Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of 40 mg Telmisartan/5 mg Amlodipine and 80 mg Telmisartan/5 mg Amlodipine in Healthy Male Volunteers
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02194309
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
To investigate safety, tolerability, and pharmacokinetics of telmisartan and amlodipine following single administration of 40 mg telmisartan/5 mg amlodipine and 80 mg telmisartan/5 mg amlodipine, and subsequently, following multiple administration of 40 mg telmisartan/5 mg amlodipine and 80 mg telmisartan/5 mg amlodipine once daily for 10 days
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 24
Inclusion Criteria
Healthy male volunteers according to the following criteria:
- No finding deviating of clinical relevance and no evidence of a clinically relevant concomitant disease based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate, body temperature), 12-lead ECG, clinical laboratory tests
- Age ≥20 and Age ≤35 years
- Body weight ≥50 kg
- Body mass index (BMI) ≥17.6 and BMI ≤26.4 kg/m2
- Signed and dated written informed consent before admission to the trial
Exclusion Criteria
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- Chronic or relevant acute infections
- Any clinical relevant findings of the laboratory test deviating from normal
- Positive result for either hepatitis B surface antigen (HBsAg), anti hepatitis C virus (HCV) antibodies, syphilitic test or human immunodeficiency virus (HIV) test
- History of surgery of gastrointestinal tract (except appendectomy)
- History of relevant orthostatic hypotension (mean standing systolic blood pressure (SBP) varied by ≥20 mmHg from mean supine SBP or mean standing diastolic blood pressure (DBP) varied by ≥10 mmHg from mean supine DBP), fainting spells or blackouts
- History of hepatic dysfunction (e.g., biliary cirrhosis, cholestasis)
- History of serious renal dysfunction
- History of bilateral renal artery stenosis or renal artery stenosis in a solitary kidney
- History of cerebrovascular disorder
- History of hyperkalemia
- Known hypersensitivity to any component of the formulation, or to any other Angiotensin Receptor Blocker (ARB), angiotensin converting enzyme or dihydropyridine
- Intake of drugs with a long half-life (≥24 hours) within at least one month or less than 10 half-lives of the respective drug before administration or during the trial
- Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 7 days before administration or during the trial
- Participation in another trial with an investigational drug within 4 months or 6 half-lives of the investigational drug before administration
- Smoker (≥20 cigarettes/day)
- Alcohol abuse (60 g or more ethanol/day: ex. 3 middle-sized bottles of beer, 3 gous (equivalent to 540 mL) of sake)
- Drug abuse
- Blood donation (more than 100 mL within 4 weeks before administration or during the trial)
- Excessive physical activities (within 1 week before administration or during the trial)
- Intake of alcohol within 2 days before administration
- Inability to comply with dietary regimen of trial centre
- Intake of any drugs/supplements with ingredient of hypericum perforatum (citrus fruits, Sevilla orange) within 5 days prior to administration
- Inability to refrain from smoking on trial days
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Telmisartan low + amlodipine Telmisartan low - Telmisartan high + amlodipine Telmisartan high - Telmisartan low + amlodipine amlodipine - Telmisartan high + amlodipine amlodipine -
- Primary Outcome Measures
Name Time Method Number of patients with adverse events up to 6 days after last administration in multiple dose phase Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG) up to 6 days after last administration in multiple dose phase Assessment of tolerability by investigator on a four-point scale up to 6 days after last administration in multiple dose phase Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate, body temperature) up to 6 days after last administration in multiple dose phase Number of patients with clinically significant changes in laboratory parameters up to 6 days after last administration in multiple dose phase
- Secondary Outcome Measures
Name Time Method Accumulation ratio (RA) based on Cmax up to day 16 MRTpo (mean residence time of the analyte in the body after oral administration) for several time points up to day 16 Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration) for several time points up to day 16 RA based on AUC up to day 16 Predose concentration (Cpre) for several time points up to day 10 Cmax (maximum measured concentration of the analyte in plasma) for several time points up to day 16 tmax (time from dosing to the maximum measured concentration of the analyte in plasma) for several time points up to day 16 AUC (area under the concentration-time curve of the analyte in plasma) for several time points up to day 16 λz (terminal rate constant in plasma) for several time points up to day 16 t1/2 (terminal half-life of the analyte in plasma) for several time points up to day 16 CL/F (apparent clearance of the analyte in plasma following extravascular administration) for several time points up to day 16 C24,10 24 hours after last administration on day 10 Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) up to day 16