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CTRI Number  CTRI/2024/05/068031 [Registered on: 29/05/2024] Trial Registered Prospectively
Last Modified On: 01/04/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Crossover Trial 
Public Title of Study   A study to investigate the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF), with HFA propellant compared to BGF formulated with a new propellant (HFO) in Chronic Obstructive Pulmonary Disease patients 
Scientific Title of Study   A Randomised, Placebo-controlled, Double-blind, Multi-centre, 4-week, 3-way Crossover Pharmacodynamic Study to Assess the Equivalence of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFO Compared With BGF Delivered by MDI HFA in Participants With Chronic Obstructive Pulmonary Disease 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
2023-506565-57-00  EudraCT 
D5985C00002 Version 1.0 dated 17 August 2023  Protocol Number 
NCT06075095  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Tapankumar M Shah 
Designation  Senior Director Cluster Head SMM BioPharmaceuticals R&D BioPharmaceuticals 
Affiliation  AstraZeneca Pharma India Ltd  
Address  AstraZeneca Pharma India Ltd Block N1 12th Floor Manyata Embassy Business Park Rachenahalli Outer Ring Road Bangalore

Bangalore
KARNATAKA
560045
India 
Phone  9535104975  
Fax    
Email  Tapankumar.shah@astrazeneca.com  
 
Details of Contact Person
Scientific Query  
Name  Tapankumar M Shah 
Designation  Senior Director Cluster Head SMM BioPharmaceuticals R&D BioPharmaceuticals 
Affiliation  AstraZeneca Pharma India Ltd  
Address  AstraZeneca Pharma India Ltd Block N1 12th Floor Manyata Embassy Business Park Rachenahalli Outer Ring Road Bangalore


KARNATAKA
560045
India 
Phone  9535104975  
Fax    
Email  Tapankumar.shah@astrazeneca.com  
 
Details of Contact Person
Public Query  
Name  Tapankumar M Shah 
Designation  Senior Director Cluster Head SMM BioPharmaceuticals R&D BioPharmaceuticals 
Affiliation  AstraZeneca Pharma India Ltd  
Address  AstraZeneca Pharma India Ltd Block N1 12th Floor Manyata Embassy Business Park Rachenahalli Outer Ring Road Bangalore


KARNATAKA
560045
India 
Phone  9535104975  
Fax    
Email  Tapankumar.shah@astrazeneca.com  
 
Source of Monetary or Material Support  
AstraZeneca AB,151 85 Södertälje, Sweden 
 
Primary Sponsor  
Name  AstraZeneca AB 
Address  151 85 Sodertalje Sweden 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
AstraZeneca Pharma India Ltd  Block N1 12th Floor Manyata Embassy Business Park Rachenahalli Outer Ring Road Bangalore 560045 Karnataka 
 
Countries of Recruitment     Argentina
Bulgaria
Canada
Hungary
India
Malaysia
Mexico
Philippines
Poland
Republic of Korea
Thailand
Turkey
United States of America
Viet Nam  
Sites of Study  
No of Sites = 7  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sharad Tikkiwal  Asthma Bhawan  Department of Pulmonary Medicine R 3 Sector 6 Vidhyadhar Nagar Jaipur 302039
Jaipur
RAJASTHAN 		 9828027022

Sharadtikkiwal@gmail.com 
Dr Parshottam Govindbhai Koradia  BAPS Pramukh Swami Hospital  Department of Medicine Shri Pramukh Swami Maharaj Marg Adajan Char Rasta Surat 395009
Surat
GUJARAT 		 9825178595

purushottam_koradia@yahoo.co.in 
Dr Anand Kumar  Dr Murari Lal Chest Hospital, GSVM Medical College  Department of Respiratory Medicine Near Rawatpur Crossing Kanpur 208002
Kanpur Nagar
UTTAR PRADESH 		 7408441501

dranandkumar.research@gmail.com 
Dr Srikanth Krishnamurthy  Hindusthan Hospital  Department of Pulmonology 522 3 523 3 Nava India Road Udaiyampalayam Coimbatore 641028
Coimbatore
TAMIL NADU 		 9894257706

drsrikanthcbe@gmail.com 
Dr Piyush Arora  Jawaharlal Nehru Medical College  Department of Respiratory Diseases Kala Bagh Ajmer 305001
Ajmer
RAJASTHAN 		 9887088122

doctor.piyusharora@gmail.com 
Dr Mohammad Shameem  Jawaharlal Nehru Medical College & Hospital Aligarh Muslim University  Department of Pulmonary Medicine Aligarh Muslim University Aligarh 202002
Aligarh
UTTAR PRADESH 		 9412731835

mshameem@myamu.ac.in 
Dr Hamsraj Alva  Vinaya Hospital and Research Centre (A Unit of KIMS)  Department of Medicine Karngalpady Mangaluru 575003
Dakshina Kannada
KARNATAKA 		 9343562622

hamsrajresearch@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 7  
Name of Committee  Approval Status 
BAPS Hospital Institutional Ethics Committee  Approved 
Ethics Committee GSVM Medical College  Approved 
Ethics Committee Vinaya Hospital  Approved 
Institutional Ethics Committee Asthma Bhawan  Approved 
Institutional Ethics Committee Jawahar Lal Nehru Medical College  Approved 
Institutional Ethics Committee Jawaharlal Nehru Medical College and Hospital AMU  Approved 
Institutional Human Ethics Committee Hindusthan Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: J449||Chronic obstructive pulmonary disease, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Budesonide Glycopyrronium and Formoterol Fumarate HFA  BGF MDI HFA 320/14.4/9.6 μg; Study interventions will be administered orally via MDI as 2 inhalations BID (every morning and evening, 160/7.2/4.8 μg per actuation, approximately 12 hours apart); Three treatment periods of approximately 4 weeks each (one period for each of 3 study interventions). 
Intervention  Budesonide Glycopyrronium and Formoterol Fumarate HFO  BGF MDI HFO 320/14.4/9.6μg; Study interventions will be administered orally via MDI as 2 inhalations BID (every morning and evening, 160/7.2/4.8 μg per actuation, approximately 12 hours apart); Three treatment periods of approximately 4 weeks each (one period for each of 3 study interventions). 
Comparator Agent  Placebo  Placebo MDI HFA; Study interventions will be administered orally via MDI as 2 inhalations BID (every morning and evening, approximately 12 hours apart); Three treatment periods of approximately 4 weeks each (one period for each of 3 study interventions). 
 
Inclusion Criteria  
Age From  40.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1.Participants must be 40 to 80 years inclusive at the time of signing the ICF. Type of Participant and Disease Characteristics
2.Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004).
3.Participants who have been receiving LABA, LAMA, LAMA/LABA, or ICS/LABA inhaled maintenance therapies for the management of their COPD for at least 4 weeks prior to Visit 1, OR Participants who have been receiving SABA, SAMA, or SABA/SAMA either scheduled or as needed for at least 4 weeks prior to Visit 1, OR Participants who are COPD treatment-naïve or have not received previously prescribed COPD treatment in the 4 weeks prior to Visit 1.
4.At Visit 1: Participants with a blood eosinophil count less than 300 cells/μL.
5.At Visit 1: Participants with a pre-bronchodilator FEV1 of less than 80percentage predicted normal.
6.At Visit 2: Participants with a post-bronchodilator FEV1/FVC ratio of less than 0.70 and a postbronchodilator FEV1 of greater than or equal 40percentage to less than 80percentage predicted normal.
7.At Visit 3 (TP 1 Day 1): Participants with a pre-dose FEV1 of less than 80percentage predicted normal that is within plus or minus 20percentage or 200 mL of their Visit 2 pre-bronchodilator FEV1 and an FEV1/FVC ratio of less than 0.70.
8.Current or former smokers with a history of at least 10 pack-years of tobacco smoking (1 pack-year equal to 20 cigarettes smoked per day for one year).
9.Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol. Sex and Contraceptive/Barrier Requirements
10.Females must not be of childbearing potential or must use a form of highly effective birth control as defined below:
a) Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:
i) Females less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) or more following cessation of exogenous hormonal treatment with FSH levels in the postmenopausal range.
ii) Females greater than or equal 50 years old would be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) or more following cessation of all exogenous hormonal treatment.
b) Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1percentage per year when used consistently and correctly. All FOCBP who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 14 days after the last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
- All FOCBP must have a negative serum pregnancy test result at Visit 1.
- Females less than 50 years of age with amenorrhoea for at least 12 months without an alternative medical cause must have a serum FSH test at Visit 1.
c) Highly effective birth control methods are listed below:
- Total sexual abstinence is an acceptable method provided it is the preferred and usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study interventions).
- Combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation:
i) Oral
ii) Intravaginal
iii) Transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation:
i) Oral
ii) Injectable
iii) Implantable
- Intrauterine device or intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Male partner sterilization or vasectomy with documentation of azoospermia prior to the female participant s entry into the study, and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel s review of participant s medical records, medical examination and or or semen analysis or medical history interview provided by her or her partner.
Informed Consent
11.Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Other Inclusion Criteria
12.Participants with calculated eGFR greater than 30 mL/min/1.73 m2 using the CKD-EPI formula.
13.Participants who demonstrate acceptable MDI administration and spirometry techniques.
14.Participants who remain compliant with placebo run-in administrations, defined as greater than or equal 80percentage of planned doses over the last 7 days prior to Visit 3, based on ePRO diary data.
15.Participants who are willing to remain at the study centre as required per protocol to complete all visit assessments.

