A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease
Condition: COPD; Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: CHF 5259; Placebo; Tiotropium Bromide 18 µg Inhalation Capsule
Intervention description: Dose Response: Test one of four different doses of CHF 5259; Placebo Control; Active Control
Intervention MeSH terms: Bromides; Tiotropium Bromide
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 733.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: CHF 5259; Chronic Obstructive Pulmonary Disease (COPD); pMDI (pressurized metered dose inhaler); GLIMMER

Summary:

      The purpose of this study is to evaluate the dose-response of different doses of CHF 5259
      pMDI on lung function and other clinical outcomes, to identify the optimal dose(s) in terms
      of benefit/ risk ratio for further development in the target subject population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged ≥ 40 who have signed an Informed Consent Form prior to
             initiation of any study-related procedure.

          -  Subjects with a diagnosis of COPD (according to GOLD 2017 Global Strategy for the
             Diagnosis, Management and Prevention of COPD Report) at least 12 months before the
             screening visit.

          -  Current smokers or ex-smokers who quit smoking at least 6 months prior to screening
             visit, with a smoking history of at least 10 pack years

          -  A post-bronchodilator forced expiratory volume in the 1st second (FEV1) ≥50% and <80%
             of the predicted normal value and,

          -  a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) < 0.7 at screening and

          -  a demonstrated reversibility to ipratropium defined as ΔFEV1 ≥ 5% over baseline 30-45
             minutes after inhaling 4 puffs of ipratropium

          -  Subjects under regular COPD therapy for at least 2 months prior to screening with
             either inhaled long-acting muscarinic antagonist (LAMA), inhaled ICS/ long-acting
             β2-agonist (LABA), inhaled ICS + LAMA

          -  Symptomatic subjects at screening with a CAT score ≥10. This criterion must be
             confirmed at randomization

          -  Symptomatic subjects with a BDI focal score ≤ 10. This criterion must be confirmed at
             randomization

          -  A cooperative attitude and ability to demonstrate correct use of the inhalers and
             e-diary.

        Exclusion Criteria:

          -  Pregnant or lactating women and all women physiologically capable of becoming pregnant
             UNLESS they are willing to use highly effective birth control methods

          -  Diagnosis of asthma or Asthma-COPD Overlap Syndrome (ACOS) as described in global
             initiative for asthma (GINA) Report 2016, history of allergic rhinitis or atopy (atopy
             which may raise contra-indications or impact the efficacy of the study treatment
             according to Investigator's judgment)

          -  COPD Exacerbations: a moderate or severe COPD exacerbation that has not resolved ≤14
             days prior to screening and ≤30 days following the last dose of any oral/systemic
             corticosteroid or antibiotic (whichever comes last). A Moderate or Severe COPD
             exacerbation during the run-in period

          -  Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to
             screening or during run-in

          -  Subjects treated with non-cardio-selective β-blockers in the month preceding screening
             or during the run-in period

          -  Subjects treated with long-acting anti-histamines unless taken at stable regimen at
             least 2 months prior to screening and to be maintained constant during the study, or
             if taken as needed

          -  Subjects requiring long term (at least 12 hours daily) oxygen therapy for chronic
             hypoxemia

          -  Known respiratory disorders other than COPD which may impact the efficacy of the study
             treatment according the Investigator's judgment.

          -  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 subject according to Investigator's
             judgement

          -  Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) >450 ms for
             males or QTcF >470 ms for females at screening visit

          -  Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy
             or bladder neck obstruction that in the opinion of the Investigator would prevent use
             of anticholinergic agents

          -  History of hypersensitivity to M3 receptor antagonists, β2-adrenergic receptor
             agonist, corticosteroids or any of the excipients contained in any of the formulations
             used in the study which may raise contra-indications or impact the efficacy of the
             study treatment according to the Investigator's judgement

          -  Clinically significant laboratory abnormalities indicating a significant or unstable
             concomitant disease which may impact the efficacy or the safety of the study treatment
             according to Investigator's judgement

          -  Subjects with serum potassium levels <3.5 mEq/L (or 3.5 mmol/L) at screening

          -  Use of potent cytochrome P450 2D6 and 3A4 inhibitors within 4 weeks prior to screening

          -  Unstable or uncontrolled concurrent disease; fever, endocrine disease,
             gastrointestinal disease; neurological disease; hematological disease; autoimmune
             disorders, or other which may impact the feasibility of the results of the study
             according to Investigator's judgment

          -  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.