Steady State Pharmacokinetics of Telmisartan, Ramipril or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Ramipril; Drug: Telmisartan

Study type: Interventional

Funder types: Industry

Identifiers

NCT02215005

1236.6

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

42 participants in 3 patient groups

Telmisartan + Ramipril

Experimental group

Description:

5 days qd

Treatment:

Drug: Telmisartan

Drug: Ramipril

Telmisartan

Active Comparator group

Description:

5 days qd

Treatment:

Drug: Telmisartan

Ramipril

Active Comparator group

Description:

5 days qd

Treatment:

Drug: Ramipril