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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Moxifloxacin; Drug: Aficamten; Drug: Aficamten-matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cytokinetics, MD; Phone Number: 650-624-2929; Email: medicalaffairs@cytokinetics.com
• Study Contact Backup: Name: Study Director Cytokinetics, MD

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion, Inc 2420

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cytokinetics
• Investigators: Study Director: Cytokinetics, MD, Cytokinetics

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): November 14, 2023
• Study Completion (Actual): November 14, 2023

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: CK-3773274; CK-274; Aficamten
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: CY 6019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No