<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/NCT03250598</url>
  </required_header>
  <id_info>
    <org_study_id>AG348-C-004</org_study_id>
    <nct_id>NCT03250598</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Pharmacokinetics, Safety, and QTc Effect of AG-348 in Healthy Subjects of Japanese Origin and Non-Asian Origin</brief_title>
  <official_title>A Phase 1, Single-Dose, Open-Label Study to Characterize and Compare the Pharmacokinetics, Safety, and Effect on QTc Interval of AG-348 in Healthy Subjects of Japanese Origin and Healthy Subjects of Non-Asian Origin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Agios Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Agios Pharmaceuticals, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this Phase I, single-dose, open-label trial is to evaluate the&#xD;
      pharmacokinetics, safety, and effect on QTc interval of AG-348 in healthy, adult Japanese and&#xD;
      Non-Asian subjects. The study plans to evaluate 3 cohorts of a single oral dose of AG-348 in&#xD;
      Japanese and Non-Asian subjects. Pharmacokinetic sampling will take place serially at&#xD;
      specified times during conduct of the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 9, 2017</start_date>
  <completion_date type="Actual">October 9, 2017</completion_date>
  <primary_completion_date type="Actual">October 2, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>Pharmacokinetic sampling for AG-348 will be taken for 72 hours (4 days) after single dose</time_frame>
    <description>AG-348 Area Under the Curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>Pharmacokinetic sampling for AG-348 will be taken for 72 hours (4 days) after single dose</time_frame>
    <description>AG-348 Maximum Plasma Concentration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>10 (± 1) days after single-dose of AG-348</time_frame>
    <description>Assessment of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QTc interval</measure>
    <time_frame>Change in QTc from baseline will be presented by race and by cohort</time_frame>
    <description>QTc interval measurements</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy</condition>
  <condition>Japanese</condition>
  <condition>Non-Asian</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG-348</intervention_name>
    <description>50 mg single-dose</description>
    <arm_group_label>Cohort A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG-348</intervention_name>
    <description>5 mg single-dose</description>
    <arm_group_label>Cohort B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG-348</intervention_name>
    <description>200 mg single-dose</description>
    <arm_group_label>Cohort C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be a male or female aged 18 to 55 years, inclusive.&#xD;
&#xD;
          -  Have a body mass index (BMI) of ≥ 18.5 to ≤ 29.0 kg/m2 at Screening.&#xD;
&#xD;
          -  Be healthy overall with no clinically significant medical abnormalities, as determined&#xD;
             by the Investigator through evaluation of the subject's medical history and Screening&#xD;
             vital signs, ECG, physical examination, and laboratory assessments.&#xD;
&#xD;
          -  Applicable to Japanese Subjects Only: Japanese subjects must have been born in Japan,&#xD;
             have both parents and all grandparents of Japanese origin, and not have lived outside&#xD;
             of Japan for more than 5 years with no significant changes in lifestyle, including&#xD;
             diet, since leaving Japan.&#xD;
&#xD;
          -  Applicable to Non-Asian Subjects Only: Non-Asian subjects must have both parents and&#xD;
             all grandparents of Non-Asian origin.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have undergone any major surgical procedure within the 3 months prior to Screening.&#xD;
&#xD;
          -  Test positive at Screening for hepatitis B surface antigen (HBsAg), hepatitis C virus&#xD;
             antibody (HCVAb), or human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Have a Screening systolic blood pressure (BP) reading of &gt; 140 mmHg (&gt; 150 mmHg in&#xD;
             subjects &gt; 45 years of age) OR a diastolic BP reading of &gt; 90 mmHg after 5 minutes of&#xD;
             supine rest.&#xD;
&#xD;
          -  Have any of the following cardiac risk factors:&#xD;
&#xD;
               1. Be taking any medication with a known effect of QT interval prolongation (see&#xD;
                  list of medications in Appendix 1)&#xD;
&#xD;
               2. Have a cardiac pacemaker&#xD;
