Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of 40 mg Telmisartan/5 mg Amlodipine and 80 mg Telmisartan/5 mg Amlodipine in Healthy Male Volunteers

Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of 40 mg Telmisartan/5 mg Amlodipine and 80 mg Telmisartan/5 mg Amlodipine (Free Dose Combination) in Healthy Male Volunteers

To investigate safety, tolerability, and pharmacokinetics of telmisartan and amlodipine following single administration of 40 mg telmisartan/5 mg amlodipine and 80 mg telmisartan/5 mg amlodipine, and subsequently, following multiple administration of 40 mg telmisartan/5 mg amlodipine and 80 mg telmisartan/5 mg amlodipine once daily for 10 days

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Telmisartan low; Drug: amlodipine; Drug: Telmisartan high

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Healthy male volunteers according to the following criteria:

1. No finding deviating of clinical relevance and no evidence of a clinically relevant concomitant disease based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate, body temperature), 12-lead ECG, clinical laboratory tests
2. Age ≥20 and Age ≤35 years
3. Body weight ≥50 kg
4. Body mass index (BMI) ≥17.6 and BMI ≤26.4 kg/m2
5. Signed and dated written informed consent before admission to the trial

Exclusion Criteria:

1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
3. Chronic or relevant acute infections
4. Any clinical relevant findings of the laboratory test deviating from normal
5. Positive result for either hepatitis B surface antigen (HBsAg), anti hepatitis C virus (HCV) antibodies, syphilitic test or human immunodeficiency virus (HIV) test
6. History of surgery of gastrointestinal tract (except appendectomy)
7. History of relevant orthostatic hypotension (mean standing systolic blood pressure (SBP) varied by ≥20 mmHg from mean supine SBP or mean standing diastolic blood pressure (DBP) varied by ≥10 mmHg from mean supine DBP), fainting spells or blackouts
8. History of hepatic dysfunction (e.g., biliary cirrhosis, cholestasis)
9. History of serious renal dysfunction
10. History of bilateral renal artery stenosis or renal artery stenosis in a solitary kidney
11. History of cerebrovascular disorder
12. History of hyperkalemia
13. Known hypersensitivity to any component of the formulation, or to any other Angiotensin Receptor Blocker (ARB), angiotensin converting enzyme or dihydropyridine
14. 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 before administration or during the trial
15. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 7 days before administration or during the trial
16. Participation in another trial with an investigational drug within 4 months or 6 half-lives of the investigational drug before administration
17. Smoker (≥20 cigarettes/day)
18. Alcohol abuse (60 g or more ethanol/day: ex. 3 middle-sized bottles of beer, 3 gous (equivalent to 540 mL) of sake)
19. Drug abuse
20. Blood donation (more than 100 mL within 4 weeks before administration or during the trial)
21. Excessive physical activities (within 1 week before administration or during the trial)
22. Intake of alcohol within 2 days before administration
23. Inability to comply with dietary regimen of trial centre
24. Intake of any drugs/supplements with ingredient of hypericum perforatum (citrus fruits, Sevilla orange) within 5 days prior to administration
25. Inability to refrain from smoking on trial days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telmisartan low + amlodipine	Drug: Telmisartan low; Drug: amlodipine
Experimental: Telmisartan high + amlodipine	Drug: amlodipine; Drug: Telmisartan high

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate, body temperature)	up to 6 days after last administration in multiple dose phase
Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)	up to 6 days after last administration in multiple dose phase
Number of patients with clinically significant changes in laboratory parameters	up to 6 days after last administration in multiple dose phase
Number of patients with adverse events	up to 6 days after last administration in multiple dose phase
Assessment of tolerability by investigator on a four-point scale	up to 6 days after last administration in multiple dose phase

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of the analyte in plasma) for several time points	up to day 16
tmax (time from dosing to the maximum measured concentration of the analyte in plasma) for several time points	up to day 16
Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)	up to day 16
AUC (area under the concentration-time curve of the analyte in plasma) for several time points	up to day 16
λz (terminal rate constant in plasma) for several time points	up to day 16
t1/2 (terminal half-life of the analyte in plasma) for several time points	up to day 16
MRTpo (mean residence time of the analyte in the body after oral administration) for several time points	up to day 16
CL/F (apparent clearance of the analyte in plasma following extravascular administration) for several time points	up to day 16
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration) for several time points	up to day 16
Accumulation ratio (RA) based on Cmax	up to day 16
RA based on AUC	up to day 16
Predose concentration (Cpre) for several time points	up to day 10
C24,10	24 hours after last administration on day 10

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (Estimate): July 18, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Telmisartan
• Other Study ID Numbers: 1235.9