Healthy Individual
Conditions
Brief 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.
Interventions
DRUGIvabradine 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).
Sponsors
Institut de Recherches Internationales Servier
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,tmax, AUC(Area under the time-concentration curve) of ivabradine and metabolite | within 60 days after blood sampling (blood sample analysis) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Countries
South Korea
Outcome results
None listed