Engage 24: Evaluation of the Safety and Effectiveness of URG101 in Subjects With Interstitial Cystitis/Bladder Pain Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine if the combination product (URG101) is safe and effective versus its individual components (Heparin Sodium and Lidocaine Hydrochloride) for the treatment of Interstitial Cystitis/Bladder Pain Syndrome. The study is randomized and double-blinded such that neither the subject nor doctor will know which drug or placebo is received.

Detailed Description
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This is a Phase 2a, randomized, double-blind, placebo controlled, multicenter, single-dose, pharmacokinetic study designed to determine the efficacy and safety of the combination product (URG101) compared with its individual components (Heparin Sodium and Lidocaine Hydrochloride). Eligible subjects exhibiting moderate to severe symptoms of bladder pain associated with their diagnosis of interstitial cystitis/bladder pain syndrome who have signed informed consent, will be screened and provisionally enrolled for intravesical treatment. On the day of study drug administration subjects will be randomized (2:1:2:1; URG101:placebo:lidocaine:heparin) and will receive a single administration of one of four intravesical treatments in a blinded fashion, based on random assignment: URG101 (buffered lidocaine-heparin) Placebo (phosphate buffer) Lidocaine hydrocholoride buffered alone Heparin sodium buffered alone Efficacy and safety assessments will be completed for 24 hours after study drug administration. End of Study Follow-up will be completed by telephone 48 to 72 hours after study drug administration.

Official Title
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A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Multi-Center Single Dose Study to Evaluate the Safety and Effectiveness of URG101 Compared With the Individual Components Lidocaine and Heparin in Subjects With Interstitial Cystitis/Bladder Pain Syndrome

Conditions
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Interstitial Cystitis, Bladder Pain Syndrome

Intervention / Treatment
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* Drug: URG101
* Drug: Placebo
* Drug: Lidocaine
* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with interstitial cystitis/bladder pain syndrome must meet all of the following criteria to participate in the study: Have provided written informed consent to participate in this trial Be male or female, ≥ 18 years of age Have moderate-to-severe symptoms of bladder pain of bladder origin for at least 9 months prior to the study May or may not have received a cystoscopy in association with their diagnosis of interstitial cystitis/bladder pain syndrome prior to or at time of screening Have a score of ≥ 15 and < 30 on the PUF questionnaire, completed at screening A minimum score of 5 is required on the VAS Have been using a stable dose of hormone therapy for ≥ 3 months, if female and currently taking hormone therapy Exclusion Criteria: Pregnant or breastfeeding. For females of child bearing potential and males, if sexually active, must be willing to commit to an acceptable method of birth control for the duration of the study. Have a known hypersensitivity to heparin or lidocaine Have used any local anesthetic by any route within 24 hours prior to study drug administration, or used a lidocaine patch within 14 days prior to study drug administration Have used a tricyclic antidepressant or a gamma-Aminobutyric acid (GABA) analogue (gabapentin or pregabalin) unless taking the medication for ≥ 3 weeks. The stable dose of gabapentin may not exceed 1,200 mg per day, and the stable dose of pregabalin may not exceed 150 mg per day. Have used any pain medication within 6 hours prior to study drug administration Have used narcotics or medical marijuana ≤ 3 weeks prior to study entry (generic names: fentanyl, hydrocodone, hydromorphone, levorphanol, medical marijuana, methadone, morphine, oxycodone, propoxyphene, tramadol). Subjects who have received codeine within this time period may be admitted if the use is not chronic, and not within 6 hours of enrollment, such that they are not at risk for GI or opiate withdrawal symptoms that in the opinion of the investigator would impact the subject's study participation due to their ability to follow the study protocol or bias study results. Have used prohibited drugs as determined by self-report, positive urine drug screen, or in the opinion of the investigator be under the influence of drugs affecting mentation precluding their ability to follow the study protocol or bias study results Have a known clinically significant abnormal laboratory test value defined by the investigator Have a neurogenic bladder or other disorder that, in the opinion of the investigator, may cause neurogenic bladder (including Parkinson's disease, multiple sclerosis, epilepsy, myasthenia gravis, movement disorders, spinal cord damage) Have pain or a pain disorder that, in the opinion of the investigator, would make it difficult to discriminate pelvic pain of bladder origin from the other pain Have severe depression, bipolar disorder, schizophrenia, anxiety, attention deficit disorder, obsessive compulsive disorder, or other major central nervous system disorder Have history of arrhythmias, conduction disturbances, or cardiac disease, or any coexisting medical condition that, in the opinion of the investigator, may be significant or interfere with study procedures or interpretation of study results Had bladder instillation therapy within 7 days prior to study entry or had a prior bladder instillation with heparin and lidocaine and did not respond Had dilatation (hydrodistention) of bladder within 3 months of study entry Evidence or suspected presence of cancer detected during cystoscopy prior to or at time of initial screening. Has received any investigational drug or device within 30 days prior to screening Is currently enrolled in another investigational drug or device study Is unwilling or unable to abide by the requirements of the study Have an actively bleeding lesion or area in the bladder as detected by dipstick urinalysis and investigator assessment, immediately prior to randomization Have had any of the following: bacterial, chemical (including ketamine and cyclophosphamide) or radiation cystitis; gynecological, urological or rectal cancer; current chemotherapy; tuberculous cystitis; urinary schistosomiasis; bladder or uretal calculi; vaginitis or genital herpes; urethral diverticulum or bladder fistulae.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: URG101<br>A single 15 mL dose of URG101,a mix of buffered Lidocaine (200 mg) and Heparin (50,000 IU), delivered to the bladder via catheter. | Drug: URG101<br> <br> |
| Placebo Comparator: Placebo<br>A single 15 mL dose of placebo delivered to the bladder via catheter. | Drug: Placebo<br> <br> |
| Experimental: Lidocaine<br>A single 15 mL dose of buffered Lidocaine (200 mg) delivered to the bladder via catheter. | Drug: Lidocaine<br> <br> |
| Experimental: Heparin<br>A single 15 mL dose of buffered Heparin (50,000 IU) delivered to the bladder. | Drug: Heparin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bladder pain differences from baseline as determined by using the Visual Analog Scale (VAS) | The primary objective is to evaluate the change in bladder pain intensity differences from baseline to either 12 hours or 24 hours after administration of URG101 compared with the administration of lidocaine alone, heparin alone, and placebo as determined by using the Visual Analog Scale (VAS). | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urgency from baseline as determined using the VAS | Evaluate the change in urgency intensity differences from baseline to 12 or 24 hours after administration of URG101 compared to lidocaine alone, heparin alone, and placebo using the VAS. | 24 hours | 
| The relationship of plasma lidocaine concentrations at 1 hour after study drug administration to bladder pain and urgency | Evaluate the relationship of plasma lidocaine concentrations at 1 hour after study drug administration to bladder pain and urgency at 1 hour, and from baseline to 12 and 24 hours after treatment with URG101 compared to lidocaine alone, heparin alone, and placebo. | 24 hours | 
| Safety and tolerability of study medication (Adverse events) | Adverse events reported after treatment with URG101 compared to lidocaine alone, heparin alone, and placebo. | Up to 72 hours |