Clinical trial NCT02259816: Pharmacokinetics of Telmisartan Alone and in Combination With Amlodipine in Healthy Volunteers
Official title: Pharmacokinetics of Repeated Oral Doses of 80 mg Telmisartan (Micardis®) at Steady State Alone and in Combination With Repeated Oral Doses of Amlodipine 10 mg (Norvasc®) at Steady State. A Two-way Crossover, Open, Randomised Design Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-09
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Study to investigate the steady state pharmacokinetics of 80 mg telmisartan alone and in combination with repeated doses of 10 mg amlodipine


Eligibility criteria: Inclusion Criteria:

1. Healthy males and females according to the following criteria:

   Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
2. Age ≥18 and Age ≤50 years
3. BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. 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 prior to administration or during the trial
10. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/corrected QT interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
11. Participation in another trial with an investigational drug within two months prior to administration or during the trial
12. Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
13. Inability to refrain from smoking on trial days
14. Alcohol abuse (more than 60 g/day)
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. Excessive physical activities (within one week prior to administration or during the trial)
18. Any laboratory value outside the reference range that is of clinical relevance
19. Inability to comply with dietary regimen of trial site
20. Any history of relevant low blood pressure
21. Supine blood pressure at screening of systolic \<110 mm Hg and/or diastolic \<60 mm Hg
22. History of urticaria

    For female subjects:
23. Pregnancy or planning to become pregnant within 2 months of study completion
24. Positive pregnancy test
25. No adequate contraception e.g. sterilisation, intrauterine device, have not been using a barrier method of contraception for at least 3 months prior to participation in the study
26. Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
27. Chronic use of oral contraception or hormone replacement containing ethinyl estradiol as the only method of contraception
28. Partner is unwilling to use condoms
29. Lactation period

Primary outcomes:
measure: Area under the concentration-time curve of telmisartan in plasma at steady state over a uniform dosing interval τ (AUCτ,ss)
timeFrame: up to 15 days after first administration of study drug
measure: Maximum measured concentration of telmisartan in plasma at steady state over a uniform dosing interval τ (Cmax,ss)
timeFrame: up to 15 days after first administration of study drug
Secondary outcomes:
measure: AUCτ,ss for amlodipine
timeFrame: up to 15 days after first administration of study drug
measure: Cmax,ss for amlodipine
timeFrame: up to 15 days after first administration of study drug
measure: Maximum measured concentration of the analyte in plasma (Cmax)
timeFrame: up to 12 hours after first administration of study drug
measure: Time from dosing to maximum measured concentration on plasma (tmax)
timeFrame: up to 12 hours after first administration of study drug
measure: Area under the plasma concentration-time curve over a uniform dosing interval τ after administration of the first dose; corresponds to AUC0-24h (AUCτ,1)
timeFrame: up to 12 hours after first administration of study drug
measure: Pre-dose concentration of the analyte in plasma immediately before the administration of the next dose N (Cpre,N)
timeFrame: pre-dose on days 2-9
measure: Time from last dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Terminal rate constant in plasma at steady state (λz,ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Terminal half-life of the analyte in plasma at steady state (t1/2, ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration (Vz/F,ss)
timeFrame: up to 144 hours after last administration of study drug
measure: Accumulation ratio of the analyte in plasma based on AUC over a uniform dosing interval after the first and last doses (RA, AUC)
timeFrame: up to 15 days after first administration of study drug
measure: Accumulation ratio of the analyte in plasma based on Cmax over a uniform dosing interval after the last and first doses (RA,Cmax)
timeFrame: up to 15 days after first administration of study drug
measure: Number of subjects with adverse events
timeFrame: up to 80 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: within 14 days after last trial procedure
Other outcomes:
Locations:
Study officials:
References: