Safety, Tolerability and Efficacy Study of LiRIS® 400 mg in Women With Interstitial Cystitis

Study Overview
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Brief Summary
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The purposes of the study is to determine if LiRIS®, an investigational drug-delivery system, is safe and tolerable in women with Interstitial Cystitis (IC), and to evaluate any change in IC symptoms following LiRIS administration.

Detailed Description
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The study is conducted in 2 parts: a randomized, blinded part in which subjects are assigned randomly (by chance) to LiRIS 400 mg or LiRIS placebo; subjects who complete this part and are eligible to continue, may participate in the open-label part in which all subjects receive LiRIS 400 mg. In both parts of the study (blinded and open-label), LiRIS is inserted into the bladder during cystoscopy, remains in the bladder for 14 days, and is removed during cystoscopy. In addition to the 14 day period with the LiRIS/LiRIS Placebo, there is a screening period of up to 2 weeks and a follow up period of 4 weeks.

Official Title
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A Phase 2 Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Safety, Tolerability and Efficacy of LiRIS® 400 mg 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: LiRIS 400 mg
* Other: LiRIS Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Blinded study: Women age 18 and over Diagnosed with Interstitial Cystitis as defined by protocol Able to report IC symptoms of bladder pain, voiding habits, as required by protocol, and record in diary Able to comply with visit schedule and diary completion at home Open-label Extension: Must have completed the blinded study prior to screening for the Open-label extension Exclusion Criteria (Blinded and Open-Label Extension): Pregnant or lactating women History or presence of any condition that would make it difficult to accurately evaluate bladder symptoms Bladder or urethral abnormality that would prevent safe insertion of investigational product Requiring medication not allowed per study protocol

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LiRIS 400 mg<br>LiRIS 400 mg: investigational drug-delivery system which contains Lidocaine; the system remains in the bladder for 14 days. If eligible, participants could participate in the Open Label Extension where all participants were treated with LiRIS 400 mg. | Drug: LiRIS 400 mg<br>* LiRIS 400 mg contains lidocaine which is gradually released into the bladder over 14 days.<br>|
| Placebo Comparator: LiRIS Placebo<br>LiRIS Placebo: investigational drug-delivery system which contains Lactose and no Lidocaine; the system remains in the bladder for 14 days. If eligible, participants could participate in the Open Label Extension where all participants were treated with LiRIS 400 mg. | Other: LiRIS Placebo<br>* LiRIS Placebo contains lactose, inactive substance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS) | Participants rated their bladder pain over the previous 24 hours in an electronic diary using a horizontal line NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. Bladder pain was averaged over a period of 3 days. A negative change from Baseline indicates improvement. | Baseline, Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Daily Voids | Participants recorded number of daily voids (day-time and night-time daily voids) in a 3 day Voiding Frequency electronic diary. The total number of daily voids was averaged over a period of 3 full days. A negative change from Baseline indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in Night-Time Daily Voids | Participants recorded number of night-time daily voids in a 3 day Voiding Frequency electronic diary. The total number of night-time daily voids was averaged over a period of 3 days. A negative change from Baseline indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in Average Void Volume Per Micturition | Participants recorded the amount of each void in millimeters (mL) in an electronic diary. The total amount of void per micturition (each void) was averaged over a period of 24 days. A negative change from Baseline indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in Post-Void Bladder Pain | Participants rated their bladder pain immediately completing voiding in an electronic diary using a horizontal line NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. The average of the data from the first 5 voids prior to Baseline and the 3 days prior to Day 12 were averaged for analyses. A negative change from Baseline indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score | The ICSI is a participant reported questionnaire to rate their symptoms by answering 4 questions. Question (Q) 1 and 2 (urine urgency) using a 6-point scale where: 0=Not at All to 5=Almost Always. Q3 (night-time voids) using a 6-point scale where: 0=None to 5=5 or More Times. Q4 (pain and burning) using a 6-point scale where: 0=Not at All to 5=Usually. The total score is the sum of the individual scores for a total possible score of 0 (best) to 20 (worst). A negative change from Baseline indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) Score | The ICPI is a participant reported questionnaire to rate their problems in the following 4 areas: Frequent urination; Getting up at Night to Urinate: Urination with little warning; Burning pain and discomfort. Questions are answered on a 5-point scale where: 0=No Problem to 4=Big Problem. The total score is the sum of the individual scores for a total possible score of 0 (best) to 20 (worst). A negative change from Baseline indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) | The BPIC-SS is a participant reported questionnaire consisting of 8 items. Questions (Q) 1-5 (How often urination because of pain; Need to urinate after just urinating; How often urination to avoid worse pain; How often feeling of pressure in bladder; How often pain in bladder) answered on a 5-point scale where: 0=Never to 4=Always. Q 6-7 (Bothered by frequent Day-time urination; Bothered by Night-time urination) answered on a 5-point scale where: 0=Not At All to 4=A Great Deal. Q8 (pain) rated on a NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. The Total Score is the sum of the individual questionnaire of all 8 items for a total possible score of 0 (best) to 38 (worst). A negative change indicates improvement. | Baseline, Day 27 | 
| Change From Baseline in Brief Pain Inventory (BPI) | The BPI is a 7-item participant completed questionnaire. The participant answered questions as to how pain interfered with: General Activity, Mood, Walking Ability, Normal work, Relations with other people, Sleep and Enjoyment of life. Questions were answered on an 11-point scale where: 0=Does not interfere to 10=Completely interferes. The total score is the average of the individual questionnaire items for a total possible score of 0 (best) to 10 (worst). A negative change from Baseline indicates improvement. | Baseline, Day 27 |