Pharmacokinetics and Safety Study of Omecamtiv Mecarbil in Healthy Japanese Adults

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02601001
• Other study ID #: 20150134
• Status: Completed
• Phase: Phase 1
• Start date: November 13, 2015
• Est. completion date: January 6, 2016

Study information

• Verified date: July 2021
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 6, 2016
• Est. primary completion date: January 6, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• Omecamtiv mecarbil
Omecamtiv mecarbil tablets for oral administration
• Placebo
Matching placebo tablets

Locations

Country	Name	City	State
Japan	Research Site	Kagoshima-shi	Kagoshima

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dosing Period 1: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1		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.
Primary	Dosing Period 1: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1		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.
Primary	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		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.
Primary	Dosing Period 1: Predose Omecamtiv Mecarbil Plasma Concentration		Day 8 predose
Primary	Dosing Period 1: Accumulation Ratio	Accumulation ratio calculated as the ratio of day 8 AUC(0-12) / day 1 AUC(0-12)	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.
Primary	Dosing Period 2: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2		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.
Primary	Dosing Period 2: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2		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.
Primary	Dosing Period 2: AUC(0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 2		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.
Primary	Dosing Period 2: Predose Omecamtiv Mecarbil Plasma Concentration		Day 27 predose
Primary	Dosing Period 2: Accumulation Ratio	Accumulation ratio calculated as the ratio of day 27 AUC(0-12) / day 20 AUC(0-12).	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	Number of Participants With Treatment-emergent Adverse Events	An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment.; A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: fatal; life threatening; required in patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Adverse events were graded for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	35 days
Secondary	Number of Participants With Grade 3 or Higher Laboratory Toxicities	Abnormal laboratory findings were graded for severity according to the NCI CTCAE version 4.0 according to the following guideline: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.; Grade 4: Life-threatening consequences; urgent intervention indicated.; Grade 5: Death related to AE.	35 days
Secondary	Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1	QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by electrocardiogram (ECG).; Maximum increase from Period 1 baseline was categorized as: = 30 milliseconds (ms) > 30 to 60 ms > 60 ms	Day 1 predose and day 8
Secondary	Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2	QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by ECG.; Maximum increase from Period 2 baseline was categorized as: = 30 ms > 30 to 60 ms > 60 ms	Day 20 predose and Day 27

External Links

•   AmgenTrials clinical trials website