A Dose Ranging Study With CHF 1531 in Subjects With Asthma (FLASH)
Condition: Asthma
MeSH terms: Asthma
Intervention: CHF 1531 pMDI; Formoterol Inhalation Solution; Placebo pMDI
Intervention description: Dose Response: Test one of five different doses of CHF 1531; Active Control; Matched Placebo
Intervention MeSH terms: Formoterol Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      To evaluate the dose-response of different doses of CHF 1531 pressurized metered dose inhaler
      (pMDI) containing formoterol fumarate, on lung function and other clinical outcomes and to
      identify the optimal dose(s) with regard to benefit/ risk ratio for further development in
      the target subject population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged ≥18 and ≤75 years who have signed an Informed Consent
             Form prior to initiation of any study-related procedure.

          -  A diagnosis of asthma as defined in the Global Initiative for Asthma (GINA) Report,
             2016, documented for at least 1 year prior to screening.

          -  Poorly controlled or uncontrolled asthma evidenced by a score ≥1.5 on the Asthma
             Control Questionnaire 7 © (ACQ-7)

          -  A pre-bronchodilator Forced Expiratory Volume in the 1st Second ( FEV1) ≥60% and <85%
             of their predicted normal value, after appropriate washout from bronchodilators, at
             the screening and randomization visits

          -  Subjects with a positive response to a reversibility test at screening, defined as
             change in FEV1 (ΔFEV1) ≥12% and ≥200 mL over baseline within 30 minutes after inhaling
             4 puffs of albuterol hydrofluoroalkane(HFA) 90 µg/actuation.

          -  Use of ICS (low/medium dose according to GINA Report, 2016) with or without a
             long-acting bronchodilator for 3 months (at a stable dose in the last 4 weeks) before
             screening visit.

          -  A cooperative attitude and ability to demonstrate correct use of the diary, peak flow
             meter, and pMDI inhaler.

        Exclusion Criteria:

          -  Pregnant or lactating women and all women physiologically capable of becoming pregnant
             UNLESS they are willing to use a highly effective birth control methods

          -  Subjects who suffer from Chronic Obstructive Pulmonary Disease (COPD) as defined by
             the Global Strategy for Prevention, Diagnosis and Management of COPD (GOLD) Report,
             2017, or are suspected of having Asthma COPD Overlap Syndrome (ACOS) as described in
             the GINA Report, 2016.

          -  Inability to carry out pulmonary function testing, to comply with study procedures or
             with study drug intake.

          -  Current smokers or ex-smokers (tobacco, vapor cigarettes, marijuana) with a smoking
             history of >10 pack-years or having stopped smoking one year or less prior to
             screening visit.

          -  History of life-threatening asthma, clinically significant uncontrolled disease or
             respiratory infection.

          -  An asthma exacerbation requiring oral/intravenous corticosteroids ≤ 30 days,
             intramuscular depot corticosteroid ≤3 months or hospitalization within 6 months prior
             to screening.

          -  Subjects with unresolved bacterial or viral respiratory tract, sinus, or middle ear
             infection affecting asthma status within 2 weeks prior to screening.

          -  Subjects who received a vaccination within 2 weeks prior to screening or during the
             run-in.

          -  Subjects with oral candidiasis at screening and at randomization.

          -  Subjects with any clinically significant, uncontrolled condition.

          -  Subjects with serum potassium levels <3.5 milliequivalents per litre (mEq/L) or (3.5
             mmol/L) at screening.

          -  Subjects who have clinically significant cardiovascular condition.

          -  Subjects who have a clinically significant abnormal 12-lead ECG that results in active
             medical problem which may impact the safety of the patient according to Investigator's
             judgment.

          -  Subjects whose 12-lead ECG shows Fridericia's corrected QT interval (QTcF) >450 ms for
             males or QTcF >470 ms for females at screening or randomization visits.

          -  Subjects with known intolerance/hypersensitivity or contra-indication to treatment
             with inhaled β2-adrenergic receptor agonists, corticosteroids or propellant
             gases/excipients.

          -  Subjects with concomitant immunosuppressive therapy, use of oral or injected
             corticosteroids, anti- Immunoglobulin E (IgE), anti-Interleukin 5 (IL5) or other
             monoclonal or polyclonal antibodies within 12 weeks prior to screening.

          -  Use of potent cytochrome P450 3A4 inhibitors and inducers within 4 weeks prior to
             screening.

          -  History of alcohol abuse and/or substance/drug abuse within 12 months prior to
             screening.

          -  Subjects who have received an investigational drug within 1 month or 5 half-lives
             (whichever is greater) prior to screening visit, or have been previously randomized in
             this trial, or are currently participating in another clinical trial.

          -  Subjects who are mentally or legally incapacitated or subjects accommodated in an
             establishment as a result of an official or judicial order.

          -  Subjects who have undergone major surgery in the 3 months prior to screening visit or
             have a planned surgery during the trial.