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
Condition: Healthy
Intervention: BI 705564; Placebo; Midazolam
Intervention description: Film-coated tablet; Film-coated tablet; Solution for injection
Intervention MeSH terms: Midazolam
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 60.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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;

          -  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

        Exclusion Criteria:

          -  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.