<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/NCT03031496</url>
  </required_header>
  <id_info>
    <org_study_id>205694</org_study_id>
    <nct_id>NCT03031496</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study Between GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Tablets and Reference Product in Healthy Adult Participants Under Fasting Conditions</brief_title>
  <official_title>An Open-label, Randomized, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Fixed Dose Combination Tablets Versus Reference Product in Healthy Adult Participants Under Fasting Conditions</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>
      The combination of the diuretics amiloride hydrochloride (HCl) and hydrochlorothiazide (HCTZ)&#xD;
      (GSK3542503) is indicated for the treatment of hypertension, congestive heart failure and&#xD;
      hepatic cirrhosis with ascites and edema. This first time in human (FTIH) study is aimed to&#xD;
      determine whether the test product GSK3542503 is bioequivalent to the reference (ref)&#xD;
      hydrochlorothiazide 50 milligram (mg)/amiloride hydrochlorothiazide 5 mg in healthy adult&#xD;
      participants under fasting conditions based on pharmacokinetic (PK) endpoints. This is a&#xD;
      phase I, open label, balanced, randomized, single dose, two-way crossover study, enroling&#xD;
      approximately 42 healthy participants at a single center. Study participants will be&#xD;
      randomized to one of two treatment sequences (A-B or B-A) in accordance with the&#xD;
      randomization schedule. A single dose of one of the two treatments A (Test: GSK3542503, a&#xD;
      hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination) or B&#xD;
      (Reference: Moduretic, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed&#xD;
      dose combination), will be administered on Day 1, in each treatment period. Each participant&#xD;
      will participate in both treatment periods and receive a single dose of each treatment. The&#xD;
      treatment periods will be separated by a washout period of at least 7 days and no more than&#xD;
      14 days. The total duration in the study for each participant is expected to be 5 to 7 weeks,&#xD;
      from screening to his or her last visit. A maximum of 42 participants will be randomized such&#xD;
      that at least 32 evaluable participants complete the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 17, 2017</start_date>
  <completion_date type="Actual">April 10, 2017</completion_date>
  <primary_completion_date type="Actual">April 10, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride</measure>
    <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
    <description>Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</measure>
    <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
    <description>Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</measure>
    <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
    <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the AUC (0-inf) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</measure>
    <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
    <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Median and full range has been presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</measure>
    <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
    <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between percent AUCex of the test and reference products in relation to the conventional bioequivalence range. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</measure>
    <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
    <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period</measure>
    <time_frame>Up to 25 days</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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Only those participants with data available at the specified time points were analyzed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Serum ALT, alk. phosph. and AST levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Urea Nitrogen (BUN) Levels at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Serum BUN levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Serum calcium, chloride, glucose, magnesium, potassium and sodium levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Serum creatinine, direct bilirubin and total bilirubin levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Protein Levels at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Serum total protein levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Rate Values at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Vital sign measurements including respiratory rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse Rate Values at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Temperature Values at Indicated Time Points</measure>
    <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
    <description>Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets)</intervention_name>
    <description>GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) are cream-colored, circular, flat faced uncoated tablets with beveled edges having break line on one side and &quot;BD&quot; embossed on the other side.</description>
    <arm_group_label>Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg</arm_group_label>
    <arm_group_label>Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)</intervention_name>
    <description>Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) tablets are peach-colored, half scored, diamond shaped tablets marked &quot;MSD917&quot;.</description>
    <arm_group_label>Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg</arm_group_label>
    <arm_group_label>Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be between18 and 65 years of age inclusive, at the time of signing&#xD;
             the informed consent.&#xD;
&#xD;
          -  Healthy, non-smoker, as determined by the investigator or medically qualified designee&#xD;
             based on a medical evaluation including medical history, physical examination,&#xD;
             laboratory tests, and cardiac monitoring.&#xD;
&#xD;
          -  A participant with a clinical abnormality or laboratory parameter(s) which is/are not&#xD;
             specifically listed in the inclusion or exclusion criteria, outside the normal&#xD;
             reference range for the population being studied may be included only if the&#xD;
             investigator in consultation with the medical monitor if required, agree and document&#xD;
             that the finding is unlikely to introduce additional risk factors and will not&#xD;
             interfere with the study procedures.&#xD;
&#xD;
          -  Body weight &gt;=50 kilogram (kg) and body mass index (BMI) within the range 19-30&#xD;
             kg/meter^2(inclusive).&#xD;
&#xD;
          -  Healthy male or female participants&#xD;
&#xD;
               -  Male participants must agree to use contraception for 3 days after each dose of&#xD;
                  study treatment and refrain from donating sperm during that period.&#xD;
&#xD;
               -  A female participant is eligible to participate if she is not pregnant, not&#xD;
                  breastfeeding, and at least one of the following conditions applies: not a woman&#xD;
                  of childbearing potential (WOCBP), or a WOCBP who agrees to follow the&#xD;
                  contraceptive guidance during the treatment period and for at least 30 days after&#xD;
                  the last dose of study treatment.&#xD;
&#xD;
        The investigator is responsible for ensuring that male and female study participants&#xD;
        understand how to correctly use the methods of contraception.&#xD;
&#xD;
        - Capable of giving signed informed consent, which includes compliance with the&#xD;
        requirements and restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,&#xD;
             endocrine, hematological, or neurological disorders capable of significantly altering&#xD;
             the absorption, metabolism, or elimination of drugs; constituting a risk when taking&#xD;
             the study treatment; or interfering with the interpretation of data.&#xD;