&#xD;
               3. Demonstrate on either the Screening ECG or the baseline ECG any evidence of&#xD;
                  atrial fibrillation, atrial flutter, complete right or left bundle branch block,&#xD;
                  or Wolff-Parkinson-White syndrome&#xD;
&#xD;
               4. Demonstrate on the Screening ECG any morphology that renders measurement of QT&#xD;
                  interval imprecise (eg, neuromuscular artifact that cannot be readily eliminated,&#xD;
                  indistinct QRS onset, low-amplitude T wave, merged T and U waves, prominent U&#xD;
                  waves, arrhythmia)&#xD;
&#xD;
          -  Have a history of a known risk factor for Torsade de Pointes, including any of the&#xD;
             following:&#xD;
&#xD;
               1. Personal or family history of congenital long QT syndrome, Brugada syndrome, or&#xD;
                  sudden death&#xD;
&#xD;
               2. Unexplained syncope&#xD;
&#xD;
               3. Heart failure&#xD;
&#xD;
               4. Myocardial infarction&#xD;
&#xD;
               5. Angina&#xD;
&#xD;
               6. Certain clinically significant laboratory assessment findings, including&#xD;
                  hypokalemia, hypercalcemia, or hypomagnesemia&#xD;
&#xD;
          -  Have had, including by voluntary donation, &gt; 400 mL of blood collected within the 3&#xD;
             months prior to Screening.&#xD;
&#xD;
          -  Have taken within the 14 days prior to study drug dosing any prescription medication,&#xD;
             over-the counter medication, or nonprescription preparation-including vitamins,&#xD;
             minerals, phytotherapeutic/herbal/plant-derived preparations, or grapefruit&#xD;
             juice-unless deemed acceptable by the Investigator OR have taken within the 28 days&#xD;
             prior to study drug dosing any restricted product known to strongly induce CYP3A4&#xD;
             metabolism (eg, St. John's Wort).&#xD;
&#xD;
          -  Have participated in another clinical research study within the 3 months prior to&#xD;
             Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Affairs Agios Pharmaceuticals, Inc</last_name>
    <role>Study Chair</role>
    <affiliation>Agios Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West Coast Clinical Trial (WCCT) Global, Inc.</name>
      <address>
        <city>Cypress</city>
        <state>California</state>
        <zip>90630</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>October 17, 2017</last_update_submitted>
  <last_update_submitted_qc>October 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy</keyword>
  <keyword>Japanese</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitapivat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03250598
org study id: AG348-C-004
nct id: NCT03250598
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this Phase I, single-dose, open-label trial is to evaluate the
      pharmacokinetics, safety, and effect on QTc interval of AG-348 in healthy, adult Japanese and
      Non-Asian subjects. The study plans to evaluate 3 cohorts of a single oral dose of AG-348 in
      Japanese and Non-Asian subjects. Pharmacokinetic sampling will take place serially at
      specified times during conduct of the study.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC
time frame: Pharmacokinetic sampling for AG-348 will be taken for 72 hours (4 days) after single dose
description: AG-348 Area Under the Curve
measure: Cmax
time frame: Pharmacokinetic sampling for AG-348 will be taken for 72 hours (4 days) after single dose
description: AG-348 Maximum Plasma Concentration
measure: Incidence of Adverse Events
time frame: 10 (± 1) days after single-dose of AG-348
description: Assessment of adverse events
measure: QTc interval
time frame: Change in QTc from baseline will be presented by race and by cohort
description: QTc interval measurements
arm group label: Cohort A
arm group type: Experimental
arm group label: Cohort B
arm group type: Experimental
arm group label: Cohort C
arm group type: Experimental
intervention type: Drug
intervention name: AG-348
description: 50 mg single-dose
arm group label: Cohort A
intervention type: Drug
intervention name: AG-348
description: 5 mg single-dose
arm group label: Cohort B
intervention type: Drug
intervention name: AG-348
description: 200 mg single-dose
arm group label: Cohort C
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Affairs Agios Pharmaceuticals, Inc
role: Study Chair
affiliation: Agios Pharmaceuticals, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mitapivat
sharing ipd: No