CHF5993 and CHF1535 pMDI on Lung Hyperinflation and Exercise Endurance Time in Subjects With COPD

NCT05097014 | Completed Phase 4

• 2 other identifiers: CLI-05993AA1-172020-004718-36
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Double Blind, Multinational, Multicentre, Randomised, Placebo-Controlled, 3-Way Cross-Over Study To Evaluate The Effect Of A Triple Combination Of Beclometasone Dipropionate And Formoterol Fumarate Plus Glycopyrronium (CHF5993) And A Dual Combination Of Beclometasone Dipropionate Plus Formoterol Fumarate (CHF1535) Both Administered Via pMDI On Lung Hyperinflation And Exercise Endurance Time In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Lung hyperinflation, exercise endurance time

Outcome Measures

Primary Outcomes (1)

• Inspiratory capacity (IC) prior to Constant Work Rate Cycle Ergometry (CWRCE) test

  Change from baseline in 2-hour post-dose

  3 weeks of treatment

Secondary Outcomes (2)

• IC at Isotime, defined as the shortest CWRCE test duration among baseline and end of treatment period.

  3 weeks of treatment

• Exercise endurance time (EET)

  3 weeks of treatment

Other Outcomes (9)

• EET between CHF5993 and CHF1535

  3 weeks of treatment

• Pre-dose morning Forced Expiratory Volume in 1 second (FEV1)

  3 weeks of treatment

• Pre-dose Forced Vital Capacity (FVC)

  3 weeks of treatment

Study Arms (3)

CHF5993

ACTIVE COMPARATOR

pMDI fixed combination product of beclometasone dipropionate (BDP) 100 µg plus 6 µg of formoterol fumarate (FF) and 10 µg of glycopyrronium (G)

Drug: CHF5993

CHF1535

ACTIVE COMPARATOR

pMDI fixed combination product beclometasone dipropionate (BDP) 100 µg plus 6 µg of formoterol fumarate (FF)

Drug: CHF1535

Matched placebo

PLACEBO COMPARATOR

Matched placebo pMDI

Other: Matched placebo

Interventions

CHF5993 DRUG

Pressurized metered dose inhaler (pMDI) 2 inhalations bid

Also known as: TRIMBOW®

CHF5993

CHF1535 DRUG

Pressurized metered dose inhaler (pMDI) 2 inhalations bid

Also known as: FOSTER®

CHF1535

Matched placebo OTHER

Pressurized metered dose inhaler (pMDI) 2 inhalations bid

Matched placebo

Eligibility Criteria

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

You may qualify if:

• A signed and dated written informed consent obtained prior to any study-related procedures.
• Outpatient population.
• Male or female subjects.
• COPD diagnosis for at least 12 months before the Screening visit in accordance with the definition by the GOLD 2020 report.
• Current or ex-smokers (who quit smoking for at least 6 months prior to Screening Visit) with a smoking history of at least 10 pack-years \[pack-years = (number of cigarettes per day x number of years)/20\]. E-cigarettes smoking cannot be used to calculate pack-year history.
• A post-bronchodilator FEV1/FVC \< 0.7 within 30 min after 4 puffs (4 x 100 µg) of salbutamol pMDI and a post-bronchodilator FEV1 ≥ 40% and \<80% of the predicted normal values. If this is not met at screening, the test can be repeated once before randomisation.
• Pre-bronchodilator functional residual capacity (FRC) of \> 120% of predicted normal FRC values at Screening visit 1. If this criterion is not met at screening, the test can be repeated once before randomisation.
• A score of \>2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1.
• Subjects on mono- or dual inhaled maintenance COPD treatment at a stable dose for at least 3 months prior to screening.
• A cooperative attitude and ability to correctly use the study inhalers.
• Female subjects must be women either of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile) or physiologically capable of becoming pregnant (i.e. women of childbearing potential (WOCBP)).
• CWRCE at Visit 1b: between 2 min and 11 min at 80% of maximum workload. In case the subject cycles for a shorter (i.e. \< 2 min) or longer (i.e. \> 11 min) period, the visit can be repeated with an adjusted workload once within a 1-week period.
• Oxygen saturation (SpO2 measured by pulse oximeter) at least 82% during the incremental exercise test (IET) performed in the run-in period.
• Subjects must be able to complete CWRCE at Visit 1b and then at Visit 2 without requirement for supplemental oxygen.

You may not qualify if:

• Pregnant or lactating women.
• Known respiratory disorders other than COPD which may impact the efficacy of the study drug according the investigator's judgment. This can include but is not limited to current diagnosis of asthma, alfa-1 antitrypsin deficiency, active tuberculosis, lung cancer, severe bronchiectasis unrelated to COPD, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease.
• Unstable concurrent disease: e.g. fever, uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; uncontrolled gastrointestinal disease (e.g. active peptic ulcer); uncontrolled cardiac disease, uncontrolled neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other which may impact the efficacy or the safety of the study drug according to investigator's judgment.
• Moderate (requiring prescriptions of systemic corticosteroids and/or antibiotics) or severe (leading to hospitalization) COPD exacerbation in the 3 and 12 months, respectively, prior to Screening visit 1 and during the run-in period.
• \. Subjects requiring long term (\> 15 hours a day) oxygen therapy for chronic hypoxemia.
• \. Subjects who have clinically severe cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class IV, left ventricular failure, myocardial infarction in the prior 6 months, not controlled arrhythmia etc.), which may impact the efficacy or the safety of the study drug according to the investigator's judgement.
• \. An abnormal and clinically significant 12-lead electrocardiogram (ECG) which may impact the safety of the subject according to investigator's judgement. Subjects whose 12-lead ECG shows QTcF \>450 ms for males or QTcF \>470 ms for females at screening visit are not eligible.
• \. History of hypersensitivity to M3 receptor 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 according to the investigator's judgement.
• \. Subjects with serum potassium levels ≤ 3.5 mEq/L (or 3.5 mmol/L) 9. Subjects with body mass index less than 15 or greater than 35 kg/m2. 10. History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
• \. Subjects with contraindications to cardiopulmonary exercise testing, including those whose exercise test is limited by non-respiratory or cardiovascular condition, e.g. by neurologic, orthopaedic, or other disorders.
• \. Participation in another clinical trial where investigational drug was received less than 30 days or 5 half-lives whichever is longer prior to screening visit.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

PAREXEL International GmbH Early Phase Clinical Unit Berlin

Berlin-Spandau, Berlin Spandauer Damm, 130 D-14050, Germany

Location

Related Publications (1)

• Watz H, Kirsten AM, Ludwig-Sengpiel A, Krull M, Mroz RM, Georges G, Varoli G, Charretier R, Cortellini M, Vele A, Galkin D. Effects of inhaled beclometasone dipropionate/formoterol fumarate/glycopyrronium vs. beclometasone dipropionate/formoterol fumarate and placebo on lung hyperinflation and exercise endurance in chronic obstructive pulmonary disease: a randomised controlled trial. Respir Res. 2024 Oct 17;25(1):378. doi: 10.1186/s12931-024-02993-x.

  PMID: 39420338 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Foster Home Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Community Health Services; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Henrik Watz, MD

  Pulmonary Research Institute at LungenClinic Grosshansdorf, German Center for Lung Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: October 27, 2021
• Study Start: October 28, 2021
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: March 24, 2023

Record last verified: 2023-03

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

DE (1)