Clinical trial NCT03279978: This Study Tests How Healthy Men Tolerate Different Doses of BI 730357 and How the Metabolism of Midazolam is Affected by BI 730357
Official title: Phase Ib Evaluation of the Safety and Tolerability and Effect on Midazolam Metabolism of the Administration of Multiple Rising Doses of BI 730357 to Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Psoriasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-09-12
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase Ib evaluation of the safety, tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) properties of Multiple Rising Dose (MRD) administration of BI 730357 to healthy volunteers for up to 28 days.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the assessment of the Investigator, based on a complete medical history, physical examination, vital signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
* Subjects with a partner who is a woman of childbearing potential (WOCBP) must be willing to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
* Age of 18 to 45 years (incl.) at screening
* Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.) at screening
* Signed and dated written informed consent prior to admission to the study in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation

Exclusion criteria

* Any finding in the medical examination (including blood pressure, pulse rate or Electrocardiogram (ECG)) deviating from normal and judged as clinically relevant by the Investigator
* Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
* Any laboratory value outside the reference range that the Investigator considers to be of clinical relevance
* Any evidence of a concomitant disease judged as clinically relevant by the Investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Cholecystectomy and/or surgery of the gastrointestinal tract (except appendectomy and simple hernia repair) that could interfere with the PK of the trial medication
* Diseases of the Central Nervous System (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Chronic or acute infections which are of relevance in the opinion of the Investigator
* History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
* Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc (corrected QT interval) interval prolongation)
* Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
* Tobacco usage (more than 10 cigarettes or 3 cigars or 3 pipes per day)
* Alcohol abuse (consumption of more than 30 g per day)
* Drug abuse or positive drug screening
* Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
* Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
* A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
* Subject is assessed as unsuitable for inclusion by the Investigator; for instance, is considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
* Unwillingness to adhere to the rules of UV-light protection

Primary outcomes:
measure: Number of Subjects With Drug-related Adverse Events (AEs)
timeFrame: From first drug administration until 7 days after last dose, up to 21 days (for 25, 50 and 100 mg dose groups) and up to 35 days (for 200 and 400 mg dose groups)
Secondary outcomes:
measure: Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1)
timeFrame: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.
measure: Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax)
timeFrame: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.
measure: Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.
timeFrame: Day 14 and Day 28 (Please refer description for the time frame in detail)
measure: Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss)
timeFrame: Day 14 and Day 28 (Please refer description for the time frame in detail)
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: CTC North GmbH & Co. KG, Hamburg
Study officials:
References: