A phase 3 clinical trial will determine the efficacy of albuterol in combination with budensonide in adult, adolescent, and pediatric patients with moderate to severe asthma. The rationale and design of this study were outlined in an article published in BMJ Open Respiratory Research.
While fast-acting bronchodilators provide rapid relief from asthma symptoms, their use for rescue fails to address underlying inflammation. Therefore, a single inhaler that combines a short-acting beta2-agonist (SABA) with an inhaled corticosteroid (ICS) is under development to help control both bronchoconstriction and inflammation and reduce the risk of asthma symptoms progressing to exacerbations. This device, the albuterol/budesonide single pressurized metered-dose inhaler (pMDI), is being designed to quickly relieve symptoms while simultaneously titrating inhaled ICS.
Researchers designed the global, randomized, double-blind, event-driven asthma exacerbation MANDALA study (ClinicalTrials.gov Identifier: NCT03769090) to evaluate the efficacy and safety of as-needed albuterol combined with budesonide (albuterol/budesonide 180/160 μg or 180/80 μg, 2 actuations of 90/80 μg
or 90/40 μg, respectively) administered via a fixed-dose combination pMDI as rescue therapy, comparing its performance with as-needed albuterol (180 μg, two actuations of 90 μg) via pMDI in adult, adolescent, and pediatric patients with moderate-to-severe asthma.
The trial includes symptomatic patients (3000 adults/adolescents and 100 children aged 4–11 years) who experienced 1 or more severe asthma exacerbations in the previous year and were receiving maintenance therapy for 3 months or more prior to entering the study. The primary efficacy endpoint is time to first severe asthma exacerbation. There are several secondary efficacy endpoints evaluating asthma and quality of life. In addition, safety endpoints are also being assessed from date of informed consent/assent through the safety follow-up period.
“It is anticipated that the albuterol/budesonide pivotal phase 3 development programme, including this MANDALA exacerbation study and the DENALI ([ClinicalTrials.gov Identifier:] NCT03847896) lung function study, will provide the evidence needed to help change the current rescue treatment paradigm by reducing the risk of exacerbations in patients with asthma,” concluded the researchers. They added, “If successful, as-needed albuterol/budesonide pMDI rescue therapy could be used irrespective of background asthma therapy, and will be the first albuterol/ICS combination inhaler available in the USA.”
Disclosure: This research was supported by Avillion, and some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Chipps BE, Albers FC, Reilly L, Johnsson E, Cappelletti C, Papi A. Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study. BMJ Open Resp Res. 2021;8(1):e001077. doi:10.1136/bmjresp-2021-001077