&#xD;
          -  Abnormal renal function measured by creatinine clearance.&#xD;
&#xD;
          -  Presence of hyperkalemia where the serum potassium is greater than upper limit of&#xD;
             normal (ULN).&#xD;
&#xD;
          -  History or known acute angle closure glaucoma or ocular complaints, which could&#xD;
             increase the risk of ophthalmic reactions as deemed by the investigator.&#xD;
&#xD;
          -  Abnormal BP as determined by the investigator.&#xD;
&#xD;
          -  Alanine transaminase (ALT) &gt;1.5 times ULN.&#xD;
&#xD;
          -  Bilirubin &gt;1.5 times ULN (isolated bilirubin &gt;1.5 times ULN is acceptable if bilirubin&#xD;
             is fractionated and direct bilirubin &lt;35 percentage).&#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;
          -  QT interval corrected for heart rate according to Bazett's formula (QTcB) &gt;450&#xD;
             milliseconds (msec). For purposes of data analysis, only QTcB, will be used.&#xD;
&#xD;
          -  Past or intended use of over-the-counter or prescription medication including herbal&#xD;
             medications, within 14 days prior to dosing. Specific medications listed in protocol&#xD;
             of this study may be allowed.&#xD;
&#xD;
          -  Where participation in the study would result in loss of blood or blood products in&#xD;
             excess of 500 milliliter (mL) within 90 days.&#xD;
&#xD;
          -  Exposure to more than 4 new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Current enrolment or past participation within the last 90 days before signing of&#xD;
             consent in this or any other clinical study involving an investigational study&#xD;
             treatment.&#xD;
&#xD;
          -  Presence of hepatitis B surface antigen (HBsAg) at screening, or a positive hepatitis&#xD;
             C antibody test result at screening. Participants with positive hepatitis C antibody&#xD;
             due to prior resolved disease can be enrolled, only if a confirmatory negative&#xD;
             hepatitis C ribonucleic acid (RNA) test is obtained.&#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;
          -  Sensitivity to heparin or heparin-induced thrombocytopenia.&#xD;
&#xD;
          -  Sensitivity to any of the study treatments, or components thereof, or drug or other&#xD;
             allergy including allergy to penicillin and sulfonamides that, in the opinion of the&#xD;
             investigator or medical monitor, contraindicates participation in the study.&#xD;
&#xD;
          -  Regular alcohol consumption within 6 months prior to the study defined as an average&#xD;
             weekly intake of &gt;21 units for males or &gt; 14 units for females. One unit is equivalent&#xD;
             to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of&#xD;
             wine or 1 (25 mL) measure of spirits.&#xD;
&#xD;
          -  Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or&#xD;
             nicotine-containing products within 6 months prior to screening.&#xD;
&#xD;
          -  Participants with any risk as defined in protocol of this study should be excluded&#xD;
             from participation in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 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>Bloemfontein</city>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <results_first_submitted>April 6, 2018</results_first_submitted>
  <results_first_submitted_qc>June 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 31, 2018</results_first_posted>
  <last_update_submitted>May 6, 2021</last_update_submitted>
  <last_update_submitted_qc>May 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cross-over</keyword>
  <keyword>Hydrochlorothiazide</keyword>
  <keyword>Amiloride hydrochloride</keyword>
  <keyword>Phase I</keyword>
  <keyword>GSK3542503</keyword>
  <keyword>Bioequivalence</keyword>
  <keyword>FTIH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrochlorothiazide</mesh_term>
    <mesh_term>Amiloride</mesh_term>
    <mesh_term>Amiloride, hydrochlorothiazide drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study is 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 (copy the URL below to your browser)</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=20806</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03031496/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This is a Phase I, open label, balanced, randomized, single dose, two-way crossover study, enrolling 42 healthy participants at a single center in South Africa.</recruitment_details>
      <pre_assignment_details>Total 42 participants were enrolled and randomized to receive a single oral dose of study treatment in a cross-over manner.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment A Followed by Treatment B</title>
          <description>Eligible participants received a single oral dose of GSK3542503 (BIDURET), hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 1. It was followed by a wash out period of 7 to 14 days. Participants received a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 2</description>
        </group>
        <group group_id="P2">
          <title>Treatment B Followed by Treatment A</title>
          <description>Eligible participants received a single dose of moduretic, hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 1. It was followed by a wash out period of 7 to 14 days. Participants received a single oral dose of GSK3542503 (BIDURET), hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination in Treatment Period 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Subjects</title>
          <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination (either test or reference product) in each of the two treatment periods, separated by a wash out period of seven calendar days.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="42"/>
          </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="24.1" spread="4.13"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black or African American Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mixed Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride</title>
        <description>Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.</description>
        <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
        <population>PK Population comprised of All participants who completed the study and for whom primary PK parameters was calculated for all treatment periods.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride</title>
          <description>Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.</description>
          <population>PK Population comprised of All participants who completed the study and for whom primary PK parameters was calculated for all treatment periods.</population>
          <units>Hour x nanograms/milliliter (h*ng/mL)</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="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hydrochlorothiazide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2160" spread="22.0"/>
                    <measurement group_id="O2" value="2360" spread="18.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amiloride</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.3" spread="22.9"/>
                    <measurement group_id="O2" value="94.1" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence of hydrochlorothiazide and amiloride hydrochloride was determined.</non_inferiority_desc>
            <param_type>Least square mean ratio</param_type>
            <param_value>91.52</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>87.77</ci_lower_limit>
            <ci_upper_limit>95.43</ci_upper_limit>
            <estimate_desc>Comparison of AUC (0-t) of hydrochlorothiazide for test and reference product has been presented.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence of hydrochlorothiazide and amiloride hydrochloride was determined.</non_inferiority_desc>
            <param_type>Least square mean ratio</param_type>
            <param_value>102.42</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>98.12</ci_lower_limit>
            <ci_upper_limit>106.91</ci_upper_limit>
