Effects of BI 44370 TA Orally Applied as Tablets on the Pharmacokinetics of Orally Administered Midazolam Solution in Healthy Volunteers

NCT02217514 | Completed Phase 1

• 1 other identifier: 1246.3
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluation of the long-term (48 h) and short-term (1 h) effects of BI 44370 BS on the pharmacokinetics of midazolam as marker of a possible inhibition of CYP 3A4; safety and tolerability.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Cmax (maximum concentration of midazolam in plasma)

  up to 24 hours after drug administration

• AUC0-tz (area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the time of the last quantifiable data point)

  up to 24 hours after drug administration

• AUC0-infinity (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)

  up to 24 hours after drug administration

Secondary Outcomes (17)

• Cmax (maximum measured concentration of the analyte in plasma)

  Up to 48 hours after drug administration

• tmax (time from dosing to maximum measured concentration)

  up to 48 hours after drug administration

• AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  up to 48 hours after drug administration

• %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)

  up to 48 hours after drug administration

• AUC0-tz (area under the concentration-time curve of the analyte in plasma in plasma over the time interval from 0 to the time of the last quantifiable data point)

  up to 48 hours after drug administration

Study Arms (5)

Treatment sequence 1 in male subjects

EXPERIMENTAL

Midazolam alone and 1 h after low dose BI44370BS in male subjects

Drug: Midazolam; Drug: BI 44370 low dose

Treatment sequence 1 in female subjects

EXPERIMENTAL

Midazolam alone and 1 h after low dose BI44370BS followed by medium dose BI 44370 in an additional visit in female subjects

Drug: Midazolam; Drug: BI 44370 low dose; Drug: BI 44370 medium dose

Treatment sequence 2

EXPERIMENTAL

Midazolam before and 48 h after high dose BI44370BS

Drug: Midazolam; Drug: BI 44370 high dose

Treatment sequence 3

EXPERIMENTAL

Midazolam before and 24 h after high dose BI44370BS

Drug: Midazolam; Drug: BI 44370 high dose

Treatment sequence 4

EXPERIMENTAL

Midazolam before and 1 h after high dose BI44370BS

Drug: Midazolam; Drug: BI 44370 high dose

Interventions

Midazolam DRUG

Also known as: Dormicum®

Treatment sequence 1 in female subjects; Treatment sequence 1 in male subjects; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4

BI 44370 low dose DRUG

Treatment sequence 1 in female subjects; Treatment sequence 1 in male subjects

BI 44370 medium dose DRUG

Treatment sequence 1 in female subjects

BI 44370 high dose DRUG

Treatment sequence 2; Treatment sequence 3; Treatment sequence 4

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 ≥21 and Age ≤50 years
• BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and the local legislation.

You may not qualify if:

• Any finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR) and Electrocardiogram (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
• 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 with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Participation in another trial with an investigational drug within 30 days 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 (more than 60 g/day)
• Drug abuse

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2014
• First Posted: August 15, 2014
• Study Start: February 1, 2008
• Primary Completion: March 1, 2008
• Last Updated: August 15, 2014

Record last verified: 2014-08