Study of How Mitapivat Affects Midazolam Blood Levels in Healthy Participants

NCT06648824 | Completed Phase 1 FDA Drug

• 1 other identifier: AG348-C-027
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to assess the effect of mitapivat on the single oral dose pharmacokinetics (PK) of midazolam in healthy participants.

Conditions

Healthy Participants

Keywords

AG-348; Mitapivat

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-Time Curve Extrapolated From Time Zero to Infinity (AUC0-infinity) of Midazolam

  Pre-dose and at multiple timepoints post-dose up to Day 14

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC0-t) of Midazolam

  Pre-dose and at multiple timepoints post-dose up to Day 14

• Maximum Observed Plasma Concentration (Cmax) of Midazolam

  Pre-dose and at multiple timepoints post-dose up to Day 14

Secondary Outcomes (22)

• Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours Post-dose (AUC0-12) of Mitapivat

  Pre-dose and at multiple timepoints post-dose up to Day 14

• Maximum Observed Plasma Concentration (Cmax) of Mitapivat

  Pre-dose and at multiple timepoints post-dose up to Day 14

• Area Under the Plasma Concentration-Time Curve Over a Dosing Interval (Tau) at Steady State (AUC0-tau,ss) of Mitapivat

  Pre-dose and at multiple timepoints post-dose up to Day 14

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Mitapivat

  Pre-dose and at multiple timepoints post-dose up to Day 14

• Time to Last Measurable Concentration (tlast) of Mitapivat

  Pre-dose and at multiple timepoints post-dose up to Day 14

Study Arms (1)

Mitapivat and Midazolam

EXPERIMENTAL

Participants will receive single oral dose of 2 milligram (mg) midazolam on Day 1 followed by 100 mg mitapivat, orally, twice daily (BID) from Day 3 to 13. On Day 14, participants will receive single oral dose of 2 mg midazolam and 100 mg mitapivat orally, BID. Midazolam will be co-administered with morning mitapivat dose.

Drug: Mitapivat; Drug: Midazolam

Interventions

Mitapivat DRUG

Oral tablets

Also known as: AG-348, PYRUKYND®, AG-348 sulfate hydrate, Mitapivat sulfate

Mitapivat and Midazolam

Midazolam DRUG

Oral syrup

Mitapivat and Midazolam

Eligibility Criteria

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

You may qualify if:

• Females must not be pregnant or lactating.
• Females of childbearing potential must agree to use contraception.
• Body mass index between 18.0 and 32.0 kilogram per meter square (kg/m\^2), inclusive.
• In good health, as determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG) and vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in, and from the physical examination at check-in, as assessed by the investigator or designee.
• Able to comprehend and willing to sign the informed consent form (ICF) and abide by the study restrictions.

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, ophthalmological (acute angle closure glaucoma), or psychiatric disorder, as determined by the investigator or designee.
• History of significant hypersensitivity, intolerance, or allergy to any relevant drug compound, food, or other substance (ie, allergy to study intervention or excipients \[microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry Blue II film-coat \[hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD\&C Blue #2\]\]).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (e.g., cholecystectomy). Uncomplicated appendectomy and hernia repair are allowed.
• Significant acute, new-onset illness (e.g., flu, gastroenteritis) within 2 weeks prior to dosing.
• Confirmed systolic blood pressure \>150 or \<90 millimeters of mercury (mmHg), diastolic blood pressure \>100 or \<50 mmHg, or pulse rate \>100 or \<40 beats per minute (bpm). If any parameter falls outside of the specified range at screening or check-in, 2 repeat measurements will be performed and the participant will be excluded only if the mean of the parameter based on the 3 replicates falls outside of the specified range.
• Clinically significant cardiac history or presence of ECG findings, including any of the following:
• Heart rate \<40 bpm or \>100 bpm
• Risk factors for torsades de pointes (e.g., heart failure, cardiomyopathy, or family history of long QT syndrome)
• Sick sinus syndrome, second- or third-degree atrioventricular block myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities
• QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 millisecond (msec) (healthy male participants) or \>470 msec (healthy female participants); if QTcF is \>450 msec (males) or \>470 msec (females), 2 repeat measurements will be performed and the participant will be excluded only if the mean QTcF based on the 3 replicate ECGs is \>450 msec (males) or \>470 msec (females).
• QRS duration \>110 msec, confirmed by manual overread; if value is \>110 msec, 2 repeat measurements will be performed and the participant will be excluded only if the mean QRS duration based on the 3 replicate ECGs is \>110 msec.
• PR interval \<120 or \>220 msec, confirmed by manual overread; if value is \<120 or \>220 msec, 2 repeat measurements will be performed and the participant will be excluded only if the mean PR interval based on the 3 replicate ECGs is \<120 or \>220 msec.
• Repeated syncope or vasovagal episodes.
• Hypertension, angina, bradycardia (if assessed as clinically significant by the investigator) or severe peripheral arterial circulatory disorders
• History of autonomic dysfunction.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

Fortrea Clinical Research Unit Inc.

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

mitapivat; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

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

Model Details: Single sequence crossover design

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 18, 2024
• Study Start: October 17, 2024
• Primary Completion: December 3, 2024
• Study Completion: December 3, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)