Healthy
Conditions
Brief summary
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
Interventions
DRUGTelmisartan
DRUGCandesartan
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males, aged 18 to 45 years. 2. Absence of any relevant disease as determined by no clinically deviation from normal in medical history, clinical laboratory determination, ECGs and physical examinations 3. 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 4. Signed informed consent form 5. No intake of drugs inbetween a waiting time of ten times of half-life
Exclusion criteria
1. Contraindications to Ang II antagonists, known hypersensitivity, history of angioedema, serious allergy, asthma, allergic skin rash, significant allergic rhinitis or sensitivity to any drug 2. 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 3. Cerebrovascular diseases: history of stroke or transitory ischemic attacks (TIAs) or history of any cerebral bleeding 4. Renal diseases: serum creatinine \>1.5 mg/dL 5. 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 6. Any history of alcohol or drug abuse 7. 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 8. Participation in any other investigational study, within the 30 days prior to enrolment 9. Blood donation within the previous 3 months 10. The investigator might disqualify a subject for a sound medical or psychiatric reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Slope of PRA increase versus DR-1 | Predose and 2, 4, 8 h following trial medication | analysis of variance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of angiotensin-1 (AT1) pressor antagonism in vivo (DR-1) | Predose and 2, 4, 8 h following trial medication | rightward shift (DR-1) of diastolic blood pressure response to Angiotensin II dose escalating challenges |
| 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 | — |
Outcome results
None listed