Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05573464
Other study ID # D5985C00003
Secondary ID 2022-001476-33
Status Completed
Phase Phase 3
First received
Last updated
Start date September 27, 2022
Est. completion date March 26, 2024

Study information

Verified date April 2024
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a 12-week (with an extension to 52 weeks in a subset of participants) study comparing the safety of BGF MDI HFO twice daily (BID) with BGF MDI HFA BID in participants with moderate to very severe COPD.


Description:

This is a Phase 3 randomized, double-blind, 12-week (with an extension to 52 weeks in a subset of participants) study comparing the safety of BGF MDI HFO 320/14.4/9.6 μg twice daily (BID) with BGF MDI HFA 320/14.4/9.6 μg BID in participants with moderate to very severe COPD. For the 12-week study, 542 participants will be randomized to treatments BGF MDI HFO and BGF MDI HFA in a 1:1 ratio. Randomization will be stratified by region (Americas, Europe) and COPD disease severity (percent predicted FEV1 ≥ 50%, percent predicted FEV1 < 50%). Subsequently, the 120 participants per treatment arm who were randomized to the extended study will continue and remain on the randomized treatment to 52 weeks.


Recruitment information / eligibility

Status Completed
Enrollment 558
Est. completion date March 26, 2024
Est. primary completion date March 26, 2024
Accepts healthy volunteers No
Gender All
Age group 40 Years to 80 Years
Eligibility Inclusion Criteria: 1. Participant must be 40 to 80 years of age inclusive, at the time of signing the ICF; 2. Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004) or by locally applicable guidelines; 3. Participants who have been regularly using dual ICS/LABA, LAMA/LABA, or ICS/LAMA/LABA (open or fixed-dose combinations) inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening; 4. Participants who have pre-bronchodilator FEV1 of < 80% predicted normal at Visit 1; 5. Participants who have post-bronchodilator FEV1/FVC ratio of < 0.70 and post-bronchodilator FEV1 of = 25% to < 80% predicted normal at Visit 2; 6. Participants who have CAT score = 10 at Visit 1; 7. Participants who are current/former smokers with a history of at least 10 pack-years of tobacco smoking (1 pack year = 20 cigarettes smoked per day for 1 year); 8. Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol; 9. Participants must be able to demonstrate acceptable MDI administration and spirometry technique; 10. Participants who are willing to remain at the study center as required per protocol to complete all visit assessments; 11. Females must either be not of childbearing potential, or using a form of highly effective birth control as defined below: - Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply: - Women < 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 and follicle stimulating hormone levels in the postmenopausal range. - Women = 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. 12. 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 1% per year when used consistently and correctly. At enrollment, women of childbearing potential who are sexually active with a non-sterilized male partner should be stable on their chosen method of highly effective birth control, as defined below, and willing to remain on the birth control until at least 14 days after 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 amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together. - All women of childbearing potential must have a negative serum pregnancy test result at Visit 1 - Women <50 years of age with amenorrhea for 12 months without an alternative medical cause must have a serum LH and FSH test (within 21-28 days before Visit 3) for study eligibility Highly effective birth control methods are listed below: - Sexual abstinence defined as complete abstinence from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant - Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: - Oral - Intravaginal - Transdermal - Progestogen-only hormonal contraception associated with inhibition of ovulation: - Oral - Injectable - Implantable - Intrauterine device or intrauterine hormone-releasing system - Male partner sterilization/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 semen analysis or medical history interview provided by her or her partner. - Bilateral tubal ligation 13. 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 Exclusion Criteria: 1. Participants who have a documented history of physician-diagnosed asthma in the opinion of the Investigator based on thorough review of medical history and medical records, within 5 years of Visit 1; 2. Participants who have COPD due to a1-Antitrypsin Deficiency; 3. Participants with historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary. Significant is defined as any uncontrolled disease or 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 analyses; 4. Sleep apnea that, in the opinion of the Investigator, cannot be controlled; 5. Other respiratory disorders including known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high resolution CT evidence of bronchiectasis that causes repeated acute exacerbations), immune deficiency disorders, severe neurological disorders affecting control of the upper airway, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease; 6. Participant with moderate or severe COPD exacerbation or respiratory infection ending within 4 weeks prior to Visit 1 or during the Screening period; 7. Participant who has had a SARS-CoV-2 infection in the 8 weeks prior to Visit 1 or during the Screening Period or that required hospitalization at any time prior to Visit 1 or during the Screening Period; 8. Pulmonary resection or lung volume reduction surgery during the 26 weeks (6 months) prior to Visit 1 (ie, lobectomy, bronchoscopy lung volume reduction [endobronchial blockers, airway bypass, endobronchial valves, thermal vapor ablation, biological sealants, and airway implants]); 9. Long-term oxygen therapy; 10. Imminent life-threatening COPD (eg, need for mechanical ventilation); 11. Participant who has significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator; 12. Participant with narrow angle glaucoma not adequately treated and/or 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 analogs. 13. Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant; Note: Participants with trans-urethral resection of prostate or full resection of the prostate within 26 weeks (6 months) prior to Visit 1 are excluded from the study 14. 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 not exclusionary 15. Known history of drug or alcohol abuse within 52 weeks (12 months) of Visit 1; 16. Unable to withhold short-acting bronchodilators for 6 hours prior to lung function testing at each applicable study visit; 17. Participant is unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods; 18. Using any herbal products either by inhalation or nebulizer within 2 weeks of Visit 1 and does not agree to stop for the duration of the study; 19. Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI; 20. Participation in another clinical study with an intervention administered in the last 30 days or 5 half-lives, whichever is longer; 21. Previous randomization in any study using BGF MDI HFO (budesonide/glycopyrronium/formoterol fumarate - HFO); 22. Participants with calculated eGFR = 30 mL/minute/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; 23. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study; Note: Participants with ECG QTcF interval (corrected for heart rate using Fridericia's formula [QTcF]) > 480 msec will be excluded. Participants with high degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker will also be excluded. 24. Planned hospitalization during the study; 25. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); 26. Study Investigators, sub-Investigators, coordinators, and their employee or immediate family members; 27. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements; 28. For women only - currently pregnant (confirmed with positive pregnancy test), breast feeding, or planned pregnancy during the study or women of childbearing potential not using acceptable contraception measures (see Inclusion criterion 12 in Section 5.1).