            <estimate_desc>Comparison of AUC (0-t) of amiloride for test and reference product has been presented.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
        <description>Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.</description>
        <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
        <population>PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
          <description>Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.</description>
          <population>PK Population</population>
          <units>ng/mL</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="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hydrochlorothiazide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="312" spread="28.5"/>
                    <measurement group_id="O2" value="377" spread="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amiloride</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.27" spread="26.8"/>
                    <measurement group_id="O2" value="8.92" spread="25.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence of hydrochlorothiazide and amiloride hydrochloride was determined.</non_inferiority_desc>
            <param_type>Least square mean ratio</param_type>
            <param_value>82.86</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.37</ci_lower_limit>
            <ci_upper_limit>88.74</ci_upper_limit>
            <estimate_desc>Comparison of Cmax of hydrochlorothiazide for test and reference product has been presented.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence of hydrochlorothiazide and amiloride hydrochloride was determined.</non_inferiority_desc>
            <param_type>Least square mean ratio</param_type>
            <param_value>103.92</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>97.42</ci_lower_limit>
            <ci_upper_limit>110.86</ci_upper_limit>
            <estimate_desc>Comparison of Cmax of amiloride for test and reference product has been presented.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
        <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the AUC (0-inf) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
        <population>PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
          <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the AUC (0-inf) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>PK Population</population>
          <units>h*ng/mL</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="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hydrochlorothiazide; n= 37, 38</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2310" spread="20.8"/>
                    <measurement group_id="O2" value="2490" spread="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amiloride; n= 22, 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="117" spread="19.5"/>
                    <measurement group_id="O2" value="112" spread="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence of hydrochlorothiazide and amiloride hydrochloride was determined.</non_inferiority_desc>
            <param_type>Least square mean ratio</param_type>
            <param_value>92.37</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>88.75</ci_lower_limit>
            <ci_upper_limit>96.12</ci_upper_limit>
            <estimate_desc>Comparison of Tmax of hydrochlorothiazide for test and reference product has been presented.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least square mean ratio</param_type>
            <param_value>101.47</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>97.84</ci_lower_limit>
            <ci_upper_limit>105.23</ci_upper_limit>
            <estimate_desc>Comparison of Tmax of amiloride for test and reference product has been presented.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
        <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Median and full range has been presented.</description>
        <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
        <population>PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
          <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Median and full range has been presented.</description>
          <population>PK Population</population>
          <units>Hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hydrochlorothiazide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.505" lower_limit="1.01" upper_limit="4.51"/>
                    <measurement group_id="O2" value="1.509" lower_limit="0.67" upper_limit="3.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amiloride</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.507" lower_limit="1.50" upper_limit="4.51"/>
                    <measurement group_id="O2" value="2.508" lower_limit="1.00" upper_limit="4.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
        <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between percent AUCex of the test and reference products in relation to the conventional bioequivalence range. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
        <population>PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
          <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between percent AUCex of the test and reference products in relation to the conventional bioequivalence range. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>PK Population</population>
          <units>Percent of area</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="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hydrochlorothiazide; n= 37, 38</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.24" spread="37.7"/>
                    <measurement group_id="O2" value="4.63" spread="33.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amiloride; n= 22, 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.68" spread="35.7"/>
                    <measurement group_id="O2" value="10.7" spread="44.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
        <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3</time_frame>
        <population>PK Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma</title>
          <description>Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>PK Population</population>
          <units>Hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hydrochlorothiazide; n= 37, 38</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.4" lower_limit="8.47" upper_limit="18.8"/>
                    <measurement group_id="O2" value="11.3" lower_limit="8.01" upper_limit="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amiloride; n= 22, 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.2" lower_limit="11.3" upper_limit="22.2"/>
                    <measurement group_id="O2" value="16.6" lower_limit="10.9" upper_limit="23.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period</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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Only those participants with data available at the specified time points were analyzed</description>
        <time_frame>Up to 25 days</time_frame>
        <population>Safety Population comprised of all randomized participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period</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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Only those participants with data available at the specified time points were analyzed</description>
          <population>Safety Population comprised of all randomized participants who received at least 1 dose of study treatment.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>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>Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points</title>
        <description>Serum ALT, alk. phosph. and AST levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points</title>
          <description>Serum ALT, alk. phosph. and AST levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
          <population>Safety Population</population>
          <units>Unit per liter (U/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ALT;Period 1 (P1);Day -1;24 hour pre-dose;n=21,21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8" spread="10.55"/>
