title: 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.
abstract: OBJECTIVE
  PSD503 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 3h following administration and to assess safety and tolerability.
  
  
  METHODS
  This 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 3h following administration. A power calculation suggested a >80% power to demonstrate (at the 5% level of significance) a difference between treatments of 10-20g with a sample size of 30 patients.
  
  
  RESULTS
  14 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 - 10.0g, 20% (w/w) PSD503 - 22.0g) from pre-dose leakage. PSD503 was absorbed into the blood within 1h (median concentration 1.490ng/ml). Plasma concentrations at 3h (median 1.305ng/ml) were less than that at 1h and lower than plasma concentrations seen following phenylephrine-containing cold remedies. There were no withdrawals, serious adverse events and it was well tolerated overall.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Kings College Hospital, United Kingdom. dudley.robinson@nhs.net
authors.forename: Dudley
authors.initials: D
authors.lastname: Robinson
authors.forename: Paul
authors.initials: P
authors.lastname: Abrams
authors.forename: Linda
authors.initials: L
authors.lastname: Cardozo
authors.forename: Julie
authors.initials: J
authors.lastname: Ellis-Jones
authors.forename: Pat
authors.initials: P
authors.lastname: Heath
authors.forename: Mike
authors.initials: M
authors.lastname: Wyllie
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005080:Exercise Test / Q000009:adverse effects; D005260:Female; D005782:Gels; D006801:Humans; D008875:Middle Aged; D018579:Patient Selection; D010656:Phenylephrine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014550:Urinary Incontinence, Stress / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014622:Vaginal Creams, Foams, and Jellies
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D005782:Gels; D014622:Vaginal Creams, Foams, and Jellies; D010656:Phenylephrine