A Study to Compare the Relative Bioavailability of Two AG-881 Formulations and Evaluate the Effect of Food and Omeprazole on the Pharmacokinetics of AG-881

NCT04128787 | Completed Phase 1 FDA Drug

• 1 other identifier: AG881-C-007
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the single-dose pharmacokinetics (PK) of two formulations (Formulation 1 and Formulation 2) of AG-881 and to examine the effect of food and multiple-dose omeprazole on the single-dose PK of AG-881 Formulation 2 in healthy adult participants. This study will also assess the safety and tolerability of single-dose AG-881 (Formulation 1 and 2) alone and of AG-881 Formulation 2 when administered with and without food and when coadministered with omeprazole in healthy adult subjects.

Conditions

Healthy Volunteers

Keywords

Bioavailability Study; Pharmacokinetic study; AG-881

Outcome Measures

Primary Outcomes (18)

• Area Under the Concentration-Time Curve From Time 0 to the Last Observed Non-Zero Concentration (AUC0-t) of AG-881 Formulation 1 without Food

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

• Area Under the Concentration-Time Curve From Time 0 to the Last Observed Non-Zero Concentration (AUC0-t) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of AG-881 Formulation 1 without Food

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

• Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Maximum Observed Concentration (Cmax) of AG-881 Formulation 1 without Food

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

• Maximum Observed Concentration (Cmax) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Area Under the Concentration-Time Curve, From Time 0 to 504 Hours Postdose (AUC0-504) of AG-881 Formulation 1 without Food

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

• Area Under the Concentration-Time Curve, From Time 0 to 504 Hours Postdose (AUC0-504) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of AG-881 Formulation 1 without Food

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

• Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Apparent Terminal Elimination Half-life (t½) of AG-881 Formulation 1 without Food

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

• Apparent Terminal Elimination Half-life (t½) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Time Delay Between Drug Administration and the Onset of Absorption (tlag) of AG-881 Formulation 1 without Food

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

• Time Delay Between Drug Administration and the Onset of Absorption (tlag) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Time to Reach Maximum Observed Concentration (Tmax) of AG-881 Formulation 1 without Food

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

• Time to Reach Maximum Observed Concentration (Tmax) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

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

• Apparent Volume of Distribution After Oral (Extravascular) Administration (Vd/F) of AG-881 Formulation 1 without Food

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

• Apparent Volume of Distribution After Oral (Extravascular) Administration (Vd/F) of AG-881 Formulation 2 with Food, without Food and when Co-administered with Omeprazole

  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 Abnormalities in Triplicate 12-lead Electrocardiograms (ECGs)

  Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days)

• Number of Participants with Abnormalities in Vital Sign Measurements

  Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days)

• Columbia-suicide Severity Rating Scale (C-SSRS) Score

  Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days)

• Number of Participants with Abnormalities in Clinical Laboratory Tests

  Up to 21 days in Period 1, 2, 3 (Each period is 21 days); up to 25 days in Period 4 (Period 4 is 25 days)

• Number of Participants with Adverse Events (AEs)

  Up to 28 Days After Last Dose of Study Drug (Up to 91 days)'

Study Arms (3)

Treatment Sequence ABCD

EXPERIMENTAL

Participants will receive Treatment A (AG-881 Formulation 1, 50 mg, tablet orally, under fasted condition once on Day 1 of Period 1) followed by Treatment B (AG-881 Formulation 2, 50 mg, tablet orally, under fasted condition once on Day 1 of Period 2) followed by Treatment C (AG-881 Formulation 2, 50 mg, tablet, orally, under fed condition once on Day 1 of Period 3) followed by Treatment D (omeprazole 40 mg capsule, orally, once daily on Days 1 to 4 and AG-881 Formulation 2, 50 mg, tablet, orally, under fasted condition, once on Day 4 of Period 4). Each period will be separated by a Washout Period of 21 days.

Drug: AG881 Formulation 1; Drug: AG881 Formulation 2; Drug: Omeprazole

Treatment Sequence BCAD

EXPERIMENTAL

Participants will receive Treatment B in Period 1 followed by Treatment C in Period 2 then Treatment A in Period 3 followed by Treatment D in Period 4. Each period will be separated by a Washout Period of 21 days.

Drug: AG881 Formulation 1; Drug: AG881 Formulation 2; Drug: Omeprazole

Treatment Sequence CABD

EXPERIMENTAL

Participants will receive Treatment C in Period 1 followed by Treatment A in Period 2 then Treatment B in Period 3 followed by Treatment D in Period 4. Each period will be separated by a Washout Period of 21 days.

Drug: AG881 Formulation 1; Drug: AG881 Formulation 2; Drug: Omeprazole

Interventions

AG881 Formulation 1 DRUG

AG881 uncoated tablets

Treatment Sequence ABCD; Treatment Sequence BCAD; Treatment Sequence CABD

AG881 Formulation 2 DRUG

AG881 film-coated tablets

Treatment Sequence ABCD; Treatment Sequence BCAD; Treatment Sequence CABD

Omeprazole DRUG

Omeprazole capsules

Treatment Sequence ABCD; Treatment Sequence BCAD; Treatment Sequence CABD

Eligibility Criteria

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

You may qualify if:

• Healthy, adult, male or female (WONCBP) participants, 18-55 years of age, inclusive, at Screening.
• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG, as deemed by the Investigator or designee. 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 non-childbearing 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 non-vasectomized, male participants 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 non-vasectomized male).
• If a 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.

You may not qualify if:

• Participant is 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 (e.g., 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 (e.g., 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 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 first check-in.
• Positive results at Screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies.
• QT interval Fridericia's formula (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.
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at Screening.
• Seated 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)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: October 4, 2019
• First Posted: October 16, 2019
• Study Start: September 30, 2019
• Primary Completion: December 18, 2019
• Study Completion: December 18, 2019
• Last Updated: July 21, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)