CTRI/2025/08/092238 [Registered on: 04/08/2025] Trial Registered Prospectively
Last Modified On:
03/11/2025
Post Graduate Thesis
Yes
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A phase III trial to evaluate the Efficacy and Safety of test and reference product in moderate-severe COPD patient.
Scientific Title of Study
Efficacy and Safety of Single-Inhaler Triple Therapy (SITT) of Glycopyrronium, Formoterol Fumarate Dihydrate and Fluticasone Propionate MDI versus SITT of Budesonide Glycopyrronium and Formoterol Fumarate Dihydrate MDI in moderate-severe COPD patients: A Multi-center, Randomized, Open-label, Comparative, Parallel Group Study.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
Study Code CT/24/010, Version No Final 00, Date 29/01/25
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Pramod Kadam
Designation
Project Head
Affiliation
Lupin Ltd.
Address
3rd Floor, Kalpataru Inspire, Off Western Express Highway,
Santacruz East
Male or female patients, aged more than equal to 18 to less than equal to 75 years at screening
Patients with a diagnosis of COPD (as defined by the GOLD COPD report 2025)
Post-bronchodilator FEV1 more than equal to 30 percentage and less than 80 percentage of the predicted normal value and post-bronchodilator FEV1-FVC (forced vital capacity) ratio 0.70
A modified Medical Research Council dyspnea scale (mMRC) grade 2
COPD Assessment Test (CAT) score more than equal to 10 even after receiving at least two inhaled maintenance therapies (LABA + LAMA or LABA + ICS) for at least 4-6 weeks at the time of screening.
History of exacerbations (more than equal to 2 moderate or more than equal to 1 severe exacerbation) of COPD within 12 months before screening.
Subjects on inhaled corticosteroid (ICS) with or without a long-acting Beta 2 agonist (LABA) (as a free or fixed combination), or ICS with a long-acting muscarinic antagonist (LAMA), or LABA with LAMA (as a free or fixed combination), or LAMA monotherapy as maintenance treatment for at least 1 month before screening.
Willingness to give their written informed consent to participate in the study and willingness to comply with study requirements and procedures.
Female subjects with negative pregnancy tests, and agreed to use adequate forms of non hormonal contraception during the study (i.e. women of childbearing potential used a highly effective method of birth control, such as condom and spermicide, diaphragm or cervical cap and spermicide, condom and diaphragm or cervical cap, non hormonal IUD), or females who were of non child bearing potential i.e. who were surgically sterile (history of hysterectomy or bilateral tubal ligation or bilateral oophorectomy; partial hysterectomy is not sufficient or vasectomized partner) or postmenopausal (12 months of spontaneous amenorrhea), or who agreed to remain abstinent.
Ability to use metered dose inhaler independently and correctly as instructed by the investigator
ExclusionCriteria
Details
1. Patient unable to perform study procedures or not willing to give informed consent
2. Patients already receiving triple drug treatment with LABA+LAMA+ICS (either in the form of SITT or MITT)
3. Patients with co-existing comorbidity such as tuberculosis, alpha-1 antitrypsin deficiency, cystic fibrosis, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, pulmonary edema, or interstitial lung disease
4. Evidence or history of other clinically significant cardiovascular disease or abnormality (such as, but not limited to, congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infraction, arrhythmia, long QT syndrome, atrial fibrillation), renal, neurological, endocrine, immunological, psychiatric, hepatic, or hematological disease or abnormality which, in the opinion of the investigator, will clinically significant and have put the patient at risk through study participation, or would have affected the study analyses if the disease exacerbates during the study
5. Significant abnormality that suggests chest disease other than COPD, on chest X-ray or computed tomography (CT) scan taken within six months before screening. If there was no chest X-ray/CT scan taken within six months prior to screening, a chest X-ray will be performed during screening to rule out any other significant abnormality.
