Phase II, multicentre, randomised, double blind, placebo conntrolled pilot study to determine proof of efficacy, safety, tolerablility and pharmacokinetics of intravesical PSD597 in the symptomatic management of interstitial cystitis/painful bladder syndrome

INTERVENTION: Eligible subjects will be randomly allocated (1:1) to receive blinded treatment with PSD597 or a placebo during the double‐blind treatment phase of the study: Group one: PSD597 treatment will consist of 5 ml of 4% lidocaine instilled into an empty bladder via a ten French urinary catheter, followed by 5 ml of 8.4% sodium bicarbonate solution. The bladder will be drained via the urinary catheter before commencing the instillation. Following instillation the catheter will be clamped and the instillate left in situ for one hour before drainage and removal of the catheter (N.B.: If a subject cannot tolerate the catheter remaining in situ for this period it may be removed and the subject re‐catheterised at one hour to drain the instillate. The instillate should not be voided by the subject to avoid unnecessary urethral pain which may result from voiding of the bicarbonate. Where possible the catheter should remain in situ during the hour of treatment. In cases where an increased number of catheterisations are required, the investigator may wish to consider use of prophylactic antibiotics). Subjects will receive daily instillations of PSD597 on five consecutive study days (days one to five, Monday ‐ Friday), administered in hospital as an outpatient. Group two: Placebo treatment will consist of 10 ml of ordinary saline instilled into an empty bladder as two 5 ml instillates. Subjects will receive daily instillations of placebo using an identical dosing schedule and administration procedure to that used for PSD597. In both cases, lidocaine must not be used as local anaesthetic when inserting the urinary catheter. At the day 15 follow‐up visit all subjects will be offered the option of open‐label treatment with PSD597 for five consecutive days (days 15‐19, Monday to Friday) to be administered in hospital as an outpatient. CONDITION: Interstitial cystitis/painful bladder syndrome ; Urological and Genital Diseases ; Interstitial cystitis/painful bladder syndrome PRIMARY OUTCOME: To assess the percentage of patients who respond to PSD597, assessed as 'moderately improved' or 'markedly improved' measured by a GRA, compared to placebo, at day 15 following a five consecutive day course of treatment. SECONDARY OUTCOME: 1. To assess changes in GRA measured by a seven point scale.; 2. To assess changes in bladder pain measured by ten point Likert scale.; 3. To assess changes in frequency measured by a voiding log.; 4. To assess changes in urgency measured by ten point Likert scale.; 5. To assess changes in symptoms and problems associated with interstitial cystitis measured by the O’Leary Sant Interstitial Cystitis symptom and problem indexes.; 6. To assess the safety and tolerability of PSD597 instilled into the bladder.; ; 7. To characterise the pharmacokinetics of single and multiple doses of intravesical PSD597 in a sub‐group of patients. INCLUSION CRITERIA: 1. Male or female patients aged between 18 and 75 years of age. 2. Women of child bearing potential or men with partners of child bearing potential willing to commit to the use of a reliable form of contraception during the course of the study (e.g contraceptive pill or condoms). 3. Symptoms of bladder pain/discomfort of more than four on a ten point Likert scale, described as suprapubic pain related to bladder filling accompanied by other symptoms including increased daytime and night‐time frequency (more than eight or more than two respectively) in the absence of infection or other pathology, with or without the typical cystoscopic appearance of IC. 4. Symptoms of abnormal urinary frequency and bladder pain/discomfort must have been present for at least three months prior to study entry. 5. Anterior vaginal wall/bladder wall pain on bimanual examination. 6. Able to understand and complete a Likert Scale, Global Risk Assessment (GRA) and O’Leary San