Clinical trial NCT01613586: A Randomized Study Comparing Placebo and ASP3652 in the Treatment of Women With Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystitis, Interstitial
Urinary Bladder Disease
Pain
Urologic Diseases
Keywords: ASP3652
Painful Bladder Syndrome
Interstitial Cystitis
Bladder Pain Syndrome
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-06-07
Enrollment: 287
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in Mean Daily Pain (MDP) at 12 weeks
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change from baseline in Mean Daily Pain (MDP) at 4, 8 weeks treatment and at 2 weeks follow-up post treatment
timeFrame: Baseline, 4 and 8 weeks treatment and 2 weeks follow-up post treatment
measure: 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
timeFrame: Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment
measure: 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
timeFrame: Baseline, 4, 8, 12 weeks treatment and at 2 weeks follow-up post treatment
measure: Daily pain, assessed with item 4 of the F-GUPI-24h during Run-in, Treatment period and Follow-up post treatment
timeFrame: Every day during the Run-in, Treatment and Follow-up post treatment periods
measure: Change from baseline in questionnaires at 12 weeks treatment
timeFrame: Baseline and 12 weeks treatment
measure: Global Response Assessment (GRA) at 0, 4, 8 and 12 weeks treatment and at 2 weeks follow-up post treatment
timeFrame: Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment
measure: 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
timeFrame: Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment
measure: Proportion of responders: at least 7-point decrease in F-GUPI Total score at 0, 4, 8 and 12 weeks treatment compared to baseline
timeFrame: Baseline, 4, 8 and 12 weeks treatment
measure: Assessment of pharmacokinetics at week 4, 8 and 12
timeFrame: 4, 8 and 12 weeks treatment
measure: Assessment of pharmacodynamics at week 4, 8 and 12
timeFrame: 4, 8 and 12 weeks treatment
measure: Safety as assessed by recording Adverse Events, Laboratory tests, electrocardiograms (ECGs) and vital signs
timeFrame: Baseline and 12 weeks treatment
measure: Safety as assessed by SteatoTest, adiponectin and PVR
timeFrame: Baseline and 12 weeks
measure: Change from baseline in questionnaires (Center for Epidemiologic Studies Depression Scale and Profile of Mood States questionnaire) at 12 weeks treatment
timeFrame: Baseline and 12 weeks treatment
measure: Physician Withdrawal Checklist at 12 weeks treatment and at 2 weeks follow-up post treatment
timeFrame: 12 weeks treatment and 2 weeks follow-up post treatment
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Site: 5101
city: Brussels
country: Belgium
facility: Site: 5103
city: Kralove
country: Czechia
facility: Site: 5202
city: Kromeriz
country: Czechia
facility: Site: 5203
city: Olomouc
country: Czechia
facility: Site: 5206
city: Plzen
country: Czechia
facility: Site: 5209
city: Sternberk
country: Czechia
facility: Site: 5210
city: Uherske Hradiste
country: Czechia
facility: Site: 5201
city: Aarhus
country: Denmark
facility: Site: 5303
city: Herlev
country: Denmark
facility: Site: 5301
city: Naestved
country: Denmark
facility: Site: 5302
city: Duisburg
country: Germany
facility: Site: 5406
city: Emmendingen
country: Germany
facility: Site: 5403
city: Frankfurt am Main
country: Germany
facility: Site: 5409
city: Holzminden
country: Germany
facility: Site: 5402
city: Kirchheim
country: Germany
facility: Site 5410
city: Mainz
country: Germany
facility: Site: 5405
city: Nurtingen
country: Germany
facility: Site: 5404
city: Offenburg
country: Germany
facility: Site: 5414
city: Liepaja
country: Latvia
facility: Site: 5602
city: Riga
country: Latvia
facility: Site: 5601
city: Riga
country: Latvia
facility: Site: 5603
city: Kaunas
country: Lithuania
facility: Site: 6304
city: Vilnius
country: Lithuania
facility: Site: 6302
city: Vilnius
country: Lithuania
facility: Site: 6301
city: Vilnius
country: Lithuania
facility: Site: 6303
city: Amsterdam
country: Netherlands
facility: Site: 5706
city: Maastricht
country: Netherlands
facility: Site: 5703
city: Nijmegen
country: Netherlands
facility: Site: 5701
city: Winterswijk
country: Netherlands
facility: Site: 5702
city: Zwijndrecht
country: Netherlands
facility: Site: 5704
city: Bialystok
country: Poland
facility: Site: 5807
city: Bydgoszcz
country: Poland
facility: Site 5806
city: Chorzow
country: Poland
facility: Site: 5811
city: Lodz
country: Poland
facility: Site: 5801
city: Piaseczno
country: Poland
facility: Site: 5805
city: Poznan
country: Poland
facility: Site: 5812
city: Warsaw
country: Poland
facility: Site: 5802
city: Warsaw
country: Poland
facility: Site: 5804
city: Warsaw
country: Poland
facility: Site: 5803
city: Coimbra
country: Portugal
facility: Site 5902
city: Porto
country: Portugal
facility: Site 5903
city: Porto
country: Portugal
facility: Site 5901
city: Brasov
country: Romania
facility: Site 6006
city: Bucharest
country: Romania
facility: Site 6003
city: Bucharest
country: Romania
facility: Site 6004
city: Bucharest
country: Romania
facility: Site 6007
city: Bucharest
country: Romania
facility: Site 6002
city: Iasi
country: Romania
facility: Site 6005
city: Targu Mures
country: Romania
facility: Site 6001
city: Moscow
country: Russian Federation
facility: Site 6108
city: Moscow
country: Russian Federation
facility: Site 6103
city: Moscow
country: Russian Federation
facility: Site: 6111
city: Moscow
country: Russian Federation
facility: Site 6106
city: Moscow
country: Russian Federation
facility: Site 6101
city: St.-Petersburg
country: Russian Federation
facility: Site 6102
city: Laguna
country: Spain
facility: Site 6202
state: Tenerife
city: Barcelona
country: Spain
facility: Site 6203
city: Barcelona
country: Spain
facility: Site 6201
city: Malaga
country: Spain
facility: Site 6204
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_DIRECTOR
References: