Study to Assess Potential Different Properties of Telmisartan Compared to Candesartan in Healthy Volunteers

Study Overview
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Brief Summary
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Study to assess potential different properties of telmisartan, which due to its Vd, should result in stronger beneficial effects of AT1 blockade in tissues (e.g. aldosterone suppression and renin increase) plus stronger AT2 stimulation compared to candesartan

Official Title
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Does Telmisartan Compared to Candesartan Due to a Distinctly Larger Volume of Distribution Exert Stronger Effects in Relevant Peripheral Tissues, e.g. Renal and Adrenal Tissues

Conditions
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Healthy

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Candesartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males, aged 18 to 45 years. Absence of any relevant disease as determined by no clinically deviation from normal in medical history, clinical laboratory determination, ECGs and physical examinations Systolic blood pressure (SBP) between 100 and 140 mmHg systolic and below 85 mmHg diastolic (both left and right arm) and a heart rate of ≥50 bpm Signed informed consent form No intake of drugs inbetween a waiting time of ten times of half-life Exclusion Criteria: Contraindications to Ang II antagonists, known hypersensitivity, history of angioedema, serious allergy, asthma, allergic skin rash, significant allergic rhinitis or sensitivity to any drug History of cardiovascular diseases: any clinically significant cardio-vascular disease, a supine diastolic blood pressure >86 mmHg and systolic >141 mmHg measured by a standard sphygmomanometer or a heart rate ≤49 bpm Cerebrovascular diseases: history of stroke or transitory ischemic attacks (TIAs) or history of any cerebral bleeding Renal diseases: serum creatinine >1.5 mg/dL Gastrointestinal/Hepatic diseases: Aspartate aminotransferase (ASAT) >40 U/l or Alanine aminotransferase (ALAT) >40 U/L, serum bilirubin >2x upper limit of normal, history of malabsorption or inability to tolerate oral medication, history of gastric or duodenal ulcers, history of significant gastrointestinal bleeding, history of hepatitis within the past years Any history of alcohol or drug abuse Use of any of the following drugs within 4 weeks of study enrolment (e.g. agents known to induce drug metabolizing enzymes): anabolic steroids and corticoids, antiarrhythmics (amiodarone, mexiletine, quinidine, propafenone), antibiotics (chloramphenicol, tetracyclines, sulfonamides, macrolides, cephalosporins, rifampicin, nalidixic acid), antiepileptics (phenytoin, carbamazepine), antifungals (e.g. griseofulvin), barbiturates, cimetidine, ethacrynic acid, fibrates, furosemide, haloperidol, lipid lowering agents (cholestyramine, hydroxymethylglutaryl, coenzyme A (HMG CoA) reductase inhibitors, dextrothyroxin), thyroid replacement therapy hormones or thyrostatics (thioureylene-type). The use of nonsteroidal antiinflammatory drugs (NSAIDs) should be discontinued 2 weeks prior to study enrolment, the one exception of aspirin should be one (1) week prior to study enrolment Participation in any other investigational study, within the 30 days prior to enrolment Blood donation within the previous 3 months The investigator might disqualify a subject for a sound medical or psychiatric reason

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

Sexes Eligible for Study
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Male

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan<br> | Drug: Telmisartan<br> <br> * Other names: Micardis®;|
| Active Comparator: Candesartan<br> | Drug: Candesartan<br> <br> * Other names: Blopress;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of PRA increase versus DR-1 | analysis of variance | Predose and 2, 4, 8 h following trial medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of angiotensin-1 (AT1) pressor antagonism in vivo (DR-1) | rightward shift (DR-1) of diastolic blood pressure response to Angiotensin II dose escalating challenges | Predose and 2, 4, 8 h following trial medication | 
| Assessment of plasma aldosterone concentration after stimulation with Angiotensin II |  | Predose and 2, 4, 8 h following trial medication | 
| Reactive response of the plasma renin activity (PRA) |  | Predose and 2, 4, 8 h following trial medication | 
| Number of subjects with adverse events |  | up to 42 days |