Multiple Doses of BI 207127 NA, BI 201335 NA Followed by the Combination of BI 207127 NA and BI 201335 NA in Healthy Male Volunteers
Phase 1
Terminated
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02182401
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Study to investigate the pharmacokinetic drug-drug interaction potential of BI 207127 NA and BI 201335 NA on each other at steady-state and to quantify the effect of BI 207127 NA, and BI 207127 NA combined with BI 201335 NA, on the activity of CYP 2C9 and CYP 3A4 using the probe substrates tolbutamide (CYP 2C9) and midazolam (CYP 3A4).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 37
Inclusion Criteria
- Healthy males (caucasian)
- Age ranging ≥ 21 and ≤ 50 years
- Body mass index (BMI) ≥ 19 and ≤ 29.9 kg/m2
- Willing to complete all study-related activities
- Volunteers give their written informed consent prior to admission to the study
Exclusion criteria:
- Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, clinically relevant electrolyte disturbances
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- History of photosensitivity or recurrent rash
- History of orthostatic hypotension, fainting spells or blackouts
- Chronic or clinically relevant acute infections
- History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- Intake of drugs with a long half-life (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study
- Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the trial or during the trial
- vulnerable subjects (that is persons kept in detention)
- exclusion of contraindications or hypersensitivity to midazolam and / or tolbutamide
- Participation in another trial with an investigational drug (within two months prior to administration or during the trial)
- Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)
- Inability to refrain from smoking on trial days
- Alcohol abuse (> 60 g/day)
- Drug abuse
- Blood donation (> 100 mL within four weeks prior to administration or during the trial)
- Any laboratory value outside the reference range if indicative of underlying disease or poor health
- Excessive physical activities within the last week before the trial or during the trial
- Hypersensitivity to treatment medication and/or related drugs of these classes
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF, or QTcB interval >450 ms)
- Homozygous carriers of the UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1) enzyme polymorphism *28 and *60
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BI 207127 NA Midazolam fixed sequence BI 207127 NA BI 207127 NA fixed sequence BI 207127 NA BI 201335 NA fixed sequence BI 207127 NA Tolbutamide fixed sequence
- Primary Outcome Measures
Name Time Method Steady-state Cmax (Maximum measured concentration of the analyte in plasma) up to day 31 Steady-state AUC (Area under concentration-time curve) up to day 31
- Secondary Outcome Measures
Name Time Method Ratio for AUC at several time points up to day 31 AUC for several time points up to day 31 t1/2 (Terminal half-life of the analyte in plasma) up to day 31 Cavg0-24 up to day 31 Ratio for Cmax,Met at several time points up to day 31 Tlast,N up to day 31 CL/F (Total apparent clearance of the analyte in plasma following extravascular administration) for several time points up to day 31 V/F (Apparent volume of distribution during following an extravascular dose) for several time points up to day 31 Cmax for several time points up to day 31 Tmax (Time from dosing to the maximum measured concentration of the analyte in plasma) up to day 31 Cx for several time points up to day 31 CLR (renal clearance of the analyte for different time points) up to day 29 Number of patients with adverse events up to 66 days Assessment of tolerability on a 4-pointe scale by investigator within 14 days after last drug administration Ae (amount of analyte eliminated in urine for different time points) up to day 29 fe (fraction of analyte eliminated in urine for different time points) up to day 29