Telmisartan/Hydrochlorothiazide (HCTZ) Fixed Dose Combination Compared to Its Monocomponents in Healthy Subjects

Study Overview
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Brief Summary
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Study to demonstrate the bioequivalence of telmisartan and HCTZ administered as fixed dose combination in comparison to the single unit formulations

Official Title
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Relative Oral Bioavailability of 80 mg Telmisartan / 12.5 mg HCTZ Fixed Dose Combination Compared With Its Monocomponents in Healthy Subjects. A 4 Period Cross-over, Open, Randomized, Replicate Design Study.

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 277 SE and HCTZ
* Drug: BIBR 277 SE
* Drug: HCTZ


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects as determined by results of screening Signed written informed consent in accordance with GCP (Good Clinical Practice) and local legislation Age ≥ 18 and ≤ 45 years Broca ≥ - 20% and ≤ + 20% Exclusion Criteria: Any findings of the medical examination (including blood pressure, pulse rate and ECG and laboratory value) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastro-intestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders Supine blood pressure at screening of systolic ≤ 110 mmHg and diastolic ≤ 60 mmHg History of orthostatic hypotension, fainting spells or blackouts Hypersensitivity to Telmisartan and/or HCTZ and/or related classes of drugs History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Use of any drugs which might influence the results of the trial (≤ 10 days prior to administration or during the trial) Participation in another trial with an investigational drug (≤ 2 months prior to administration or during the trial) Smoker (≥ 10 cigarettes or ≥ 3 cigars or ≥ 3 pipes/day) Inability to refrain from smoking on study days Known alcohol abuse Known drug abuse Blood donation (≤ 1 month prior to administration) Excessive physical activities (≤ 5 days prior to administration) For female subjects: Pregnancy Positive pregnancy test No adequate contraception Inability to maintain this adequate contraception during the whole study period Lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Sequence 1<br>four treatment periods: Treatment A Treatment B Treatment B Treatment A | Drug: BIBR 277 SE and HCTZ<br>* Treatment A - fixed dose combination<br>Drug: BIBR 277 SE<br>* Treatment B - Monocomponent<br>Drug: HCTZ<br>* Treatment B -Monocomponent<br>|
| Active Comparator: Sequence 2<br>four treatment periods: Treatment B Treatment A Treatment A Treatment B | Drug: BIBR 277 SE and HCTZ<br>* Treatment A - fixed dose combination<br>Drug: BIBR 277 SE<br>* Treatment B - Monocomponent<br>Drug: HCTZ<br>* Treatment B -Monocomponent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (total area under the plasma drug concentration-time curve from time zero to infinity) |  | up to 96 hours post-dose | 
| Cmax (maximum drug plasma concentration) |  | up to 96 hours post-dose | 
| Amount of Hydrochlorothiazide (HCTZ) excreted in urine over 48 hours (Ae(0-48h)) |  | 0-6, 6-12, 12-24, 24-32, 32-48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax (time to achieve Cmax) |  | up to 96 hours post-dose | 
| t1/2 (apparent terminal elimination half-life) |  | up to 96 hours post-dose | 
| CLtot/f (total clearance of a drug from plasma, divided by bioavailability) |  | up to 96 hours post-dose | 
| MRTtot (mean time of residence of drug molecules in the body) |  | up to 96 hours post-dose | 
| Vz/f (apparent volume of distribution during terminal phase) |  | up to 96 hours post-dose | 
| Number of patients with adverse events |  | Up to 62 days |