2-arm Parallel Group Study of Fixed Combination of CHF 5993 vs Ultibro® in COPD Patients

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— TRIBUTE  

Official title:

52-week, Double Blind, Randomized, 2 Active Parallel Arms Study of Fixed Combination CHF 5993 Administered vs Ultibro® in COPD Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02579850
• Other study ID #: CCD-05993AA1-08
• Secondary ID: 2014-001704-22
• Status: Completed
• Phase: Phase 3
• Start date: May 29, 2015
• Est. completion date: July 10, 2017

Study information

• Verified date: October 2021
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1532
• Est. completion date: July 10, 2017
• Est. primary completion date: July 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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 ß-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, 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

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• CHF 5993 + Ultibro matched placebo
Active medication treatment CHF 5993 and Ultibro matched placebo administered twice a day
• Ultibro + CHF 5993 matched placebo
Active medication treatment Ultibro and CHF 5993 matched placebo administered twice a day

Procedure:
• Central spirometry
Central spirometry to assess forced expiratory volume at one second and forced vital capacity

Other:
• COPD assessment test
COPD assessment test (CAT) at visit 1

Procedure:
• Local laboratory Assessments
ECG + Standard Haematology and Biochemistry

Other:
• Saint George's Respiratory Questionnaire
Saint George's Respiratory Questionnaire
• EXACT-pro questionnaire
daily from randomization (Visit 2) to end of study (Visit 7)

Locations

Country	Name	City	State
Italy	Chiesi Farmaceutici S.p.A.	Parma

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Papi A, Petruzzelli S, Vezzoli S, Georges G, Fabbri LM. Triple therapy for all patients with severe symptomatic COPD at risk of exacerbations. Eur Respir J. 2019 Apr 18;53(4). pii: 1900147. doi: 10.1183/13993003.00147-2019. Print 2019 Apr. — View Citation

Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, Guasconi A, Montagna I, Vezzoli S, Petruzzelli S, Scuri M, Roche N, Singh D. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE) — View Citation

Singh D, Fabbri LM, Corradi M, Georges G, Guasconi A, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation. Eur Respir J. 2019 May 18;53(5). pii: 1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May. — View Citation

Singh D, Fabbri LM, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019. — View Citation

Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018 Dec 12;13:3971-3981. doi: 10.2147/COPD.S185975. eCollection 2018. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Moderate and severe COPD exacerbation rate over 52 weeks of treatment	Exacerbations will be evaluated at each study visit and collected using EXACT-PRO filled-in by patient every day throughout the study	1 year
Secondary	Time to first moderate to severe COPD exacerbation		1 year
Secondary	Rate of severe COPD exacerbation over 52 weeks of treatment		1 year
Secondary	Rate of moderate COPD exacerbation over 52 weeks of treatment		1 year
Secondary	Change from Baseline at each visit and over the entire treatment period in pre-dose morning FEV1		1 year

External Links

•   CSR Synopsis available in the CHIESI Clinical Study Register
•   Study Record on EU Clinical Trials Register including results