A Study To Investigate Tanezumab In Patients With Interstitial Cystitis/ Painful Bladder Syndrome

Study Overview
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Brief Summary
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In a previous study in patients with interstitial cystitis/ painful bladder syndrome (IC/PBS), tanezumab has shown to be efficacious in relieving the pain associated with IC/PBS, as well as some effect on reducing urinary urgency. Only one dose was studied, and tanezumab was well tolerated. In this study, the hypothesis being tested is that tanezumab will show efficacy at several doses on reducing pain with sufficient tolerability. Tanezumab's safety will also be assessed at different dose levels

Detailed Description
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This study was terminated on 16 November 2010 following a US FDA partial clinical hold for the tanezumab interstitial cystitis clinical study announced on 19 July 2010 for potential safety issues, and following a pre-planned interim analysis.

Official Title
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A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE RANGING STUDY EVALUATING THE EFFICACY AND SAFETY OF TANEZUMAB FOR THE TREATMENT OF MODERATE TO SEVERE PAIN ASSOCIATED WITH INTERSTITIAL CYSTITIS/ PAINFUL BLADDER SYNDROME (IC/PBS).

Conditions
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Cystitis, Interstitial

Intervention / Treatment
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* Biological: Tanezumab
* Biological: Tanezumab
* Biological: Tanezumab
* Biological: Tanezumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with interstitial cystitis/ painful bladder syndrome for more than 6 months with moderate to severe pain and a micturition frequency greater than 7 per day. Patients who have been on stable oral medicines for interstitial cystitis/ painful bladder syndrome for at least 3 months. Other therapies might need to be stopped. Exclusion Criteria: Patients on certain recent treatments for interstitial cystitis/ painful bladder syndrome. Body mass index (BMI) of >39 kg/m2. History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein. Patients with peripheral neuropathy. Patients with Type I or type II diabetes mellitus who have an HbA1c > 8.0%.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Biological: Tanezumab<br>* 1 mg dose given subcutaneously twice at an 8-week interval.<br>|
| Experimental: Group 2<br> | Biological: Tanezumab<br>* 2.5 mg dose given subcutaneously twice at an 8-week interval.<br>|
| Experimental: Group 3<br> | Biological: Tanezumab<br>* 10 mg dose given subcutaneously twice at an 8-week interval.<br>|
| Experimental: Group 4<br> | Biological: Tanezumab<br>* 20 mg dose given subcutaneously twice at an 8-week interval.<br>|
| Placebo Comparator: Group 5<br> | Other: Placebo<br>* Placebo dose given subcutaneously twice at an 8-week interval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Average Daily Pain Score at Week 8 | Average daily pain score was defined as the mean of the last 7 daily diary pain ratings prior to each assessment time point. Participants rated their average bladder pain due to interstitial cystitis/painful bladder syndrome (IC/PBS) over the past 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 = no bladder pain to 10 = worst possible bladder pain. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Average Daily Pain Score at Week 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 | Average daily pain score was defined as the mean of the last 7 daily diary pain ratings prior to each assessment time point. Participants rated their average bladder pain due to interstitial cystitis/painful bladder syndrome (IC/PBS) over the past 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 = no bladder pain to 10 = worst possible bladder pain. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 | 
| Percentage of Participants Who Achieved At Least 30 Percent (%) and 50% Reduction in Mean Average Daily Pain Score | Average daily pain score was defined as the mean of the last 7 daily diary pain ratings prior to each assessment time point. Participants rated their average bladder pain due to interstitial cystitis/painful bladder syndrome (IC/PBS) over the past 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 = no bladder pain to 10 = worst possible bladder pain. | Week 8, 16 | 
| Change From Baseline in Mean Worst Daily Pain Score at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 | Worst daily pain score was defined as the mean of the last 7 daily diary pain ratings prior to each assessment time point. Participants rated their worst bladder pain due to IC/PBS over the past 24 hours on an 11-point NRS ranging from 0 = no bladder pain to 10 = worst possible bladder pain. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 | 
