Efficacy, safety, and pharmacokinetics of budesonide/formoterol fumarate delivered via metered dose inhaler using innovative co-suspension delivery technology in patients with moderate-to-severe COPD
Received 1 February 2018
Accepted for publication 21 March 2018
Published 8 May 2018 Volume 2018:13 Pages 1483—1494
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Charles Downs
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Edward M Kerwin,1 Thomas M Siler,2 Samir Arora,3 Patrick Darken,4 Earl St Rose,4 Colin Reisner4,5
1Clinical Research Institute of Southern Oregon, Medford, OR, USA; 2Midwest Chest Consultants, St Charles, MO, USA; 3Aventiv Research, Columbus, OH, USA; 4Pearl – a member of the AstraZeneca Group, Morristown, NJ, USA; 5AstraZeneca, Gaithersburg, MD, USA
Purpose: This study investigated the efficacy, safety, and pharmacokinetics of the inhaled corticosteroid/long-acting β2-agonist fixed-dose combination budesonide/formoterol fumarate (BFF) metered dose inhaler (MDI), compared with the monocomponents budesonide (BD) MDI and formoterol fumarate (FF) MDI, in patients with moderate-to-severe COPD.
Materials and methods: In this Phase IIb, randomized, double-blind, four-period, five-treatment, incomplete-block, crossover study (NCT02196077), all patients received BFF MDI 320/9.6 μg and FF MDI 9.6 μg, and two of either BFF MDI 160/9.6 μg, BFF MDI 80/9.6 μg, or BD MDI 320 μg twice daily for 28 days. The primary efficacy endpoint was forced expiratory volume in 1 second area under the curve from 0 to 12 hours on Day 29. Secondary efficacy endpoints included additional lung function assessments, and evaluation of dyspnea and rescue medication use. Safety was monitored throughout. The systemic exposure to budesonide and formoterol was assessed on Day 29.
Results: Overall, 180 patients were randomized. For forced expiratory volume in 1 second area under the curve from 0 to 12 hours on Day 29, all BFF MDI doses showed significant improvements versus BD MDI 320 μg (least squares mean differences 186–221 mL; all p<0.0001), and BFF MDI 320/9.6 μg demonstrated a significant improvement versus FF MDI 9.6 μg (least squares mean difference 56 mL; p=0.0013). Furthermore, all BFF MDI doses showed significant improvements versus BD MDI 320 μg for all lung function, dyspnea, and rescue medication use secondary efficacy endpoints. All BFF MDI doses were well tolerated, and the safety profile was not substantially different from the monocomponents. There was no evidence of clinically meaningful pharmacokinetic interactions when budesonide and formoterol were formulated together in BFF MDI.
Conclusion: The findings presented here confirm that BFF MDI 320/9.6 μg is an appropriate dose to take forward into Phase III studies in patients with COPD.
Keywords: BFF MDI, COPD, fixed-dose combination, inhaled corticosteroid, long-acting β2-agonist, single-inhaler triple therapy
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