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

Healthy Clinical Trial

Official title:

An Open-label, Fixed Sequence Phase I Study in Healthy Male Volunteers to Assess Sequentially the Effects of Multiple Doses of BI 207127 NA, BI 201335 NA Followed by the Combination of BI 207127 NA and BI 201335 NA, on the Single Dose Pharmacokinetics of Midazolam and Tolbutamide and on the Systemic Exposure of BI 207127 NA and BI 201335 NA

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02182401
• Other study ID #: 1241.18
• Status: Terminated
• Phase: Phase 1
• First received: July 2, 2014
• Last updated: July 17, 2014
• Start date: July 2009

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 50 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BI 207127 NA
Days 3-8 and days 25-30
• BI 201335 NA
Days 15-30
• Midazolam
Days 1, 7, 23 and 29
• Tolbutamide
Days 1, 7, 23 and 29

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steady-state Cmax (Maximum measured concentration of the analyte in plasma)		up to day 31	No
Primary	Steady-state AUC (Area under concentration-time curve)		up to day 31	No
Secondary	Cmax for several time points		up to day 31	No
Secondary	Tmax (Time from dosing to the maximum measured concentration of the analyte in plasma)		up to day 31	No
Secondary	Cx for several time points		up to day 31	No
Secondary	AUC for several time points		up to day 31	No
Secondary	CL/F (Total apparent clearance of the analyte in plasma following extravascular administration) for several time points		up to day 31	No
Secondary	V/F (Apparent volume of distribution during following an extravascular dose) for several time points		up to day 31	No
Secondary	t1/2 (Terminal half-life of the analyte in plasma)		up to day 31	No
Secondary	Cavg0-24		up to day 31	No
Secondary	Ratio for Cmax,Met at several time points		up to day 31	No
Secondary	Ratio for AUC at several time points		up to day 31	No
Secondary	Tlast,N		up to day 31	No
Secondary	Ae (amount of analyte eliminated in urine for different time points)		up to day 29	No
Secondary	CLR (renal clearance of the analyte for different time points)		up to day 29	No
Secondary	fe (fraction of analyte eliminated in urine for different time points)		up to day 29	No
Secondary	Number of patients with adverse events		up to 66 days	No
Secondary	Assessment of tolerability on a 4-pointe scale by investigator		within 14 days after last drug administration	No

External Links

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