A Randomized, 2-Part, Single-Dose, Crossover Study to Evaluate the Effect of Aficamten Administration on QT/QTc Interval in Healthy Participants
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Part A: To determine the dose for Part B
Study Overview
Brief Summary
This is a single-center, 2-part (Part A and Part B) study in healthy participants. Part A (Dose Finding) is an open-label, SAD study to identify the dose for Part B. Part B (TQT Study) is a randomized, double-blind (with respect to aficamten and matching placebo), positive- and placebo-controlled, single-dose, 3-way crossover study to evaluate the effect of aficamten administration on QT/QTc interval.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy, adult, male or female, 18-45 years of age, inclusive, at the screening visit.
- •Continuous non-smoker who has not used nicotine- and tobacco -containing products for at least 3 months prior to the first dosing based on participant self- reporting.
- •Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 at the screening visit.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the PI or designee, including the following:
- •Supine blood pressure is ≥ 90/40 mmHg and ≤ 140/90 mmHg at the screening visit.
- •Oxygen saturation (SpO2) is ≥ 95% at the screening visit.
- •Liver function tests (e.g., bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]) considered not clinically significant in the opinion of the PI or designee at the screening visit.
- •Estimated creatinine clearance ≥ 90 mL/min at the screening visit.
- •No clinically significant history and presence of ECG findings as judged by the PI or designee at the screening visit and first check-in, including each of the following:
- •HR between 50 bpm and 100 bpm, inclusive.
- •QTcF interval is ≤450 msec (males) and ≤460 msec (females).
- •QRS ≤110 msec; if >110 msec, result will be confirmed by a manual over read.
- •PR ≤220 msec.
- •LVEF ≥65% at the screening visit.
Exclusion Criteria
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- •History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
Arms & Interventions
Part A (Dose Finding Cohort 1): Aficamten 50 mg
Participants in this arm will receive a single oral dose of 50 mg aficamten.
Intervention: Aficamten (Drug)
Part A (Dose Finding Cohort 2): Aficamten 75 mg
Participants in this arm will receive a single oral dose up to 75 mg aficamten.
Intervention: Aficamten (Drug)
Part A (Dose Finding Cohort 3): Aficamten 100 mg
Participants in this arm will receive a single oral dose up to 100 mg aficamten.
Intervention: Aficamten (Drug)
Part B (TQT Study): Aficamten
Participants will receive a single oral dose of aficamten. The dose will be determined based on review of Part A PK parameters, echocardiogram parameters, safety, and tolerability for aficamten.
Intervention: Aficamten (Drug)
Part B (TQT Study): Aficamten-matching Placebo
Participants in this arm will receive a single oral dose of aficamten-matching placebo.
Intervention: Aficamten-matching Placebo (Drug)
Part B (TQT Study): Moxifloxacin 400 mg
Participants will receive a single oral dose of 400 mg moxifloxacin
Intervention: Moxifloxacin (Drug)
Outcomes
Primary Outcomes
Part A: To determine the dose for Part B
Time Frame: Baseline to End of Study, up to 8 weeks
To determine the dose for Part B based on Part A PK and safety data.
Part B: placebo-corrected dQTcF for aficamten
Time Frame: Baseline to End of Study, up to 14.5 weeks
To evaluate the effect of a single oral dose of aficamten on the QTc interval in healthy participants.
Secondary Outcomes
- Part B: placebo-corrected dQTcF for moxifloxacin(Baseline to End of Study, up to 14.5 weeks)