Pharmacokinetics and Safety Study of Omecamtiv Mecarbil in Healthy Japanese Adults

NCT02601001 | Completed Phase 1 Results

• 1 other identifier: 20150134
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteer

Keywords

Heart failure

Outcome Measures

Primary Outcomes (10)

• 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.

• 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.

• 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.

• Dosing Period 1: Predose Omecamtiv Mecarbil Plasma Concentration

  Day 8 predose

• 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.

• 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.

• 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.

• 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.

• Dosing Period 2: Predose Omecamtiv Mecarbil Plasma Concentration

  Day 27 predose

• 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 Outcomes (4)

• Number of Participants With Treatment-emergent Adverse Events

  35 days

• Number of Participants With Grade 3 or Higher Laboratory Toxicities

  35 days

• Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1

  Day 1 predose and day 8

• Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2

  Day 20 predose and Day 27

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants received placebo tablets twice a day (BID) in dosing period 1 (days 1 to 8) and in dosing period 2 (days 20 to 27).

Drug: Placebo

Omecamtiv mecarbil 25 mg / 37.5 mg

EXPERIMENTAL

Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg or 37.5 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose): If day 8 Cpredose was \< 200 ng/mL, participants received 37.5 mg BID; if day 8 Cpredose was ≥ 200 ng/mL or a day 8 PK value was not available participants continued to receive 25 mg BID.

Drug: Omecamtiv mecarbil

Omecamtiv mecarbil 25 mg / 50 mg

EXPERIMENTAL

Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg or 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose): If day 8 Cpredose was \< 200 ng/mL, participants received 50 mg BID; if day 8 Cpredose was ≥ 200 ng/mL or a day 8 PK value was not available participants continued to receive 25 mg BID.

Drug: Omecamtiv mecarbil

Interventions

Omecamtiv mecarbil DRUG

Omecamtiv mecarbil tablets for oral administration

Also known as: AMG 423

Omecamtiv mecarbil 25 mg / 37.5 mg; Omecamtiv mecarbil 25 mg / 50 mg

Placebo DRUG

Matching placebo tablets

Placebo

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (1)

Research Site

Kagoshima, Kagoshima-ken, 890-0081, Japan

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Heart Failure

Interventions

omecamtiv mecarbil

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: November 10, 2015
• Study Start: November 13, 2015
• Primary Completion: January 6, 2016
• Study Completion: January 6, 2016
• Last Updated: July 27, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-07

Locations

JP (1)