 
 
ExclusionCriteria 
Details  Participants are excluded from the study if any of the following criteria apply.
Medical Conditions
1.Confirmed diagnosis of asthma, in the opinion of the Investigator based on thorough review of medical history and medical records.
2.COPD due to α1-antitrypsin deficiency.
3.A COPD exacerbation treated with systemic corticosteroids or antibiotics within 4 months prior to Visit 1 or during the Screening Period.
4.A COPD exacerbation that required hospitalisation within 12 months prior to Visit 1 or during the Screening Period.
5.A respiratory infection ending within 4 weeks prior to Visit 1 or beginning or ending during the Screening Period, per the Investigator s judgement.
6.Life-threatening COPD (eg, need for mechanical ventilation) at any time prior to Visit 1 or during the Screening Period.
7.A SARS-CoV-2 infection in the 8 weeks prior to Visit 1 or during the Screening Period, or that required hospitalisation at any time prior to Visit 1 or during the Screening Period.
8.Sleep apnoea that, in the opinion of the Investigator, is uncontrolled.
9.Other respiratory disorders including, but not limited to, known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high-resolution CT evidence of bronchiectasis that causes repeated acute exacerbations), severe neurological disorders affecting control of the upper airway, sarcoidosis, primary ciliary dyskinesia, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease.
10.Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.
11.Diagnosis of narrow-angle glaucoma that has not been adequately treated, or a change in vision that may be relevant, in the opinion of the Investigator.
Note: All medications approved for control of intraocular pressures are allowed, including topical ophthalmic nonselective beta-blockers and prostaglandin analogues.
12.Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant.
13.Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin are allowed.
14.Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, haematological, neurological, endocrine, gastrointestinal, or pulmonary. Immune deficiency disorders (ie, HIV infection) should be excluded even if controlled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety analysis if the disease/condition is exacerbated during the study.
15.Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI.
16.Known history of drug or alcohol abuse within 12 months of Visit 1 or known abuse at any time during the study.
17.History of QT prolongation associated with another medication that required discontinuation of that medication.
Prior/Concomitant Therapy
18.Unable to abstain from short-acting bronchodilators within 6 hours prior to lung function testing at each study visit.
19.Pulmonary resection or lung volume reduction surgery during the 6 months prior to Visit 1 (ie, lobectomy, bronchoscopic lung volume reduction [endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation, biological sealants, and airway implants]).
20.Long-term-oxygen therapy or nocturnal oxygen therapy required for greater than 15 hours per day.
Note: As-needed oxygen use is allowed.
21.Trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Visit 1.
22.Unable to abstain from any protocol-defined prohibited medications during the Screening or Treatment Periods (see Section 6.9).
23.Use of any herbal products by either inhalation or nebuliser within 2 weeks prior to Visit 1 or refusal to stop use for the duration of the study.

