RPL554, an inhaled PDE3/4 inhibitor, causes comparable bronchodilation to high dose nebulised salbutamol in asthmatics with fewer systemic effects

RPL554 has bronchodilator, bronchoprotective, & anti-inflammatory effects. We investigated the dose-ranging effects & safety of a nebulized suspension formulation of RPL554 vs salbutamol (Salb) & placebo (PBO) in 29 mild-moderate asthmatics. This was a randomized double-blind, PBO controlled, 7 way cross-over study. Each patient received 4 doses of RPL554 (0.4mg-24mg), Salb (2.5mg, 7.5mg) & PBO separated by 3-14 days. FEV₁ FVC, safety & pharmacokinetic evaluations up to 12h post-dose were performed. RPL554 produced a similar degree of bronchodilation to a maximal dose of Salb (Fig 1). RPL554 was well tolerated. Occurrence of systemic AEs was more frequent in patients treated with Salb vs RPL554; tremor (37.5% vs 1.9%), hypokalemia (5.4% vs 0) & palpitations (12.5% vs 0.9%). There was an increase in peak heart rate only for the highest dose of RPL554 24 mg (6.4 bpm), however this was less than for Salb 2.5 mg (9.0 bpm) & Salb 7.5 mg (21.8 bpm). There were no SAEs or AEs leading to discontinuation. In summary, RPL554 caused a dose dependent bronchodilation with comparable magnitude to a maximal dose of Salb, but with fewer systemic side effects. RPL554 represents a well tolerated first in class compound with bronchodilator & anti-inflammatory effects in a single molecule making it a very exciting novel treatment for obstructive lung diseases. Fig 1 Average FEV1