6. History of paradoxical bronchospasm, narrow-angle glaucoma, prostatic hyperplasia, bladder neck obstruction, severe renal impairment or urinary retention, or any other condition, which, in the opinion of the investigator, would have contraindicated the use of an anticholinergic or long-acting beta agonist agent
7. History of allergy or hypersensitivity to any of the ingredients of study drugs or components of the delivery system
8. Hospitalization for COPD exacerbation or pneumonia within three months prior to screening.
9. Use of oral/parenteral corticosteroids or antibiotics for COPD exacerbation within six weeks prior to screening.
10. A clinically significant abnormal electrocardiogram (ECG) at screening.
11. Lung volume reduction surgery within 12 months prior to the initiation of the study.
12. Requirement of long-term (12 hours daily) oxygen therapy.
13. Unable to stop the following medications at the defined times prior to screening spirometry:
a. Ipratropium or ipratropium/salbutamol combination product-8 hours, Inhaled short-acting beta-agonists 6 hours, Oral beta2-agonists 48 hours, Long-acting beta-agonists (salmeterol and formoterol) or ICS/LABA combination products-48 hours,
b. Xanthines- 48 hours, Cromolyn and nedocromil inhalers 24 hours
c. Zafirlukast, montelukast, zileuton- 48 hours
d. Long-acting anticholinergics (Tiotropium etc.)-48 hours
e. Oral or parenteral corticosteroids- 6 weeks
f. Any other investigational medication 30 days or 5 half-lives of the investigational drug (whichever is longer),
g. Depot corticosteroids- 3 months,
h. Inhaled corticosteroids (ICS)- Washout not required
14. Currently enrolled in another interventional clinical study or have used any IPs, study drug, or device within 30 days or 5 times the half-life, whichever is longer preceding informed consent or scheduled to participate in another clinical study involving an IP.
15. Patients who are currently taking alcohol products.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of SITT of Glycopyrronium, Formoterol Fumarate and Fluticasone Propionate MDI versus SITT of Budesonide, Glycopyrronium and Formoterol Fumarate Dihydrate MDI in moderate to severe COPD patients.
Mean change of FEV1 test from baseline to end of week 12.
Secondary Outcome
Outcome
TimePoints
To evaluate the safety of SITT of Glycopyrronium, Formoterol Fumarate & Fluticasone Propionate MDI versus SITT of Budesonide, Glycopyrronium & Formoterol Fumarate Dihydrate MDI in moderate to severe COPD patients.
Mean change of FEV1 test from baseline to end of week 4
Mean change of 2 hours post-dose FEV1 from baseline to week 12
Proportion of patients with COPD exacerbations during the treatment period of 12 Weeks
Mean change of mMRC Dyspnea score from baseline to week 4 & week 12 & CAT score from baseline to week 12.
Proportion of patients with COPD related hospitalization during the treatment period of 12 weeks.
Proportion COPD related/all cause death during the treatment period of 12 weeks.
Target Sample Size
Total Sample Size="230" Sample Size from India="230" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Chronic obstructive pulmonary disease (COPD)
is a progressive chronic disease which is subject to acute exacerbations. COPD
is a multicomponent integration of chronic and progressive illnesses,
characterized by airway obstruction, inflammation, hyperinflation and acute-on-chronic
exacerbations. Airway obstruction in COPD is an important cause of exertional
breathlessness. It slowly progresses to marked disability and respiratory failure
to limit the daily activities of an individual, finally confining him to bed.
COPD
is a multicomponent disease that affects the systems and organs outside the
lungs. These systemic effects of COPD include weight loss, muscle dysfunction
and cardiovascular disease. The subjects with COPD have a lower physical
activity level even earlier in the disease process.
The Purpose of the study
is to Efficacy and Safety of Single-Inhaler Triple Therapy (SITT) of
Glycopyrronium, Formoterol Fumarate Dihydrate and Fluticasone Propionate MDI
versus SITT of Budesonide, Glycopyrronium and Formoterol Fumarate Dihydrate MDI
in moderate-severe COPD patients