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

NCT05924815 | Completed Phase 1 FDA Drug

• 1 other identifier: CY 6019
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Keywords

CK-3773274; CK-274; Aficamten

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Part B: placebo-corrected dQTcF for moxifloxacin

  Baseline to End of Study, up to 14.5 weeks

Study Arms (6)

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

EXPERIMENTAL

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

Drug: Aficamten

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

EXPERIMENTAL

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

Drug: Aficamten

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

EXPERIMENTAL

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

Drug: Aficamten

Part B (TQT Study): Aficamten

EXPERIMENTAL

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

Part B (TQT Study): Aficamten-matching Placebo

PLACEBO COMPARATOR

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

Drug: Aficamten-matching Placebo

Part B (TQT Study): Moxifloxacin 400 mg

ACTIVE COMPARATOR

Participants will receive a single oral dose of 400 mg moxifloxacin

Drug: Moxifloxacin

Interventions

Aficamten DRUG

Oral Tablet

Part A (Dose Finding Cohort 1): Aficamten 50 mg; Part A (Dose Finding Cohort 2): Aficamten 75 mg; Part A (Dose Finding Cohort 3): Aficamten 100 mg; Part B (TQT Study): Aficamten

Aficamten-matching Placebo DRUG

Oral Tablet

Part B (TQT Study): Aficamten-matching Placebo

Moxifloxacin DRUG

Oral Tablet

Part B (TQT Study): Moxifloxacin 400 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (1)

Celerion, Inc 2420

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Cytokinetics, MD

  Cytokinetics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 29, 2023
• Study Start: May 15, 2023
• Primary Completion: November 14, 2023
• Study Completion: November 14, 2023
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)