Bioequivalence of Telmisartan as Telmisartan 80 mg/HCTZ 12.5 mg Fixed-dose Combination Tablet or as Two Telmisartan 40 mg Tablets in Healthy Male Volunteers

Study Overview
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Brief Summary
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To establish bioequivalence of telmisartan orally administrated in two different ways: either with a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination tablet or with two telmisartan 40 mg tablets

Official Title
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Bioequivalence of Telmisartan Administrated in Two Different Ways: Either in Telmisartan 80 mg/HCTZ 12.5 mg Fixed-dose Combination Tablet or as Two Telmisartan 40 mg Tablets (an Open-label, Randomised, Single-dose, Four-period Replicated Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Telmisartan/HCTZ combination
* Drug: Telmisartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature), 12-lead ECG (electrocardiogram), clinical laboratory tests Age ≥20 and Age ≤35 years Body weight ≥50 kg Body Mass Index (BMI) ≥18.0 and BMI ≤25.0 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation. 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 (HBs) antigen, 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, fainting spells or blackouts Known hypersensitivity to any component of the formulation (telmisartan and hydrochlorothiazide), or to any other angiotensin II receptor blocker (ARBs), any other thiazides, or thiazide derivatives (e.c. sulfonamide derivatives like a chlorthalidone) 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 History of impaired glucose tolerance History of hypokalemia History of hyperuricemia Salt restriction therapy 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 Inability to refrain from smoking on trial days Subjects judged to be inappropriate by the investigator or the sub-investigator

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | Up to 72 hours after drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | Up to 72 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | Up to 72 hours after drug administration | 
| tmax (time from dosing to the maximum measured concentration of the analyte in plasma) |  | Up to 72 hours after drug administration | 
| λz (terminal rate constant of the analyte in plasma) |  | Up to 72 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | Up to 72 hours after drug administration | 
| MRTpo (mean residence time of the analyte in the body after po administration) |  | Up to 72 hours after drug administration | 
| Number of participants with clinically significant findings in physical examination |  | Up to 72 hours after last drug administration | 
| Number of participants with clinically significant findings in vital signs |  | Up to 72 hours after last drug administration | 
| Number of participants with clinically significant findings in 12-lead ECG (electrocardiogram) |  | Up to 72 hours after last drug administration | 
| Number of participants with clinically significant findings in clinical laboratory parameters |  | Up to 72 hours after last drug administration | 
| Number of participants with adverse events |  | Up to 72 hours after last drug administration |