A Randomized Study Comparing Placebo and ASP3652 in the Treatment of Women With Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC)

Study Overview
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Brief Summary
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In this study several dose levels of ASP3652, given orally for 12 weeks, will be compared with placebo in the treatment of female patients with Bladder Pain Syndrome / Interstitial Cystitis.

Detailed Description
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This study consists of a screening phase, an initial 3 weeks Run-in period, a 12 weeks Treatment period and a 2 weeks Follow-up (FU) period. This study will investigate the efficacy and safety of a 12 week treatment with ASP3652 in female patients with Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC). Different dose levels of ASP3652 will be compared with placebo. ASP3652 is administered as oral tablets. The objectives of the study are to investigate efficacy of ASP3652 in patients with BPS/IC, to assess the optimal dose of ASP3652, to investigate safety and tolerability and to investigate pharmacokinetics and pharmacodynamics of ASP3652 in patients with BPS/IC in an out-patient setting.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Adaptive, Combined Proof of Concept and Dose-Finding Study to Investigate Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of ASP3652 in the Treatment of Female Patients With Bladder Pain Syndrome / Interstitial Cystitis

Conditions
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Cystitis, Interstitial, Urinary Bladder Disease, Pain, Urologic Diseases

Intervention / Treatment
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* Drug: ASP3652
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has previously been diagnosed with BPS/IC; i.e., pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency, for at least 3 months prior to screening in absence of urinary infection or other obvious pathology or identifiable causes Has at enrolment a score of 4 or greater on the 11-point (0-10) NRS for average pain over the previous week, which is item 4 of the F-GUPI Has a mean pain score of 4.0 or greater on the 11-point (0-10) NRS for daily assessed pain (item 4 of F-GUPI-24H) over the last 7 days prior to randomization Is willing to comply with study requirements such as completing the questionnaires and diaries and attend all study visits and practicing birth control Exclusion Criteria: Undergone a cystoscopy with hydrodistension or undergone Botox injections in the bladder within 6 months prior to screening Use of pentosan polysulphate sodium within 4 weeks prior to screening Any intravesicular pharmacological treatment or other interventions for BPS/IC or bladder, urethral, ureteral, pelvic or peri-pelvic invasive procedure within 3 months prior to screening Cystitis or documented symptomatic bacterial cystitis in the last 3 months prior to screening Lower urinary tract malignancy, such as positive (micro) hematuria in urine sediment Neurologic disease or defect affecting bladder function or symptomatic urethral diverticulum or any post-partum or surgery related genital tract conditions, symptomatic bladder or ureteral calculi or Post Void Residual volume greater than 150 mL Clinically significant abnormalities observed during cystoscopy or on transabdominal ultrasound Currently active or treated sexual transmittable diseases Substance abuse or any use of delta-9-tertrahydrocannabinol (THC) as assessed by a positive urine test for THC at screening Any clinically relevant concomitant disease (past or present) which would, in the opinion of the investigator, put the subject at risk or mask measures of efficacy Symptoms of depression, defined as a Center for Epidemiological Studies Depression Scale score of 27 or more Use of steroids, immunomodulators, cytochrome P4502C8 inhibitors, cannabis / THC based medication, opioid analgesics or antiviral / antibacterial / antifungal agents during the last 4 weeks before the screening Initiation, discontinuation, or variation in the dose of antidepressants, anticonvulsants, antimuscarinics, benzodiazepines, skeletal muscle relaxants, non-steroid anti-inflammatory drugs, non