Clinical trial NCT02782624: Relative Bioavailability of BI 10773 Administered Twice Daily Compared BI 10773 Given Once Daily After Multiple Oral Doses in Healthy Male and Female Volunteers
Official title: Relative Bioavailability of 5 mg BI 10773 Administered Twice Daily Compared to 10 mg BI 10773 Given Once Daily After Multiple Oral Doses in Healthy Male and Female 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: 2016-05-25
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: To investigate the influence of different dosage regimen (5 mg twice daily versus 10 mg once daily) on the steady state pharmacokinetics and pharmacodynamics of BI 10773 administered orally


Eligibility criteria: Inclusion criteria:

- Healthy males and females 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 and Age = 50 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 GCP 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 6. 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 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 (average consumption of more than 20 g/day in females and 30 g/day in males)
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to the start of study)
* 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 TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

For female subjects:

* Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 1 month after study completion
* No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD A record of all subjects screened, in- or excluded, will be maintained. (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide)
* Lactation

Primary outcomes:
measure: AUC (area under the concentration-time curve of the analyte in plasma) - AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) for 10 mg BI 10773 QD.
timeFrame: up to 168 hours
measure: AUC (area under the concentration-time curve of the analyte in plasma) - AUC0-24,ss (area under the concentration-time curves of the analyte in plasma at steady-state over two dosing intervals) for 5 mg BI 10773 BID after the morning dose on Day 5.
timeFrame: up to 168 hours
measure: AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773.
timeFrame: up to 168 hours
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773.
timeFrame: up to 168 hours
Secondary outcomes:
measure: C12,N (concentration of analyte in plasma at 12 hours post-drug administration after administration of the Nth dose for the BID regimen) of BI 10773.
timeFrame: up to 168 hours
measure: C24,N (concentration of analyte in plasma at 24 hours post-drug administration after administration of the Nth dose for the QD regimen) of BI 10773.
timeFrame: up to 168 hours
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773
timeFrame: up to 168 hours
measure: Cavg (average concentration of the analyte in plasma at steady state) of BI 10773
timeFrame: up to 168 hours
measure: ¿z,ss (terminal half-life of the analyte in plasma at steady state) of BI 10773
timeFrame: up to 168 hours
measure: t½,ss (terminal half-life of the analyte in plasma at steady state) of BI 10773
timeFrame: up to 168 hours
measure: tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773.
timeFrame: up to 168 hours
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) of BI 10773.
timeFrame: up to 168 hours
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) of BI 10773.
timeFrame: up to 168 hours
measure: Vz/F,ss (apparent volume of distribution during the terminal phase tau z at steady state following extravascular administration) of BI 10773.
timeFrame: up to 168 hours
measure: PTF (percentage peak-trough fluctuation)
timeFrame: up to 168 hours
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: 1276.9.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: