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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: Aficamten; Drug: Aficamten-matching Placebo; Drug: Moxifloxacin

• Registration Number: NCT05924815
• Lead Sponsor: Cytokinetics

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-15
• Study First Submitted: 2023-06-07
• Study First Submitted QC: 2023-06-27
• Study First Posted: 2023-06-29
• Primary Completion: 2023-11-14
• Study Completion: 2023-11-14
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-15
• Last Update Posted: 2023-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part A (Dose Finding Cohort 1): Aficamten 50 mg	Aficamten	Participants in this arm will receive a single oral dose of 50 mg aficamten.
Part A (Dose Finding Cohort 2): Aficamten 75 mg	Aficamten	Participants in this arm will receive a single oral dose up to 75 mg aficamten.
Part A (Dose Finding Cohort 3): Aficamten 100 mg	Aficamten	Participants in this arm will receive a single oral dose up to 100 mg aficamten.
Part B (TQT Study): Aficamten	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.
Part B (TQT Study): Aficamten-matching Placebo	Aficamten-matching Placebo	Participants in this arm will receive a single oral dose of aficamten-matching placebo.
Part B (TQT Study): Moxifloxacin 400 mg	Moxifloxacin	Participants will receive a single oral dose of 400 mg moxifloxacin

Primary Outcome Measures

Name	Time	Method
Part A: To determine the dose for Part B	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	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 Outcome Measures

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

Trial Locations

Locations (1)

Celerion, Inc 2420; 🇺🇸 Tempe, Arizona, United States