately 2 months from screening
      to follow-up.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population is defined as all participants who administered at least one dose of study treatment and who have PK sample taken and analyzed.
measure: Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Cmax of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Tmax of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: T1/2 of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: CL/F of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Vd/F of Pyrimethamine in Healthy Caucasian Male Participants
time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
time frame: Up to Day 23
description: An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who take at least one dose of study treatment were included in Safety Population.
measure: Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea.
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of clinical chemistry parameters including glucose, sodium, calcium, potassium, and urea at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphatase, ALT and AST at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine.
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, bilirubin and creatinine at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline of Clinical Chemistry Parameters: Protein
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of clinical chemistry parameter including protein at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value. Data was not available as all basophil values were below the detection limit. Hence, the change from baseline in basophil values were not calculated.
measure: Change From Baseline in Hematology Parameter: Reticulocytes
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameter including reticulocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Hematocrit
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Hemoglobin
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameter including mean corpuscular hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Mean Corpuscular Volume
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameter including mean corpuscular volume at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Erythrocytes
time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
description: Blood samples were collected for the analysis of hematology parameter including erythrocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Number of Participants With Abnormal Urinalysis Parameter
time frame: Day -1, 24, 96, 168, 336 and follow up (504 hours)
description: The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of can be read as Trace, + and ++ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.
measure: Specific Gravity at Indicated Time Points
time frame: Day -1, 24, 96, 168, 336 hours and follow up (504 hours)
description: Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
measure: Urine Potential of Hydrogen (pH) at Indicated Time Points
time frame: Day -1, 24, 96, 168, 336 hours and follow up (504 hours)
description: Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
measure: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours
description: Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Pulse Rate
time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours
description: Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline in Temperature
time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours
description: Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, and QT Interval Corrected for Heart Rate by Fredericia's Formula (QTcF) Interval
time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours
description: A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically measures PR, QRS, QT, and QTcF intervals. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
measure: Change From Baseline of ECG Parameter: ECG Mean Heart Rate
time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours
description: A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically calculates mean ECG heart rate. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
arm group label: Healthy Japanese male subjects
arm group type: Experimental
description: Healthy Japanese male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.
arm group label: Healthy Caucasian male subjects
arm group type: Experimental
description: Healthy Caucasian male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.
intervention type: Drug
intervention name: Pyrimethamine
description: Pyrimethamine will be available as 25 mg tablets. Subjects will be orally administered two pyrimethamine tablets on Day 1 in a fasted condition with 240 mL of water.
arm group label: Healthy Caucasian male subjects
arm group label: Healthy Japanese male subjects
intervention type: Drug
intervention name: Calcium folinate
description: Calcium folinate will be available as 5 mg tablets. Subjects will be orally administered three calcium folinate tablets on Day 1 along with pyrimethamine followed by once daily administration of calcium folinate until Day 8. Each administration will be with 240 mL water.
arm group label: Healthy Caucasian male subjects
arm group label: Healthy Japanese male subjects
criteria: 
gender: Male
gender based: Yes
minimum age: 20 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: Australia
citation: Iida T, Nand RA, Ino H, Ogura H, Itoh H, Igarashi H, Numachi Y, Gross AS. Evaluation of the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Pyrimethamine in Healthy Male Subjects of Japanese and European Ancestry. Clin Pharmacol Drug Dev. 2020 Aug;9(6):768-773. doi: 10.1002/cpdd.771. Epub 2020 Jan 16.
PMID: 31950646
responsible party type: Sponsor
mesh term: Toxoplasmosis
mesh term: Leucovorin
mesh term: Pyrimethamine
mesh term: Calcium
mesh term: Levoleucovorin
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: https://clinicalstudydatarequest.com/Posting.aspx?ID=20305
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 