The efficacy and safety of PSD503 (phenylephrine 20%, w/w) for topical application in women with stress urinary incontinence. A phase II, multicentre, double-blind, placebo controlled, 2-way cross over study

ObjectivePSD503 is a topical gel containing phenylephrine 20% weight/weight (w/w) intended for vaginal application close to the area of the urethral sphincter in women with SUI and has been used in patients with faecal incontinence. The primary objective of this proof of concept study was to evaluate the efficacy of PSD503 in women with SUI as measured by the change in pad weight following an exercise stress pad test. The secondary objectives were to evaluate plasma concentrations of PSD503, BP changes and pulse rate over 3 h following administration and to assess safety and tolerability.Study designThis was a phase II multi-centre, double-blind, placebo-controlled, 2 way cross-over study. Women were assessed objectively pre and post PSD503 administration using a standardised exercise stress pad test. Safety was assessed by monitoring pulse, BP and plasma levels of PSD503 over 3 h following administration. A power calculation suggested a >80% power to demonstrate (at the 5% level of significance) a difference between treatments of 10-20 g with a sample size of 30 patients.Results14 patients were screened and 12 patients randomised over 20 months. Projections indicated the study would not attain its full quota within 1 year and it was terminated early. Treatment with PSD503 resulted in a greater reduction in pad weight gain than placebo, when expressed as both a percentage change (median % change: placebo - 38.00%, PSD503 - 54.33%) and absolute change (median absolute change: placebo - 10.0 g, 20% (w/w) PSD503 - 22.0 g) from pre-dose leakage. PSD503 was absorbed into the blood within 1 h (median concentration 1.490 ng/ml). Plasma concentrations at 3 h (median 1.305 ng/ml) were less than that at 1 h and lower than plasma concentrations seen following phenylephrine-containing cold remedies. There were no withdrawals, serious adverse events and it was well tolerated overall.ConclusionThis is the first proof of concept study to demonstrate that a topical α adrenergic agonist gel is rapidly and consistently absorbed vaginally and may have a role in the management of female SUI. However, since recruitment was difficult this may indicate that whilst objectively effective, acceptability in clinical practice may be poor.