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

NCT02256748 | Completed Phase 1

• 1 other identifier: 1206.9
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (14)

• 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

Study Arms (1)

BIRT 2584 XX + Midazolam

EXPERIMENTAL

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: BIRT 2584 XX; Drug: Midazolam

Interventions

BIRT 2584 XX DRUG

BIRT 2584 XX + Midazolam

Midazolam DRUG

BIRT 2584 XX + Midazolam

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2014
• First Posted: October 6, 2014
• Study Start: June 1, 2005
• Primary Completion: August 1, 2005
• Last Updated: October 6, 2014

Record last verified: 2014-10