                    <measurement group_id="O2" value="16.6" spread="6.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT; P1; Day 3; 48 hour post-dose; n= 21,20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.9" spread="7.92"/>
                    <measurement group_id="O2" value="14.1" spread="5.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT; P2; Day -1; 24 hour pre-dose; n= 19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.8" spread="7.03"/>
                    <measurement group_id="O2" value="17.6" spread="9.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.8" spread="7.18"/>
                    <measurement group_id="O2" value="16.9" spread="10.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alk.phosph.; P1; Day -1; 24 hour pre-dose; n=21,21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.5" spread="16.59"/>
                    <measurement group_id="O2" value="71.1" spread="13.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alk.phosph.; P1; Day 3; 48 hour post-dose; n=21,20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.1" spread="17.83"/>
                    <measurement group_id="O2" value="69.9" spread="14.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alk.phosph.; P2; Day -1; 24 hour pre-dose; n=19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.1" spread="12.52"/>
                    <measurement group_id="O2" value="63.6" spread="18.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alk.phosph.; P2; Day 3; 48 hour post-dose; n=19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.8" spread="13.76"/>
                    <measurement group_id="O2" value="65.2" spread="15.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST; P1; Day -1; 24 hour pre-dose; n=21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.9" spread="8.56"/>
                    <measurement group_id="O2" value="20.1" spread="4.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST; P1; Day 3; 48 hour post-dose; n=21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.5" spread="4.26"/>
                    <measurement group_id="O2" value="17.8" spread="3.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST; P2; Day -1; 24 hour pre-dose; n=19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.6" spread="5.81"/>
                    <measurement group_id="O2" value="21.1" spread="5.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST; P2; Day 3; 48 hour post-dose; n=19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.9" spread="4.67"/>
                    <measurement group_id="O2" value="18.4" spread="5.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Blood Urea Nitrogen (BUN) Levels at Indicated Time Points</title>
        <description>Serum BUN levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Blood Urea Nitrogen (BUN) Levels at Indicated Time Points</title>
          <description>Serum BUN levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
          <population>Safety Population</population>
          <units>Milligrams per deciliter (mg/dL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>P1; Day-1; 24 hour pre-dose; n=21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.519" spread="3.327"/>
                    <measurement group_id="O2" value="12.702" spread="3.954"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day 3; 48 hour post-dose; n=21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.970" spread="3.626"/>
                    <measurement group_id="O2" value="15.593" spread="3.020"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day -1; 24 hour pre-dose; n=19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.185" spread="2.345"/>
                    <measurement group_id="O2" value="12.164" spread="3.216"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day 3; 48 hour post-dose; n=19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.372" spread="4.446"/>
                    <measurement group_id="O2" value="15.208" spread="3.493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points</title>
        <description>Serum calcium, chloride, glucose, magnesium, potassium and sodium levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points</title>
          <description>Serum calcium, chloride, glucose, magnesium, potassium and sodium levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
          <population>Safety Population</population>
          <units>Millimoles per liter (Mmol/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Calcium; P1; Day-1; 24 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.400" spread="0.075"/>
                    <measurement group_id="O2" value="2.418" spread="0.085"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium; P1; Day 3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.396" spread="0.078"/>
                    <measurement group_id="O2" value="2.393" spread="0.071"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.374" spread="0.053"/>
                    <measurement group_id="O2" value="2.335" spread="0.074"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.415" spread="0.078"/>
                    <measurement group_id="O2" value="2.379" spread="0.069"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride; P1; Day-1; 24 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.80" spread="2.286"/>
                    <measurement group_id="O2" value="103.62" spread="2.225"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride; P1; Day 3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="103.27" spread="1.755"/>
                    <measurement group_id="O2" value="102.63" spread="2.011"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.36" spread="1.729"/>
                    <measurement group_id="O2" value="104.85" spread="2.252"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="102.62" spread="1.985"/>
                    <measurement group_id="O2" value="103.49" spread="1.882"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose; P1; Day-1; 24 hour pre-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.746" spread="0.777"/>
                    <measurement group_id="O2" value="4.643" spread="0.427"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose; P1; Day 3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.006" spread="0.597"/>
                    <measurement group_id="O2" value="4.827" spread="0.368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.754" spread="0.316"/>
                    <measurement group_id="O2" value="4.765" spread="0.354"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.652" spread="0.357"/>
                    <measurement group_id="O2" value="4.732" spread="0.282"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Magnesium; P1; Day-1; 24 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.782" spread="0.066"/>
                    <measurement group_id="O2" value="0.801" spread="0.049"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Magnesium; P1; Day 3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.781" spread="0.039"/>
                    <measurement group_id="O2" value="0.804" spread="0.044"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Magnesium; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.826" spread="0.053"/>
                    <measurement group_id="O2" value="0.805" spread="0.053"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Magnesium; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.821" spread="0.051"/>
                    <measurement group_id="O2" value="0.783" spread="0.052"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium; P1; Day-1; 24 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.287" spread="0.347"/>
                    <measurement group_id="O2" value="4.294" spread="0.390"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium; P1; Day 3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.303" spread="0.346"/>
                    <measurement group_id="O2" value="4.222" spread="0.438"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.300" spread="0.374"/>
                    <measurement group_id="O2" value="4.225" spread="0.289"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.364" spread="0.303"/>