| Patient Global Assessment of Health Status Scores | Participants answered: Considering all the ways your bladder condition (IC/PBS) affects you, how are you doing today? Participants responded on a 5-point scale where 1 = very good and 5 = very poor. | Baseline, Week 2, 8, 16, 24 | 
| Number of Participants With Global Response Assessment Scores | Participants were asked: compared to when you began this trial, how would you rate your IC/PBS symptoms now? Participants responded by using a 7-point symmetric scale where 1 = markedly worse, 2 = moderately worse, 3 = slightly worse, 4 = no change, 5 = slightly improved, 6 = moderately improved, and 7 = markedly improved. | Week 8, 16, 24 | 
| Number of Micturitions Per 24 Hours | The micturition frequency per 24 hours was calculated from the sum of voids divided by the diary period over which they were collected. | Baseline, Week 4, 8, 12, 16, 20, 24 | 
| Number of Nocturnal Micturitions Per 24 Hours | The nocturnal frequency per 24 hours was defined as the number of voids after going to bed and before getting up (the times of going to bed and getting up were recorded in the diary). The nocturnal micturition per 24 hours was calculated as the sum of voluntary voids that occurred during a night's sleep, divided by the number of nights over which this was collected. | Baseline, Week 4, 8, 12, 16, 20, 24 | 
| Number of Micturition-related Urgency Episodes Per 24 Hours | The micturition urgency frequency per 24 hours was calculated as the sum of urgency episodes (when participant had to rush to get to the bathroom to urinate) occurring during the diary period when this was measured, divided by the number of days over which they were recorded. | Baseline, Week 4, 8, 12, 16, 20, 24 | 
| Participant's Urge to Urinate | Participants completed 7-item questionnaire assessing their urge to urinate over the past 24 hours. The items were assessed on a 5-point response scale ranging from 0 (never) to 4 (always). Urge to urinate was calculated as the total of the 7 'urge' items with a minimum total score of 0 and a maximum total score of 28. Higher scores indicated greater symptom severity. An average was determined from the 3 days recorded in the 7-day diary period prior to each assessment time point. | Baseline, Week 4, 8, 12, 16, 20, 24 | 
| Mean Voided Volume Per Micturition | Mean volume voided per micturition was calculated as the total urine volume voided during the diary period when this was measured over 1 day, divided by the number of voids (with non missing volumes) during that day. | Baseline, Week 4, 8, 12, 16, 20, 24 | 
| O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score | The ICSI contained 4 questions that measured symptom severity including urinary urgency, urinary frequency, nocturia and pain/burning in the bladder. Each question in the ICSI was rated on a 0-5 scale. The sum of the individual question ratings was the total score for the ICSI. Total scores ranged from 0 to 20, with higher scores indicating greater symptom severity and bother. | Baseline, Week 2, 8, 16, 24 | 
| Brief Pain Inventory-Short Form (BPI-sf) Score | BPI-sf is a 7-item self-administered questionnaire to assess the pain severity and pain interference on daily functions. Pain Severity Index (PSI) is an average of Questions 2-5 which measured the severity of pain (worst, least, average, right now) over past 24-hours on an 11-point scale (0=no pain to 10=pain as bad as you can imagine). Pain Interference Index (PII) is an average of 7 pain interference items of Question 7 that measured the level of interference of pain on daily function (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life) on an 11-point scale (0=did not interfere to 10=completely interfered). Pain Severity Index and Pain Interference Index total scores ranged from 0 to 10, where higher scores indicate greater pain or greater interference. | Baseline, Week 8, 16, 24 | 
| Number of Participants With Patient Global Satisfaction Assessment Scores | Participant global satisfaction is assessed using Patient Reported Treatment Impact (PRTI) which is a self-administered questionnaire containing 4 items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. Participants were asked: Overall, how satisfied are you with the drug that you received since you entered this trial? Participant's response is rated on a 5-point scale where 1=extremely dissatisfied (dissatisf), 2=dissatisfied, 3=neither satisfied nor dissatisfied (satisfy/dissatisfy), 4=satisfied and 5=extremely satisfied. Number of participants with each response is reported. | Week 8, 16, 24 | 
