Bioequivalence of Telmisartan / Ramipril Fixed Dose Combination Compared With the Monocomponents Given Concomitantly to Healthy Male and Female Volunteers

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 to demonstrate the bioequivalence (BE) of 40 mg telmisartan/ 2.5 mg ramipril fixed-dose combination (FDC) versus its monocomponents given concomitantly

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Telmisartan/Ramipril; Drug: Telmisartan; Drug: Ramipril capsule; Drug: Ramipril tablet

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telmisartan/Ramipril	Drug: Telmisartan/Ramipril; fixed dose combination tablet
Active Comparator: Telmisartan + Ramipril capsule	Drug: Telmisartan; Other Names: Micardis®; Drug: Ramipril capsule; Other Names: Altace®
Active Comparator: Telmisartam + Ramipril tablet	Drug: Telmisartan; Other Names: Micardis®; Drug: Ramipril tablet; Other Names: Delix®

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): June 1, 2007
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: August 12, 2014
• First Submitted That Met QC Criteria: August 12, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 12, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Telmisartan; Ramipril
• Other Study ID Numbers: 1236.4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No