                    <measurement group_id="O2" value="4.336" spread="0.288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium; P1; Day-1; 24 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140.86" spread="2.242"/>
                    <measurement group_id="O2" value="140.67" spread="1.958"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium; P1; Day 3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="138.90" spread="1.480"/>
                    <measurement group_id="O2" value="139.25" spread="1.410"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140.11" spread="1.410"/>
                    <measurement group_id="O2" value="139.68" spread="2.187"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium; P2; Day 3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139.11" spread="1.761"/>
                    <measurement group_id="O2" value="139.11" spread="2.424"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points</title>
        <description>Serum creatinine, direct bilirubin and total bilirubin levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points</title>
          <description>Serum creatinine, direct bilirubin and total bilirubin levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
          <population>Safety Population</population>
          <units>Micromoles per liter (µmol/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Creatinine; P1; Day-1; 24 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.2" spread="13.69"/>
                    <measurement group_id="O2" value="85.0" spread="11.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine; P1; Day3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.0" spread="15.26"/>
                    <measurement group_id="O2" value="87.3" spread="12.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine; P2; Day-1; 24 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.1" spread="10.99"/>
                    <measurement group_id="O2" value="82.5" spread="13.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine; P2; Day3; 48 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.6" spread="15.31"/>
                    <measurement group_id="O2" value="88.7" spread="16.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin;P1;Day-1;24 hour pre-dose;n=21,21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.25" spread="1.771"/>
                    <measurement group_id="O2" value="4.52" spread="1.825"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin;P1;Day3;48 hour post-dose;n=21,20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.20" spread="1.599"/>
                    <measurement group_id="O2" value="3.72" spread="1.493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin;P2;Day-1;24 hour pre-dose;n=19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.94" spread="1.357"/>
                    <measurement group_id="O2" value="3.64" spread="1.446"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct bilirubin;P2;Day3;48 hour post-dose;n=19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.77" spread="1.559"/>
                    <measurement group_id="O2" value="3.14" spread="1.340"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total bilirubin;P1;Day-1;24 hour pre-dose;n=21,21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.10" spread="6.208"/>
                    <measurement group_id="O2" value="13.48" spread="6.923"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total bilirubin;P1;Day3;48 hour post-dose;n=21,20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.40" spread="5.265"/>
                    <measurement group_id="O2" value="10.80" spread="5.601"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total bilirubin;P2;Day-1;24 hour pre-dose;n=19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.61" spread="4.651"/>
                    <measurement group_id="O2" value="10.08" spread="5.119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total bilirubin;P2;Day3;48 hour post-dose;n=19,19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.83" spread="5.920"/>
                    <measurement group_id="O2" value="8.67" spread="4.492"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Protein Levels at Indicated Time Points</title>
        <description>Serum total protein levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Total Protein Levels at Indicated Time Points</title>
          <description>Serum total protein levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).</description>
          <population>Safety Population</population>
          <units>Grams per liter (g/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>P1; Day-1; 24 hours pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.08" spread="4.943"/>
                    <measurement group_id="O2" value="76.06" spread="3.733"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day 3; 48 hours post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.53" spread="5.259"/>
                    <measurement group_id="O2" value="74.99" spread="3.844"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day-1; 24 hours pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.29" spread="3.369"/>
                    <measurement group_id="O2" value="70.06" spread="4.002"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day 3; 48 hours post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.56" spread="3.676"/>
                    <measurement group_id="O2" value="72.33" spread="4.241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points</title>
        <description>Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points</title>
          <description>Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>Safety Population</population>
          <units>Millimeters 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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SBP; P1; Day-1; 12 hour pre-dose; n=21,21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="115.9" spread="6.88"/>
                    <measurement group_id="O2" value="115.8" spread="8.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day1; 1 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112.8" spread="8.90"/>
                    <measurement group_id="O2" value="111.6" spread="7.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day1; 1.5 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.5" spread="8.15"/>
                    <measurement group_id="O2" value="110.8" spread="11.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day1; 2 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.3" spread="9.59"/>
                    <measurement group_id="O2" value="112.6" spread="7.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP: P1; Day1; 4 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112.5" spread="8.66"/>
                    <measurement group_id="O2" value="114.0" spread="9.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day1; 6 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110.9" spread="6.69"/>
                    <measurement group_id="O2" value="113.0" spread="8.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day1; 8 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.0" spread="8.66"/>
                    <measurement group_id="O2" value="111.8" spread="8.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day2; 24 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.4" spread="6.99"/>
                    <measurement group_id="O2" value="110.5" spread="6.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P1; Day3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.5" spread="9.11"/>
                    <measurement group_id="O2" value="113.8" spread="9.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P2; Day-1; 12 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.8" spread="7.38"/>
                    <measurement group_id="O2" value="116.2" spread="10.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P2; Day1; 1 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110.0" spread="8.54"/>
                    <measurement group_id="O2" value="113.7" spread="11.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P2; Day1; 1.5 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.9" spread="8.14"/>
