TRIMBOW® and RELVAR® on Lung Stiffness Reduction Assessed Through Forced Oscillation Technique in Patients With COPD

NCT04671355 | Withdrawn Phase 4

• 2 other identifiers: CLI-05993AA1-212019-002744-24
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Efficacy of TRIMBOW® pMDI and RELVAR® ELLIPTA® DPI on lung stiffness reduction assessed through area under the reactance curve (AX) using oscillometry in chronic obstructive pulmonary disease (COPD).

Conditions

COPD

Keywords

Small Airways Disorders and Forced Oscillation Technique

Outcome Measures

Primary Outcomes (1)

• Oscillometry - Reactance (AX)

  Area under the curve of Reactance (AX) 5-120 minutes post-dose

  4 weeks

Secondary Outcomes (7)

• Oscillometry - Resistance at 5 Hertz (R5)

  4 weeks

• Spirometry - Forced Expiratory Volume in the first second

  4 weeks

• Health status

  4 weeks

• Safety monitoring - incidence of adverse events (AEs) and adverse drug reactions (ADRs)

  Overall study period and by Treatments (4 weeks)

• Oscillometry - Resistance at 19 Hertz (R19) and 20 Hertz (R20)

  4 weeks

Study Arms (2)

Trimbow

EXPERIMENTAL

Pressurized metered dose inhaler

Drug: Beclometasone Dipropionate / Formoterol Fumarate / Glycopyrronium 100/6/10 mcg

Relvar

ACTIVE COMPARATOR

Dry powder inhaler

Drug: Fluticasone Furoate / Vilanterol Trifenatate 100/25 mcg

Interventions

Beclometasone Dipropionate / Formoterol Fumarate / Glycopyrronium 100/6/10 mcg DRUG

Pressurized metered dose inhaler

Trimbow

Fluticasone Furoate / Vilanterol Trifenatate 100/25 mcg DRUG

Dry powder inhaler

Relvar

Eligibility Criteria

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

You may qualify if:

• Patient's written informed consent obtained prior to any study related procedures.
• Male or female patients aged 40 years and above.
• 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 \[pack-years = (number of cigarettes per day x number of years)/20\]. If patients underwent any kind of smoking cessation therapy, it should be finished at least 2 months prior to screening.
• A post-bronchodilator FEV1 \<60 % of the predicted normal value and a post-bronchodilator FEV1/FVC \< 0.7 within 30 min after 4 puffs (4 x 100 µg) of salbutamol pMDI.
• If this criterion is not met at screening, the test can be repeated once before randomisation.
• Patients under double or triple therapy for at least 2 months prior to screening visit in stable doses and regimens with either:
• inhaled corticosteroids/long-acting β2-agonist combination (ICS/LABA) (fixed or free), or
• inhaled corticosteroids/long-acting muscarinic antagonist free combination (ICS/LAMA), or
• Inhaled long-acting β2-agonist / long-acting muscarinic antagonist (LABA/LAMA) (fixed or free), or
• fixed or free combination of an inhaled corticosteroid /long-acting β2-agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA)
• A cooperative attitude and ability to correctly use the study inhalers and spacer.
• Female patients must be 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) fulfilling one of the following criteria:
• WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up contact or
• WOCBP with non-fertile male partners (contraception is not required in this case).For the definition of WONCBP, WOCBP, fertile men, and the list of highly effective birth control methods, refer to Appendix 3 (or section 4.1 of the CTFG guidance).
• Any postmenopausal women (physiologic menopause defined as "12 consecutive months of amenorrhea") or women permanently sterilized (e.g. bilateral oophorectomy, hysterectomy or bilateral salpingectomy) may be enrolled in the Study.

You may not qualify if:

• 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 of the highly effective birth control method as reported in Appendix 3 (or section 4.1 of the CTFG guidance).
• Diagnosis of asthma.
• Patients requiring use of the following medications:
• i. A course of systemic steroids longer than 3 days for COPD exacerbation in the 4 weeks prior to screening.
• ii. A longer than 7-day course of antibiotics for the treatment of COPD exacerbation in the 4 weeks prior to screening.
• iii. Use of antibiotics for a lower respiratory tract infection (e.g pneumonia) in the 4 weeks prior to screening.
• COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period.
• Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
• 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 alfa-1 antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease.
• Patients who have clinically severe cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV, left ventricular failure, acute myocardial infarction, 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 ECG which may impact the safety of the patient according to investigator's judgement. Patients whose electrocardiogram (ECG) (12 lead) shows QTcF \>450 ms for males or QTcF \>470 ms for females at screening or at randomisation visits are not eligible. The QTcF criterion should not be applicable to patients with pacemaker or permanent atrial fibrillation.
• 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.
• History of hypersensitivity to anticholinergics, 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.
• 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.
• 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 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.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Related Links

• EMA Register - EudraCT results section

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Beclomethasone; Formoterol Fumarate; Glycopyrrolate; fluticasone furoate

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Quaternary Ammonium Compounds; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Brian Lipworth, MD

  Ninewells Hospital, University of Dundee, Scotland, UK

  STUDY DIRECTOR

• Catherine Jackson, MD

  University of Central Lancashire, Burnley, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: December 17, 2020
• Study Start: October 4, 2021
• Primary Completion: December 22, 2021
• Study Completion: February 18, 2022
• Last Updated: February 3, 2022

Record last verified: 2022-01

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.