Pharmacokinetics of Simvastatin and Its Metabolite Simvastatin Acid With and Without Concomitant Administration of Telmisartan in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
To assess the pharmacokinetics of simvastatin and simvastatin acid with/without concomitant administration of telmisartan

Official Title
-----------------
Pharmacokinetics of Single Oral Doses of 40 mg Simvastatin and Its Metabolite Simvastatin Acid With and Without Concomitant Administration of Telmisartan 80 mg Daily, Given Orally Over 6 Days. A Randomised, Placebo Controlled, Double Blind (for Telmisartan), Two Way Cross Over Trial in Healthy Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Telmisartan
* Drug: Simvastatin
* Drug: Telmisartan placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 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 of 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 (30 days prior to administration or during the trial) Smoker Alcohol abuse (> 60 g/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 simvastatin 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
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan combined with Simvastatin<br>Telmisartan once daily (day 1 to day 6) and Simvastatin given once (day 6) | Drug: Telmisartan<br> <br> Drug: Simvastatin<br> <br> |
| Active Comparator: Simvastatin and telmisartan placebo<br>Telmisartan placebo once daily (day 1 to day 6) and Simvastatin given once (day 6) | Drug: Simvastatin<br> <br> Drug: Telmisartan placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of simvastatin and simvastatin acid in plasma at different time points (AUC) |  | Pre-dose, up to day 32 after start of treatment | 
| Maximum concentration of simvastatin and simvastatin acid in plasma (Cmax) |  | Pre-dose, up to day 32 after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Cmax after a single extravascular dose (tmax) |  | Pre-dose, up to day 32 after start of treatment | 
| Elimination half-life in plasma (t1/2) |  | Pre-dose, up to day 32 after start of treatment | 
| Total clearance from plasma (CLtot/f) |  | Pre-dose, up to day 32 after start of treatment | 
| Mean time of residence in the body (MRTtot) |  | Pre-dose, up to day 32 after start of treatment | 
| Apparent volume of distribution during the terminal phase (Vz/f) |  | Pre-dose, up to day 32 after start of treatment | 
| Area under the plasma concentration-time curve of telmisartan at steady state (AUCss) |  | Pre-dose, up to day 32 after start of treatment | 
| Maximum concentration of telmisartan in plasma at steady state (Cmax,ss) |  | Pre-dose, up to day 32 after start of treatment | 
| Number of patients with clinically relevant findings in laboratory values |  | Pre-dose, up to day 32 after start of treatment | 
| Number of patients with clinically relevant findings in vital signs (blood pressure, pulse rate) |  | Pre-dose, up to day 32 after start of treatment | 
| Number of patients with adverse events |  | Up to day 32 after start of treatment | 
| Number of patients with clinically relevant findings in ECG |  | Pre-dose, up to day 32 after start of treatment |