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

Pain Clinical Trial

— AMARANTH  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01613586
• Other study ID #: 3652-CL-0018
• Secondary ID: 2011-004555-39
• Status: Completed
• Phase: Phase 2
• Start date: May 31, 2012
• Est. completion date: March 18, 2014

Study information

• Verified date: January 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 287
• Est. completion date: March 18, 2014
• Est. primary completion date: March 18, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystitis
• Cystitis, Interstitial
• Pain
• Syndrome
• Urinary Bladder Disease
• Urinary Bladder Diseases
• Urologic Diseases

Intervention

Drug:
• ASP3652
Oral
• Placebo
Oral

Locations

Country	Name	City	State
Belgium	Site: 5101	Antwerp
Belgium	Site: 5103	Brussels
Czechia	Site: 5202	Kralove
Czechia	Site: 5203	Kromeriz
Czechia	Site: 5206	Olomouc
Czechia	Site: 5209	Plzen
Czechia	Site: 5210	Sternberk
Czechia	Site: 5201	Uherske Hradiste
Denmark	Site: 5303	Aarhus
Denmark	Site: 5301	Herlev
Denmark	Site: 5302	Naestved
Germany	Site: 5406	Duisburg
Germany	Site: 5403	Emmendingen
Germany	Site: 5409	Frankfurt am Main
Germany	Site: 5402	Holzminden
Germany	Site 5410	Kirchheim
Germany	Site: 5405	Mainz
Germany	Site: 5404	Nurtingen
Germany	Site: 5414	Offenburg
Latvia	Site: 5602	Liepaja
Latvia	Site: 5601	Riga
Latvia	Site: 5603	Riga
Lithuania	Site: 6304	Kaunas
Lithuania	Site: 6301	Vilnius
Lithuania	Site: 6302	Vilnius
Lithuania	Site: 6303	Vilnius
Netherlands	Site: 5706	Amsterdam
Netherlands	Site: 5703	Maastricht
Netherlands	Site: 5701	Nijmegen
Netherlands	Site: 5702	Winterswijk
Netherlands	Site: 5704	Zwijndrecht
Poland	Site: 5807	Bialystok
Poland	Site 5806	Bydgoszcz
Poland	Site: 5811	Chorzow
Poland	Site: 5801	Lodz
Poland	Site: 5805	Piaseczno
Poland	Site: 5812	Poznan
Poland	Site: 5802	Warsaw
Poland	Site: 5803	Warsaw
Poland	Site: 5804	Warsaw
Portugal	Site 5902	Coimbra
Portugal	Site 5901	Porto
Portugal	Site 5903	Porto
Romania	Site 6006	Brasov
Romania	Site 6002	Bucharest
Romania	Site 6003	Bucharest
Romania	Site 6004	Bucharest
Romania	Site 6007	Bucharest
Romania	Site 6005	Iasi
Romania	Site 6001	Targu Mures
Russian Federation	Site 6101	Moscow
Russian Federation	Site 6103	Moscow
Russian Federation	Site 6106	Moscow
Russian Federation	Site 6108	Moscow
Russian Federation	Site: 6111	Moscow
Russian Federation	Site 6102	St.-Petersburg
Spain	Site 6201	Barcelona
Spain	Site 6203	Barcelona
Spain	Site 6202	Laguna	Tenerife
Spain	Site 6204	Malaga

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Countries where clinical trial is conducted

Belgium,  Czechia,  Denmark,  Germany,  Latvia,  Lithuania,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Assessment of pharmacokinetics at week 4, 8 and 12	Plasma levels of ASP3652	4, 8 and 12 weeks treatment
Secondary	Assessment of pharmacodynamics at week 4, 8 and 12	Plasma levels of anandamides	4, 8 and 12 weeks treatment
Secondary	Safety as assessed by recording Adverse Events, Laboratory tests, electrocardiograms (ECGs) and vital signs		Baseline and 12 weeks treatment
Secondary	Safety as assessed by SteatoTest, adiponectin and PVR		Baseline and 12 weeks
Secondary	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
Secondary	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

External Links

•   Link to results on the Astellas Clinical Study Results website