Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial.


Journal

Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335

Informations de publication

Date de publication:
09 2023
Historique:
received: 30 11 2022
revised: 16 03 2023
accepted: 26 03 2023
medline: 11 9 2023
pubmed: 2 4 2023
entrez: 1 4 2023
Statut: ppublish

Résumé

In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy. Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma? This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV Of 1,001 patients randomized, 989 were ≥ 12 years old and evaluable for efficacy. Change from baseline in FEV Both monocomponents contributed to albuterol-budesonide lung function efficacy. Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel rescue therapy. ClinicalTrials.gov; No.: NCT03847896; URL: www. gov.

Sections du résumé

BACKGROUND
In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy.
RESEARCH QUESTION
Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma?
STUDY DESIGN AND METHODS
This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV
RESULTS
Of 1,001 patients randomized, 989 were ≥ 12 years old and evaluable for efficacy. Change from baseline in FEV
INTERPRETATION
Both monocomponents contributed to albuterol-budesonide lung function efficacy. Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel rescue therapy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov; No.: NCT03847896; URL: www.
CLINICALTRIALS
gov.

Identifiants

pubmed: 37003355
pii: S0012-3692(23)00463-4
doi: 10.1016/j.chest.2023.03.035
pii:
doi:

Substances chimiques

Budesonide 51333-22-3
Formoterol Fumarate W34SHF8J2K
Albuterol QF8SVZ843E
Bronchodilator Agents 0

Banques de données

ClinicalTrials.gov
['NCT03847896']

Types de publication

Randomized Controlled Trial Clinical Trial, Phase III Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

585-595

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Bradley E Chipps (BE)

Capital Allergy and Respiratory Disease Center, Sacramento, CA. Electronic address: bchipps@capitalallergy.com.

Elliot Israel (E)

Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Richard Beasley (R)

Medical Research Institute of New Zealand, Wellington, New Zealand.

Reynold A Panettieri (RA)

Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ.

Frank C Albers (FC)

Avillion US Inc., Northbrook, IL.

Robert Rees (R)

Avillion LLP, London, UK.

Lynn Dunsire (L)

BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.

Anna Danilewicz (A)

Avillion LLP, London, UK.

Eva Johnsson (E)

BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Christy Cappelletti (C)

BioPharmaceuticals R&D, AstraZeneca, Durham, NC.

Alberto Papi (A)

Department of Translational Medicine, University of Ferrara, Ferrara, Italy.

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Classifications MeSH