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
BGF MDI HFO 320/14.4/9.6 µg
Budesonide, Glycopyrronium, and Formoterol Fumarate
BGF MDI HFA 320/14.4/9.6 µg
Budesonide, Glycopyrronium, and Formoterol Fumarate

Locations

Country Name City State
Argentina Research Site Buenos Aires
Argentina Research Site Buenos Aires
Argentina Research Site Quilmes
Argentina Research Site Rosario
Argentina Research Site San Fernando
Bulgaria Research Site Blagoevgrad
Bulgaria Research Site Dupnitsa
Bulgaria Research Site Lom
Bulgaria Research Site Pernik
Bulgaria Research Site Sandanski
Bulgaria Research Site Sevlievo
Bulgaria Research Site Sofia
Bulgaria Research Site Veliko Tarnovo
Bulgaria Research Site Vidin
Canada Research Site Ajax Ontario
Canada Research Site Burlington Ontario
Canada Research Site Guelph Ontario
Canada Research Site Montreal Quebec
Canada Research Site Quebec
Canada Research Site Quebec
Canada Research Site Quebec
Canada Research Site St Charles Borromee Quebec
Canada Research Site Trois-Rivières Quebec
Canada Research Site Truro Nova Scotia
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Dresden
Germany Research Site Elsterwerda
Germany Research Site Essen
Germany Research Site Halle
Germany Research Site Hamburg
Germany Research Site Hannover
Germany Research Site Hannover
Germany Research Site Hannover
Germany Research Site Karlsruhe
Germany Research Site Koblenz
Germany Research Site Magdeburg
Germany Research Site Rheine
Germany Research Site Schwerin
Germany Research Site Wiesbaden
Germany Research Site Witten
Mexico Research Site Cuernavaca
Mexico Research Site Culiacán
Mexico Research Site Merida
Mexico Research Site México
Mexico Research Site Monterrey
Poland Research Site Bedzin
Poland Research Site Bydgoszcz
Poland Research Site Grodzisk Mazowiecki
Poland Research Site Inowroclaw
Poland Research Site Jelenia Góra
Poland Research Site Kraków
Poland Research Site Lódz
Poland Research Site Lublin
Poland Research Site Piaseczno
Poland Research Site Skórzewo
Poland Research Site Szczecin
Poland Research Site Zamosc
Turkey Research Site Ankara
Turkey Research Site Istanbul
Turkey Research Site Izmir
Turkey Research Site Mersin
Turkey Research Site Pamukkale
United Kingdom Research Site Blackpool
United Kingdom Research Site Corby
United Kingdom Research Site Liverpool
United Kingdom Research Site Poole
United Kingdom Research Site Thetford
United States Research Site Anderson South Carolina
United States Research Site Charlotte North Carolina
United States Research Site Columbia South Carolina
United States Research Site Crowley Louisiana
United States Research Site Dublin Ohio
United States Research Site Gaffney South Carolina
United States Research Site Grants Pass Oregon
United States Research Site Longview Texas
United States Research Site McKinney Texas
United States Research Site Miami Florida
United States Research Site Newport Beach California
United States Research Site North Dartmouth Massachusetts
United States Research Site Phoenix Arizona
United States Research Site Portland Oregon
United States Research Site Richmond Virginia
United States Research Site Saint Louis Missouri
United States Research Site Sarasota Florida
United States Research Site Tampa Florida
United States Research Site Valparaiso Indiana
United States Research Site Wilmington North Carolina