Prior/Concurrent Clinical Study Experience
24.Participation in another clinical study with a study intervention administered within 30 days or 5 half-lives, whichever is longer, prior to Visit 1.
Diagnostic Assessments
25.Participants with ECG QTcF interval greater than 480 milliseconds.
26.Participants with high-degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker.
27.Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, or ECG which, in the opinion of the Investigator, may put the participant at risk because of their participation in the study.
Other Exclusions
28.Planned hospitalisation during the study.
29.Involvement in the planning or conduct of the study (applies to both AstraZeneca staff and staff at the study sites).
30.Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.
31.Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
32.Previous randomisation in the present study.
33.For women only: currently pregnant (confirmed with positive pregnancy test), breastfeeding, or planned pregnancy during the study, or FOCBP not using acceptable contraception measures.
 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
Changes in FEV1 AUC 0-4: To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on lung function in COPD and to demonstrate assay sensitivity via superiority of BGF MDI HFA relative to placebo MDI HFA on lung function in COPD
Change in morning pre-dose trough FEV1: To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on lung function in COPD and to demonstrate assay sensitivity via superiority of BGF MDI HFA relative to placebo MDI HFA on lung function in COPD 		 - Change from baseline in FEV1 AUC0-4 at Day 29
- Change from baseline in morning pre-dose trough FEV1 at Day 29 
 
Secondary Outcome  
Outcome  TimePoints 
Nil  Nil 
 
Target Sample Size   Total Sample Size="240"
Sample Size from India="15" 
Final Enrollment numbers achieved (Total)= "9"
Final Enrollment numbers achieved (India)="297" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   14/06/2024 
Date of Study Completion (India) 26/07/2025 
Date of First Enrollment (Global)  11/01/2024 
Date of Study Completion (Global) 12/08/2025 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

The purpose of this study is to demonstrate that the lung function effect from orally inhaled BGF delivered via HFO propellant is equivalent to the lung function effect from orally inhaled BGF delivered via HFA propellant in participants with COPD. The study duration for each participant will be approximately 15 to 16 weeks and consist of:

  1. A screening and placebo run-in period of approximately 2 weeks prior to first dosing
  2. Three treatment periods of approximately 4 weeks each (one period for each of 3 study interventions)
  3. A final safety follow-up visit via telephone contact approximately 1 to 2 weeks after the final dose administration Participants will be provided with rescue SABA - albuterol or salbutamol to be used as needed throughout the study. Participants will attend in-clinic study visits approximately weekly during the screening/run-in period (Visits 1, 2, and 3), then every 4 weeks (Visits 4, 5, and 6) to receive take-home study treatment, measure their lung function, and assess their health and safety

Eligible participants are between 40 and 80 years of age, inclusive, who have an established clinical history of COPD as defined by the ATS/ERS. Participants are required to have an FEV1orFVC ratio of less than 0.70, have a post-bronchodilator FEV1 greater than or equal to 40percentage and less than 80percentage predicted normal value, have a blood eosinophil count less than 300 cells/μL, and be current or former cigarette smokers with a history of at least 10 pack-years. Participants must not have had a COPD exacerbation treated with oral corticosteroids or antibiotics within 4 months prior to initiation of screening, and must not have had a COPD exacerbation that required hospitalisation within 12 months prior to initiation of screening. Eligible participants are those on treatment with LABA, LAMA, LAMA/LABA (open or fixed-dose combination), ICS/LABA (open or fixed-dose combination) inhaled maintenance therapies, or SABA, SAMA, or SAMA/SABA scheduled or as-needed inhaled therapies, or who are naïve to COPD therapy.

This study will be conducted at approximately 95 sites globally. After screening, participants will be randomised 1:1:1:1:1:1 to receive study interventions in one of 6 possible treatment sequences.
 
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