A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease

• Status: Completed
• Trial end date: 2018-06-06
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chiesi Farmaceutici S.p.A.
• Treatments: Bromides; Tiotropium Bromide

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.