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

Phase 1

Conditions: Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 21.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2022-001476-33-PL

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 542

Inclusion Criteria

Age
1.Participant must be 40 to 80 years of age 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) 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;
Sex
11.Females must either be not of childbearing potential, or using a form of highly effective birth control as defined below:
oWomen 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:
oWomen < 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.
oWomen = 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.
oAll women of childbearing potential must have a negative serum pregnancy test result at Visit 1
oWomen <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

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.
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, 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
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
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
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, clini

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Safety objectives: To assess the safety and tolerability of BGF MDI HFO as compared to BGF MDI HFA over 12 to 52 weeks in participants with moderate to very severe COPD;Secondary Objective: Exploratory objectives: <br>1. To assess the safety and tolerability of BGF MDI HFO compared to BGF MDI HFA over 12 to 52 weeks in participants with moderate to very severe COPD<br>2. To explore the effect of BGF MDI HFO compared to BGF MDI HFA over 12 to 52 weeks on respiratory health status;Primary end point(s): 1. AEs (including SAEs, DAEs, AEOSIs, non-serious AEs) <br>2. Digital 12-lead Holter electrocardiogram (ECG) <br>3. 12-lead ECG<br>4. Clinical laboratory testing<br>5. Vital signs;Timepoint(s) of evaluation of this end point: 1. Over 16 or 56 Weeks (if attending 56 weeks study)<br>2. Week 0 and week 12<br>3. Week 4, 8 and 52 (if attending 56 weeks study)<br>4. Week 0, 12 and 52 (if attending 56 weeks study)<br>5. Over 14 or 54 Weeks (if attending 56 weeks study)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Change from pre-dose value in FEV1 at 5, 15, 30, and 60 min post dose<br>2. Change from baseline COPD Assessment Test (CAT) at 12 and 52 weeks;Timepoint(s) of evaluation of this end point: 1. Over 12 or 52 Weeks (if attending 56 weeks study)<br>2. Week 12 and 52 (if attending 56 weeks study)

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