Study to Assess the Effect of Omecamtiv Mecarbil (OM) on QT/QTc Intervals in Healthy Adults

NCT04175808 | Completed Phase 1 Results

• 2 other identifiers: 200902312018-003157-19
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the effect of a single therapeutic (50 mg) oral dose of omecamtiv mecarbil (OM) on the QT interval / QT interval corrected for heart rate (QTc), relative to placebo, in healthy adults. The QT interval is the section on an electrocardiogram (ECG) that represents the time it takes for the electrical system to fire an impulse through the ventricles and then recharge, or the time it takes for the heart muscle to contract and then recover.

Conditions

QT Intervals Changes; QTc Intervals Changes

Keywords

Thorough QT; QTc study

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected Change From Baseline in QT Interval Corrected for Heart Rate Based on the Fridericia Method (QTcF) After Omecamtiv Mecarbil Dosing in Part B

  Continuous 12-lead digital ECG recording was performed on day 1 of each period. ECGs were analyzed by a blinded, central reader. At each specified timepoint, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QT in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that timepoint. QT interval was corrected for heart rate using Fridericia's correction (QTcF). Change from baseline (ΔQTcF) was calculated based on a linear mixed-effects model with period, sequence, time (categorical), treatment, and time-by-treatment interaction as fixed effects and baseline QTcF as covariate. Placebo-corrected ΔQTcF (ΔΔQTcF) was calculated as the adjusted mean ΔQTcF after OM dosing minus adjusted mean ΔQTcF after placebo. If the upper bound of the confidence interval of ΔΔQTcF was \< 10 ms for all post-dose time points, OM was to be concluded to not have a significant effect on QT interval prolongation.

  Baseline (average of samples taken at -1.25, -1, and -0.75 hours predose on day 1 of the treatment period) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, and 24 hours post-dose

Secondary Outcomes (20)

• Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil in Part B

  Day 1 of the OM treatment period at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours post-dose.

• Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil In Part B

  Day 1 of the OM treatment period at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours post-dose.

• Apparent Terminal Elimination Half-life (T1/2) of Omecamtiv Mecarbil in Part B

  Day 1 of the OM treatment period at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours post-dose.

• Apparent Total Plasma Clearance (CL/F) for Omecamtiv Mecarbil in Part B

  Day 1 of the OM treatment period at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours post-dose.

• Apparent Volume of Distribution (VZ/F) for Omecamtiv Mecarbil in Part B

  Day 1 of the OM treatment period at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours post-dose.

Study Arms (2)

Part A

EXPERIMENTAL

After an overnight fast of at least 10 hours participants received a single oral dose of 25 mg omecamtiv mecarbil on Day 1.

Drug: Omecamtiv Mecarbil (OM)

Part B

EXPERIMENTAL

Participants with a maximum observed plasma OM concentration ≤ 350 ng/mL in Part A were randomly assigned to receive a single dose of each the following 3 treatments in one of six treatment sequences: * Placebo * 50 mg omecamtiv mecarbil * 400 mg moxifloxacin Each treatment was separated by a washout of at least 7 days.

Drug: Omecamtiv Mecarbil (OM); Drug: Placebo; Drug: Moxifloxacin

Interventions

Omecamtiv Mecarbil (OM) DRUG

Oral solution

Also known as: AMG 423

Part A; Part B

Placebo DRUG

Placebo oral solution

Part B

Moxifloxacin DRUG

400 mg moxifloxacin oral tablet

Part B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has provided informed consent before initiation of any study-specific activities/procedures.
• Healthy male or healthy female subjects greater than or equal to 18 to less than or equal to 50 years of age.
• No history or evidence of clinically relevant medical disorders as determined by the Investigator at Screening.
• Physical examination at Screening and vital signs, clinical laboratory values, and electrocardiogram (ECG) at Screening and Day -1 of each period are clinically acceptable to the Investigator.
• Body mass index (BMI) greater than, or equal to 18.0 kg/m\^2 and less than, or equal to 30.0 kg/m\^2.
• Willing to maintain current general diet and physical activity regimen.

You may not qualify if:

• History or evidence of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• Any users of tobacco- or nicotine-containing products within 6 months before Day -1 of Part A.
• History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration or bowel disease (including, but not limited to, peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease, or irritable bowel syndrome); or a history of gastrointestinal surgery other than uncomplicated appendectomy.
• History or current signs or symptoms of cardiovascular disease, including but not limited to myocardial infarction, congenital heart disease, valvular heart disease, coronary revascularization, or angina.
• Known substance abuse (eg, alcohol, licit or illicit drugs) within 1 year prior to Screening.
• Subjects with poor peripheral venous access.
• Use of any medications/substances outside the allowed timeframes as specified in Section 6.1.2.
• Currently receiving treatment in another investigational device or drug study, or less than 3 months, or 5 half-lives if longer, prior to receiving the first dose of study drug. Other investigational procedures while participating in this study are excluded.
• Donated blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• Subjects who were previously exposed to OM.
• Hepatic impairment defined by a total bilirubin (TBL) greater than or equal to 1.2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than ULN (and confirmed upon repeat).
• Systolic blood pressure (BP) greater than 140 mmHg or less than 90 mmHg, or diastolic BP greater than 90 mmHg.
• Troponin I or creatine kinase MB fraction (CK-MB) greater than ULN at Screening or Check-in for Part A or B.
• Estimated glomerular filtration rate (eGFR) less than 80 mL/min/1.73 m\^2 at Screening as calculated by the Modified Diet in Renal Disease (MDRD) equation;
• Any positive test for drugs, cotinine (tobacco or nicotine use), and/or alcohol use.

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (1)

Research Site

Leeds, LS2 9LH, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

omecamtiv mecarbil; Moxifloxacin

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This was a partially double-blind study. In Part B, placebo and OM treatments were double-blinded, moxifloxacin treatment was open-label, and the core ECG laboratory was blinded to all treatment information. Except for the moxifloxacin treatment in 1 of 3 periods in Part B, treatment assignment was blinded to all participants, site personnel, the Medical Monitor, and Clinical Research Associates.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 25, 2019
• Study Start: November 14, 2019
• Primary Completion: March 4, 2020
• Study Completion: March 4, 2020
• Last Updated: March 30, 2025
• Results First Posted: July 20, 2021

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

GB (1)