A Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Participants

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Open-label, Randomized 4-period Crossover Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04565678
• Other study ID #: AG348-C-019
• Status: Completed
• Phase: Phase 1
• Start date: September 21, 2020
• Est. completion date: December 3, 2020

Study information

• Verified date: December 2020
• Source: Agios Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to assess the relative bioavailability of the mitapivat coated granule formulation compared to the tablet formulation following a single oral dose of mitapivat under fasted conditions in healthy adult participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 3, 2020
• Est. primary completion date: December 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Body mass index between 18.0 and 32.0 kilograms per square meter (kg/m^2), inclusive;

• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations;

• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception;

• Participant has no clinically significant history or presence of ECG findings as judged by the Investigator at Screening and Check-in.

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator;

• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, including the 2 soft foods administered in this study, or other substance, unless approved by the Investigator;

• History of stomach or intestinal surgery or resection including cholecystectomy that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed);

• History of any malignancy with the exception of non-melanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;

• Participant has liver function tests including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and total bilirubin that are greater than the upper limit of normal at Screening or Check-in;

• Participant has platelet count or hemoglobin and hematocrit values that are below the lower limit of normal at Screening or Check-in;

• Confirmed (eg, original value and 2 consecutive repeat measurements) systolic blood pressure >150 or <90 millimeters of mercury (mmHg), diastolic blood pressure >90 or <50 mmHg, and pulse rate >100 or <45 beats per minute (bpm);

• Confirmed QT interval corrected for heart rate using Fridericia's method (QTcF) >450 milliseconds (msec) (male participants) or >470 msec (female participants);

• History of active alcoholism or drug/chemical abuse within 2 years prior to Check-in;

• Alcohol consumption of >21 units per week for males and >14 units for females;

• Positive urine drug screen at Screening or positive alcohol breath test result or positive urine drug screen at Check-in;

• Positive hepatitis panel and/or positive human immunodeficiency virus test;

• Participants with an active infection requiring systemic antimicrobial therapy, or with an active infection deemed clinically significant by the Investigator during Screening;

• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to dosing (whichever is longer);

• Participant has used any over-the-counter medications, including herbal or nutritional supplements, within 28 days (or 5 half-lives, whichever is longer) before the first dose of study drug until after the Follow up phone call;

• Participant has used any prescription (excluding hormone replacement therapy and hormonal birth control) medications within 30 days (or 5 half-lives, whichever is longer) before the first dose of study drug until after the Follow up phone call;

• Use of tobacco- or nicotine-containing products including cigarettes, snuff, nicotine patch, nicotine chewing gum, vaporizers, or inhalers, within 6 months prior to Screening until after the Follow up phone call, or positive cotinine at Screening or Check-in;

• Participant must refrain from marijuana or cannabinol-containing products for 7 days before Screening until after the Follow up phone call;

• Ingestion of poppy seed within 7 days prior to Check-in until after the Follow up phone call;

• Participant has consumed grapefruit or grapefruit juice, Seville orange, or Seville orange containing products (eg, marmalade) within 7 days before the first dose of study drug until after the Follow up phone call;

• Participant has consumed caffeine- or xanthine-containing products within 24 hours prior to first dose of study drug until after the Follow up phone call;

• Participant has consumed vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard), or charbroiled meats for 7 days prior to first dose of study drug until after the Follow-up phone call;

• Participant is involved in strenuous activity or contact sports from 7 days before Check-in until after the Follow-up phone call;

• Receipt of blood products within 2 months prior to Check-in;

• Participant has donated blood or blood products >450 milliliters (mL) within 30 days before the first dose of study drug;

• Participant has a poor peripheral venous access;

• Have previously completed or withdrawn from this study or any other study investigating mitapivat sulfate, and have previously received the mitapivat sulfate;

• Participant has a history of allergy to sulfonamides (eg, co-trimoxazole antibiotic, silver sulfadiazine topical antibiotic for burn wounds) that has been characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type, or Stevens-Johnson syndrome.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Mitapivat tablets
Oral tablets
• Mitapivat coated granules
Oral coated granules

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit Inc.	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Agios Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax) of Mitapivat Under Fasted Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Primary	Area Under the Plasma Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-t) of Mitapivat Under Fasted Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Primary	Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-8) of Mitapivat Under Fasted Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Primary	Time to Reach Maximum Observed Concentration (Tmax) of Mitapivat Under Fasted Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Cmax of Mitapivat Under Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	AUC0-t of Mitapivat Under Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	AUC0-8 of Mitapivat Under Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Tmax of Mitapivat Under Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Relative Bioavailability (Frel) Under Fasted and Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Area Under the Plasma Concentration-Time Curve from Time Zero to Twelve Hours (AUC0-12) of Mitapivat Under Fasted and Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Apparent Plasma Terminal Elimination Half-life (t½) of Mitapivat Under Fasted and Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Apparent Total Plasma Clearance (CL/F) of Mitapivat Under Fasted and Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Apparent Volume of Distribution (Vz/F) of Mitapivat Under Fasted and Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Apparent Terminal Elimination Rate Constant (?z) of Mitapivat Under Fasted and Fed Conditions		Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary	Number of Participants With Adverse Event (AEs)		Up to approximately 9 weeks
Secondary	Number of Participants With AEs, Graded by Severity		Up to approximately 9 weeks
Secondary	Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values		Up to approximately 9 weeks
Secondary	Number of Participants With Clinically Significant Abnormal Findings for 12-lead Electrocardiogram (ECG) Parameters		Up to approximately 9 weeks
Secondary	Number of Participants With Clinically Significant Abnormal Findings for Vital Signs Parameters		Up to approximately 9 weeks
Secondary	Number of Participants With Clinically Significant Abnormal Physical Examination Findings		Up to approximately 9 weeks