Efficacy of Fixed Combination of Beclomethasone Dipropionate (BDP) + Formoterol Fumarate (FF) + Glycopyrronium Bromide (GB) (CHF 5993)Administered Via Dry Powder Inhaler (DPI) in Chronic Obstructive Pulmonary Disease (COPD) (TRI-D)

A Phase II, Multicentre, Randomised, Double-blind, Double-dummy, Active-controlled, 3-way Cross-over Study to Evaluate the Efficacy of CHF 5993 Administered Via Dry Powder Inhaler (DPI) Versus CHF 5993 Via Pressurized Metered Dose Inhaler (pMDI) and CHF 1535 pMDI in Patients With Chronic Obstructive Pulmonary Disease

The purpose of this study is to evaluate the efficacy of Fixed Combination of Beclomethasone Dipropionate + Formoterol Fumarate + Glycopyrronium Bromide Administered Via Dry Powder Inhaler in COPD

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: CHF 5993 DPI; Drug: Placebo pMDI; Drug: CHF5993 pMDI; Drug: Placebo DPI; Drug: CHF 1535 pMDI

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1680
    • Medical Center Convex EOOD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female adults (40 ≤ age ≤ 85 years) with a diagnosis of COPD;
• Current smokers or ex-smokers;
• A Post-bronchodilator FEV1 ≥30% and <80% of the predicted normal value and FEV1/FVC (Forced Vital Capacity) < 0.7;

• Patients' COPD therapy (stable regimen at least 30 days before screening) with either:

  • Inhaled corticosteroids/long-acting β2-agonist/long-acting muscarinic antagonist (free or fixed) combination
  • Inhaled corticosteroids/long-acting β2-agonist (free or fixed) combination
  • Inhaled long-acting β2-agonist/long-acting muscarinic antagonist (free or fixed) combination
  • Inhaled long-acting muscarinic antagonist alone.

Exclusion Criteria:

• Pregnant and lactating women;
• Diagnosis of asthma;
• Known respiratory disorders other than COPD;
• Patients treated for a moderate or severe COPD exacerbation within 6 weeks prior to screening or during the run-in period;
• Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia;
• Patients who have clinically significant cardiovascular condition;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CHF 5993 DPI; BDP/FF/GB DPI 100/6/12,5 mcg	Drug: CHF 5993 DPI; BDP/FF/GB DPI; Drug: Placebo pMDI; CHF 5993 pMDI matched Placebo (direct blinding of active CHF 5993 and CHF 1535 pMDIs)
Active Comparator: CHF 5993 pMDI; BDP/FF/GB pMDI 100/6/12,5 mcg	Drug: CHF5993 pMDI; BDP/FF/GB pMDI; Drug: Placebo DPI; CHF 5993 DPI matched placebo
Active Comparator: CHF 1535 pMDI; BDP/FF pMDI 100/6 mcg	Drug: Placebo DPI; CHF 5993 DPI matched placebo; Drug: CHF 1535 pMDI; BDP/FF pMDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC0-12h (Area Under the Curve for Forced Expiratory Volume in 1 second measured serially for 0-12 hours) normalised by time (L) on dosing Day 28	To demonstrate the non-inferiority between CHF 5993 DPI and CHF 5993 pMDI in terms of FEV1 AUC0-12h normalized by time, in COPD patients	Day 28
Trough FEV1 at 24 hours (L) on dosing Day 28.	To demonstrate the non-inferiority between CHF 5993 DPI and CHF 5993 pMDI in terms of trough FEV1 at 24h on dosing Day 28 in COPD patients	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in pre-dose morning FEV1 (L) on Day 28	To evaluate the efficacy of CHF 5993 DPI on other lung function parameters and clinical outcome measures.	from Baseline to Day 28
Change from baseline in FEV1 AUC0-4h normalised by time (L) on Day 28	To evaluate the efficacy of CHF 5993 DPI on other lung function parameters and clinical outcome measures.	from Baseline to Day 28
Change from baseline in FEV1 AUC0-12h normalised by time (L) on Day 1	To evaluate the efficacy of CHF 5993 DPI on other lung function parameters and clinical outcome measures.	from Baseline to Day 1

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Kai-Michael Beeh, MD, Institut fuer Atemwegsforschung GmbH, Wiesbaden, Germany

Publications and helpful links

General Publications

• Beeh KM, Kuna P, Corradi M, Viaud I, Guasconi A, Georges G. Comparison of Dry-Powder Inhaler and Pressurized Metered-Dose Inhaler Formulations of Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium in Patients with COPD: The TRI-D Randomized Controlled Trial. Int J Chron Obstruct Pulmon Dis. 2021 Jan 14;16:79-89. doi: 10.2147/COPD.S291030. eCollection 2021.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Actual): October 16, 2018
• Study Completion (Actual): March 6, 2019

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CLI-05993BA1-02; 2017-004405-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol and the full CSR, providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared Patient-level Data is anonymized to protect personally identifiable information.

Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No