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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Telmisartan; Drug: Candesartan

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Telmisartan	Drug: Telmisartan; Other Names: Micardis®
Active Comparator: Candesartan	Drug: Candesartan; Other Names: Blopress

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): August 1, 2002

Study Registration Dates

• First Submitted: October 9, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Estimate): October 10, 2014
• Last Update Submitted That Met QC Criteria: October 9, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Candesartan; Telmisartan
• Other Study ID Numbers: 502.402