Study to Evaluate the Pharmacokinetics, Safety, and QTc Effect of AG-348 in Healthy Subjects of Japanese Origin and Non-Asian Origin

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy, Japanese, Non-Asian

Intervention / Treatment
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* Drug: AG-348
* Drug: AG-348
* Drug: AG-348


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be a male or female aged 18 to 55 years, inclusive. Have a body mass index (BMI) of ≥ 18.5 to ≤ 29.0 kg/m2 at Screening. Be healthy overall with no clinically significant medical abnormalities, as determined by the Investigator through evaluation of the subject's medical history and Screening vital signs, ECG, physical examination, and laboratory assessments. Applicable to Japanese Subjects Only: Japanese subjects must have been born in Japan, have both parents and all grandparents of Japanese origin, and not have lived outside of Japan for more than 5 years with no significant changes in lifestyle, including diet, since leaving Japan. Applicable to Non-Asian Subjects Only: Non-Asian subjects must have both parents and all grandparents of Non-Asian origin. Exclusion Criteria: Have undergone any major surgical procedure within the 3 months prior to Screening. Test positive at Screening for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), or human immunodeficiency virus (HIV). Have a Screening systolic blood pressure (BP) reading of > 140 mmHg (> 150 mmHg in subjects > 45 years of age) OR a diastolic BP reading of > 90 mmHg after 5 minutes of supine rest. Have any of the following cardiac risk factors: Be taking any medication with a known effect of QT interval prolongation (see list of medications in Appendix 1) Have a cardiac pacemaker Demonstrate on either the Screening ECG or the baseline ECG any evidence of atrial fibrillation, atrial flutter, complete right or left bundle branch block, or Wolff-Parkinson-White syndrome Demonstrate on the Screening ECG any morphology that renders measurement of QT interval imprecise (eg, neuromuscular artifact that cannot be readily eliminated, indistinct QRS onset, low-amplitude T wave, merged T and U waves, prominent U waves, arrhythmia) Have a history of a known risk factor for Torsade de Pointes, including any of the following: Personal or family history of congenital long QT syndrome, Brugada syndrome, or sudden death Unexplained syncope Heart failure Myocardial infarction Angina Certain clinically significant laboratory assessment findings, including hypokalemia, hypercalcemia, or hypomagnesemia Have had, including by voluntary donation, > 400 mL of blood collected within the 3 months prior to Screening. Have taken within the 14 days prior to study drug dosing any prescription medication, over-the counter medication, or nonprescription preparation-including vitamins, minerals, phytotherapeutic/herbal/plant-derived preparations, or grapefruit juice-unless deemed acceptable by the Investigator OR have taken within the 28 days prior to study drug dosing any restricted product known to strongly induce CYP3A4 metabolism (eg, St. John's Wort). Have participated in another clinical research study within the 3 months prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br> | Drug: AG-348<br>* 50 mg single-dose<br>|
| Experimental: Cohort B<br> | Drug: AG-348<br>* 5 mg single-dose<br>|
| Experimental: Cohort C<br> | Drug: AG-348<br>* 200 mg single-dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | AG-348 Area Under the Curve | Pharmacokinetic sampling for AG-348 will be taken for 72 hours (4 days) after single dose | 
| Cmax | AG-348 Maximum Plasma Concentration | Pharmacokinetic sampling for AG-348 will be taken for 72 hours (4 days) after single dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Assessment of adverse events | 10 (± 1) days after single-dose of AG-348 | 
| QTc interval | QTc interval measurements | Change in QTc from baseline will be presented by race and by cohort | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Japanese