Study to Assess the Effect of Omecamtiv Mecarbil (OM) on QT/QTc Intervals in Healthy Adults
Condition: QT Intervals Changes; QTc Intervals Changes
Intervention: Omecamtiv Mecarbil (OM); Placebo; Moxifloxacin
Intervention description: Oral solution; Placebo oral solution; 400 mg moxifloxacin oral tablet
Intervention MeSH terms: Moxifloxacin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: 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.
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Thorough QT; QTc study

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  QTcF interval greater than 450 msec in male or greater than 470 msec in female or
             history/evidence of long QT syndrome, or PR of greater than or equal to 200 msec; or
             2nd degree atrioventricular (AV) block or 3rd degree AV block, or heart rate greater
             than 100 bpm (and confirmed upon repeat, except 2nd or 3rd degree AV block, which are
             exclusionary based on a single finding).

          -  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.

          -  Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects
             whose results are compatible with prior immunization may be included.

          -  Subject has known sensitivity to any of the products or components to be administered
             during dosing, including history of hypersensitivity to moxifloxacin or any member of
             the quinolone class of antibacterials.

          -  History of tendon rupture or connective tissue disorders.

          -  Female subjects with a positive pregnancy test.

          -  Female subjects lactating/breastfeeding or who plans to breastfeed during the study
             through 90 days after the end of study (EOS) visit.

          -  Unwilling to adhere to contraceptive requirements through 90 days after the EOS visit.

          -  Unwilling to abstain from sperm and ovum donation through 90 days after the EOS visit.

          -  Male subjects with a female partner of childbearing potential and not willing to
             inform his partner of his participation in this clinical study.

          -  Male subjects with a pregnant partner or partner planning to become pregnant while the
             subject is on study through 90 days after the EOS visit.

          -  Subject likely to not be available to complete all protocol-required study visits or
             procedures, and/or to comply with all required study procedures (eg, Clinical Outcome
             Assessments) to the best of the subject and Investigator's knowledge.