                    <measurement group_id="O2" value="112.2" spread="12.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P2; Day1; 2 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.6" spread="7.73"/>
                    <measurement group_id="O2" value="113.8" spread="12.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP: P2; Day1; 4 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.5" spread="9.54"/>
                    <measurement group_id="O2" value="113.5" spread="11.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP: P2; Day1; 6 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.5" spread="7.57"/>
                    <measurement group_id="O2" value="112.4" spread="10.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP: P2; Day1; 8 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.8" spread="8.53"/>
                    <measurement group_id="O2" value="111.5" spread="12.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP: P2; Day2; 24 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.1" spread="7.13"/>
                    <measurement group_id="O2" value="110.6" spread="10.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP; P2; Day3; 48 hour post-dose; n= 18, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112.9" spread="8.56"/>
                    <measurement group_id="O2" value="116.5" spread="9.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P1; Day-1; 12 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.4" spread="7.32"/>
                    <measurement group_id="O2" value="64.9" spread="7.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P1; Day1; 1 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.7" spread="6.79"/>
                    <measurement group_id="O2" value="63.5" spread="5.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P1; Day1; 1.5 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.0" spread="7.08"/>
                    <measurement group_id="O2" value="63.9" spread="8.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P1; Day1; 2 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.4" spread="7.10"/>
                    <measurement group_id="O2" value="65.7" spread="9.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P1; Day1; 4 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.8" spread="6.82"/>
                    <measurement group_id="O2" value="64.4" spread="7.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P1; Day1; 6 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.4" spread="4.34"/>
                    <measurement group_id="O2" value="62.7" spread="6.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P1; Day1; 8 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.0" spread="6.00"/>
                    <measurement group_id="O2" value="63.7" spread="6.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P1; Day2; 24 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.9" spread="5.06"/>
                    <measurement group_id="O2" value="64.2" spread="5.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P1; Day3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.3" spread="5.55"/>
                    <measurement group_id="O2" value="66.0" spread="6.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P2; Day-1; 12 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.1" spread="6.03"/>
                    <measurement group_id="O2" value="65.8" spread="7.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P2; Day1; 1 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.9" spread="6.86"/>
                    <measurement group_id="O2" value="64.1" spread="8.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P2; Day1; 1.5 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.1" spread="5.36"/>
                    <measurement group_id="O2" value="63.4" spread="8.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P2; Day1; 2 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" spread="6.87"/>
                    <measurement group_id="O2" value="65.3" spread="7.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P2; Day1; 4 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.8" spread="7.73"/>
                    <measurement group_id="O2" value="65.3" spread="8.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P2; Day1; 6 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.4" spread="5.85"/>
                    <measurement group_id="O2" value="61.5" spread="6.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP; P2; Day1; 8 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.1" spread="5.91"/>
                    <measurement group_id="O2" value="62.9" spread="6.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P2; Day2; 24 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.9" spread="5.62"/>
                    <measurement group_id="O2" value="64.4" spread="7.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP: P2; Day3; 48 hour post-dose; n= 18, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.9" spread="7.28"/>
                    <measurement group_id="O2" value="67.2" spread="6.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Rate Values at Indicated Time Points</title>
        <description>Vital sign measurements including respiratory rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Rate Values at Indicated Time Points</title>
          <description>Vital sign measurements including respiratory rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>Safety Population</population>
          <units>Breaths 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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>P1; Day-1; 12 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.5" spread="1.63"/>
                    <measurement group_id="O2" value="17.0" spread="1.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 1 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.3" spread="2.70"/>
                    <measurement group_id="O2" value="17.0" spread="2.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 1.5 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.7" spread="1.91"/>
                    <measurement group_id="O2" value="17.9" spread="1.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 2 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.0" spread="2.06"/>
                    <measurement group_id="O2" value="17.5" spread="2.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 4 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.9" spread="2.49"/>
                    <measurement group_id="O2" value="17.0" spread="2.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 6 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" spread="2.49"/>
                    <measurement group_id="O2" value="18.4" spread="2.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 8 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.9" spread="2.24"/>
                    <measurement group_id="O2" value="18.2" spread="1.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day2; 24 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2" spread="1.41"/>
                    <measurement group_id="O2" value="18.0" spread="1.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.1" spread="1.53"/>
                    <measurement group_id="O2" value="17.7" spread="1.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day-1; 12 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.9" spread="1.47"/>
                    <measurement group_id="O2" value="17.2" spread="1.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 1 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.7" spread="2.03"/>
                    <measurement group_id="O2" value="17.9" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 1.5 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.8" spread="1.65"/>
                    <measurement group_id="O2" value="16.3" spread="1.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 2 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.0" spread="1.89"/>
                    <measurement group_id="O2" value="17.3" spread="2.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 4 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.9" spread="2.26"/>
