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A Study to Assess the Safety of Budesonide/Glycopyrronium/Formoterol Fumarate With the Hydrofluoroolefin Propellant in Participants With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05573464
Collaborator
(none)
542
Enrollment
97
Locations
2
Arms
20.8
Anticipated Duration (Months)
5.6
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: BGF MDI HFO 320/14.4/9.6 μg
  • Drug: BGF MDI HFA 320/14.4/9.6 μg
 Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
542 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, 12-Week (With an Extension to 52 Weeks in a Subset of Participants), Multi-Center Study to Assess the Safety of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFO Compared to BGF Delivered by MDI HFA in Participants With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
Actual Study Start Date :
Sep 27, 2022
Anticipated Primary Completion Date :
Aug 16, 2023
Anticipated Study Completion Date :
Jun 21, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: BGF MDI HFO 320/14.4/9.6μg

Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFO (HFO-1234ze)

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

    		•
    Active Comparator: BGF MDI HFA 320/14.4/9.6 μg

    Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFA

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number (and percentage) of participants with adverse Events - AEs (including SAEs, DAEs, AEOSIs, non-serious AEs) [Over 16 or 56 Weeks (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: AEs (including SAEs, DAEs, AEOSIs, non-serious AEs)

    2. Number (and percentage) of participants with potentially clinically significant changes in Digital 12-lead Holter electrocardiogram (ECG) [Week 0 and week 12]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: Digital 12-lead Holter electrocardiogram (ECG)

    3. Number (and percentage) of participants with potentially clinically significant changes in 12-lead ECG [Week 4, 8 and 52 (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: 12-lead ECG

    4. Number (and percentage) of participants with potentially clinically significant changes in laboratory values (hematology, clinical chemistry and urinalysis) [Week 0, 12 and 52 (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: Clinical laboratory testing

    5. Number (and percentage) of participants with potentially clinically significant changes in Blood Pressure [Over 14 or 54 weeks (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: Blood Pressure

    6. Number (and percentage) of participants with potentially clinically significant changes in pulse rate [Over 14 or 54 weeks (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: pulse rate

    7. Number (and percentage) of participants with potentially clinically significant changes in respiratory rate [Over 14 or 54 weeks (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: respiratory rate

    8. Number (and percentage) of participants with potentially clinically significant changes in body temperature [Over 14 or 54 weeks (if attending 56 weeks study)]

      To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA: body temperature

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. 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, postovulation 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

    1. for study eligibility
    Highly effective birth control methods are listed below:

    • Sexual abstinence defined as complete abstinence from intercourse when it is the preferred and usual lifestyle of the participant (however, periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception)

    • Contraceptive subdermal implant

    • Intrauterine device or intrauterine system

    • Oral contraceptive (combined or progesterone only)

    • Injectable progestogen

    • Contraceptive vaginal ring

    • Percutaneous contraceptive patches

    • Male partner sterilization 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