opioid analgesics, homeopathic medication and herbal therapies during the last 4 weeks before the screening. Subjects should continue these medications at that same stable dose throughout the study Clinically relevant abnormal urine or blood safety laboratory values or active hepatic and/or biliary disease (AST or ALT should not be >2 times the upper limit of normal, total bilirubin should not be >1.5 times the upper limit of normal) Participated in any clinical study or has been treated with any investigational drug or device within 84 days or the period stipulated by local regulations, whichever is longer, prior to the screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose ASP3652 twice daily<br>50 mg twice daily for 12 weeks | Drug: ASP3652<br>* Oral<br>|
| Experimental: Medium dose ASP3652 twice daily<br>150 mg twice daily for 12 weeks | Drug: ASP3652<br>* Oral<br>|
| Experimental: High dose ASP3652 twice daily<br>300 mg twice daily for 12 weeks | Drug: ASP3652<br>* Oral<br>|
| Placebo Comparator: Placebo<br>Matching placebo twice daily for 12 weeks | Drug: Placebo<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Mean Daily Pain (MDP) at 12 weeks | Pain is assessed on an 11 point (0-10) Numerical Rating Scale (NRS), which is item 4 of the Female GenitoUrinary Pain Index (24 hours recall) (F-GUPI-24h) | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Mean Daily Pain (MDP) at 4, 8 weeks treatment and at 2 weeks follow-up post treatment | Pain is assessed on an 11 point (0-10) Numerical Rating Scale (NRS), which is item 4 of the F-GUPI-24h | Baseline, 4 and 8 weeks treatment and 2 weeks follow-up post treatment | 
| Change from baseline in Female GenitoUrinary Pain Index (one week recall) (F-GUPI) Total score at 4, 8, 12 weeks treatment and at 2 weeks follow-up post treatment |  | Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment | 
| Change from baseline in F-GUPI Pain subscale score, Urinary subscale score, and Quality of Life Impact score at 4, 8, 12 weeks treatment and at 2 weeks follow-up post treatment |  | Baseline, 4, 8, 12 weeks treatment and at 2 weeks follow-up post treatment | 
| Daily pain, assessed with item 4 of the F-GUPI-24h during Run-in, Treatment period and Follow-up post treatment |  | Every day during the Run-in, Treatment and Follow-up post treatment periods | 
| Change from baseline in questionnaires at 12 weeks treatment | Bladder Pain/IC Symptom Score; O'Leary-Sant IC Symptom & Problem Index; Short form McGill pain questionnaire; Female Sexual Function Index; European Quality of Life questionnaire in 5 Dimensions | Baseline and 12 weeks treatment | 
| Global Response Assessment (GRA) at 0, 4, 8 and 12 weeks treatment and at 2 weeks follow-up post treatment | GRA is assessed as change from baseline which is here start of Run-in period | Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment | 
| Change from baseline in Voiding parameters (urinary frequency, urinary urgency, nocturia and total urgency score ) at 4, 8, 12 weeks treatment and at 2 weeks Follow-up post treatment |  | Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment | 
| Proportion of responders: at least 7-point decrease in F-GUPI Total score at 0, 4, 8 and 12 weeks treatment compared to baseline |  | Baseline, 4, 8 and 12 weeks treatment | 
| Assessment of pharmacokinetics at week 4, 8 and 12 | Plasma levels of ASP3652 | 4, 8 and 12 weeks treatment | 
| Assessment of pharmacodynamics at week 4, 8 and 12 | Plasma levels of anandamides | 4, 8 and 12 weeks treatment | 
| Safety as assessed by recording Adverse Events, Laboratory tests, electrocardiograms (ECGs) and vital signs |  | Baseline and 12 weeks treatment | 
| Safety as assessed by SteatoTest, adiponectin and PVR |  | Baseline and 12 weeks | 
| Change from baseline in questionnaires (Center for Epidemiologic Studies Depression Scale and Profile of Mood States questionnaire) at 12 weeks treatment |  | Baseline and 12 weeks treatment | 
| Physician Withdrawal Checklist at 12 weeks treatment and at 2 weeks follow-up post treatment |  | 12 weeks treatment and 2 weeks follow-up post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP3652, Painful Bladder Syndrome, Interstitial Cystitis, Bladder Pain Syndrome