Overview

This trial is active, not recruiting.

Condition chronic obstructive pulmonary disease (copd)
Treatments chf 5993 + ultibro matched placebo, ultibro + chf 5993 matched placebo, central spirometry, copd assessment test, local laboratory assessments, saint george's respiratory questionnaire, exact-pro questionnaire
Phase phase 3
Sponsor Chiesi Farmaceutici S.p.A.
Start date May 2015
End date July 2017
Trial size 1534 participants
Trial identifier NCT02579850, CCD-05993AA1-08

Summary

The aim of the present study is to evaluate the superiority of the fixed triple therapy with BDP/FF/GB at a daily dose of 400/24/50 mcg respectively with that of Ultibro® Breezhaler® (DPI), fixed combination of indacaterol 85 mcg and of glycopyrronium 43 mcg in COPD patients.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Fixed triple therapy with BDP/FF/GB 100/6/12.5 mcg (CHF 5993) administered 2 puffs twice daily via pMDI + Fixed combination of indacaterol and of glycopyrronium (Ultibro® Breezhaler®) matched placebo administered once daily via DPI for 52-week treatment. Patient used to take pMDI medication using a spacer will be provided with a new spacer for the study. 7 study visits including : central spirometry tests, Local laboratory, COPD assessment test (visit 1 only), Local laboratory Assessments Saint George's Respiratory Questionnaire EXACT-pro questionnaire
chf 5993 + ultibro matched placebo CHF 5993
Active medication treatment CHF 5993 and Ultibro matched placebo administered twice a day
central spirometry
Central spirometry to assess forced expiratory volume at one second and forced vital capacity
copd assessment test
COPD assessment test (CAT) at visit 1
local laboratory assessments
ECG + Standard Haematology and Biochemistry
saint george's respiratory questionnaire
Saint George's Respiratory Questionnaire
exact-pro questionnaire
daily from randomization (Visit 2) to end of study (Visit 7)
(Active Comparator)
Fixed combination of indacaterol 85 mcg and of glycopyrronium 43 mcg (Ultibro® Breezhaler®) administered once daily via DPI + Fixed triple therapy with BDP/FF/GB (CHF 5993) matched placebo administered 2 puffs twice daily via pMDI for 52-week treatment. Patient used to take pMDI medication using a spacer will be provided with a new spacer for the study. 7 study visits including : central spirometry tests, Local laboratory, COPD assessment test (visit 1 only), Local laboratory Assessments, Saint George's Respiratory Questionnaire, EXACT-pro questionnaire
ultibro + chf 5993 matched placebo Ultibro Breezhaler
Active medication treatment Ultibro and CHF 5993 matched placebo administered twice a day
central spirometry
Central spirometry to assess forced expiratory volume at one second and forced vital capacity
copd assessment test
COPD assessment test (CAT) at visit 1
local laboratory assessments
ECG + Standard Haematology and Biochemistry
saint george's respiratory questionnaire
Saint George's Respiratory Questionnaire
exact-pro questionnaire
daily from randomization (Visit 2) to end of study (Visit 7)

Primary Outcomes

Measure
Moderate and severe COPD exacerbation rate over 52 weeks of treatment
time frame: 1 year

Secondary Outcomes

Measure
Time to first moderate to severe COPD exacerbation
time frame: 1 year
Rate of severe COPD exacerbation over 52 weeks of treatment
time frame: 1 year
Rate of moderate COPD exacerbation over 52 weeks of treatment
time frame: 1 year
Change from Baseline at each visit and over the entire treatment period in pre-dose morning FEV1
time frame: 1 year

Eligibility Criteria

Male or female participants at least 40 years old.

Inclusion : 1. Male and female ≥ 40 years 2. Severe or very severe COPD diagnosed for at least 12 months 3. 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 4. Post-bronchodilator FEV1 < 50% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio < 0.7 5. Documented history of at least one exacerbation in the 12 months 6. Patient under double therapy for at least 2 months prior to screening. Double therapy will be defined by treatment with any of the following: Orally inhaled corticosteroid (ICS) and (long-acting beta2-agonist) LABA ICS and long-acting muscarinic antagonist (LAMA) Orally LABA and LAMA Monotherapy with LAMA for at least 2 months prior to screening 7. Symptomatic patient at screening with a CAT score ≥ 10. 8. Cooperative attitude and ability to use correctly the inhalers, the spacer AeroChamber Plus (only to patients who are using a spacer), the electronic devices with COPD questionnaire. Exclusion : 1. Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS are willing to use one or more of the reliable methods of contraception 2. Patient with a current clinical diagnosis of asthma with a physician-judged need for inhaled or oral corticosteroid therapy 3. Patient requiring use of the following medications: Course of systemic steroids > 3 days for COPD exacerbation in the 4 weeks prior to screening Course of antibiotics for COPD exacerbation > 7 days in the 4 weeks prior to screening Phosphodiesterase-4 inhibitor in the 4 weeks prior to screening Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening 4. COPD exacerbation requiring prescription of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period 5. Patient treated with non-cardioselective β-blockers in the month preceding the screening or during the run-in period. 6. Patient treated with long-acting antihistamines 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 7. Patient requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia 8. Known respiratory disorders other than COPD which may impact the efficacy of the study drug 9. Patient who have clinically significant cardiovascular condition 10. Patient with atrial fibrillation (AF): Paroxysmal atrial fibrillation, Persistent, Long standing or Permanent 11. Abnormal and clinically significant 12-lead ECG that results in active medical problem which may impact the safety of the patient 12. Patient whose ECG shows QTcF >450 ms for males or QTcF >470 ms for females at screening visit are not eligible (not applicable for patient with pacemaker) 13. Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction would prevent use of anticholinergic agents 14. History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug 15. Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug 16. Patients with hypokalaemia (serum potassium <3.5 mEq/L or 3.5 mmol/L) or uncontrolled hyperkalaemia 17. Unstable concurrent disease which may impact the results of the study 18. Patients with any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next six months (after V1) or with malignancy for which they are currently undergoing radiation therapy or chemotherapy 19. History of alcohol abuse or substance/drug abuse within 12 months prior to screening visit 20. Participation in another clinical trial if investigational drug was received less than 8 weeks prior to screening visit

Additional Information

Official title 52-week, Double Blind, Randomized, 2 Active Parallel Arms Study of Fixed Combination CHF 5993 Administered vs Ultibro® in COPD Patients
Principal investigator Nicolas Roche, Pr
Description Outpatients attending the hospital clinics/study centres will be recruited. Patients with severe and very severe COPD airflow obstruction according to GOLD 2014 criteria. A total of approximately 2192 patients will need to be screened in order to obtain 1534 (767 per arm) randomized and evaluable patients. Approximately 200 sites will be involved worldwide. Each patient will perform a total of 8 clinic visits (V0 to V7) during the study. The Primary objective is to demonstrate the superiority of CHF 5993 pMDI over Ultibro® in terms of moderate and severe COPD exacerbation rate over 52 weeks of treatment. The Secondary objectives are: 1. To evaluate the effect of CHF 5993 pMDI on other lung function parameters, patient's health status and clinical outcome measures; 2. To assess the safety and the tolerability of the study treatments. A 2-week open-label run-in period under Ultibro® followed by a 52-week randomised treatment period. The trial design will be optimised to measure exacerbation rates by using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), developed means of collecting patient-reported outcome (PRO) data, which helps to capture the frequency of exacerbations.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Chiesi Farmaceutici S.p.A..