Study to demonstrate the bioequivalence (BE) of 40 mg telmisartan/ 2. 5 mg ramipril
fixed-dose combination (FDC) versus its monocomponents given concomitantly
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)AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval from t1 to t2)
tmax (time from dosing to the maximum concentration of the analyte in plasma)
λz (terminal rate constant in plasma)
t1/2 (terminal half-life of the analyte in plasma)
MRTpo (mean residence time of the analyte in the body after po administration)
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Number of patients with adverse events
Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse Rate)
Number of patients with clinically relevant changes in laboratory tests
Number of patients with clinically relevant changes in 12-lead electrocardiogram
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
