Clinical trial NCT02194309: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-18
Enrollment: 24
Sex: MALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate, body temperature)
timeFrame: up to 6 days after last administration in multiple dose phase
measure: Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)
timeFrame: up to 6 days after last administration in multiple dose phase
measure: Number of patients with clinically significant changes in laboratory parameters
timeFrame: up to 6 days after last administration in multiple dose phase
measure: Number of patients with adverse events
timeFrame: up to 6 days after last administration in multiple dose phase
measure: Assessment of tolerability by investigator on a four-point scale
timeFrame: up to 6 days after last administration in multiple dose phase
Secondary outcomes:
measure: Cmax (maximum measured concentration of the analyte in plasma) for several time points
timeFrame: up to day 16
measure: tmax (time from dosing to the maximum measured concentration of the analyte in plasma) for several time points
timeFrame: up to day 16
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to day 16
measure: AUC (area under the concentration-time curve of the analyte in plasma) for several time points
timeFrame: up to day 16
measure: λz (terminal rate constant in plasma) for several time points
timeFrame: up to day 16
measure: t1/2 (terminal half-life of the analyte in plasma) for several time points
timeFrame: up to day 16
measure: MRTpo (mean residence time of the analyte in the body after oral administration) for several time points
timeFrame: up to day 16
measure: CL/F (apparent clearance of the analyte in plasma following extravascular administration) for several time points
timeFrame: up to day 16
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration) for several time points
timeFrame: up to day 16
measure: Accumulation ratio (RA) based on Cmax
timeFrame: up to day 16
measure: RA based on AUC
timeFrame: up to day 16
measure: Predose concentration (Cpre) for several time points
timeFrame: up to day 10
measure: C24,10
timeFrame: 24 hours after last administration on day 10
Other outcomes:
Locations:
Study officials:
References: