Evaluation of Safety and Tolerability of BI 894416 in Patients With Mild Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: BI 894416; Placebo
Intervention description: BI 894416 film-coated tablet.; Placebo film-coated tablet matching BI 894416.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 68.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      In both parts, the primary comparisons of interest are between the percentage of patients
      with drug-related adverse events at each dose and placebo during single and multiple dosing
      regimens. Based on these, the primary trial objective is to assess safety and tolerability of
      BI 894416 at each dose.

      Secondary measures of interest are the geometric means of BI 894416 plasma AUC0-∞ and Cmax
      after single dose in SRD part and AUC0-8 and Cmax after single dose as well as AUCτ,ss and
      Cmax,ss after 7 days multiple dosing in MRD part. The objective is to assess the
      pharmacokinetics of BI 894416 following single and multiple administration.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated written informed consent in accordance with ICH-GCP and local
             legislation prior to admission to the trial. Medication washout and medication
             restrictions according to protocol are allowed only after informed consent is
             obtained.

          -  Male patients aged at least 18 years but not more than 55 years at the time of
             informed consent.

          -  Men able to father a child must be ready and able to use highly effective methods of
             birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per
             year when used consistently and correctly. A list of contraception methods meeting
             these criteria is provided in the patient information.

          -  Pre-bronchodilator clinic measured FEV1 of ≥ 70% of predicted normal at the screening
             visit (Visit 1). Calculations will be based on Global Lung Function Initiative (GLI)
             formula

          -  A diagnosis of asthma, diagnosed by a physician.

          -  Patients should be non-smokers or ex-smokers who stopped smoking at least 12 weeks
             prior to screening and are expected to be able to not smoke for the duration of the
             study.

          -  Patients must be able to perform all trial related procedures including pulmonary
             function tests, nasal brushings.

          -  BMI of 18.5 to 32 kg/m2 (incl.)

          -  For MRD part: Patients are allowed to be on stable inhaled low dose corticosteroid
             (please refer to GINA guidelines) for at least 4 weeks prior to screening.

        Exclusion Criteria:

          -  Any finding in the medical examination (including BP, PR, echocardiography and
             echocardiography stress test or ECG and including the neurological examination) 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 (stress), 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
             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 prior to administration of trial medication that might
             reasonably influence the results of the trial (incl. QT/QTc interval prolongation)

          -  Participation in another trial where an investigational drug other than BI 894416 has
             been administered within 60 days or 5 half-lives (whichever is greater) prior to
             planned administration of trial medication, or current participation in another trial
             involving administration of investigational drug. In case of planned participation in
             the MRD part in this trial the previous participation in one dose group of the SRD
             part is allowed if BI 894416 has been administered more than 21 days prior to planned
             administration of BI 894416 in the MRD part. (Participation in an SRD dose group after
             the patient has participated in the MRD part is not allowed.)

          -  Alcohol abuse (consumption of more than 24 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

          -  Inability to comply with dietary regimen of 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 Torsades de Pointes (such as heart failure,
             hypokalemia, or family history of Long QT Syndrome)

          -  Patient unable or unwilling to comply with study requirements, or has a condition that
             would not allow safe participation in the study

          -  History of relevant neurological disorder affecting the peripheral or central nervous
             system (this includes, but is not limited to: stroke, epilepsy, inflammatory or
             atrophic diseases affecting the nervous system, cluster headache or any cancer of the
             nervous system)

          -  History of immunological disease except allergy not relevant to the trial (such as
             mild hayfever or dust mite allergy) and except asthma in childhood or adolescence

          -  History of cancer (other than successfully treated basal cell carcinoma)

          -  Use of any drug that could reasonably inhibit platelet aggregation or coagulation
             (e.g. acetylsalicylic acid) within 10 days prior to administration of trial
             medication, or planned use during the trial or within 7 days after last dose of trial
             medication.

          -  Further exclusion criteria apply.