This Study in Healthy Men Tests How Different Doses of BI 705564 Are Taken up in the Body and How Well They Are Tolerated. The Study Also Tests How BI 705564 Affects the Way the Body Breaks Down Midazolam
- Registration Number
- NCT03325712
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this trial is to investigate safety and tolerability of BI 705564 in healthy male subjects, following oral administration of multiple rising doses.
Secondary objectives are the exploration of the pharmacokinetics, including dose proportionality and investigation of linearity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 60
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Dose Groups (DGs)1 to 5: Healthy male subjects according to the assessment of the investigator, based on a complete medical history, a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests;
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DG 8, only: Otherwise healthy male subjects (as defined for DGs 1 to 5) with a history (of at least 1 year) of IgE-mediated, perennial allergies, predominantly to (house) dust mite (dermatophagoides pteronyssinus or dermatophagoides farina) as documented by a positive Skin prick test (SPT)(largest diameter of wheal at screening > 5 mm)
- Age of 18 to 50 years (incl.)
- Body Max Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
- Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is 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 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 that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
- Diseases of the central nervous system (including but not limited to any kind of seizure or stroke), and other relevant neurological or psychiatric disorders
- History of relevant orthostatic hypotension, fainting spells, or blackouts
- Chronic or relevant acute infections
- 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 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.
- Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
- Inability to refrain from smoking on specified trial days
- 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 the administration of trial medication or intended donation during the trial
- Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
- Inability to comply with dietary regimen of the trial site
- A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant Electrocardiogram (ECG) finding at screening
- 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, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
In addition, the following trial-specific exclusion criteria apply:
- Male subject with women of child bearing potential (WOCBP) partner who is unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
- Subjects who, in the investigator's judgement, are perceived as having an increased risk of bleeding, e.g. history of haemorrhagic disorders, clinical relevant petechial bleeding, occult blood in faeces, haematuria in repeated urine tests, trauma or surgery within the last month planned surgery during trial participation, history of arteriovenous malformation or aneurysm, history of gastroduodenal ulcer disease or gastrointestinal haemorrhage, history of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding, use of drugs that may interfere with haemostasis during trial conduct (e.g. acetylic salicylic acid or other non-steroidal anti-inflammatory drugs)
- Repeated platelet counts below 100 cells/nL at screening
- Bleeding times (to monitor platelet function) above reference range at screening
- Repeated absolute B cell (CD19+) counts below 40/μL at screening
- Serum potassium below normal range at screening
- A history or current clinical signs of acute pancreatitis
- Further exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo matching BI 705564 - SPT Placebo SPT stands for skin prick test. Dose group 2: BI 705564 20 mg BI 705564 - Dose group 2: BI 705564 20 mg Midazolam - Dose group 3: BI 705564 40 mg BI 705564 - Dose group 3: BI 705564 40 mg Midazolam - Dose group 5: BI 705564 60 mg BI 705564 - Dose group 4: BI 705564 80 mg BI 705564 - Placebo matching BI 705564 Placebo - Dose group 1: BI 705564 10 mg BI 705564 - Dose group 8: BI 705564 40 mg - SPT BI 705564 SPT stands for skin prick test. Dose group 5: BI 705564 60 mg Midazolam - Dose group 4: BI 705564 80 mg Midazolam - Placebo matching BI 705564 Midazolam -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Drug-related Adverse Events From first drug administration until 10 days after last drug administration, up to 27 days (for dose groups 1 to 5 and "Placebo Matching BI 705564") or up to 37 days (for dose group 8 and "Placebo Matching BI 705564 - SPT"). Percentage of participants with drug-related adverse events is reported.
- Secondary Outcome Measures
Name Time Method Maximum Measured Concentration of BI 705564 in Plasma (Cmax) After the Administration of the First Dose 1 hour(s) (h) prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after first BI 705564 dose (for dose groups 1 to 5); 1.5 h prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after first BI 705564 dose (for dose group 8). Maximum measured concentration of BI 705564 in plasma (Cmax) after the administration of the first dose of BI 705564 is reported.
Maximum Measured Concentration of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) After the Administration of the Last Dose 1 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after last BI 705564 dose on Day 17 (for dose groups 1 to 5); 1.5 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after last BI 705564 dose on Day 28 (for dose group 8). Maximum measured concentration of BI 705564 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after the administration of the last dose.
As per the protocol, day is counted as "Day 1 = 0:00".Area Under the Concentration-time Curve of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After the Administration of the Last Dose 1 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after last BI 705564 dose on Day 17 (for dose groups 1 to 5); 1.5 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after last BI 705564 dose on Day 28 (for dose group 8). Area under the concentration-time curve of BI 705564 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after the administration of the last dose of BI 705564 is reported.
As per the protocol, day is counted as "Day 1 = 0:00".Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) After the First and Last Dose 1.5 h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after first midazolam dose on Day -1 and 1h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after last midazolam dose on Day 17. Area under the concentration-time curve of Midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) after the first and last dose for "Placebo Matching BI 705564" group and for dose groups 2 to 5 is reported.
Area Under the Concentration-time Curve of BI 705564 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1) 1 hour(s) (h) prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after first BI 705564 dose (for dose groups 1 to 5); 1.5 h prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after first BI 705564 dose (for dose group 8). Area under the concentration-time curve of BI 705564 in plasma over a uniform dosing interval τ after administration of the first dose of BI 705564 (AUCτ,1) is reported. Here AUCτ,1 = AUC0-24.
Maximum Measured Concentration of Midazolam in Plasma (Cmax) After the First and Last Dose 1.5 h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after first midazolam dose on Day -1 and 1h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after last midazolam dose on Day 17. Maximum measured concentration of Midazolam in plasma (Cmax) after the first and last dose for "Placebo Matching BI 705564" group and for dose groups 2 to 5 is reported.
Trial Locations
- Locations (1)
CRS Clinical Research Services Mannheim GmbH
🇩🇪Mannheim, Germany