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Germany,  Mexico,  Poland,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number (and percentage) of participants with adverse Events - AEs (including SAEs, DAEs, AEOSIs, non-serious AEs) To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: AEs (including SAEs, DAEs, AEOSIs, non-serious AEs) Over 16 or 56 Weeks (if attending 56 weeks study)
Primary Number (and percentage) of participants with potentially clinically significant changes in Digital 12-lead Holter electrocardiogram (ECG) To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: Digital 12-lead Holter electrocardiogram (ECG) Week 0 and week 12
Primary Number (and percentage) of participants with potentially clinically significant changes in 12-lead ECG To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: 12-lead ECG Week 4, 8 and 52 (if attending 56 weeks study)
Primary Number (and percentage) of participants with potentially clinically significant changes in laboratory values (hematology, clinical chemistry and urinalysis) To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: Clinical laboratory testing Week 0, 12 and 52 (if attending 56 weeks study)
Primary Number (and percentage) of participants with potentially clinically significant changes in Blood Pressure To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: Blood Pressure Over 14 or 54 weeks (if attending 56 weeks study)
Primary Number (and percentage) of participants with potentially clinically significant changes in pulse rate To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: pulse rate Over 14 or 54 weeks (if attending 56 weeks study)
Primary Number (and percentage) of participants with potentially clinically significant changes in respiratory rate To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: respiratory rate Over 14 or 54 weeks (if attending 56 weeks study)
Primary Number (and percentage) of participants with potentially clinically significant changes in body temperature To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: body temperature Over 14 or 54 weeks (if attending 56 weeks study)
See also
  Status Clinical Trial Phase
Completed NCT03282019 - Study of Long-term HFNC for COPD Patients With HOT N/A
Recruiting NCT06040086 - Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations Phase 3
Not yet recruiting NCT06376994 - Multi-Center Clean Air Randomized Controlled Trial in COPD Phase 3
Completed NCT02926534 - Cross-Sectional Study of COPD Prevalence Among Smokers, Ex-smokers and Never-Smokers in Almaty, Kazakhstan N/A
Completed NCT02797392 - Feasibility of a Preventive Program Against Lifestyle Related Diseases N/A
Completed NCT02728674 - Management of Patients With Respiratory Symptoms in Sweden N/A
Recruiting NCT02415478 - Bronchioscopic Lung Volume Reduction (BLVR) N/A
Completed NCT02774226 - Long Term Nitric Oxide Bioavailability on Vascular Health in Chronic Obstructive Pulmonary Disease Phase 2
Completed NCT02512510 - Efficacy Study of Nebulized TD-4208 for Chronic Obstructive Pulmonary Disease (COPD) Phase 3
Completed NCT02459080 - Efficacy Study of Nebulized TD-4208 for Chronic Obstructive Pulmonary Disease (COPD) Phase 3
Completed NCT02518139 - A 52-Week Parallel Group Safety Study of TD-4208 in Chronic Obstructive Pulmonary Disease (COPD) Phase 3
Completed NCT03487406 - Anti-platelet Therapy in the Prevention of Cardiovascular Disease in Patients With COPD (APPLE-COPD: ICON 2) Phase 2
Completed NCT01908140 - Study of Aclidinium Bromide/Formoterol Fumarate Compared With Salmeterol/Fluticasone Propionate in Patients With Chronic Obstructive Pulmonary Disease (COPD) Phase 3
Completed NCT01893476 - A Pragmatic Cluster Trial of a Tailored Intervention to Improve COPD Management N/A
Completed NCT01615484 - Ex-vivo Perfusion and Ventilation of Lungs Recovered From Non-Heart-Beating Donors to Assess Transplant Suitability N/A
Withdrawn NCT01908933 - Study of the AeriSeal System Treatment in Patients With Advanced Non-Upper Lobe Predominant Heterogeneous Emphysema Phase 3
Completed NCT01701869 - Microbiology & Immunology of the Chronically-inflamed Airway N/A
Recruiting NCT02527486 - Seoul National University Airway Registry N/A
Withdrawn NCT01377428 - Efficacy of Indacaterol 150 µg Versus Formoterol Phase 4
Terminated NCT01388920 - Efficacy and Safety Study of Tesamorelin in Chronic Obstructive Pulmonary Disease (COPD) Subjects With Muscle Wasting Phase 2