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

Healthy Individual Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01804010
• Other study ID #: 2007-0114
• Status: Completed
• Phase: Phase 1
• First received: February 27, 2013
• Last updated: March 4, 2013
• Start date: May 2007
• Est. completion date: November 2007

Study information

• Verified date: March 2013
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review BoardKorea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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. The pharmacodynamic profile of ivabradine versus placebo by measuring its effects on heart rate after single and then after repeated administrations.

3. Clinical safety of ivabradine versus placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Individual

Intervention

Drug:
• Ivabradine and placebo
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).

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Institut de Recherches Internationales Servier

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	pharmacodynamics: The change of heart rate between baseline and over 24-hour, diurnal, nocturnal, awake, and asleep periods after administration of ivabradine	For PD measurements, 24-hour Holter recordings were performed on Day0, Day1, Day8, and Day10. a resting 12-lead ECG were also performed.; The changes of heart rate between day 1 and baseline values, between day 8 and baseline values were studied over 24-hour, diurnal, nocturnal, awake and asleep period for each ivabradine dose in comparison with placebo. Descriptive statistics by dose were performed and confidence intervals of the differences between each dose of ivabradine and placebo were constructed using a non-parametric method based on Hodges & Lehman estimate for independent samples.	within 10 days after administration	No