A Study in Healthy People to Test How Combining BI 1467335 and Tyramine Affects Blood Pressure
Condition: Healthy
Intervention: BI 1467335; Placebo; Phenelzine sulfate; Tyramine
Intervention description: Film-coated tablet; Film-coated tablet; Film-coated tablet; Capsules
Intervention MeSH terms: Phenelzine; Tyramine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The main objective of the study is investigate the effect of escalating doses of oral
      tyramine on systolic blood pressure (SBP) at baseline and following an oral treatment with BI
      1467335 up to 39 days at a low or high dose once daily compared to placebo and phenelzine
      (Nardil®) as positive control.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male or female 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

          -  Age of 18 to 45 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

          -  Male subjects, or female subjects who meet any of the following criteria before the
             first administration of trial medication until 30 days after trial completion:

               -  Use of adequate contraception, e.g. any of the following methods plus condom:
                  implants, injectables, combined oral or vaginal contraceptives, intrauterine
                  device (in case of oral contraceptives start of contraception at least 30 days
                  before administration of trial medication)

               -  Sexually abstinent

               -  A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)

               -  Surgically sterilised (including hysterectomy)

          -  Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable
             cases a blood sample with levels of FSH above 33,4 U/L and estradiol below 71,6 pmol/L
             is confirmatory) 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 45 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 assessed as clinically relevant by the
             investigator

          -  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 60 days of planned
             administration of investigational drug in the current trial, or concurrent
             participation in another clinical trial in which investigational drug is administered

          -  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 20 g per day for females and 30 g per day for
             males)

          -  Drug abuse 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 in males or repeatedly greater than 470 ms in females)
             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

          -  Use of monoamine oxidase (MAO) inhibitors within 90 days before tyramine dosing

          -  Use of fluoxetine within 5 weeks before tyramine dosing

          -  Use of over-the-counter sympathomimetic or grapefruit products within 7 days before
             tyramine dosing

          -  Subject has a known intolerability to tyramine-containing foods

          -  At screening, no increase of systolic blood pressure > 30 mmHg during tyramine
             challenge at the highest tested dose of 700 mg tyramine

        Female subjects will not be allowed to participate, if any of the following apply:

          -  Positive pregnancy test, pregnancy, or plans to become pregnant within 30 days after
             study completion

          -  Lactation