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

Cytokinetics

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Aficamten; Drug: Aficamten-matching Placebo; Drug: Moxifloxacin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05924815

CY 6019

Details and patient eligibility

About

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.

Enrollment: 44 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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44 participants in 6 patient groups, including a placebo group

Part A (Dose Finding Cohort 1): Aficamten 50 mg

Experimental group

Description:

Participants in this arm will receive a single oral dose of 50 mg aficamten.

Treatment:

Drug: Aficamten

Part A (Dose Finding Cohort 2): Aficamten 75 mg

Experimental group

Description:

Participants in this arm will receive a single oral dose up to 75 mg aficamten.

Treatment:

Drug: Aficamten

Part A (Dose Finding Cohort 3): Aficamten 100 mg

Experimental group

Description:

Participants in this arm will receive a single oral dose up to 100 mg aficamten.

Treatment:

Drug: Aficamten

Part B (TQT Study): Aficamten

Experimental group

Description:

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.

Treatment:

Drug: Aficamten

Part B (TQT Study): Aficamten-matching Placebo

Placebo Comparator group

Description:

Participants in this arm will receive a single oral dose of aficamten-matching placebo.

Treatment:

Drug: Aficamten-matching Placebo

Part B (TQT Study): Moxifloxacin 400 mg

Active Comparator group

Description:

Participants will receive a single oral dose of 400 mg moxifloxacin

Treatment:

Drug: Moxifloxacin