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

NCT02579850 | Completed Phase 3

• 2 other identifiers: CCD-05993AA1-082014-001704-22
• Study Type: interventional
• Target: 1,532
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD; COPD Exacerbation; EXACT-PRO

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Time to first moderate to severe COPD exacerbation

  1 year

• Rate of severe COPD exacerbation over 52 weeks of treatment

  1 year

• Rate of moderate COPD exacerbation over 52 weeks of treatment

  1 year

• Change from Baseline at each visit and over the entire treatment period in pre-dose morning FEV1

  1 year

Study Arms (2)

CHF 5993 + Ultibro matched placebo

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

Drug: CHF 5993 + Ultibro matched placebo; Procedure: Central spirometry; Other: COPD assessment test; Procedure: Local laboratory Assessments; Other: Saint George's Respiratory Questionnaire; Other: EXACT-pro questionnaire

Ultibro + CHF 5993 matched placebo

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

Drug: Ultibro + CHF 5993 matched placebo; Procedure: Central spirometry; Other: COPD assessment test; Procedure: Local laboratory Assessments; Other: Saint George's Respiratory Questionnaire; Other: EXACT-pro questionnaire

Interventions

CHF 5993 + Ultibro matched placebo DRUG

Active medication treatment CHF 5993 and Ultibro matched placebo administered twice a day

Also known as: CHF 5993

CHF 5993 + Ultibro matched placebo

Ultibro + CHF 5993 matched placebo DRUG

Active medication treatment Ultibro and CHF 5993 matched placebo administered twice a day

Also known as: Ultibro Breezhaler

Ultibro + CHF 5993 matched placebo

Central spirometry PROCEDURE

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

CHF 5993 + Ultibro matched placebo; Ultibro + CHF 5993 matched placebo

COPD assessment test OTHER

COPD assessment test (CAT) at visit 1

CHF 5993 + Ultibro matched placebo; Ultibro + CHF 5993 matched placebo

Local laboratory Assessments PROCEDURE

ECG + Standard Haematology and Biochemistry

CHF 5993 + Ultibro matched placebo; Ultibro + CHF 5993 matched placebo

Saint George's Respiratory Questionnaire OTHER

Saint George's Respiratory Questionnaire

CHF 5993 + Ultibro matched placebo; Ultibro + CHF 5993 matched placebo

EXACT-pro questionnaire OTHER

daily from randomization (Visit 2) to end of study (Visit 7)

CHF 5993 + Ultibro matched placebo; Ultibro + CHF 5993 matched placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Chiesi Farmaceutici S.p.A.

Parma, 43123, Italy

Location

Related Publications (5)

• 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.

  PMID: 30587953 BACKGROUND

• 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.

  PMID: 30880943 BACKGROUND

• 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):1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May.

  PMID: 30792343 BACKGROUND

• 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):1900147. doi: 10.1183/13993003.00147-2019. Print 2019 Apr. No abstract available.

  PMID: 31000665 BACKGROUND

• 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): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-1084. doi: 10.1016/S0140-6736(18)30206-X. Epub 2018 Feb 9.

  PMID: 29429593 RESULT

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mario Scuri, MD

  Chiesi Farmaceutici S.p.A.

  STUDY CHAIR

• Nicolas Roche, Pr

  Hopitaux Universitaires Paris Centre - Groupe Hospitalier Cochin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: October 20, 2015
• Study Start: May 29, 2015
• Primary Completion: July 10, 2017
• Study Completion: July 10, 2017
• Last Updated: October 29, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.

Locations

IT (1)