Study to Evaluate the Effect of Aficamten Administration on QT/QTc Interval

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, 2-Part, Single-Dose, Crossover Study to Evaluate the Effect of Aficamten Administration on QT/QTc Interval in Healthy Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Aficamten
* Drug: Aficamten-matching Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A (Dose Finding Cohort 1): Aficamten 50 mg<br>Participants in this arm will receive a single oral dose of 50 mg aficamten. | Drug: Aficamten<br>* Oral Tablet<br>|
| Experimental: Part A (Dose Finding Cohort 2): Aficamten 75 mg<br>Participants in this arm will receive a single oral dose up to 75 mg aficamten. | Drug: Aficamten<br>* Oral Tablet<br>|
| Experimental: Part A (Dose Finding Cohort 3): Aficamten 100 mg<br>Participants in this arm will receive a single oral dose up to 100 mg aficamten. | Drug: Aficamten<br>* Oral Tablet<br>|
| Experimental: Part B (TQT Study): Aficamten<br>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. | Drug: Aficamten<br>* Oral Tablet<br>|
| Placebo Comparator: Part B (TQT Study): Aficamten-matching Placebo<br>Participants in this arm will receive a single oral dose of aficamten-matching placebo. | Drug: Aficamten-matching Placebo<br>* Oral Tablet<br>|
| Active Comparator: Part B (TQT Study): Moxifloxacin 400 mg<br>Participants will receive a single oral dose of 400 mg moxifloxacin | Drug: Moxifloxacin<br>* Oral Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: To determine the dose for Part B | To determine the dose for Part B based on Part A PK and safety data. | Baseline to End of Study, up to 8 weeks | 
| Part B: placebo-corrected dQTcF for aficamten | To evaluate the effect of a single oral dose of aficamten on the QTc interval in healthy participants. | Baseline to End of Study, up to 14.5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: placebo-corrected dQTcF for moxifloxacin | To demonstrate assay sensitivity of the study to detect a small QTc effect using moxifloxacin as a positive control in healthy participants. | Baseline to End of Study, up to 14.5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CK-3773274, CK-274, Aficamten