Bioavailability of Telmisartan/Amlodipine Fixed-dose Combination Compared to Its Mono-components in Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to investigate the relative bioavailability of fixed-dose combination tablet vs. mono-components of telmisartan and amlodipine

Official Title
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Relative Bioavailability of Telmisartan 40 mg/Amlodipine 5 mg Fixed-dose Combination Tablet Compared to Concomitant Use of Its Mono-components (i.e., Telmisartan 40 mg Tablet and Amlodipine 5 mg Tablet in Concomitant Use) Following Oral Administration in Healthy Male Volunteers (an Open-label, Randomised, Single Dose, Two-way Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Telmisartan/amlodipine fixed-dose combination tablet
* Drug: Telmisartan
* Drug: Amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate and body temperature), 12-lead ECG, clinical laboratory tests, no finding of clinical relevance, no evidence of a clinically relevant concomitant disease Age ≥20 and Age ≤35 years Body weight ≥50 kg BMI ≥17.6 and BMI ≤26.4 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice 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 hepatitis B antigen, anti hepatitis C virus anti bodies, syphilitic test or HIV test Surgery of gastrointestinal tract (except appendectomy) History of relevant orthostatic hypotension (mean standing systolic blood pressure (SBP) varies by ≥20 mmHg from mean supine SBP or mean standing diastolic blood pressure (DBP) varies 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 II receptor antagonists, 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 prior to 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 prior to administration or during the trial Participation in another trial with an investigational drug within 4 months or 6 half-lives of the investigational drug prior to 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 prior to administration or during the trial) Excessive physical activities (within 1 week prior to administration or during the trial) Intake of alcohol within 2 days prior to administration Inability to comply with dietary regimen of study centre Intake of any drugs/supplements with ingredient of hypericum perforatum or citrus fruits (e.g. grapefruits, Sevilla orange) within 5 days prior to administration Inability to refrain from smoking on trial days Any other volunteers whom, the principal investigator or sub investigator would not allow to participate in this study

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

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan/amlodipine fixed-dose combination<br> | Drug: Telmisartan/amlodipine fixed-dose combination tablet<br> <br> |
| Active Comparator: Telmisartan tablet and amlodipine tablet<br> | Drug: Telmisartan<br> <br> Drug: Amlodipine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) |  | up to 144 hours after administration of study drug | 
| Maximum measured concentration of the analyte in plasma (Cmax) |  | up to 144 hours after administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) |  | up to 144 hours after administration of study drug | 
| Time from administration to the maximum concentration of the analyte in plasma (tmax) |  | up to 144 hours after administration of study drug | 
| Terminal rate constant of the analyte in plasma (λz) |  | up to 144 hours after administration of study drug | 
| Terminal half-life of the analyte in plasma (t1/2) |  | up to 144 hours after administration of study drug | 
| Mean residence time of the analyte in the body after po administration (MRTpo) |  | up to 144 hours after administration of study drug | 
| Number of subjects with adverse events |  | up to 56 days | 
| Number of subjects with clinically significant changes in vital signs |  | up to 144 hours after administration of study drug | 
| Number of subjects with clinically significant changes in 12-lead ECG (electrocardiogram) |  | up to 144 hours after administration of study drug | 
| Number of subjects with clinically significant changes in laboratory tests |  | up to 144 hours after administration of study drug |