Abstract Rationale Combination of a long-acting beta-agonist (LABA) bronchodilator and a long-acting muscarinic antagonist (LAMA) bronchodilator is the preferred choice for initial therapy for COPD patients with severe symptoms and/or with exacerbation risk. Although there are multiple LABA+LAMA combination bronchodilators available in an inhaler, many COPD patients do not receive optimal benefit from inhalers; nebulized delivery provides an effective alternative. Inhaled AERO-007 is currently in clinical development as a fixed-dose combination of indacaterol and glycopyrrolate for nebulization delivery for maintenance treatment of COPD. Methods This was a Phase 2a, randomized, double-blind, placebo-controlled, single dose, 3-period crossover, dose-ranging study to determine the safety, tolerability, pharmacokinetics and efficacy of inhaled AERO-007 in COPD patients. AERO-007 was delivered using a standard nebulizer (LC Sprint, Pari) and tested at two dose levels (100/50μg and 200/100μg) in 16 patients with moderate to severe COPD (post-bronchodilator FEV1 40-80% predicted, FEV1/FVC ratio 0.70). Each treatment was separated by a washout period of 10-14 days. Long-acting bronchodilators (LABA, LAMA, or LABA/LAMA combinations) were discontinued for at least 1 week prior to the study start and were switched to ipratropium (20 µg x2 puffs 4 times daily) while inhaled corticosteroid use was allowed at stable doses throughout the study. Rescue albuterol was provided for as needed use throughout the study. Pulmonary function tests by serial spirometry were performed after each treatment for 24 hours. Results The mean age of COPD patients (6 females, 10 males) was 68±5 years with a mean COPD duration of 12±7 years since diagnosis, mean post-bronchodilator % predicted FEV1 of 60.2±12.7, FEV1/FVC of 49.7±8.7 and FEV1 reversibility of 318±149 mL at baseline. AERO-007 was well tolerated at both levels. Treatment with AERO-007 provided a rapid, clinically meaningful and statistically significant bronchodilator response that was comparable at both dose levels. With low dose AERO-007 (100/50μg), the change from baseline in standardized FEV1 AUC 0-24h (L) was 0.251±0.031 (p 0.001), the peak change from baseline in FEV1 (L) was 0.311±0.035 (p 0.001) compared to placebo, and the PK exposures were comparable to the published data using DPI inhaler of the same LABA+LAMA. Conclusions Inhaled AERO-007, the fixed-dose combination of indacaterol and glycopyrrolate administered by nebulization, demonstrated an efficacy and safety profile representing a best-in-class LABA+LAMA combination drug for once daily dosing as first line treatment option in patients with moderate to severe COPD who need to be or prefer to be on nebulized treatments. This abstract is funded by: AeroRx Therapeutics, Inc.
Tutuncu et al. (Fri,) studied this question.