Double-Blind Placebo Controlled Study of Safety,Tolerability, and Efficacy of LiRIS® in Women With Interstitial Cystitis

Study Overview
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Brief Summary
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The purpose of this study is to determine if LiRIS®, an investigational drug-delivery system, is safe, tolerable and effective in women with Interstitial Cystitis. LiRIS® is inserted into the bladder via cystoscopy , remains in the bladder for 14 days, and is removed via cystoscopy.

Detailed Description
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The study is conducted in 2 parts - a randomized, blinded part in which patients are randomly assigned to one of 3 possible arms (LiRIS® - contains lidocaine), LiRIS Placebo (LiRIS with inactive substance) or Sham(Insertion procedure only with neither LiRIS nor LiRIS Placebo), followed by an open extension part in which all patients are assigned to receive LiRIS® (with lidocaine). In part 1 of the study, treatment is managed in a double-blind manner for LiRIS® and LiRIS Placebo arms; and in a single-blind manner for the Sham arm (e.g.,the study doctor will know the treatment assignment for patients assigned to Sham). All patients who complete part 1 of the study have the option to enter the extension.

Official Title
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A Phase 2a Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Safety, Tolerability and Efficacy of LiRIS® in Women With Interstitial Cystitis Followed by an Open Label Extension

Conditions
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Interstitial Cystitis

