Healthy
Conditions
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
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC0-inf. (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) | up to 96 hours after drug administration |
| Cmax (maximum measured concentration of the analyte in plasma) | up to 96 hours after drug administration |
Secondary
| Measure | Time frame |
|---|---|
| tmax (time from dosing to the maximum concentration of the analyte in plasma) | up to 96 hours after drug administration |
| λz (terminal rate constant in plasma) | up to 96 hours after drug administration |
| t1/2 (terminal half-life of the analyte in plasma) | up to 96 hours after drug administration |
| MRTpo (mean residence time of the analyte in the body after po administration) | up to 96 hours after drug administration |
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) | up to 96 hours after drug administration |
| 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) | up to 96 hours after drug administration |
| Number of patients with adverse events | up to 73 days |
| Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse Rate) | up to 73 days |
| Number of patients with clinically relevant changes in laboratory tests | up to 73 days |
| Number of patients with clinically relevant changes in 12-lead electrocardiogram | up to 73 days |
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) | up to 96 hours after drug administration |
| AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval from t1 to t2) | up to 96 hours after drug administration |
Outcome results
None listed