Pharmacokinetics of Telmisartan Alone and in Combination With Amlodipine in Healthy Volunteers

Study Overview
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Brief Summary
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Study to investigate the steady state pharmacokinetics of 80 mg telmisartan alone and in combination with repeated doses of 10 mg amlodipine

Official Title
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Pharmacokinetics of Repeated Oral Doses of 80 mg Telmisartan (Micardis®) at Steady State Alone and in Combination With Repeated Oral Doses of Amlodipine 10 mg (Norvasc®) at Steady State. A Two-way Crossover, Open, Randomised Design Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Amlodipine


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 (BP, PR), 12-lead ECG, clinical laboratory tests Age ≥18 and Age ≤50 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 or that prolong the QT/corrected QT 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 on trial days Alcohol abuse (more than 60 g/day) 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 Any history of relevant low blood pressure Supine blood pressure at screening of systolic <110 mm Hg and/or diastolic <60 mm Hg History of urticaria For female subjects: Pregnancy or planning to become pregnant within 2 months of study completion Positive pregnancy test No adequate contraception e.g. sterilisation, intrauterine device, have not been using a barrier method of contraception for at least 3 months prior to participation in the study Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial Chronic use of oral contraception or hormone replacement containing ethinyl estradiol as the only method of contraception Partner is unwilling to use condoms Lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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 |
| --- | --- |
| Active Comparator: Telmisartan<br> | Drug: Telmisartan<br> <br> * Other names: Micardis®;|
| Experimental: Telmisartan and amlodipine<br> | Drug: Telmisartan<br> <br> * Other names: Micardis®;Drug: Amlodipine<br> <br> * Other names: Norvasc®;|

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 telmisartan in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) |  | up to 15 days after first administration of study drug | 
| Maximum measured concentration of telmisartan in plasma at steady state over a uniform dosing interval τ (Cmax,ss) |  | up to 15 days after first administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss for amlodipine |  | up to 15 days after first administration of study drug | 
| Cmax,ss for amlodipine |  | up to 15 days after first administration of study drug | 
| Maximum measured concentration of the analyte in plasma (Cmax) |  | up to 12 hours after first administration of study drug | 
| Time from dosing to maximum measured concentration on plasma (tmax) |  | up to 12 hours after first administration of study drug | 
| Area under the plasma concentration-time curve over a uniform dosing interval τ after administration of the first dose; corresponds to AUC0-24h (AUCτ,1) |  | up to 12 hours after first administration of study drug | 
| Pre-dose concentration of the analyte in plasma immediately before the administration of the next dose N (Cpre,N) |  | pre-dose on days 2-9 | 
| Time from last dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss) |  | up to 144 hours after last administration of study drug | 
| Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss) |  | up to 144 hours after last administration of study drug | 
| Terminal rate constant in plasma at steady state (λz,ss) |  | up to 144 hours after last administration of study drug | 
| Terminal half-life of the analyte in plasma at steady state (t1/2, ss) |  | up to 144 hours after last administration of study drug | 
| Mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss) |  | up to 144 hours after last administration of study drug | 
| Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss) |  | up to 144 hours after last administration of study drug | 
| Apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration (Vz/F,ss) |  | up to 144 hours after last administration of study drug | 
| Accumulation ratio of the analyte in plasma based on AUC over a uniform dosing interval after the first and last doses (RA, AUC) |  | up to 15 days after first administration of study drug | 
| Accumulation ratio of the analyte in plasma based on Cmax over a uniform dosing interval after the last and first doses (RA,Cmax) |  | up to 15 days after first administration of study drug | 
| Number of subjects with adverse events |  | up to 80 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | within 14 days after last trial procedure |