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.
Concentration of the analytes in plasmapre-dose concentration of the analytes in plasma immediately before the administration of the next dose
tmax,ss (time from last dosing to the maximum concentration of the analytes in plasma at steady state)
Cmin,ss (minimum concentration of the analytes in plasma at steady state over a uniform dosing interval Ï„)
Cpre,ss (pre-dose concentration of the analytes in plasma immediately before the administration of the next dose at steady state)
Cavg (average concentration of the analytes in plasma at steady state)
λz,ss (terminal rate constant in plasma at steady state)
t1/2, ss (terminal half-life of the analyte in plasma at steady state)
MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)
CL/F,ss (apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration)
Vz/F,ss (apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration)
PTF (Peak-Trough Fluctuation)
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)
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 12-lead electrocardiogram
Number of patients with clinically relevant changes in laboratory tests
Assessment of tolerability by the investigator on a 4-point scale
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
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