Relative Oral Bioavailability of Telmisartan / Hydrochlorothiazide (HCTZ) Fixed Dose Combination (FDC) Compared With Its Monocomponents in Healthy Subjects

Relative Oral Bioavailability of 40 mg Telmisartan / 12.5 mg HCTZ Fixed Dose Combination Compared With Its Monocomponents in Healthy Subjects. A 4 Period Cross-over, Open, Randomized, Replicate Design Study

A study to demonstrate the bioequivalence of telmisartan and HCTZ administered as fixed dose combination in comparison to the single unit formulations

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Telmisartan; Drug: Hydrochlorothiazide; Drug: Telmisartan/HCTZ FDC

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects as determined by results of screening
• Signed written informed consent in accordance with good clinical practice (GCP) and local legislation
• Age ≥ 18 and ≤ 55 years
• Broca ≥ -20 % and ≤ +20 %

Exclusion Criteria:

• Any findings of the medical examination (including blood pressure, pulse rate and electrocardiogram (ECG)) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastro-intestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Supine blood pressure at screening of systolic ≤ 110 mmHg and diastolic ≤ 60 mmHg
• History of orthostatic hypotension, fainting, spells or blackouts
• Chronic or relevant acute infection
• History or allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of drugs with a long half-life (> 24 hours) ≤ 1 month prior to administration or during the trial
• Use of any drugs which might influence the results of the trial (≤ 10 days prior to administration or during the trial)
• Participation in another trial with an investigational drug (≤ 2 months prior to administration or during the trial)
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• Inability to refrain from smoking on study days
• Alcohol abuse (> 60g/day)
• Drug abuse
• Blood donation (≤ 1 month prior to administration or during the trial)
• Excessive physical activities (≤ 5 days prior to administration or during the trial)
• Any laboratory value outside the reference range of clinical relevance
• Hypersensitivity to Telmisartan and/or HCTZ and/or related classes of drugs

For female subjects:

• Pregnancy
• Positive pregnancy test
• No adequate contraception (e.g. sterilization, intrauterine device (IUD), oral contraceptives)
• Inability to maintain this adequate contraception during the whole study period
• Lactation period

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telmisartan/HCTZ FDC	Drug: Telmisartan/HCTZ FDC
Active Comparator: Telmisartan and HCTZ individual tablets	Drug: Telmisartan; Drug: Hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total area under concentration-time curve of the analytes in plasma from time zero to infinity (AUC0-∞)	Pre-dose up to day 54
Maximum concentration of the analytes in plasma (Cmax)	Pre-dose up to day 54
Amount of HCTZ excreted in urine over 48 h (Ae(0-48))	Pre-dose up to day 50

Secondary Outcome Measures

Outcome Measure	Time Frame
time to achieve maximum concentration of the analytes in plasma (tmax)	Pre-dose up to day 54
Terminal elimination half life of the analytes in plasma (t1/2)	Pre-dose up to day 54
Total clearance of the of the analytes after oral administration (CLtot/f)	Pre-dose up to day 54
Total mean residence time of the analytes (MRTtot)	Pre-dose up to day 54
Apparent volume of distribution of the analytes during the terminal phase (Vz/f)	Pre-dose up to day 54
Number of patients with relevant changes in laboratory values	Screening (day -14 to day 0) and day 72
Number of patients with relevant changes in vital signs (blood pressure, pulse rate)	Up to day 72
Number of patients with Adverse events	Up to day 72
Number of patients with relevant changes in ECG	Screening (day -14 to day 0) and day 72
Number of patients with relevant changes in physical examination	Screening (day -14 to day 0) and day 72

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 1999
• Primary Completion (Actual): December 1, 1999

Study Registration Dates

• First Submitted: July 9, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Estimate): July 11, 2014
• Last Update Submitted That Met QC Criteria: July 9, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide; Telmisartan
• Other Study ID Numbers: 502.324