Clinical trial NCT02172196: Bioavailability of BI 10773 and Sitagliptin in Healthy Male Volunteers
Official title: Relative Bioavailability of Both BI 10773 and Sitagliptin After Co-administration Compared to Multiple Oral Doses of BI 10773 (50 mg q.d.) Alone and Sitagliptin (100 mg q.d.) Alone in Healthy Male Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objective was to investigate whether there was a drug-drug interaction between BI 10773 and sitagliptin when co-administered as multiple oral doses. Therefore, the relative bioavailabilities of BI 10773 and sitagliptin were determined when both drugs were given in combination compared with BI 10773 or sitagliptin given alone.


Eligibility criteria: Inclusion Criteria:

* Healthy male volunteers according to the following criteria:

  * Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
* Age 18 to 50 years (incl.)
* BMI 18.5 to 29.9 kg/m2 (incl.)
* Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion Criteria:

* Any finding of the medical examination deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg
* 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 within one month or less than 10 half-lives of the respective drug prior to first study drug administration except if a relevant interaction can be ruled out
* Participation in another trial with an investigational drug within two months prior to first study drug administration
* Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (average consumption of more than 30 g/day)
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to the start of study)
* 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 TdP (Torsades de pointes) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Primary outcomes:
measure: AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: Days 1-8
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: Days 1-8
Secondary outcomes:
measure: C24,N (concentration of analyte in plasma at 24 hours post-drug administration after administration of the Nth dose)
timeFrame: Days 1-8
measure: λz,ss (terminal half-life of the analyte in plasma)
timeFrame: Days 1-8
measure: t½,ss (terminal half-life of the analyte in plasma at steady state)
timeFrame: Days 1-8
measure: tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: Days 1-8
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)
timeFrame: Days 1-8
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
timeFrame: Days 1-8
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration)
timeFrame: Days 1-8
measure: Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: CLR,ss (renal clearance of the analyte at steady state)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: UGE0-24 (Urinary glucose excretion of the analyte in urine over the time interval from time zero to 24 h)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: Abnormal findings in physical examination
timeFrame: Baseline and within 3-10 days after last study drug administration
measure: Changes from baseline in vital sings (blood pressure, pulse rate)
timeFrame: Baseline, day 1 and within 3-10 days after last study drug administration
measure: Changes from baseline in 12-lead ECG (electrocardiogram)
timeFrame: Baseline and within 3-10 days after last study drug administration
measure: Changes from baseline in clinical laboratory tests
timeFrame: Baseline, day 1, 5 and within 3-10 days after last study drug administration
measure: Incidence of adverse events
timeFrame: up to 28 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: Within 3-10 days after last study drug administration
Other outcomes:
Locations:
Study officials:
References: