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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02217514

1246.3

Details and patient eligibility

About

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.

Enrollment: 48 patients

Sex: All

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >470 ms);
• A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

For Male Subjects:

• Not willing to use adequate contraception (condom use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device (IUD)) during the whole study period from the time of the first intake of study drug until three months after the last intake

For Female Subjects:

• Pregnancy
• Positive pregnancy test
• No adequate contraception (adequate contraception e.g. sterilisation, intrauterine pessary (IUP), oral contraceptives)
• Inability to maintain this adequate contraception during the whole study period during the whole study period from the time of the first intake of study drug until one month after the last intake

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 5 patient groups

Treatment sequence 1 in male subjects

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: BI 44370 low dose

Treatment sequence 1 in female subjects

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: BI 44370 medium dose

Drug: BI 44370 low dose

Treatment sequence 2

Experimental group

Description:

Midazolam before and 48 h after high dose BI44370BS

Treatment:

Drug: Midazolam

Drug: BI 44370 high dose

Treatment sequence 3

Experimental group

Description:

Midazolam before and 24 h after high dose BI44370BS

Treatment:

Drug: Midazolam

Drug: BI 44370 high dose

Treatment sequence 4

Experimental group

Description:

Midazolam before and 1 h after high dose BI44370BS

Treatment:

Drug: Midazolam

Drug: BI 44370 high dose