RPL554, an inhaled PDE3/4 inhibitor, causes profound and sustained bronchodilation in healthy volunteers and COPD patients

RPL554 has previously been shown to be a well tolerated bronchodilator, bronchoprotective, & anti-inflammatory agent in clinical studies. We performed a randomised, double blind, placebo (PBO) controlled, study to assess the safety, tolerability & pharmacokinetics of single ascending (SAD) & multiple ascending doses (MAD) (5.5 days bid) of a new pH neutral, commercially scalable inhaled suspension RPL554 formulation administered by nebuliser to healthy subjects (HV) & stable COPD patients. Each cohort comprised 7-9 active & 3 PBO treated subjects. RPL554 was well tolerated at all dose levels in HV & COPD patients. As part of this study, the effect of RPL554 on FEV₁ up to 24h post dose was studied. Single doses of RPL554 (1.5, 3, 6, 12, 24mg) caused a profound sustained dose dependent increase in FEV₁ in HV (Fig 1). MAD of RPL554 administered to HV (6, 12, 24mg) & COPD patients (1.5, 6, 12mg) also caused marked increases in FEV₁ at all doses tested with a duration supportive of bid dosing. In summary, this new suspension formulation of RPL554, which has potential benefits in terms of dose levels & stability, is a potent bronchodilator drug with what appears to be a large safety margin. This potent & sustained bronchodilator activity in combination with its9 anti-inflammatory activity make RPL554 a promising new potential therapy for COPD & other obstructive lung diseases. Fig.1