                    <measurement group_id="O2" value="17.4" spread="2.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 6 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" spread="1.92"/>
                    <measurement group_id="O2" value="18.3" spread="2.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 8 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.7" spread="1.52"/>
                    <measurement group_id="O2" value="18.2" spread="2.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day2; 24 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.5" spread="2.72"/>
                    <measurement group_id="O2" value="17.6" spread="1.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day3; 48 hour post-dose; n= 18, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.4" spread="1.62"/>
                    <measurement group_id="O2" value="17.2" spread="2.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pulse Rate Values at Indicated Time Points</title>
        <description>Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Pulse Rate Values at Indicated Time Points</title>
          <description>Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>Safety Population</population>
          <units>Beats per minute (bpm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>P1; Day-1; 12 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.9" spread="9.22"/>
                    <measurement group_id="O2" value="64.7" spread="9.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 1 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.8" spread="11.26"/>
                    <measurement group_id="O2" value="62.0" spread="10.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 1.5 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" spread="10.95"/>
                    <measurement group_id="O2" value="60.9" spread="11.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 2 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.7" spread="10.55"/>
                    <measurement group_id="O2" value="60.7" spread="8.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 4 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.1" spread="11.32"/>
                    <measurement group_id="O2" value="62.5" spread="9.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 6 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.5" spread="13.85"/>
                    <measurement group_id="O2" value="70.8" spread="10.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 8 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.0" spread="9.93"/>
                    <measurement group_id="O2" value="67.8" spread="9.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day2; 24 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.0" spread="11.26"/>
                    <measurement group_id="O2" value="68.6" spread="10.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.4" spread="12.93"/>
                    <measurement group_id="O2" value="73.0" spread="9.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day-1; 12 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.2" spread="9.15"/>
                    <measurement group_id="O2" value="65.2" spread="11.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 1 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.5" spread="8.82"/>
                    <measurement group_id="O2" value="60.1" spread="9.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 1.5 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.5" spread="8.02"/>
                    <measurement group_id="O2" value="62.8" spread="10.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 2 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.7" spread="8.33"/>
                    <measurement group_id="O2" value="59.2" spread="8.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 4 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.4" spread="8.58"/>
                    <measurement group_id="O2" value="62.7" spread="11.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 6 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.9" spread="8.23"/>
                    <measurement group_id="O2" value="71.4" spread="13.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 8 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.2" spread="8.89"/>
                    <measurement group_id="O2" value="66.2" spread="11.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day2; 24 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.0" spread="9.99"/>
                    <measurement group_id="O2" value="68.8" spread="13.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day3; 48 hour post-dose; n= 18, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.3" spread="11.69"/>
                    <measurement group_id="O2" value="73.4" spread="17.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Body Temperature Values at Indicated Time Points</title>
        <description>Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
        <time_frame>Day -1 and Day 3 of each treatment period</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment A</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>Treatment B</title>
            <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</description>
          </group>
        </group_list>
        <measure>
          <title>Body Temperature Values at Indicated Time Points</title>
          <description>Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</description>
          <population>Safety Population</population>
          <units>Degree 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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>P1; Day-1; 12 hour pre-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.42" spread="0.339"/>
                    <measurement group_id="O2" value="36.43" spread="0.376"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 1 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.44" spread="0.262"/>
                    <measurement group_id="O2" value="36.40" spread="0.392"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 1.5 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.06" spread="0.294"/>
                    <measurement group_id="O2" value="36.05" spread="0.314"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 2 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.42" spread="0.339"/>
                    <measurement group_id="O2" value="36.38" spread="0.314"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 4 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.45" spread="0.364"/>
                    <measurement group_id="O2" value="36.46" spread="0.365"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 6 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.59" spread="0.422"/>
                    <measurement group_id="O2" value="36.61" spread="0.309"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day1; 8 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.64" spread="0.461"/>
                    <measurement group_id="O2" value="36.75" spread="0.357"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day2; 24 hour post-dose; n= 21, 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.28" spread="0.387"/>
                    <measurement group_id="O2" value="36.30" spread="0.322"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P1; Day3; 48 hour post-dose; n= 21, 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.26" spread="0.334"/>
                    <measurement group_id="O2" value="36.28" spread="0.374"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day-1; 12 hour pre-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.41" spread="0.358"/>
                    <measurement group_id="O2" value="36.34" spread="0.383"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 1 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.28" spread="0.302"/>
                    <measurement group_id="O2" value="36.24" spread="0.435"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 1.5 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.06" spread="0.263"/>
                    <measurement group_id="O2" value="36.19" spread="0.336"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 2 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.41" spread="0.294"/>
