Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers

A Study to Evaluate the Effect of Multiple Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers

The objective of the study was to investigate the effect of BIRT 2584 XX and its metabolite BI 610100 when BIRT 2584 XX is administered as a tablet to near steady state in estimated high therapeutic dose on the pharmacokinetics (PK) of midazolam, a probe substrate for CYP3A4. The PK of midazolam was measured before dosing of BIRT 2584 XX, after a single dose of BIRT 2584 XX and after repeated doses of BIRT 2584 XX for 3 and 12 days

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: BIRT 2584 XX

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects as determined by results of the screening
• Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
• Age ≥ 18 and ≤ 55 years
• BMI ≥ 18.5 and ≤ 29.9 kg/m2

Exclusion Criteria:

• Any finding during the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, oncological, or hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Relevant history of orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) considered relevant to the trial as judged by the investigator
• Intake of drugs with a long half-life (greater than 24 hours) (less than 1 month prior to administration or during the trial)
• Use of any drugs, which might influence the results of the trial (less than 10 days prior to study drug administration or expected during the trial)
• Participation in another trial with an investigational drug (less than 2 months prior to administration or expected during trial)
• Smoker (more than 10 cigarettes/day or more than 3 cigars/day or more than 3 pipes/day)
• Alcohol abuse (more than 60 g of ethanol per day)
• Drug abuse
• Blood donation or loss greater than 400 mL (less than 1 month prior to administration or expected during the trial)
• Clinically relevant laboratory abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIRT 2584 XX + Midazolam; BIRT 2584 XX: Multiple doses for 12 days (bid on days 1 and 2, qd from days 3 to 12) Midazolam: Administration on days -2, 1, 3, and 12	Drug: Midazolam; Drug: BIRT 2584 XX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-∞ of midazolam (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)	up to 13 days
Cmax of midazolam (maximum concentration of midazolam in plasma)	up to 13 days
AUC0-∞ of 1'-hydroxymidazolam (area under the concentration-time curve of 1'-hydroxymidazolam in plasma over the time interval from 0 extrapolated to infinity)	up to 13 days
Cmax of 1'-hydroxymidazolam (maximum concentration of 1'-hydroxymidazolam in plasma)	up to 13 days
AUC0-∞ ratio of 1'-hydroxymidazolam to midazolam	up to 13 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events		up to 44 days
AUC0-tz (area under the concentration-time curve of the analytes in plasma over the time interval from 0 to the time of the last quantifiable data point)		up to 13 days
tmax (time from dosing to the maximum concentration of the analytes in plasma)		up to 13 days
λz (terminal rate constant of the analytes in plasma)		up to 13 days
t1/2 (terminal half-life of the analytes in plasma)		up to 13 days
MRTpo (mean residence time of the analytes in the body after po administration)		up to 13 days
CL/F (apparent clearance of the analytes in the plasma after extravascular administration)		up to 13 days
Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose)		up to 13 days
Pre-dose levels of BIRT 2584 XX and BI 610100		days 1, 3 and 12
Number of subjects with abnormal findings in physical examination		up to 29 days
Number of subjects with abnormal changes in laboratory parameters		up to 29 days
Number of subjects with clinically significant changes in 12-lead ECG		up to 29 days
Number of subjects with clinically significant changes in vital signs	Pulse rate, systolic, and diastolic blood pressure	up to 29 days
Assessment of tolerability by investigator on a 4-point scale		Day 29

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimate): October 6, 2014

Study Record Updates

• Last Update Posted (Estimate): October 6, 2014
• Last Update Submitted That Met QC Criteria: October 2, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 1206.9