Clinical trial NCT02262780: Safety, Tolerability and Pharmacokinetics of Single Rising and Multiple Oral Doses of Telmisartan / Hydrochlorothiazide (HCTZ) in Healthy Male Volunteers
Official title: Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses (40 mg Telmisartan / 12.5 mg HCTZ to 80 mg Telmisartan / 12.5 mg HCTZ) and Multiple Oral Doses (80 mg Telmisartan / 12.5 mg HCTZ) of Drug in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 20
Sex: MALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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)"

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

Primary outcomes:
measure: Number of patients with clinically relevant findings in physical examination
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically relevant findings in vital signs
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically relevant findings in 12-lead ECG
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically relevant findings in clinical laboratory tests
timeFrame: up to 10 days after last drug administration
measure: Number of patients with adverse events
timeFrame: up to 10 days after last drug administration
measure: Global assessment of tolerability by the investigator
timeFrame: up to 10 days after last drug administration
Secondary outcomes:
measure: Maximum concentration of the analytes in plasma (Cmax)
timeFrame: Up to 96 hours after drug administration
measure: Area under the concentration time curve of the analytes in plasma (AUC)
timeFrame: Up to 96 hours after drug administration
measure: Time from dosing to maximum concentration of the analytes in plasma (tmax)
timeFrame: Up to 96 hours after drug administration
measure: Terminal rate constant of the analytes in plasma (λz)
timeFrame: Up to 96 hours after drug administration
measure: Terminal half-life of the analytes in plasma (t1/2)
timeFrame: Up to 96 hours after drug administration
measure: Mean residence time of the analytes in the body after po administration (MRTpo)
timeFrame: Up to 96 hours after drug administration
measure: Apparent clearance of the analytes in the plasma after extravascular administration (CL/F)
timeFrame: Up to 96 hours after drug administration
measure: Apparent volume of distribution of the analytes in plasma during the terminal phase λz following an extravascular dose (Vz/F)
timeFrame: Up to 96 hours after drug administration
measure: Amount of HCTZ that is eliminated in urine from the time interval t1 to t2 (Aet1-t2)
timeFrame: Up to 48 hours after drug administration
measure: Fraction of HCTZ excreted unchanged in urine from time point t1 to t2 (fet1-t2)
timeFrame: Up to 48 hours after drug administration
measure: Renal clearance of HCTZ in plasma from the time point t1 until the time point t2 (CLR, t1-t2)
timeFrame: Up to 48 hours after drug administration
measure: Minimum measured concentration of the analytes in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
timeFrame: Up to 96 hours after drug administration
measure: Average concentration of the analytes in plasma at steady state (Cavg)
timeFrame: Up to 96 hours after drug administration
measure: Accumulation ratio of the analytes in plasma after multiple dose administration over a uniform dosing interval τ (RA)
timeFrame: Up to 96 hours after drug administration
Other outcomes:
Locations:
Study officials:
References: