Clinical trial NCT02215746: Bioavailability of BI 44370 TA Drinking Solution or Tablets With and Without a High Fat Meal in Healthy Male and Female Volunteers
Official title: Relative Oral Bioavailability of BI 44370 TA Drinking Solution (100 mg and 200 mg) and BI 44370 TA Tablets (100 mg as Two 50 mg Tablets) With and Without a High Fat Meal in Healthy Male and Female Volunteers: A Single Dose, Open-label, Randomised Six-way Cross-over Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-13
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objective of this trial was to evaluate the relative oral bioavailability and pharmacokinetics of BI 44370 TA drinking solution (100 mg and 200 mg) and BI 44370 TA tablets (100 mg as two 50 mg tablets) with and without a high fat meal and to assess the safety and tolerability of the substances.


Eligibility criteria: Inclusion Criteria:

* Healthy male and female subjects 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 ≥21 and ≤55 years
* BMI ≥18.5 and ≤29.9 kg/m2 (Body Mass Index)
* Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

* Any finding of the medical examination (including BP, PR, and ECG) deviating from normal and of clinical relevance
* 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 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 or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
* Participation in another trial with an investigational drug within two months prior to administration or during the trial
* Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (more than 60 g/day)
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
* Excessive physical activities (within one week prior to administration or during the trial)
* 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 torsade de pointes (e.g., heart failure, hypokalemia, family, history of Long QT Syndrome)

For Male Subjects:

* Not willing to use adequate contraception (condoms use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device) during the whole study period from the time of the first intake of study drug until three months after the last intake

For Female Subjects:

* Pregnancy
* Positive pregnancy test
* No adequate contraception (adequate contraception e.g. sterilisation, intrauterine pessary (IUP), oral contraceptives)
* Inability to maintain this adequate contraception during the whole study period during the whole study period from the time of the first intake of study drug until one month after the last intake
* Lactation period

Primary outcomes:
measure: Cmax (maximum concentration of the analyte in plasma)
timeFrame: up to 24 hours after drug administration
measure: AUC0-2 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 2 h after drug administration)
timeFrame: up to 2 hours after drug administration
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 24 hours after drug administration
measure: tmax (time from dosing to maximum measured concentration)
timeFrame: up to 24 hours after drug administration
Secondary outcomes:
measure: %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
timeFrame: up to 24 hours after drug administration
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
timeFrame: up to 24 hours after drug administration
measure: AUCt1-t2 (Area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
timeFrame: up to 24 hours after drug administration
measure: λz (terminal rate constant in plasma)
timeFrame: up to 24 hours after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: up to 24 hours after drug administration
measure: MRTp.o. (mean residence time of the analyte in the body after p.o. administration)
timeFrame: up to 24 hours after drug administration
measure: CL/F (total/apparent clearance of the analyte in plasma after extravascular administration)
timeFrame: up to 24 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
timeFrame: up to 24 hours after drug administration
measure: Number of patients with clinically relevant findings in vital signs (blood pressure and pulse rate)
timeFrame: up to 11 days
measure: Number of patients with clinically relevant findings in 12-lead ECG (electrocardiogram)
timeFrame: up to 11 days
measure: Number of patients with clinically relevant laboratory findings
timeFrame: up to 11 days
measure: Number of patients with adverse events
timeFrame: up to 34 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: within 10 days after administration of study drug
Other outcomes:
Locations:
Study officials:
References: