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

• Register: EUCTR
• Last refreshed on: 8 May 2017
• Main ID: EUCTR2014-001487-35-LT
• Date of registration: 22/01/2015
• 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 combination of licensed medicines (combination of fluticasone plus vilanterol and tiotropium) in patient with chronic obstructive pulmonary disease.
• Scientific title: A Multinational, Multicentre, Randomised, Open-Label, Active-Controlled, 26-Week, 2-Arm, Parallel Group Study to Evaluate the Non-Inferiority of Fixed Combination of Beclometasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrronium Bromide Administered Via pMDI (CHF 5993) Versus Fixed Combination Of Fluticasone Furoate Plus Vilanterol Administered Via DPI (Relvar®) Plus Tiotropium Bromide (Spiriva®) for the Treatment of Patients With Chronic Obstructive Pulmonary Disease - Tristar
• Date of first enrolment: 10/03/2015
• Target sample size: 1142
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001487-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no 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

Belgium, Germany, Hungary, Lithuania, Netherlands, Poland, Romania, Russian Federation, South Africa, Sweden, Turkey, United Kingdom

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 COPD at least 12 months before the screening visit (according to GOLD document updated 2014).
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 < 0.7 at least 10-15 min after 4 puffs (4 x 100 µg) 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 visit of an inhaled corticosteriod (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 patients at screening with a CAT score =10.
8. A cooperative attitude and ability to use correctly the inhalers.
9. A cooperative attitude and ability to use correctly the daily eDiary.
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 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 342

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 of 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-cardio selective 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 the investigator’s judgment
9. Patients who have clinically significant cardiovascular condition
10. Patients with atrial fibrillation (AF)
11. An abnormal and clinically significant 12-lead ECG which may impact the safety of the patient according to investigator’s judgement
12. Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic agents
13. History of hypersensitivity to anticholinergics, 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 according to investigator’s judgment
16. Unstable concurrent disease which may impact the efficacy or the safety of the study drug 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 and/or substance/drug abuse within 12 months prior to screening visit
19. Participation in another clinical trial where investigation 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

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

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

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-

Trade Name: Relvar Ellipta®
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: FLUTICASONE FUROATE
CAS Number: 397864-44-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 92-
INN or Proposed INN: VILANTEROL TRIFENATATE
CAS Number: 503070-58-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 22-

Trade Name: SPIRIVA®
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TIOTROPIUM BROMIDE
CAS Number: 139404-48-1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Secondary Objective: • To evaluate the effect of CHF 5993 pMDI on lung function parameters, patient’s health status and on clinical outcome measures.
• To collect data in order to assess the impact of study treatments on health economic outcomes.
• To assess the safety and tolerability of the study treatments.

Timepoint(s) of evaluation of this end point: Visit 2 (week 0) to visit 5 (week 26)

Primary end point(s): Change from baseline in the SGRQ total score

Main Objective: To demonstrate the non-inferiority of CHF 5993 pMDI versus fixed combination of fluticasone furoate/vilanterol plus tiotropium in terms of quality of life (change from baseline in the St. George’s Respiratory Questionnaire [SGRQ] total score after 26 weeks of treatment).

Secondary Outcome(s)

Secondary end point(s): • SGRQ response (change from baseline in total score = -4)
• Change from baseline in the SGRQ total score
• Change from baseline in pre-dose morning FEV1, FVC and FEV1 response
• Change from baseline of night-time COPD symptoms on sleep
• Use of rescue medication
• CAT score at the end of treatment
• Rate of moderate and severe COPD exacerbation over 26 weeks of treatment.

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

Secondary ID(s)

2014-001487-35-SE

CCD-05993AA1-07

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.