A Randomized, Double-Blind, Double Dummy, Parallel Group, Multicenter 24 to 52 Week Variable Length Study to Assess the Efficacy and Safety of Budesonide, Glycopyrronium, and Formoterol Fumarate Metered Dose Inhaler (MDI) Relative to Budesonide and Formoterol Fumarate MDI and Symbicort® Pressurized MDI in Adult and Adolescent Participants with Inadequately Controlled Asthma (KALOS)
- Conditions
- AsthmaRespiratory Disease10006436
- Registration Number
- NL-OMON51184
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 28
(1.) Female or male subjects between 12-80 years inclusive, at the time of
signing the ICF. (2.) Participants who have a documented history of
physician-diagnosed asthma *1 year prior to Visit 1, according to GINA
guidelines [GINA 2020]. Healthcare records for 1 year prior to Visit 1 must be
provided for adolescent participants (12 to <18 years of age) to ensure
consistent evaluation and follow-up of treatment in those participants. (3.)
Participants who have been regularly using a stable daily ICS/LABA regimen
(including a stable ICS dose), for at least 4 weeks prior to Visit 1. (4.) Have
a documented history of at least one asthma exacerbation requiring use of
systemic corticosteroids (oral or IV) for at least 3 days AND an associated
physician visit, hospitalization, or ER visit due to asthma (within 3 days of
the corticosteroid use) in the 12 months prior to Visit 1. (5.) ACQ-7 total
score *1.5 at Visits 1, 3, and 5 (pre-randomization). (6.) A pre-bronchodilator
FEV1 <80% predicted normal value at Visits 1, 2, 3, 4, and 5
(pre-randomization) for participants *18 years of age OR a pre-bronchodilator
FEV1 <90% predicted normal value at Visits 1, 2, 3, 4, and 5
(pre-randomization) for participants 12 to <18 years of age. (7.) Documented
reversibility to albuterol, which is defined as a post-albuterol increase in
FEV1 of *12% and *200 mL for participants *18 years of age OR a post-albuterol
increase of FEV1 of *12% for participants 12 to <18 years of age at Visit 2, or
at Visit 3 if repeat testing necessary. (8.) Willing and, in the opinion of the
Investigator, able to adjust current asthma therapy, as required by the
protocol. (9.) Received no asthma medication other than run-in BFF MDI BID and
albuterol as needed during screening, except for allowed medications defined in
Table 8 and systemic corticosteroid or ICS for the treatment of an asthma
exacerbation (see Section 5.5.2 regarding Screening extension). (10.) No
respiratory infection within 4 weeks of randomization, or asthma exacerbation
treated with systemic corticosteroid and/or additional ICS treatment within 4
weeks of randomization.
(1.) Life-threatening asthma defined as a history of significant asthma
episode(s) requiring intubation associated with hypercapnia, respiratory
arrest, hypoxic seizures, or asthma-related syncopal episode(s). (2.) Completed
treatment for respiratory infection or asthma exacerbation with systemic
corticosteroids within 4 weeks of Visit 1. (3.) Hospitalization for asthma
within 2 months of Visit 1. (4.) Historical or current evidence of a clinically
significant disease including, but not limited to: cardiovascular, hepatic,
renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary.
(5.) Narrow angle glaucoma not adequately treated and/or change in vision that
may be relevant, in the opinion of the Investigator, within 3 months of Visit
1. (6.) Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary
retention that, in the opinion of the Investigator, is clinically significant.
(7.) Unresectable cancer that has not been in complete remission for at least 5
years prior to Visit 1. (8.) Oral and IV corticosteroid use (any dose) within 4
weeks of Visit 1. (9.) Depot corticosteroid use for any reason within 12 months
of Visit 1. (10.) Use of LAMA as maintenance treatment, either alone or as part
of an inhaled combination therapy, within 12 months prior to Visit 1. (11.) Use
of oral beta2-agonist within 3 months of Visit 1. (12.) Any marketed (e.g.,
omalizumab, mepolizumab, benralizumab, reslizumab) or investigational biologic
within 3 months or 5 half-lives of Visit 1 (13.) Regular use of a nebulizer or
a home nebulizer for receiving asthma medications. (14.) Use of any
immunomodulators or immunosuppressive medication within 3 months or 5
half-lives. (15.) Participants with a known hypersensitivity to beta2-agonists,
corticosteroids, anticholinergics, or any component of the MDI or pMDI. (16.)
Current smokers, former smokers with >10 pack-years history, or former smokers
who stopped smoking <6 months prior to Visit 1. (17.) Planned hospitalization
during the study. (18.) Previous or current randomization in any budesonide and
formoterol fumarate studies (PT009), budesonide, glycopyrronium, and formoterol
fumarate studies (PT010), or glycopyrronium studies (PT001). (19.) For women
only * currently pregnant (confirmed with positive pregnancy test),
breastfeeding, or planned pregnancy during the study or not using acceptable
contraception measures, as judged by the Investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objective is to assess the effect of BGF MDI relative to BFF MDI or<br /><br>Symbicort pMDI on lung function in participants with inadequately controlled<br /><br>asthma, using the primary endpoint of change from baseline in morning pre-dose<br /><br>trough FEV1 over 24 Weeks</p><br>
- Secondary Outcome Measures
Name Time Method