Relative Oral Bioavailability of Telmisartan / Hydrochlorothiazide (HCTZ) Fixed Dose Combination (FDC) Compared With Its Monocomponents in Healthy Subjects

Study Overview
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Brief Summary
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A 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 40 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: Hydrochlorothiazide
* Drug: Telmisartan
* Drug: Telmisartan/HCTZ FDC


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 good clinical practice (GCP) and local legislation Age ≥ 18 and ≤ 55 years Broca ≥ -20 % and ≤ +20 % Exclusion Criteria: Any findings of the medical examination (including blood pressure, pulse rate and electrocardiogram (ECG)) 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 or neurological disorders Supine blood pressure at screening of systolic ≤ 110 mmHg and diastolic ≤ 60 mmHg History of orthostatic hypotension, fainting, spells or blackouts Chronic or relevant acute infection History or allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) ≤ 1 month prior to administration or during the trial 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 Alcohol abuse (> 60g/day) Drug abuse Blood donation (≤ 1 month prior to administration or during the trial) Excessive physical activities (≤ 5 days prior to administration or during the trial) Any laboratory value outside the reference range of clinical relevance Hypersensitivity to Telmisartan and/or HCTZ and/or related classes of drugs For female subjects: Pregnancy Positive pregnancy test No adequate contraception (e.g. sterilization, intrauterine device (IUD), oral contraceptives) 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: 55 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: Telmisartan/HCTZ FDC<br> | Drug: Telmisartan/HCTZ FDC<br> <br> |
| Active Comparator: Telmisartan and HCTZ individual tablets<br> | Drug: Hydrochlorothiazide<br> <br> Drug: Telmisartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total area under concentration-time curve of the analytes in plasma from time zero to infinity (AUC0-∞) |  | Pre-dose up to day 54 | 
| Maximum concentration of the analytes in plasma (Cmax) |  | Pre-dose up to day 54 | 
| Amount of HCTZ excreted in urine over 48 h (Ae(0-48)) |  | Pre-dose up to day 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to achieve maximum concentration of the analytes in plasma (tmax) |  | Pre-dose up to day 54 | 
| Terminal elimination half life of the analytes in plasma (t1/2) |  | Pre-dose up to day 54 | 
| Total clearance of the of the analytes after oral administration (CLtot/f) |  | Pre-dose up to day 54 | 
| Total mean residence time of the analytes (MRTtot) |  | Pre-dose up to day 54 | 
| Apparent volume of distribution of the analytes during the terminal phase (Vz/f) |  | Pre-dose up to day 54 | 
| Number of patients with relevant changes in laboratory values |  | Screening (day -14 to day 0) and day 72 | 
| Number of patients with relevant changes in vital signs (blood pressure, pulse rate) |  | Up to day 72 | 
| Number of patients with Adverse events |  | Up to day 72 | 
| Number of patients with relevant changes in ECG |  | Screening (day -14 to day 0) and day 72 | 
| Number of patients with relevant changes in physical examination |  | Screening (day -14 to day 0) and day 72 |