A Study in Healthy Men to Test the Effects of Different Doses of BI 1467335 on MAO-B Activity in the Brain.
Condition: Healthy
Intervention: BI 1467335
Intervention description: tablet
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: Male
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The main objective of this trial is to investigate the effect of multiple oral dosing of high
      dose BI 1467335 over 28 days and multiple oral dosing of low dose BI 1467335 over 42 days on
      MAO-B occupancy in the brain compared to baseline using [11C]-L-deprenyl-D2 PET tracer in
      healthy male subjects.
    

Eligibility criteria:

        Inclusion criteria:

          -  Healthy male subjects according to the assessment of the investigator, as based on a
             complete medical history including a physical examination, vital signs (Blood pressure
             (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests

          -  Age of 21 to 55 years (inclusive)

          -  Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)

          -  Signed and dated written informed consent prior to admission to the study, in
             accordance with Good Clinical Practice (GCP) and local legislation

          -  Non-smoker with no history of smoking

          -  Subjects who are sexually active must use, with their partner, highly effective
             contraception from the time of administration of trial medication until 4 months after
             administration of trial medication. Adequate methods are:

               -  Condoms plus use of hormonal contraception by the female partner that started at
                  least 2 months prior to administration of trial medication (e.g., implants,
                  injectables, combined oral or vaginal contraceptives, intrauterine device) or

               -  Condoms plus surgical sterilization (vasectomy at least 1 year prior to
                  enrolment) or

               -  Condoms plus surgically sterilised partner (including hysterectomy) or

               -  Condoms plus intrauterine device or

               -  Condoms plus partner of non-childbearing potential (including homosexual men)
                  Subjects are required to use condoms to prevent unintended exposure of the
                  partner to the study drug via seminal fluid. Alternatively, true abstinence is
                  acceptable when it is in line with the subject's preferred and usual lifestyle.
                  If a subject is usually not sexually active but becomes active, with their
                  partner, they must comply with the contraceptive requirements detailed above.

        Exclusion criteria:

          -  Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR)
             or Electrocardiogram (ECG)) deviating from normal and assessed 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 assessed as clinically relevant by the
             investigator

          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
             immunological or hormonal disorders

          -  Cholecystectomy or other surgery of the gastrointestinal tract that could interfere
             with the pharmacokinetics of the trial medication (except appendectomy or simple
             hernia repair)

          -  Diseases of the central nervous system (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 relevant acute infections

          -  History of relevant allergy or hypersensitivity (including allergy to the trial
             medication or its excipients)

          -  Use of drugs within 30 days of planned administration of trial medication that might
             reasonably influence the results of the trial (including drugs that cause QT/QTc
             interval prolongation)

          -  Intake of an investigational drug in another clinical trial within 90 days or within 5
             half-lives, whichever is longer, of planned administration of investigational drug in
             the current trial, or concurrent participation in another clinical trial in which
             investigational drug is administered

          -  Alcohol abuse (consumption of more than 30 g per day for males) within the 24 months
             prior to dosing

          -  Drug abuse within the 24 months prior to dosing or positive drug screening

          -  Blood donation of more than 100 mL within 30 days of planned administration of trial
             medication or intended blood 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 the 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) or any other relevant ECG finding at screening

          -  A history of additional risk factors for Torsade de Pointes (such as heart failure,
             hypokalaemia, or family history of Long QT Syndrome)

          -  Subject is assessed as unsuitable for inclusion by the investigator, for instance,
             because the subject is not considered able to understand and comply with study
             requirements, or has a condition that would not allow safe participation in the study

          -  Structural brain abnormality has been shown on an Magnetic Resonance Imaging (MRI)

          -  Severe anxiety of enclosed spaces

          -  Contraindication for arterial cannulation: Allen's test indicating potential risk in
             placement of the arterial cannula.

          -  Contraindication to MRI as determined by screening and safety questionnaire including
             but not limited to significant tattoos (as determined by the radiographer), cardiac
             pacemakers, aneurysm clips and cochlear implants.

          -  Unable to lie flat on the MRI or Positron emission tomography (PET) scanner for a
             prolonged period of time.

          -  Prior participation in other research protocols in the past year such that the total
             effective dose including this study would exceed 10 mSv.