A study to evaluate whether a new inhaled medicine (combination of beclometasone plus formoterol plus glycopyrronium) works as well as a licensed medicine (combination of indacaterol and glycopyrronium) in patients with chronic obstructive pulmonary disease.

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2014-001704-22-HU
• Date of registration: 09/02/2015
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: A study to evaluate whether a new inhaled medicine (combination of beclometasone plus formoterol plus glycopyrronium) works as well as a licensed medicine (combination of indacaterol and glycopyrronium) in patients with chronic obstructive pulmonary disease.
• Scientific title: A 52-week, Double Blind, Double dummy, Randomized, Multinational, Multicentre, 2-arm Parallel Group, active Controlled Clinical Trial of fixed combination of beclometasone dipropionate plus formoterol fumarate plus Glycopyrronium bromide administered via pMDI (CHF 5993) versus indacaterol/glycopyrronium (Ultibro®) via DPI in patients with Chronic Obstructive Pulmonary Disease - TRIBUTE
• Date of first enrolment: 17/03/2015
• Target sample size: 1534
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001704-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Chile, Croatia, Czech Republic, Denmark, Germany, Hungary, Latvia, Mexico, Norway, Peru, Poland, Portugal

Contacts

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female adults aged = 40 years with written informed consent obtained prior to any study-related procedure.
2. Patients with a diagnosis of severe or very severe COPD airflow obstruction (according to GOLD guidelines, updated 2014) at least 12 months before the screening visit.
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. A post-bronchodilator FEV1 < 50% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio < 0.7. [Post bronchodilator means at least 10-15 min after 4 puffs (4 x 100 mcg) of salbutamol pMDI].
5. A documented history of at least one exacerbation in the 12 months preceding the screening visit.
6. Patients under double therapy for at least 2 months prior to screening with either an inhaled corticosteroid (ICS)
plus a long-acting muscarinic antagonist (LAMA) or long-acting ß2-agonist (LABA) or a double combination of LABA/LAMA or LAMA alone
7. Symptomatic patient at screening with a CAT score = 10.
8. A cooperative attitude and ability to use correctly the pMDI inhalers and Breezhaler® inhalers.
9. A cooperative attitude and ability to use correctly the spacer AeroChamber PlusTM Flow-Vu antistatic.
10. A cooperative attitude and ability to use correctly electronic devices with COPD questionnaire.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 534

Exclusion criteria:
1. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are willing to use one or more methods of contraception as defined in the protocol
2. Patients with a current clinical diagnosis of asthma with a physician-judged need for inhaled or oral corticosteroid therapy
3. Patients requiring use systemic steroids, antibiotics, PDE4 inhibitors in the 4 weeks prior to screening
4. COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period.
5. Patients treated with non-cardioselective ß-blockers for at least 10 days before randomization.
6. Patients 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 PRN.
7. Patients 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 according to the investigator’s judgment.
9. Patients who have clinically significant cardiovascular conditions
10. Patients with atrial fibrillation (AF)
11. An abnormal and clinically significant 12-lead ECG that results in active medical problem which may impact the safety of the patient according to investigator’s judgement.
12. 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.
13. History of hypersensitivity to M3 Antagonists, ß2-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 according to the investigator’s judgement.
14. Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator’s judgement.
15. Patients with hypokalaemia or uncontrolled hyperkalaemia
16. Unstable concurrent disease which may impact the feasibility of the results of the study according to investigator’s judgment.
17. 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.
18. History of alcohol abuse or substance/drug abuse within 12 months prior to screening visit.
19. Participation in another clinical trial where investigational drug was received less than 8 weeks prior to screening visit.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease
MedDRA version: 19.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: CHF 5993 pMDI
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: BECLOMETASONE DIPROPIONATE
CAS Number: 5534-09-8
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: FORMOTEROL FUMARATE
CAS Number: 43229-80-7
Other descriptive name: FF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Trade Name: Ultibro Breezhaler®
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: INDACATEROL
CAS Number: 312753-06-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 85-
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 43-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: To demonstrate the superiority of CHF 5993 pMDI over Ultibro® in terms of moderate and severe COPD exacerbation rate over 52 weeks of treatment.

Primary end point(s): • Moderate and severe COPD exacerbation rate over 52 weeks of treatment.

Secondary Objective: • To evaluate the effect of CHF 5993 pMDI on other lung function parameters, patient’s health status and clinical outcome measures.
• To assess the safety and the tolerability of the study treatments.

Timepoint(s) of evaluation of this end point: Study duration

Secondary Outcome(s)

Secondary end point(s): • Time and rate of COPD exacerbation
• Change from baseline pre-dose morning FEV1, FVC and FEV1 response
• Change in SGRQ, CAT, EXACT-PRO score
• Use of rescue medication and nocturnal symptoms

Timepoint(s) of evaluation of this end point: Study duration

Secondary ID(s)

2014-001704-22-LV

CCD-05993AA1-08

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.