Clinical trial NCT04565678: A Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Agios Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Mitapivat Under Fasted Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-t) of Mitapivat Under Fasted Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of Mitapivat Under Fasted Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Time to Reach Maximum Observed Concentration (Tmax) of Mitapivat Under Fasted Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
Secondary outcomes:
measure: Cmax of Mitapivat Under Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: AUC0-t of Mitapivat Under Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: AUC0-∞ of Mitapivat Under Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Tmax of Mitapivat Under Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Relative Bioavailability (Frel) Under Fasted and Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Twelve Hours (AUC0-12) of Mitapivat Under Fasted and Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Apparent Plasma Terminal Elimination Half-life (t½) of Mitapivat Under Fasted and Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Apparent Total Plasma Clearance (CL/F) of Mitapivat Under Fasted and Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Apparent Volume of Distribution (Vz/F) of Mitapivat Under Fasted and Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Apparent Terminal Elimination Rate Constant (λz) of Mitapivat Under Fasted and Fed Conditions
timeFrame: Pre-dose and multiple time points post-dose (up to 72 hours)
measure: Number of Participants With Adverse Event (AEs)
timeFrame: Up to approximately 9 weeks
measure: Number of Participants With AEs, Graded by Severity
timeFrame: Up to approximately 9 weeks
measure: Number of Participants With Clinically Significant Abnormal Clinical Laboratory Values
timeFrame: Up to approximately 9 weeks
measure: Number of Participants With Clinically Significant Abnormal Findings for 12-lead Electrocardiogram (ECG) Parameters
timeFrame: Up to approximately 9 weeks
measure: Number of Participants With Clinically Significant Abnormal Findings for Vital Signs Parameters
timeFrame: Up to approximately 9 weeks
measure: Number of Participants With Clinically Significant Abnormal Physical Examination Findings
timeFrame: Up to approximately 9 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit Inc.
state: Texas
Study officials:
References: