Clinical trial NCT02215005: Steady State Pharmacokinetics of Telmisartan, Ramipril or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers
Official title: Steady State Pharmacokinetics of 80 mg Telmisartan (Micardis®), 10 mg Ramipril (Delix®) or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers (an Open-label, Randomised, Multiple-dose, Three-way Crossover Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-13
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main objective was to investigate the effect of concurrent dosing of 10 mg ramipril and 80 mg telmisartan on the multiple-dose pharmacokinetics of telmisartan and ramipril. Therefore the relative bioavailability of telmisartan and ramipril given in combination was determined in comparison with either telmisartan or ramipril given alone.


Eligibility criteria: Inclusion Criteria:

* Healthy males and females according to the following criteria based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
* Age ≥18 and ≤55 years
* Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2
* Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

* Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
* Any evidence of a clinically relevant concomitant disease
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Surgery of the gastrointestinal tract (except appendectomy)
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
* History of relevant orthostatic hypotension, fainting spells or blackouts
* Chronic or relevant acute infections
* History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
* 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
* Use of drugs which might reasonably influence the results of the trial (especially unspecific inducing agents like St.John´s wort (Hypericum perforatum) or inhibitors like cimetidine) or drugs that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration of trial drug or during the trial
* Participation in another trial with an investigational drug within two months prior to administration or during the trial
* Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
* Alcohol abuse (more than 60 g/day) or inability to stop alcoholic beverages for 24 hours prior to dosing and up to the last sampling time point
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration of trial drug or during the trial)
* Excessive physical activities (within one week prior to administration of trial drug or during the trial)
* Any laboratory value outside the reference range that is of clinical relevance
* Inability to comply with dietary regimen of trial site
* A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms)
* A history of additional risk factors for torsade de pointes (e.g., heart failure, hyperkalaemia, hypokalemia, family history of Long QT Syndrome)
* Any history of relevant low blood pressure
* Supine blood pressure at screening of systolic \<110 mm Hg and diastolic \<60 mm Hg
* History of urticaria
* History of angioneurotic edema
* Hereditary fructose intolerance
* Salt and/or volume depletion

For female subjects:

* Pregnancy or planning to become pregnant during the study or within 1 months of study completion
* Positive pregnancy test
* Not willing or unable to use a reliable method of contraception such as implants, injectables, combined oral contraceptives, sterilisation, intrauterine device, double barrier method, sexual abstinence for at least 1 month, or vasectomised partner as only method of contraception for at least 6 months prior to participation in the trial, during and up to 1 month after completion/termination of the trial
* Chronic use of oral contraception containing ethinyl estradiol as the only method of contraception
* Currently lactating

Primary outcomes:
measure: AUCτ,ss (area under the concentration-time curve in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: Cmax,ss (maximum measured concentration in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to 72 hours after last drug administration of each treatment
Secondary outcomes:
measure: Concentration of the analytes in plasma
timeFrame: 2, 4, and 12 hours after administration of the first dose of each treatment on day 1
measure: pre-dose concentration of the analytes in plasma immediately before the administration of the next dose
timeFrame: pre-dose up to day 5 of each treatment
measure: tmax,ss (time from last dosing to the maximum concentration of the analytes in plasma at steady state)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: Cmin,ss (minimum concentration of the analytes in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: Cpre,ss (pre-dose concentration of the analytes in plasma immediately before the administration of the next dose at steady state)
timeFrame: pre-dose up to day 5 of each treatment
measure: Cavg (average concentration of the analytes in plasma at steady state)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: λz,ss (terminal rate constant in plasma at steady state)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: t1/2, ss (terminal half-life of the analyte in plasma at steady state)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: CL/F,ss (apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: Vz/F,ss (apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: PTF (Peak-Trough Fluctuation)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: AUC0-tz,ss (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
timeFrame: up to 72 hours after last drug administration of each treatment
measure: Number of patients with adverse events
timeFrame: up to day 76
measure: Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse rate)
timeFrame: up to day 76
measure: Number of patients with clinically relevant changes in 12-lead electrocardiogram
timeFrame: up to day 76
measure: Number of patients with clinically relevant changes in laboratory tests
timeFrame: up to day 76
measure: Assessment of tolerability by the investigator on a 4-point scale
timeFrame: Day 8 of each treatment
Other outcomes:
Locations:
Study officials:
References: