Pharmacokinetic, Pharmacodynamic Profiles and Safety After Oral Administration of Ivabradine in Male Healthy Korean Volunteers

NCT01804010 | Completed Phase 1

• 1 other identifier: 2007-0114
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To assess the pharmacokinetic profile of ivabradine (S 16257) and its main active metabolite S 18982 in Korean healthy volunteers after oral administration of ivabradine at the doses of 2.5, 5, 10mg and after repeated oral administrations of ivabradine for 4.5 days at the same doses twice daily versus placebo and to use the study results for bridging with Caucasian data.
2. 2.The pharmacodynamic profile of ivabradine versus placebo by measuring its effects on heart rate after single and then after repeated administrations.
3. 3.Clinical safety of ivabradine versus placebo.

Conditions

Healthy Individual

Outcome Measures

Primary Outcomes (1)

• Cmax,tmax, AUC(Area under the time-concentration curve) of ivabradine and metabolite

  For PK measurements, blood samplings were done: pre-dose then 20 min, 40 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 36 h, 48 h, 60 h, and 72 h following the D1 single administration (P1) and the Day 8 (D8) last repeated dose (P2), respectively.Ivabradine and its main metabolite were determined using LC-MS/MS, then pharmacokinetic parameters were calculated by noncompartmental approach. Descriptive statistics were performed on the PK individual parameters calculated from the plasma concentration-time profiles.

  within 60 days after blood sampling (blood sample analysis)

Secondary Outcomes (1)

• pharmacodynamics: The change of heart rate between baseline and over 24-hour, diurnal, nocturnal, awake, and asleep periods after administration of ivabradine

  within 10 days after administration

Study Arms (2)

Ivabradine

ACTIVE COMPARATOR

Single and repeated oral administrations of 3 doses of ivabradine

Drug: Ivabradine and placebo

Placebo

PLACEBO COMPARATOR

Placebo administration

Drug: Ivabradine and placebo

Interventions

Ivabradine and placebo DRUG

Single and repeated oral administrations of 3 doses of ivabradine (2.5, 5, and 10 mg). Subjects were given a single administration of ivabradine during Period 1 (P1), following a 3-day washout, they were given repeated administrations twice daily for 4.5 days during Period 2 (P2).

Also known as: Ivabradine, Placebo

Ivabradine; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• age between 18 and 40 years and Korean
• Nonsmoker or smoke less than 5 cigarettes per day
• normal dietary habits
• BMI ranging from 18 to 25 kg/m2
• good physical and mental status, determined by the investigator
• vital signs in resting condition within range: SBP 100-139 mmHg, DBP 50-89 mmHg
• Normal ECG

You may not qualify if:

• Participate any other trial in the last 3 months prior to the study
• History of major psychiatric, medical, surgical disorders
• Acute, or chronic disease
• History of hypersensitivity to at least one drug
• History of alcoholism or positive alcohol breath test
• Positive drug screening results
• known positive serology for HIV1, HIV2, hepatitis B or C
• blood donor within the last 3 month of the study
• regular use of sedatives, hypnotics, tranquillisers

Sponsors & Collaborators

• Asan Medical Center: lead
• Institut de Recherches Internationales Servier: collaborator

Study Sites (1)

Asan Medical Center

Seoul, Seoul, 138-736, South Korea

Location

MeSH Terms

Interventions

Ivabradine

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kyun-Seop Bae, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dep. of clinical pharmacology and therapeutics

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 5, 2013
• Study Start: May 1, 2007
• Primary Completion: September 1, 2007
• Study Completion: November 1, 2007
• Last Updated: March 5, 2013

Record last verified: 2013-03

Locations

KR (1)