Safety, Tolerability and Pharmacokinetics of Single Rising and Multiple Oral Doses of Telmisartan / Hydrochlorothiazide (HCTZ) in Healthy Male Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: High dose of telmisartan; Drug: Low dose of telmisartan; Drug: HCTZ

• Registration Number: NCT02262780
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Group 1:

To investigate safety, tolerability and pharmacokinetics of Telmisartan + HCTZ (T40/H12.5 and T80/H12.5)

Group 2:

To investigate safety, tolerability and pharmacokinetics of Telmisartan + HCTZ (T80/H12.5 x 7 days)

Detailed Description

Not available

Study Timeline

• Study Start: 2003-12-01
• Primary Completion: 2004-02-15
• Study First Submitted: 2014-10-10
• Study First Submitted QC: 2014-10-10
• Study First Posted: 2014-10-13
• Status Verified: 2023-11
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

• Healthy males according to the following criteria: No finding deviating of clinical relevance and no evidence of a clinically relevant concomitant disease based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature), 12-lead ECG, clinical laboratory tests
• Age ≥20 and Age ≤35 years
• Body Mass Index (BMI) ≥17.6 and BMI ≤26.4 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with "Good Clinical Practice (GCP)"

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Exclusion Criteria

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Chronic or relevant acute infections
• Any laboratory value outside the reference range that is of clinical relevance
• Positive result for hepatitis B surface (HBs) antigen, anti hepatitis C virus (HCV) antibodies, Syphilitic test or HIV test
• Surgery of gastrointestinal tract (except appendectomy)
• History of relevant orthostatic hypotension (mean standing SBP varies by ≥ 20 mmHg from mean supine systolic blood pressure (SBP) and/or mean standing diastolic blood pressure (DBP) varies by ≥ 10 mmHg from mean supine DBP), fainting spells or blackouts.
• History of hepatic dysfunction (e.g. biliary cirrhosis, cholestasis)
• History of serious renal dysfunction
• History of bilateral renal artery stenosis or renal artery stenosis in a solitary kidney
• History of cerebrovascular disorder
• History of hyperkalemia
• Known hypersensitivity to any component of the formulation; known hypersensitivity to any other angiotensin II receptor antagonist; known hypersensitivity to sulfonamides or sulphonamide-derived drugs (e.g. thiazides)
• History of impaired glucose tolerance
• History of hypokalemia
• History of hyperuricemia
• Salt restriction therapy
• 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 based on the knowledge at the time of protocol preparation within 7 days prior to administration or during the trial
• Participation in another trial with an investigational drug within four months or 6 half-lives of the investigational drug, whichever is longer, prior to administration or during the trial
• Smoker (more than 20 cigarettes /day)
• Alcohol abuse
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within seven days prior to administration)
• Intake of alcohol within two days prior to administration
• Inability to comply with dietary regimen of study centre
• Inability to comply with smoking cessation during hospitalization

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single high dose Telmisartan with HCTZ	High dose of telmisartan	-
Single low dose Telmisartan with HCTZ	Low dose of telmisartan	-
Multiple high dose Telmisartan with HCTZ	High dose of telmisartan	-
Multiple high dose Telmisartan with HCTZ	HCTZ	-
Single low dose Telmisartan with HCTZ	HCTZ	-
Single high dose Telmisartan with HCTZ	HCTZ	-

Primary Outcome Measures

Name	Time	Method
Global assessment of tolerability by the investigator	up to 10 days after last drug administration	verbal rating scale
Number of patients with clinically relevant findings in clinical laboratory tests	up to 10 days after last drug administration
Number of patients with adverse events	up to 10 days after last drug administration
Number of patients with clinically relevant findings in physical examination	up to 10 days after last drug administration
Number of patients with clinically relevant findings in vital signs	up to 10 days after last drug administration	blood pressure, pulse rate, body temperature
Number of patients with clinically relevant findings in 12-lead ECG	up to 10 days after last drug administration

Secondary Outcome Measures

Name	Time	Method
Average concentration of the analytes in plasma at steady state (Cavg)	Up to 96 hours after drug administration
Maximum concentration of the analytes in plasma (Cmax)	Up to 96 hours after drug administration
Mean residence time of the analytes in the body after po administration (MRTpo)	Up to 96 hours after drug administration
Apparent volume of distribution of the analytes in plasma during the terminal phase λz following an extravascular dose (Vz/F)	Up to 96 hours after drug administration
Amount of HCTZ that is eliminated in urine from the time interval t1 to t2 (Aet1-t2)	Up to 48 hours after drug administration
Renal clearance of HCTZ in plasma from the time point t1 until the time point t2 (CLR, t1-t2)	Up to 48 hours after drug administration
Terminal rate constant of the analytes in plasma (λz)	Up to 96 hours after drug administration
Fraction of HCTZ excreted unchanged in urine from time point t1 to t2 (fet1-t2)	Up to 48 hours after drug administration
Terminal half-life of the analytes in plasma (t1/2)	Up to 96 hours after drug administration
Area under the concentration time curve of the analytes in plasma (AUC)	Up to 96 hours after drug administration
Time from dosing to maximum concentration of the analytes in plasma (tmax)	Up to 96 hours after drug administration
Apparent clearance of the analytes in the plasma after extravascular administration (CL/F)	Up to 96 hours after drug administration
Accumulation ratio of the analytes in plasma after multiple dose administration over a uniform dosing interval τ (RA)	Up to 96 hours after drug administration
Minimum measured concentration of the analytes in plasma at steady state over a uniform dosing interval τ (Cmin,ss)	Up to 96 hours after drug administration