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

• ClinicalTrials.gov Identifier: NCT05924815
• Recruitment Status: Completed
• First Posted: June 29, 2023
• Last Update Posted: December 19, 2023
• Sponsor: Cytokinetics
• Information provided by (Responsible Party): Cytokinetics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: Aficamten; Drug: Aficamten-matching Placebo; Drug: Moxifloxacin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Randomized, 2-Part, Single-Dose, Crossover Study to Evaluate the Effect of Aficamten Administration on QT/QTc Interval in Healthy Participants
• Actual Study Start Date: May 15, 2023
• Actual Primary Completion Date: November 14, 2023
• Actual Study Completion Date: November 14, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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 Outcome Measures :

1. Part B: placebo-corrected dQTcF for moxifloxacin [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Celerion, Inc 2420

Tempe, Arizona, United States, 85283

Sponsors and Collaborators

Cytokinetics

Investigators

• Study Director: Cytokinetics, MD; Cytokinetics

More Information

• Responsible Party: Cytokinetics
• ClinicalTrials.gov Identifier: NCT05924815
• Other Study ID Numbers: CY 6019
• First Posted: June 29, 2023
• Last Update Posted: December 19, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cytokinetics:

CK-3773274; CK-274; Aficamten

Additional relevant MeSH terms:

Moxifloxacin; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents