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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01613586
First received: June 5, 2012
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cystitis, Interstitial
Urologic Diseases
Urinary Bladder Disease
Pain
Drug: ASP3652
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Subjects With Bladder Pain Syndrome / Interstitial Cystitis

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change from baseline in Mean Daily Pain (MDP) at 12 weeks [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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:
  • Change from baseline in Mean Daily Pain (MDP) at 4, 8 weeks treatment and at 2 weeks follow-up post treatment [ Time Frame: Baseline, 4 and 8 weeks treatment and 2 weeks follow-up post treatment ] [ Designated as safety issue: No ]
    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 treatment [ Time Frame: Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline, 4, 8, 12 weeks treatment and at 2 weeks follow-up post treatment ] [ Designated as safety issue: No ]
  • Daily pain, assessed with item 4 of the F-GUPI-24h during Run-in, Treatment period and Follow-up post treatment [ Time Frame: Every day during the Run-in, Treatment and Follow-up post treatment periods ] [ Designated as safety issue: No ]
  • Change from baseline in questionnaires at 12 weeks treatment [ Time Frame: Baseline and 12 weeks treatment ] [ Designated as safety issue: No ]
    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 treatment [ Time Frame: Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment ] [ Designated as safety issue: No ]
    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 treatment [ Time Frame: Baseline, 4, 8, 12 weeks treatment and 2 weeks follow-up post treatment ] [ Designated as safety issue: No ]
  • Proportion of responders: at least 7-point decrease in F-GUPI Total score at 0, 4, 8 and 12 weeks treatment compared to baseline [ Time Frame: Baseline, 4, 8 and 12 weeks treatment ] [ Designated as safety issue: No ]
  • Assessment of pharmacokinetics at week 4, 8 and 12 [ Time Frame: 4, 8 and 12 weeks treatment ] [ Designated as safety issue: No ]
    Plasma levels of ASP3652

  • Assessment of pharmacodynamics at week 4, 8 and 12 [ Time Frame: 4, 8 and 12 weeks treatment ] [ Designated as safety issue: No ]
    Plasma levels of anandamides

  • Safety as assessed by recording Adverse Events, Laboratory tests, electrocardiograms (ECGs) and vital signs [ Time Frame: Baseline and 12 weeks treatment ] [ Designated as safety issue: Yes ]
  • Safety as assessed by SteatoTest, adiponectin and PVR [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in questionnaires (Center for Epidemiologic Studies Depression Scale and Profile of Mood States questionnaire) at 12 weeks treatment [ Time Frame: Baseline and 12 weeks treatment ] [ Designated as safety issue: Yes ]
  • Physician Withdrawal Checklist at 12 weeks treatment and at 2 weeks follow-up post treatment [ Time Frame: 12 weeks treatment and 2 weeks follow-up post treatment ] [ Designated as safety issue: Yes ]

Enrollment: 287
Study Start Date: May 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose ASP3652 twice daily Drug: ASP3652
Oral
Experimental: Medium dose ASP3652 twice daily Drug: ASP3652
Oral
Experimental: High dose ASP3652 twice daily Drug: ASP3652
Oral
Placebo Comparator: Placebo Drug: Placebo
Oral

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01613586

  Show 60 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Director: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01613586     History of Changes
Other Study ID Numbers: 3652-CL-0018, 2011-004555-39
Study First Received: June 5, 2012
Last Updated: March 26, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health

Keywords provided by Astellas Pharma Inc:
Interstitial Cystitis
Bladder Pain Syndrome
Painful Bladder Syndrome
ASP3652

Additional relevant MeSH terms:
Syndrome
Cystitis, Interstitial
Cystitis
Urologic Diseases
Urinary Bladder Diseases
Disease
Pathologic Processes

ClinicalTrials.gov processed this record on September 18, 2014