Telmisartan/Hydrochlorothiazide (HCTZ) Fixed Dose Combination Compared to Its Monocomponents in Healthy Subjects

Relative Oral Bioavailability of 80 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.

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: BIBR 277 SE and HCTZ; Drug: BIBR 277 SE; Drug: HCTZ

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 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 GCP (Good Clinical Practice) and local legislation
• Age ≥ 18 and ≤ 45 years
• Broca ≥ - 20% and ≤ + 20%

Exclusion Criteria:

• Any findings of the medical examination (including blood pressure, pulse rate and ECG and laboratory value) 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
• Supine blood pressure at screening of systolic ≤ 110 mmHg and diastolic ≤ 60 mmHg
• History of orthostatic hypotension, fainting spells or blackouts
• Hypersensitivity to Telmisartan and/or HCTZ and/or related classes of drugs
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• 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
• Known alcohol abuse
• Known drug abuse
• Blood donation (≤ 1 month prior to administration)
• Excessive physical activities (≤ 5 days prior to administration)

• For female subjects:

  • Pregnancy
  • Positive pregnancy test
  • No adequate contraception
  • 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: Sequence 1; four treatment periods: Treatment A; Treatment B; Treatment B; Treatment A	Drug: BIBR 277 SE and HCTZ; Treatment A - fixed dose combination; Drug: BIBR 277 SE; Treatment B - Monocomponent; Drug: HCTZ; Treatment B -Monocomponent
Active Comparator: Sequence 2; four treatment periods: Treatment B; Treatment A; Treatment A; Treatment B	Drug: BIBR 277 SE and HCTZ; Treatment A - fixed dose combination; Drug: BIBR 277 SE; Treatment B - Monocomponent; Drug: HCTZ; Treatment B -Monocomponent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-∞ (total area under the plasma drug concentration-time curve from time zero to infinity)	up to 96 hours post-dose
Cmax (maximum drug plasma concentration)	up to 96 hours post-dose
Amount of Hydrochlorothiazide (HCTZ) excreted in urine over 48 hours (Ae(0-48h))	0-6, 6-12, 12-24, 24-32, 32-48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
tmax (time to achieve Cmax)	up to 96 hours post-dose
t1/2 (apparent terminal elimination half-life)	up to 96 hours post-dose
CLtot/f (total clearance of a drug from plasma, divided by bioavailability)	up to 96 hours post-dose
MRTtot (mean time of residence of drug molecules in the body)	up to 96 hours post-dose
Vz/f (apparent volume of distribution during terminal phase)	up to 96 hours post-dose
Number of patients with adverse events	Up to 62 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (Actual): October 1, 1998

Study Registration Dates

• First Submitted: June 26, 2014
• First Submitted That Met QC Criteria: June 26, 2014
• First Posted (Estimate): June 27, 2014

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 7, 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: 502.136