Both Drugs in Albuterol-Budesonide Asthma Inhaler Contribute to Efficacy

The albuterol-budesonide combination pressurized metered-dose inhaler (pMDI) was well-tolerated by those with mild-to-moderate asthma, even at relatively high daily doses, and both drugs in the inhaler contribute to the therapy’s effectiveness. These were among clinical trial findings published in CHEST.

The albuterol-budesonide pMDI is an as-needed asthma rescue therapy combining a short-acting β2-agonist (albuterol) for alleviation of symptoms with an inhaled corticosteroid (budesonide) that simultaneously treats the increasing inflammation that precedes an asthma exacerbation. The DENALI trial (ClinicalTrials.gov Identifier: NCT03847896) was conducted to demonstrate that each component drug of the albuterol-budesonide combination pMDI were safe and contributed to the therapy’s efficacy, as is required by the US Food and Drug Administration. 

The study’s twin primary efficacy outcomes were trough forced expiratory volume in 1 second (FEV₁) after 12 weeks (budesonide) and change over 12 weeks in FEV₁ area under the curve from 0 to 6 hours (FEV₁AUC_0-6h) (albuterol). Notably, although the albuterol-budesonide pMDI is intended for as-needed use, a scheduled-dosing design was needed to assess clinical trial outcomes. Time to onset of FEV₁ response and response duration on Day 1 were secondary efficacy outcomes.

The phase 3, multi-center, double-blind DENALI trial, conducted between March 2019 and July 2021 at 126 centers in Europe, South America, and the US, included 989 patients (at least 12 years of age) with mild-to-moderate asthma. Participants were randomly assigned to receive 1 of the following regimes 4-times-daily for 12 weeks: (1) albuterol-budesonide 180/160 µg or 180/80 µg; (2) albuterol 180 µg; (3) budesonide 160µg; or (4) placebo. Overall, 928 patients completed the trial. Almost 90% of participants were White, over 60% women, about 18% were age 65 years or older, and less than 3% were under the age of 18 years. Medication compliance across groups was similar (mean [SD], 89.4 [12.2]%).

The researchers found change in trough FEV₁ with albuterol-budesonide 180/160 µg (n=186) at week 12 was greater than change in albuterol 180 µg (n=172) (least squares mean [LSM] difference, 132.8 mL; 95% CI, 63.6-201.9; P <.001); albuterol-budesonide 180/160 µg vs placebo (n=175) (LSM difference, 99.9 mL; 95% CI, 30.9-168.8; P =.005).

Change in trough FEV₁ with albuterol-budesonide 180/80 µg (n=184) at week 12 was greater than change in albuterol 180 µg (n=172) (LSM difference, 120.8 mL; 95% CI, 51.5-190.1; P <.001); albuterol-budesonide 180/80 µg vs placebo (n=175) (LSM difference, 87.9 mL; 95% CI, 18.8-156.9; P =.013). Change in trough FEV₁ with budesonide 160 µg (n=187) was greater than change in placebo (LSM difference, 73.3 mL; 95% CI, 4.4 -142.2; P =.037).

Over 12 weeks, the researchers noted change in FEV₁AUC_0-6h was greater with albuterol-budesonide 180/160 µg (n=197) vs budesonide 160 µg (n=199) (LSM difference, 80.7 mL; 95% CI, 28.4-132.9; P =.003); albuterol-budesonide 180/160 µg vs placebo (n=196) (LSM difference, 161.9mL; 95% CI, 109.4-214.5; P <.001). Change was greater in FEV₁AUC_0-6h with albuterol 180 µg (n=195) vs placebo (LSM difference, 60.5 mL; 95% CI, 7.7-113.4; P =.025).

Researchers noted time to onset and duration of bronchodilation on day 1 with albuterol-budesonide proved a similar rapid time to albuterol. The adverse event (AE) profile of mono-components albuterol and budesonide was similar to the profile for albuterol-budesonide combination with 31%-35% of patients across treatment groups reporting AEs, most frequently headache and nasopharyngitis. Less than 2% of patients discontinued due to AEs and there were no deaths during the trial.

Significant trial limitations include: (1) the fact that the trial’s scheduled 4-times daily dosing does not correspond with the intended as-needed use of the albuterol-budesonide combination pMDI; and (2) use of albuterol as needed was permitted for symptoms during the trial treatment period.

“The DENALI trial met both dual-primary endpoints, demonstrating the contribution of both mono‑components to the lung function efficacy of albuterol-budesonide pMDI,” the study authors concluded. “In addition, albuterol-budesonide demonstrated a similar rapid time to onset and duration of bronchodilation on Day 1 to that of albuterol,” the researchers added.

Disclosure: This research was supported by Bond Avillion 2 Development LP. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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