A Study to Evaluate AG-881 in Healthy Japanese and Non-Asian Participants

NCT04145128 | Completed Phase 1 FDA Drug

• 1 other identifier: AG881-C-008
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the pharmacokinetics (PK) and safety of AG-881 in healthy Japanese and Non-Asian participants after single oral doses of 10 mg and 50 mg of AG-881.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetic study; AG-881

Outcome Measures

Primary Outcomes (7)

• Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUC0-last) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

• Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-∞) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

• Apparent Clearance Following Extravascular Dosing (CL/F) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

• Maximum Plasma Concentration Observed (Cmax) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

• Apparent Terminal Elimination Half-life (t1/2) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

• Time of Maximum Plasma Concentration (tmax) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

• Apparent Volume of Distribution (Vd/F) of AG881

  Pre-dose and multiple time points post-dose (up to 504 hours) after each administration of AG-881

Secondary Outcomes (6)

• Number of Participants with Changes in Clinical Laboratory Tests from Screening to 22 days in Period 1 and 2

  Screening (Day -1) up to 22 days in Period 1 and 2 (Each Period is 22 days)

• Number of Participants with Changes in Physical Examinations from Screening to 22 days in Period 1 and 2

  Screening (Day -1) up to 22 days in Period 1 and 2 (Each Period is 22 days)

• Number of Participants with Changes in Vital Sign Measurements from Screening to 22 days in Period 1 and 2

  Screening (Day -1) up to 22 days in Period 1 and 2 (Each Period is 22 days)

• Number of Participants with Changes in Electrocardiograms (ECGs) from Screening to 22 days in Period 1 and 2

  Screening (Day -1) up to 22 days in Period 1 and 2 (Each Period is 22 days)

• Number of Participants with Adverse Events (AEs)

  Up to 28 days after last dose of AG-881 (Up to 71 days)

Study Arms (1)

AG-881

EXPERIMENTAL

Participants will receive AG-881 10 mg, tablet orally, once in Period 1 followed by AG-881 50 mg, tablet orally, once in Period 2. Period 1 and Period 2 will be separated by a washout period of 20 days between doses.

Drug: AG881

Interventions

AG881 DRUG

AG-881 tablets.

Also known as: Vorasidenib, AGI 23088, AGI 0023088

AG-881

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have provided voluntary written informed consent.
• Adult male or female, 18 to 55 years of age, inclusive, at Screening.
• Continuous nonsmoker who has not used nicotine containing products for at least 3 months prior to the first dosing and throughout the study.
• Have a body mass index (BMI) of ≥ 18.0 and ≤ 32.0 kg/m\^2 at Screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG. Liver function tests (serum alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase \[ALP\], and bilirubin \[total and direct\]) must be ≤ the upper limit of normal (ULN).
• Female participants must be of nonchildbearing potential defined as a female who has undergone one of the following sterilization procedures at least 6 months prior to the first dosing: hysteroscopic sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy. Or is postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.
• A nonvasectomized, male participant must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to the first dosing of study drug. A male who has been vasectomized less than 4 months prior to study first dosing must follow the same restrictions as a nonvasectomized male).
• Male participants must agree not to donate sperm from the first dosing until 90 days after the last dosing.
• Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
• Additional Criteria for Japanese participants only: be first-generation Japanese, defined as meeting all of the following conditions: born in Japan; has 2 Japanese biological parents and 4 Japanese biological grandparents; has lived outside of Japan for \<5 years; has made no significant changes in lifestyle, including diet, since leaving Japan.
• Additional Criteria for Non-Asian participants only: Non-Asian participants will have 2 biological parents and 4 biological grandparents of Non-Asian descent.

You may not qualify if:

• Mentally or legally incapacitated or has significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee.
• History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or pose an additional risk to the participant (eg, history or presence of rashes) by their participation in the study.
• History of stomach or intestinal surgery that would potentially alter absorption/secretion; or any major surgical procedure within the previous 3 months prior to Screening.
• History of severe and/or uncontrolled ventricular arrhythmias, or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome).
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
• Any positive responses on the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Female participants of childbearing potential.
• Female participants with a positive pregnancy test or who are lactating.
• Positive urine drug or alcohol results at Screening or Day -1/Day 21.
• Positive results at Screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibodies.
• QTcF interval is \>450 msec, or QRS interval \>110 msec, or PR interval \>220 msec, or participants who have ECG findings deemed abnormal with clinical significance by the Investigator or designee at Screening.
• Supine blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at Screening.
• Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

WCCT GLobal

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

vorasidenib

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: October 30, 2019
• Study Start: October 2, 2019
• Primary Completion: December 11, 2019
• Study Completion: December 18, 2019
• Last Updated: April 2, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)