Bioequivalence of Telmisartan / Ramipril Fixed Dose Combination Compared With the Monocomponents Given Concomitantly to Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Study to demonstrate the bioequivalence (BE) of 40 mg telmisartan/ 2.5 mg ramipril fixed-dose combination (FDC) versus its monocomponents given concomitantly

Official Title
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Bioequivalence of 40 mg Telmisartan / 2.5 mg Ramipril Fixed Dose Combination Compared With the Monocomponents, Telmisartan and Ramipril (Two Different Formulations) Given Concomitantly to Healthy Male and Female Volunteers (an Open-label, Randomised, Single-dose, Three-way Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Telmisartan/Ramipril
* Drug: Telmisartan
* Drug: Ramipril capsule
* Drug: Ramipril tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females according to the following criteria based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests Age ≥18 and Age ≤55 years BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation Exclusion Criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 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 (especially unspecific inducing agents like St.John´s wort (Hypericum perforatum) or inhibitors like cimetidine) or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking during 24 hours prior to dosing and 24 hours after dosing Alcohol abuse (more than 60 g/day) or inability to stop alcoholic beverages for 24 hours prior to dosing and up to the last sampling time point, 96 hours after dosing. Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms) A history of additional risk factors for torsade de pointes (e.g., heart failure, hyperkalemia, hypokalemia, family history of Long QT Syndrome) Any history of relevant low blood pressure Supine blood pressure at screening of systolic <110 mm Hg and diastolic <60 mm Hg History of urticaria History of angioneurotic edema Hereditary fructose intolerance For female subjects: Pregnancy or planning to become pregnant during the study or within 2 months of study completion Positive pregnancy test Are not willing or are unable to use a reliable method of contraception (such as implants, injectables and combined oral contraceptives, sterilisation, intrauterine device, double barrier method, sexual abstinence) for at least 1 month prior to participation in the trial, during and up to 1 month after completion/termination of the trial Chronic use of oral contraception or hormone replacement containing ethinyl estradiol as the only method of contraception Currently lactating

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/Ramipril<br> | Drug: Telmisartan/Ramipril<br>* fixed dose combination tablet<br>|
| Active Comparator: Telmisartan + Ramipril capsule<br> | Drug: Telmisartan<br> <br> * Other names: Micardis®;Drug: Ramipril capsule<br> <br> * Other names: Altace®;|
| Active Comparator: Telmisartam + Ramipril tablet<br> | Drug: Telmisartan<br> <br> * Other names: Micardis®;Drug: Ramipril tablet<br> <br> * Other names: Delix®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf. (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 96 hours after drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 96 hours after drug administration | 

Secondary 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 96 hours after drug administration | 
| AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval from t1 to t2) |  | up to 96 hours after drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | up to 96 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | up to 96 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 96 hours after drug administration | 
| MRTpo (mean residence time of the analyte in the body after po administration) |  | up to 96 hours after drug administration | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | up to 96 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 96 hours after drug administration | 
| Number of patients with adverse events |  | up to 73 days | 
| Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse Rate) |  | up to 73 days | 
| Number of patients with clinically relevant changes in laboratory tests |  | up to 73 days | 
| Number of patients with clinically relevant changes in 12-lead electrocardiogram |  | up to 73 days |