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

Study Overview
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Brief Summary
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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

Official Title
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Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of 40 mg Telmisartan/5 mg Amlodipine and 80 mg Telmisartan/5 mg Amlodipine (Free Dose Combination) in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Telmisartan low
* Drug: Telmisartan high
* Drug: amlodipine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan low + amlodipine<br> | Drug: Telmisartan low<br> <br> Drug: amlodipine<br> <br> |
| Experimental: Telmisartan high + amlodipine<br> | Drug: Telmisartan high<br> <br> Drug: amlodipine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 12-lead electrocardiogram (ECG) |  | 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 | 
| Number of patients with adverse events |  | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) |  | 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 | 
| MRTpo (mean residence time of the analyte in the body after oral administration) 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 | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration) for several time points |  | up to day 16 | 
| Accumulation ratio (RA) based on Cmax |  | up to day 16 | 
| RA based on AUC |  | up to day 16 | 
| Predose concentration (Cpre) for several time points |  | up to day 10 | 
| C24,10 |  | 24 hours after last administration on day 10 |