Intervention / Treatment
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* Drug: Lidocaine Releasing Intravesical System - LiRIS®
* Other: LiRIS Placebo
* Procedure: Sham Cystoscopy Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women age 18 and over Diagnosed with Interstitial Cystitis as defined by protocol Able and willing to complete questionnaires and diary Able to comply with visit schedule including Day 14 Removal visit Completion of blinded study prior to enrolling in unblinded part of study Exclusion Criteria: Pregnant or lactating women Bladder or urethra anatomical feature that would prevent the safe indwelling or insertion of the investigational product History or presence of any condition that would make it difficult to evaluate symptoms Did not complete blinded study (unblinded part of study only)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine Releasing Intravesical System<br>Lidocaine Releasing Intravesical System (LiRIS®) is inserted into the bladder via cystoscopy on Study Day 0 and removed on Study Day 14. LiRIS releases lidocaine gradually during the 14 day indwelling period. | Drug: Lidocaine Releasing Intravesical System - LiRIS®<br>* Lidocaine Releasing Intravesical System (LiRIS®) is inserted into the bladder via cystoscopy on Study Day 0 and removed on Study Day 14. LiRIS releases lidocaine gradually during the 14 day indwelling period.<br>* Other names: LiRIS® 400 mg (Active);|
| Placebo Comparator: LiRIS containing inactive substance only<br>LiRIS Placebo is inserted into the bladder via cystoscopy on study Day 0 and removed via cystoscopy on study Day 14. | Other: LiRIS Placebo<br>* LiRIS Placebo contains inactive substance only; LiRIS Placebo is inserted into the bladder via cystoscopy on study Day 0 and removed via cystoscopy on study Day 14.<br>* Other names: LiRIS® 400 mg Placebo;|
| Sham Comparator: Cystoscopy Procedure<br>No intervention. Cystoscopy procedure is performed on study Day 0 and study Day 14 to mimick active and placebo study arms without insertion of Investigational Product into the bladder. | Procedure: Sham Cystoscopy Procedure<br>* Cystoscopy procedure only; no investigational product is inserted/removed from the bladder.<br>* Other names: Sham arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Participant Reported Bladder Pain as Assessed by a Visual Analog Scale (VAS) at Day 7 | Participant reported symptom of bladder pain in the prior 24 hours using a 10 centimeter (cm) horizontal line Pain Visual Analog Scale recorded in a diary. Participants were instructed to to put a mark on the line at the point that best described their bladder pain with 0 (far left on the line) reflecting no pain and 10 (far right on the line) reflecting worse possible pain. A negative change from Baseline indicates improvement. | Baseline, Day 7 | 
| Change From Baseline in Participant Reported Bladder Pain as Assessed by a Visual Analog Scale (VAS) at Day 14 | Participant reported symptom of bladder pain in the prior 24 hours using a 10 centimeter horizontal line Pain Visual Analog Scale recorded in a diary. Participants were instructed to to put a mark on the line at the point that best described their bladder pain with 0 (far left on the line) reflecting no pain and 10 (far right on the line) reflecting worse possible pain. A negative change from Baseline indicates improvement. | Baseline, Day 14 | 
| Change From Baseline in Participant Reported Bladder Pain as Assessed by a Visual Analog Scale (VAS) ay Day 28 | Participant reported symptom of bladder pain in the prior 24 hours using a 10 centimeter horizontal line Pain Visual Analog Scale recorded in a diary. Participants were instructed to to put a mark on the line at the point that best described their bladder pain with 0 (far left on the line) reflecting no pain and 10 (far right on the line) reflecting worse possible pain. A negative change from Baseline indicates improvement. | Baseline, Day 28 | 
| Change From Baseline in Participant Reported Bladder Pain as Assessed by a Visual Analog Scale (VAS) at Day 42 | Participant reported symptom of bladder pain in the prior 24 hours using a 10 centimeter horizontal line Pain Visual Analog Scale recorded in a diary. Participants were instructed to to put a mark on the line at the point that best described their bladder pain with 0 (far left on the line) reflecting no pain and 10 (far right on the line) reflecting worse possible pain. A negative change from Baseline indicates improvement. | Baseline, Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders Using the Global Response Assessment (GRA) | Participants assessed their response to treatment using a seven item scale from Markedly improved to Markedly worse. A responder was defined as a participant who rated their symptoms as either Moderately or Markedly improved. | Baseline, Days 7, 14, 28 and 42 | 
| Change From Baseline in Urinary Urgency as Assessed by VAS | Urinary urgency was defined as an immediate unstoppable urge to urinate which may be due to a sudden involuntary contraction of the muscular wall of the bladder and may be accompanied by discomfort in the bladder. Participants reported symptom of urinary urgency in the last 24 hours using a Urgency Visual Analogue Scale (VAS). The Urgency VAS consists of a 10 centimeter (cm) horizontal line with the words No Urgency (best) at the left end (0 cm) and the words Urgency as bad as you can imagine (worst) at the right end (10 cm). Participants were instructed to complete the Pain VAS by marking the spot on the line that corresponded to their urinary urgency. A negative change from Baseline indicates improvement. | Baseline, Days 7, 14, 28 and 42 | 
| Change From Baseline in Voiding Frequency | Participants recorded Voiding Frequency in a 72 hour voiding log at Day 7, 14, 28 and 42. Lower numbers of voiding frequency is the best. A negative change from Baseline indicates improvement. | Baseline, Days 7, 14, 28 and 42 | 
| Change Form Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score | Participants answered four questions about bladder/voiding symptoms over the past month. 2 questions were on a scale of 0=Not at all to 5=Almost always, 1 question on a scale of 0=Not at all to 5=5 or more times per night and 1 questions from 0=Not at all to 4=Almost always for a total possible score of 0 (best) to19 (worst). A negative change from Baseline indicates improvement | Baseline, Days 7, 14, 28 and 42 | 
| Change From Baseline in Interstitial Cystitis Problem Index (ICPI) Score | Participants answered four questions about how bothersome their symptoms were over the past month using a 5 point scale: 1=No problem to 4=Big problem for a total possible score of 0 (best) to 16 worst). A negative change from Baseline indicates improvement. | Baseline, Days 7, 14, 28 and 42 | 
| Percentage of Participants With Change From Baseline in Cystoscopic Examination Findings | Cystoscopic examinations were performed at Baseline and Day 14. The investigator assessed the urethra and bladder for the following: visibility of ureters, stricture, erythema, presence and number of Hunner's lesion(s) and the extent of erythema. For sites with the capability, videography or high resolution digital photographs of the bladder were taken. The findings at Day 14 were compared to the findings at Baseline and were reported as Improvement, Worsening or No Change. | Baseline, Day 14 |