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

Phase 2
Completed
Conditions
Cystitis, Interstitial
Urinary Bladder Disease
Pain
Urologic Diseases
Interventions
Drug: Placebo
Registration Number
NCT01613586
Lead Sponsor
Astellas Pharma Europe B.V.
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
287
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low dose ASP3652 twice dailyASP365250 mg twice daily for 12 weeks
Medium dose ASP3652 twice dailyASP3652150 mg twice daily for 12 weeks
PlaceboPlaceboMatching placebo twice daily for 12 weeks
High dose ASP3652 twice dailyASP3652300 mg twice daily for 12 weeks
Primary Outcome Measures
NameTimeMethod
Change from baseline in Mean Daily Pain (MDP) at 12 weeksBaseline and 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)

Secondary Outcome Measures
NameTimeMethod
Assessment of pharmacokinetics at week 4, 8 and 124, 8 and 12 weeks treatment

Plasma levels of ASP3652

Assessment of pharmacodynamics at week 4, 8 and 124, 8 and 12 weeks treatment

Plasma levels of anandamides

Safety as assessed by recording Adverse Events, Laboratory tests, electrocardiograms (ECGs) and vital signsBaseline and 12 weeks treatment
Change from baseline in questionnaires (Center for Epidemiologic Studies Depression Scale and Profile of Mood States questionnaire) at 12 weeks treatmentBaseline and 12 weeks treatment
Change from baseline in Mean Daily Pain (MDP) at 4, 8 weeks treatment and at 2 weeks follow-up post treatmentBaseline, 4 and 8 weeks treatment and 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

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 treatmentBaseline, 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 treatmentBaseline, 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 treatmentEvery day during the Run-in, Treatment and Follow-up post treatment periods
Change from baseline in questionnaires at 12 weeks treatmentBaseline and 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

Global Response Assessment (GRA) at 0, 4, 8 and 12 weeks treatment and at 2 weeks follow-up post treatmentBaseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment

GRA is assessed as change from baseline which is here start of Run-in period

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 treatmentBaseline, 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 baselineBaseline, 4, 8 and 12 weeks treatment
Safety as assessed by SteatoTest, adiponectin and PVRBaseline and 12 weeks
Physician Withdrawal Checklist at 12 weeks treatment and at 2 weeks follow-up post treatment12 weeks treatment and 2 weeks follow-up post treatment

Trial Locations

Locations (60)

Site: 5101

🇧🇪

Antwerp, Belgium

Site: 5201

🇨🇿

Uherske Hradiste, Czechia

Site: 5209

🇨🇿

Plzen, Czechia

Site: 5202

🇨🇿

Kralove, Czechia

Site: 5406

🇩🇪

Duisburg, Germany

Site 5410

🇩🇪

Kirchheim, Germany

Site: 5601

🇱🇻

Riga, Latvia

Site: 5402

🇩🇪

Holzminden, Germany

Site: 5301

🇩🇰

Herlev, Denmark

Site: 5302

🇩🇰

Naestved, Denmark

Site 6201

🇪🇸

Barcelona, Spain

Site: 5103

🇧🇪

Brussels, Belgium

Site: 5203

🇨🇿

Kromeriz, Czechia

Site: 5210

🇨🇿

Sternberk, Czechia

Site: 5206

🇨🇿

Olomouc, Czechia

Site: 5303

🇩🇰

Aarhus, Denmark

Site: 5403

🇩🇪

Emmendingen, Germany

Site: 5409

🇩🇪

Frankfurt am Main, Germany

Site: 5405

🇩🇪

Mainz, Germany

Site: 5404

🇩🇪

Nurtingen, Germany

Site: 5805

🇵🇱

Piaseczno, Poland

Site: 5414

🇩🇪

Offenburg, Germany

Site: 5602

🇱🇻

Liepaja, Latvia

Site: 5703

🇳🇱

Maastricht, Netherlands

Site: 5603

🇱🇻

Riga, Latvia

Site: 5702

🇳🇱

Winterswijk, Netherlands

Site: 6301

🇱🇹

Vilnius, Lithuania

Site: 6304

🇱🇹

Kaunas, Lithuania

Site: 6302

🇱🇹

Vilnius, Lithuania

Site: 6303

🇱🇹

Vilnius, Lithuania

Site: 5706

🇳🇱

Amsterdam, Netherlands

Site: 5701

🇳🇱

Nijmegen, Netherlands

Site: 5704

🇳🇱

Zwijndrecht, Netherlands

Site: 5811

🇵🇱

Chorzow, Poland

Site 5806

🇵🇱

Bydgoszcz, Poland

Site: 5801

🇵🇱

Lodz, Poland

Site: 5803

🇵🇱

Warsaw, Poland

Site 5902

🇵🇹

Coimbra, Portugal

Site: 5804

🇵🇱

Warsaw, Poland

Site 5901

🇵🇹

Porto, Portugal

Site 6003

🇷🇴

Bucharest, Romania

Site 6004

🇷🇴

Bucharest, Romania

Site 6007

🇷🇴

Bucharest, Romania

Site 6002

🇷🇴

Bucharest, Romania

Site 6103

🇷🇺

Moscow, Russian Federation

Site 6108

🇷🇺

Moscow, Russian Federation

Site 6101

🇷🇺

Moscow, Russian Federation

Site 6106

🇷🇺

Moscow, Russian Federation

Site: 6111

🇷🇺

Moscow, Russian Federation

Site 6202

🇪🇸

Laguna, Tenerife, Spain

Site 6203

🇪🇸

Barcelona, Spain

Site 6102

🇷🇺

St.-Petersburg, Russian Federation

Site 6204

🇪🇸

Malaga, Spain

Site 6006

🇷🇴

Brasov, Romania

Site: 5807

🇵🇱

Bialystok, Poland

Site 6005

🇷🇴

Iasi, Romania

Site 5903

🇵🇹

Porto, Portugal

Site 6001

🇷🇴

Targu Mures, Romania

Site: 5812

🇵🇱

Poznan, Poland

Site: 5802

🇵🇱

Warsaw, Poland

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