Clinical trial NCT02214979: Bioequivalence of Telmisartan / Ramipril Fixed Dose Combination Compared With the Monocomponents Given Concomitantly to Healthy Male and Female Volunteers
Official title: Bioequivalence of 40 mg Telmisartan / 2.5 mg Ramipril Fixed Dose Combination Compared With the Monocomponents, Telmisartan and Ramipril (Two Different Formulations) Given Concomitantly to Healthy Male and Female Volunteers (an Open-label, Randomised, Single-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: 84
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: Study to demonstrate the bioequivalence (BE) of 40 mg telmisartan/ 2.5 mg ramipril fixed-dose combination (FDC) versus its monocomponents given concomitantly


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 Age ≤55 years
* BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
* 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 that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration 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)
* Inability to refrain from smoking during 24 hours prior to dosing and 24 hours after dosing
* 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, 96 hours after dosing.
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
* Excessive physical activities (within one week prior to administration 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, hyperkalemia, 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

For female subjects:

* Pregnancy or planning to become pregnant during the study or within 2 months of study completion
* Positive pregnancy test
* Are not willing or are unable to use a reliable method of contraception (such as implants, injectables and combined oral contraceptives, sterilisation, intrauterine device, double barrier method, sexual abstinence) for at least 1 month prior to participation in the trial, during and up to 1 month after completion/termination of the trial
* Chronic use of oral contraception or hormone replacement containing ethinyl estradiol as the only method of contraception
* Currently lactating

Primary outcomes:
measure: AUC0-inf. (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 96 hours after drug administration
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: up to 96 hours after drug administration
Secondary outcomes:
measure: AUC0-tz (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 96 hours after drug administration
measure: AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval from t1 to t2)
timeFrame: up to 96 hours after drug administration
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
timeFrame: up to 96 hours after drug administration
measure: λz (terminal rate constant in plasma)
timeFrame: up to 96 hours after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: up to 96 hours after drug administration
measure: MRTpo (mean residence time of the analyte in the body after po administration)
timeFrame: up to 96 hours after drug administration
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
timeFrame: up to 96 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
timeFrame: up to 96 hours after drug administration
measure: Number of patients with adverse events
timeFrame: up to 73 days
measure: Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse Rate)
timeFrame: up to 73 days
measure: Number of patients with clinically relevant changes in laboratory tests
timeFrame: up to 73 days
measure: Number of patients with clinically relevant changes in 12-lead electrocardiogram
timeFrame: up to 73 days
Other outcomes:
Locations:
Study officials:
References: