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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Japanese; Non-Asian
• Intervention / Treatment: Drug: AG-348; Drug: AG-348; Drug: AG-348

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • West Coast Clinical Trial (WCCT) Global, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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:

  1. Be taking any medication with a known effect of QT interval prolongation (see list of medications in Appendix 1)
  2. Have a cardiac pacemaker
  3. 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
  4. 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:

  1. Personal or family history of congenital long QT syndrome, Brugada syndrome, or sudden death
  2. Unexplained syncope
  3. Heart failure
  4. Myocardial infarction
  5. Angina
  6. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort B	Drug: AG-348; 50 mg single-dose; Drug: AG-348; 5 mg single-dose; Drug: AG-348; 200 mg single-dose
Experimental: Cohort A	Drug: AG-348; 50 mg single-dose; Drug: AG-348; 5 mg single-dose; Drug: AG-348; 200 mg single-dose
Experimental: Cohort C	Drug: AG-348; 50 mg single-dose; Drug: AG-348; 5 mg single-dose; Drug: AG-348; 200 mg single-dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Agios Pharmaceuticals, Inc.
• Investigators: Study Chair: Medical Affairs Agios Pharmaceuticals, Inc, Agios Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2017
• Primary Completion (Actual): October 2, 2017
• Study Completion (Actual): October 9, 2017

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 11, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Healthy; Japanese
• Other Study ID Numbers: AG348-C-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No