| Number of Participants With Patient Global Preference Assessment Score | Participant global preference is assessed using PRTI which is self-administered questionnaire containing 4 items to assess participant satisfaction, previous treatment (T/T), preference and willingness to continue using study medication. Participant reported previous T/T under following categories: lifestyle interventions, physical therapies, toileting programs, drug given into bladder, drug taken by mouth, surgery, and no T/T. Participant preference was assessed on a 5-point scale where, 1=No, I definitely prefer my prior T/T (Def Pref Prior), 2=I have a slight preference for my prior T/T (Slight Pref Prior T/T), 3=I have no preference either way (No preference), 4=I have a slight preference for the drug that I am receiving now (Slight Pref Current), 5=Yes, I definitely prefer the drug that I am receiving (Def Pref Current Drug) now. Number of participants under each of the categories is reported. For previous T/T, a single participant may be represented in more than 1 category. | Week 8, 16, 24 | 
| Number of Participants With Willingness to Re-use Medicine Assessment | Participant willingness to re-use study medication is assessed using PRTI which is a self-administered questionnaire containing four items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. Participants were asked: In the future, would you be willing to use the same drug that you have received since you entered this trial for your chronic prostatitis? Participants responded on 5-point scale where, 1=No, I definitely would not want to use the same drug again (definitely not want), 2=I might not want to use the same drug again (might not want), 3=I am not sure (not sure), 4=I might want to use the same drug again (might want), 5=Yes, I would definitely want to use the same drug again (definitely want). | Week 8, 16, 24 | 
| Euro Quality of Life (EQ-5D) - Health State Profile Utility Score | EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Baseline, Week 8, 16, 24 | 
| Painful Bladder/Interstitial Cystitis Quality of Life Questionnaire (PBIC-QoL) Total Score | PBIC-QoL: 25-item questionnaire to assess impact of IC/PBS on health related quality of life over past 7 days. PBIC-QoL included 17 items (Items 2, 5, 8, 11, 14, 18, 20 and 21 did not form part of final instrument), of which 13 were divided into 3 dimensions: activity limitations (Items 1, 3, 4, 6, 7), impact on emotional wellbeing (Items 13, 15, 16, 17, 19), impact on sleep (Items 22, 23, 24). Four items: Item 9 (impact on going out with friends), Item 10 (impact on concentration), Item 12 (impact on eating and drinking), Item 25 (impact on sex life) were scored separately to dimension scores as single items. Items were scored from 4 'not at all' to 0 'extremely difficult' or 'a very great deal'. Eight items included a 'not applicable' response option. Dimension scores ranged from 0 to 4, higher score indicate better quality of life. Total score=sum of the dimension and single item scores, ranged from 0 to 28, higher score indicated better quality of life. | Baseline, Week 2, 8, 16, 24 | 
| Percentage of Participants Who Received Rescue Medication | For inadequate pain relief or worsening symptoms of IC/PBS, participants took acetaminophen up to 3000 mg per day (1500 mg/day for Japanese population) as rescue medication. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 | 
| Number of Days of Rescue Medication Usage Per Week | In case of inadequate pain relief or worsening symptoms of IC/PBS, participants took acetaminophen up to 3000 mg per day (1500 mg/day for Japanese population) as rescue medication. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 | 
| Number of Rescue Medication Doses Used Per Week | In case of inadequate pain relief or worsening symptoms of IC/PBS, participants took acetaminophen up to 3000 mg per day (1500 mg/day for Japanese population) as rescue medication. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 | 
| Amount of Rescue Medication Taken Per Week | In case of inadequate pain relief or worsening symptoms of IC/PBS, acetaminophen up to 3000 mg per day (1500 mg/day for Japanese population) could be taken as rescue medication. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 | 
| Serum Total Nerve Growth Factor (NGF) Levels | Serum samples were analyzed for total NGF using a validated, sensitive and specific immunoaffinity enrichment liquid chromatography tandem mass spectrometric method (IA/LC/MS/MS) method. | Baseline, Week 1, 2, 8, 16, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized double blind placebo-controlled parallel-group dose-range finding interstitial cystitis efficacy pain urinary symptoms safety