Clinical trial NCT02601001: Pharmacokinetics and Safety Study of Omecamtiv Mecarbil in Healthy Japanese Adults
Official title: A Phase 1, Single Center Double-blind, Randomized, Placebo-controlled Study to Evaluate the Pharmacokinetics and Safety of Omecamtiv Mecarbil in Healthy Japanese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Heart failure
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2015-11-10
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of omecamtiv mecarbil in healthy volunteers in Japan.

Detailed description: This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Eligibility criteria: Inclusion Criteria:

* No history or evidence of clinically relevant medical disorders as determined by the Investigator, and in good health as determined by a pre-study physical examination and medical history with no clinically significant abnormalities, normal vital signs and no history or presence of a clinically significant abnormal electrocardiogram finding
* Subjects' pre-study clinical laboratory findings (including creatine phosphokinase) should be within normal range or if outside of the normal range, are deemed not clinically significant by the Investigator.

Exclusion Criteria:

* A clinically significant disorder/disease, including gastro intestinal abnormalities that might interfere with absorption
* An unstable medical condition, defined as having been hospitalized within 28 days before day 1, major surgery within 6 months before day 1, or otherwise unstable in the judgment of the Investigator
* History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
* History of malignancy of any type other than surgically excised non-melanomatous skin cancers or in situ cervical cancer within 5 years before the day of dosing
* Use of any prescription or over-the-counter medications within 14 days or 5 half-lives (whichever time period is greater), prior to receiving the first dose of omecamtiv mecarbil (acetaminophen up to 2 grams per day for analgesia and hormone replacement therapy (e.g., estrogen) will be allowed
* Use of any known inhibitors of CYP3A4/p-glycoprotein (P-gp) or CYP2D6 within 14 days or 5 half-lives, whichever is longer; or use of grapefruit juice or grapefruit containing products within 7 days prior to receiving the first dose of omecamtiv mecarbil
* Use of any known CYP3A4 inducers within 30 days or 5 half-lives, whichever is longer, before receiving omecamtiv mecarbil

Primary outcomes:
measure: Dosing Period 1: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
timeFrame: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
measure: Dosing Period 1: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
timeFrame: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
measure: Dosing Period 1: Area Under the Concentration-time Curve for a Dosing Interval of 12 Hours (AUC0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 1
timeFrame: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
measure: Dosing Period 1: Predose Omecamtiv Mecarbil Plasma Concentration
timeFrame: Day 8 predose
measure: Dosing Period 1: Accumulation Ratio
timeFrame: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
measure: Dosing Period 2: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
timeFrame: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
measure: Dosing Period 2: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
timeFrame: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
measure: Dosing Period 2: AUC(0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 2
timeFrame: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
measure: Dosing Period 2: Predose Omecamtiv Mecarbil Plasma Concentration
timeFrame: Day 27 predose
measure: Dosing Period 2: Accumulation Ratio
timeFrame: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 35 days
measure: Number of Participants With Grade 3 or Higher Laboratory Toxicities
timeFrame: 35 days
measure: Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1
timeFrame: Day 1 predose and day 8
measure: Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2
timeFrame: Day 20 predose and Day 27
Other outcomes:
Locations:
city: Kagoshima-shi
country: Japan
facility: Research Site
state: Kagoshima
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: