BI 443651 Methacholine Challenge
Condition: Asthma
MeSH terms: Asthma
Intervention: BI 443651; Placebo
Intervention description: Three doses, each 12 hours apart; Three doses, each 12 hours apart
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to investigate safety and tolerability of three
      consecutive administrations, 12 hours apart, at three different dose-levels of BI 443651
      administered via oral inhalation in male and female mild asthmatic subjects after a bolus
      methacholine challenge.
    

Eligibility criteria:

        Inclusion criteria:

          -  Male or female subjects must have a diagnosis of asthma by a physician at least 3
             months prior to screening. The diagnosis of asthma must meet the following spirometric
             criteria:

             -- Pre-bronchodilator clinic measured FEV1 >=70% of predicted normal (calculated by
             the Global Lung Function Initiative equation (GLI)) measured >= 8 hours after the last
             use of short acting bronchodilator at the screening visit and on the day of
             randomisation.

          -  Age >= 18 <= 60 years. Subjects must be within the eligible age range on the day of
             signing informed consent.

          -  Diagnosis of asthma must have been made before the subject's age of 40. Or If the
             subject is >= 40 years and the diagnosis has not yet been recorded in the subject's
             medical files, the investigator should assess whether the subject's medical history
             (e.g. symptoms and prescribed medications) confirms the subject suffered from asthma
             since before the age of 40. If so, this subject may be considered for inclusion after
             consultation with the sponsor.

          -  ACQ value < 1.5 at the screening visit.

          -  PD20 (Provocative dose causing at least a 20% decline in FEV1) at the screening visit
             of methacholine <= 1mg

          -  Body mass index (BMI) >= 18.5 and <= 32.0 kg/m2 at the screening visit

          -  Subjects must be able to perform all study related procedures and assessments,
             including pulmonary function tests, as required by the protocol.

        Exclusion criteria:

          -  Significant pulmonary diseases other than asthma (up to GINA treatment step 2) or
             other medical conditions (as determined by medical history, examination and clinical
             investigations at screening) that may, in the opinion of the investigator result in
             any of the following:

               -  Put the subject at risk because of participation in the study

               -  Influence the results of the study

               -  Cause concern regarding the subject's ability to participate in the study.

          -  Respiratory tract infection or asthma exacerbation in the 4 weeks prior to the
             screening visit. Subjects can be rescreened 4 weeks after resolution of the infection
             or exacerbation.

          -  Hospitalisation for asthma exacerbation within 3 months or intubation for asthma
             within 3 years of the screening visit.

          -  Serum potassium measurement above the ULN at the screening visit. Any value about the
             ULN excludes the subject irrespective of clinical relevance.

          -  Blood donation (more than 100mL within 30 days prior to the administration of trial
             medication or intended during the trial)

          -  Subjects who have been treated with any of the following asthma medications in the
             given interval prior to Visit 1:

               -  Non-approved asthma therapies such as methotrexate,

               -  Intravenous, intramuscular or oral corticosteroids

               -  Inhaled corticosteroids (iCS) other than low dose iCS (defined as equivalent to
                  equal to, or less than 250 μg fluticasone / day)

               -  A long acting beta agonist or anticholinergic bronchodilator (Visit 1), including
                  fixed dose beta agonist/inhaled corticosteroid combinations and oral
                  bronchodilators.

               -  A biological based antagonist therapy including Omalizumab, or immune modulators

               -  Asthma controller medications (e.g: leukotriene modifier, methylxanthines,
                  nedocromil or cromolyn sodium)

               -  Mucolytics

               -  Systemically available immunomodulatory treatments for allergic rhinitis or
                  atopic dermatitis.

          -  Use of any diuretics (including loop diuretics or potassium sparing diuretics (such as
             amiloride), renin-angiotensin antihypertensive drugs in the 28 days prior to the
             screening visit (Visit 1)

          -  Use of drugs that might reasonably influence the results of the trial or that might
             prolong the QT/QTc interval within 10 days prior to the randomisation visit.

          -  A marked baseline prolongation of QT/QTcF interval (such as QTcF 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 and prior to randomisation

          -  A history of additional risk factors for Torsades de Pointes (such as heart failure,
             hypokalemia, or family history of Long QT Syndrome)

          -  History of relevant allergies/hypersensitivities (including allergy to the trial
             medication or its excipients)

          -  Contraceptive measures for male and female patients may be required

          -  Current smokers or ex-smokers who have given up smoking for < 12 months and / or have
             a smoking pack history of > 5 pack years (1 pack year = 20 cigarettes per day for 1
             year of 5 cigarettes per day for 4 years)

          -  Further exclusion criteria apply