A combined phase I/IIa study of the safety, bronchodilator and bronchoprotective effects of nebulized RPL554, a dual PDE3/4-inhibitor, in healthy subjects and asthmatics
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چکیده
Methods The safety of RPL554 0.003 and 0.009 mg/kg was evaluated in 18 healthy males (age 18-41 years; weight 58-90 kg; height 168-196 cm; BMI 18-29 kg/m) in a randomised, double-blind study. For each dose group, 6 subjects inhaled RPL554 and 3 placebo. Study medication was administered by a calibrated electronic nebuliser and oronasal mask. Subsequently, RPL554 0.009 and 0.018 mg/kg were evaluated in 6 asthmatic males (22-29 years; 58-98 kg; 174-198 cm; BMI 19-27 kg/m, FEV1 75-118% pred.) using an open, adaptive design to select an effective dose. This dose (0.018 mg/kg) was further evaluated in a randomised, double-blind, placebo-controlled, cross-over study in 10 allergic asthmatics (20-50 years; 67-112 kg; 171-191 cm; BMI 21-33 kg/m, FEV1 82-112% pred.; baseline PC20(methacholine=MCh) 0.07-1.49 mg/ml; not on controller medication) to assess its bronchodilator effects and bronchoprotective activity against methacholine (MCh) challenge.
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