                    <measurement group_id="O2" value="36.38" spread="0.405"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 4 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.53" spread="0.335"/>
                    <measurement group_id="O2" value="36.44" spread="0.380"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 6 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.59" spread="0.331"/>
                    <measurement group_id="O2" value="36.57" spread="0.406"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day1; 8 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.64" spread="0.383"/>
                    <measurement group_id="O2" value="36.65" spread="0.399"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day2; 24 hour post-dose; n= 19, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.15" spread="0.301"/>
                    <measurement group_id="O2" value="36.17" spread="0.437"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P2; Day3; 48 hour post-dose; n= 18, 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.08" spread="0.323"/>
                    <measurement group_id="O2" value="36.28" spread="0.486"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>On-therapy serious adverse events (SAEs) and non-serious AEs are presented from the start of study treatment up to follow up visit 7 days post-last dose (Up to 25 days).</time_frame>
      <desc>On-therapy SAEs and non-serious AEs are reported for the safety Population, comprising of all participants who received at least one dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment A</title>
          <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination test product in each of the two treatment periods.</description>
        </group>
        <group group_id="E2">
          <title>Treatment B</title>
          <description>Participants received a single oral dose of hydrochlorothiazide 50 milligrams (mg) and amiloride hydrochloride 5 mg fixed dose combination reference product in each of the two treatment periods</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="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Crystal Urine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
              </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/NCT03031496
org study id: 205694
nct id: NCT03031496
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The combination of the diuretics amiloride hydrochloride (HCl) and hydrochlorothiazide (HCTZ)
      (GSK3542503) is indicated for the treatment of hypertension, congestive heart failure and
      hepatic cirrhosis with ascites and edema. This first time in human (FTIH) study is aimed to
      determine whether the test product GSK3542503 is bioequivalent to the reference (ref)
      hydrochlorothiazide 50 milligram (mg)/amiloride hydrochlorothiazide 5 mg in healthy adult
      participants under fasting conditions based on pharmacokinetic (PK) endpoints. This is a
      phase I, open label, balanced, randomized, single dose, two-way crossover study, enroling
      approximately 42 healthy participants at a single center. Study participants will be
      randomized to one of two treatment sequences (A-B or B-A) in accordance with the
      randomization schedule. A single dose of one of the two treatments A (Test: GSK3542503, a
      hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination) or B
      (Reference: Moduretic, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed
      dose combination), will be administered on Day 1, in each treatment period. Each participant
      will participate in both treatment periods and receive a single dose of each treatment. The
      treatment periods will be separated by a washout period of at least 7 days and no more than
      14 days. The total duration in the study for each participant is expected to be 5 to 7 weeks,
      from screening to his or her last visit. A maximum of 42 participants will be randomized such
      that at least 32 evaluable participants complete the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride
time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
description: Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.
measure: Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
description: Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.
measure: AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
description: Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the AUC (0-inf) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
measure: Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
description: Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Median and full range has been presented.
measure: Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
description: Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between percent AUCex of the test and reference products in relation to the conventional bioequivalence range. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
measure: Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
description: Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period
time frame: Up to 25 days
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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Only those participants with data available at the specified time points were analyzed
measure: Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Serum ALT, alk. phosph. and AST levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
measure: Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Serum BUN levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
measure: Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Serum calcium, chloride, glucose, magnesium, potassium and sodium levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
measure: Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Serum creatinine, direct bilirubin and total bilirubin levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
measure: Total Protein Levels at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Serum total protein levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
measure: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
measure: Respiratory Rate Values at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Vital sign measurements including respiratory rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
measure: Pulse Rate Values at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
measure: Body Temperature Values at Indicated Time Points
time frame: Day -1 and Day 3 of each treatment period
description: Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
arm group label: Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg
arm group type: Experimental
description: Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration.
arm group label: Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg
arm group type: Experimental
description: Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration.
intervention type: Drug
intervention name: GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets)
description: GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) are cream-colored, circular, flat faced uncoated tablets with beveled edges having break line on one side and "BD" embossed on the other side.
arm group label: Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg
arm group label: Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg
intervention type: Drug
intervention name: Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)
description: Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) tablets are peach-colored, half scored, diamond shaped tablets marked "MSD917".
arm group label: Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg
arm group label: Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Hydrochlorothiazide
mesh term: Amiloride
mesh term: Amiloride, hydrochlorothiazide drug combination
sharing ipd: Yes
ipd description: IPD for this study is 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 (copy the URL below to your browser)
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=20806
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 