    1. 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 α1-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).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Phoenix Arizona United States 85032
    2 Research Site Newport Beach California United States 92663
    3 Research Site Miami Florida United States 33175
    4 Research Site Sarasota Florida United States 34239
    5 Research Site Tampa Florida United States 33606
    6 Research Site Valparaiso Indiana United States 46383
    7 Research Site Crowley Louisiana United States 70526
    8 Research Site North Dartmouth Massachusetts United States 02747
    9 Research Site Saint Louis Missouri United States 63141
    10 Research Site Charlotte North Carolina United States 28209
    11 Research Site Wilmington North Carolina United States 28401
    12 Research Site Dublin Ohio United States 43016
    13 Research Site Grants Pass Oregon United States 97527
    14 Research Site Portland Oregon United States 97202
    15 Research Site Anderson South Carolina United States 29621
    16 Research Site Columbia South Carolina United States 29204
    17 Research Site Gaffney South Carolina United States 29340
    18 Research Site Longview Texas United States 75605
    19 Research Site McKinney Texas United States 75069
    20 Research Site Richmond Virginia United States 23219
    21 Research Site Buenos Aires Argentina C1414AIF
    22 Research Site Buenos Aires Argentina C1425BEN
    23 Research Site Quilmes Argentina B1878FNR
    24 Research Site Rosario Argentina S2000DEJ
    25 Research Site San Fernando Argentina B1646EBJ
    26 Research Site Blagoevgrad Bulgaria 2700
    27 Research Site Dupnitsa Bulgaria 2602
    28 Research Site Lom Bulgaria 3600
    29 Research Site Pernik Bulgaria 2300
    30 Research Site Sandanski Bulgaria 2800
    31 Research Site Sevlievo Bulgaria 5400
    32 Research Site Sofia Bulgaria 1618
    33 Research Site Veliko Tarnovo Bulgaria 5000
    34 Research Site Vidin Bulgaria 3700
    35 Research Site Moncton New Brunswick Canada E1G 1A7
    36 Research Site Truro Nova Scotia Canada B2N 1L2
    37 Research Site Ajax Ontario Canada L1S 2J5
    38 Research Site Burlington Ontario Canada L7N 3V2
    39 Research Site Guelph Ontario Canada N1H 6J2
    40 Research Site Mississauga Ontario Canada L4V 1P1
    41 Research Site Montreal Quebec Canada H1M 1B1
    42 Research Site St Charles Borromee Quebec Canada J6E 2B4
    43 Research Site Trois-Rivières Quebec Canada G8T 7A1
    44 Research Site Quebec Canada G1G 3Y8
    45 Research Site Quebec Canada G1V 4G5
    46 Research Site Quebec Canada G2J 0C4
    47 Research Site Berlin Germany 10629
    48 Research Site Berlin Germany 10787
    49 Research Site Berlin Germany 10969
    50 Research Site Berlin Germany 12159
    51 Research Site Berlin Germany 13156
    52 Research Site Dresden Germany 01069
    53 Research Site Elsterwerda Germany 04910
    54 Research Site Essen Germany 45359
    55 Research Site Halle Germany 06108
    56 Research Site Hamburg Germany 20253
    57 Research Site Hannover Germany 30159
    58 Research Site Hannover Germany 30449
    59 Research Site Hannover Germany D-30173
    60 Research Site Karlsruhe Germany 76137
    61 Research Site Koblenz Germany 56068
    62 Research Site Magdeburg Germany 39120
    63 Research Site Rheine Germany 48431
    64 Research Site Schwerin Germany 19055
    65 Research Site Wiesbaden Germany 65189
    66 Research Site Witten Germany 58452
    67 Research Site Cuernavaca Mexico 62290
    68 Research Site Culiacán Mexico 80200
    69 Research Site Guadalajara Mexico 44100
    70 Research Site Merida Mexico 97130
    71 Research Site Mexico City Mexico 0 3100
    72 Research Site Monterrey Mexico 64020
    73 Research Site México Mexico 03300
    74 Research Site Bydgoszcz Poland 85-231
    75 Research Site Bydgoszcz Poland 85-605
    76 Research Site Będzin Poland 42-500
    77 Research Site Grodzisk Mazowiecki Poland 05-825
    78 Research Site Inowrocław Poland 88-100
    79 Research Site Jelenia Góra Poland 58-506
    80 Research Site Kraków Poland 31-011
    81 Research Site Lublin Poland 20-412
    82 Research Site Piaseczno Poland 05-500
    83 Research Site Skórzewo Poland 60-185
    84 Research Site Szczecin Poland 70-111
    85 Research Site Zamość Poland 22-400
    86 Research Site Łódź Poland 91-053
    87 Research Site Ankara Turkey 06620
    88 Research Site Istanbul Turkey 34020
    89 Research Site Izmir Turkey 35110
    90 Research Site Izmir Turkey 35360
    91 Research Site Mersin Turkey 33343
    92 Research Site Pamukkale Turkey 20070
    93 Research Site Blackpool United Kingdom FY3 7EN
    94 Research Site Corby United Kingdom NN17 2UR
    95 Research Site Northwich United Kingdom CW9 7LS
    96 Research Site Poole United Kingdom BH15 2HX
    97 Research Site Thetford United Kingdom IP24 1JD

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05573464
    Other Study ID Numbers:
    • D5985C00003
    • 2022-001476-33
    First Posted:
    Oct 10, 2022
    Last Update Posted:
    Jan 25, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lung Diseases
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive

    Study Results

    No Results Posted as of Jan 25, 2023