The Safety and Efficacy of Gefapixant (AF-219/MK-7264) in Female Participants With Interstitial Cystitis /Bladder Pain Syndrome (MK-7264-005)

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of gefapixant (AF-219/MK-7264) in female participants with moderate to severe pain associated with interstitial cystitis/bladder pain syndrome (IC/BPS) after 4 weeks of treatment.

Detailed Description
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This study is a double-blind, placebo-controlled, randomized trial designed to assess the efficacy and safety of gefapixant in female participants with moderate to severe pain associated with IC/BPS. The study will consist of 4 phases: Screening, Baseline, Treatment, and Follow-up.

Official Title
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A Four-Week, Double-Blind, Placebo-Controlled, Randomized, Multicenter Study Evaluating the Safety and Efficacy of AF-219 in Female Subjects With Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)

Conditions
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Bladder Pain Syndrome

Intervention / Treatment
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* Drug: Gefapixant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women Women of child bearing potential must not be pregnant during the study and must use two forms of birth control Clinical evidence of Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS) Have provided written informed consent Exclusion Criteria: History of diseases that can be confused for IC/BPS Unable to void spontaneously Immunosuppressant, intravesicular, nerve stimulator or opioid treatment for certain periods prior to start of the study Changes to doses of Elmiron®, antidepressant, alpha-adrenergic antagonist, H1 antagonist, or anti-muscarinic treatment within a certain period prior to the start of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gefapixant<br>Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred. | Drug: Gefapixant<br>* 50 or 300 mg tablets for a total daily dose of 50, 100, 150, 200, 250 or 300 mg BID, orally with food for 4 weeks<br>* Other names: MK-7264;|
| Placebo Comparator: Placebo<br>Female participants receive dose matched placebo tablets, BID, orally, with food for 4 weeks. | Drug: Placebo<br>* Dose matched placebo tablets, BID, orally, with food for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Average Mean Numeric Pain Rating Scale (NPRS) Score at Week 4 | The bladder pain severity was measured using 0-10 NPRS, with 0 representing 'no pain' and 10 representing 'the worst pain possible'. Participants were asked to select a number on the scale that best described the severity of bladder pain during past 24 hours over telephone using an interactive voice response system (IVRS) every evening at bedtime during the baseline assessment phase and treatment phase (up to 4 weeks). The primary analysis was conducted using a Mixed Model with Repeated Measures (MMRM) approach to calculate the Least Squares (LS) mean change from baseline in NPRS score and associated Standard Error (SE) at Week 4 for each treatment arm. Negative values indicate decrease in bladder pain severity. | Baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Genitourinary Pain Index (GUPI) Score at Week 4 | To measure the degree of genitourinary pain symptoms, an 8-item self-report GUPI measure was used. Participants were asked to select a number on the scale that best described the severity of symptoms over telephone using an IVRS every evening at bedtime during the baseline assessment phase and treatment phase (up to 4 weeks). The GUPI instrument yields a total score of 0-45 and 3 subscales: pain (score = 0-23), urinary (score = 0-10), and quality of life (score = 0-12). Higher scores indicate more severe symptoms. The analysis was conducted using one-way ANCOVA model to calculate the LS mean change from baseline GUPI total score and associated SE at Week 4 for each treatment arm. Negative values indicate decrease in degree of genitourinary pain symptoms. | Baseline and Week 4 | 
| Change From Baseline in Painful Bladder/Interstitial Cystitis Symptom Diary (PBIC-SD) Score at Week 4 | To assess the severity of bladder pain syndrome (BPS), an 8-item participant self-report PBIC-SD measure was used. Participants were asked to select a number on the scale that best described the severity of bladder pain over telephone using an IVRS each evening on the three consecutive days (during the Baseline Assessment Phase and during each Treatment Week up to 4 weeks). Each item was graded on a scale from 0 (good condition) to 4 (poor condition) with a total score range 0-32. Higher scores indicate more severe BPS. The analysis was conducted using a MMRM approach to calculate the LS mean change from baseline PBIC-SD total score and associated SE at Week 4 for each treatment arm. Negative values indicate decrease in severity of BPS. | Baseline and Week 4 | 
| Change From Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score at Week 4 | To measure the severity of BPS (urgency and frequency of urination, nighttime urination, and pain or burning) over past month, a 4-item self-report ICSI measure was used. Participants were asked to select a number on the scale that best described the severity of symptoms over telephone using an IVRS every evening at bedtime during the baseline assessment phase and treatment phase (up to 4 weeks). The ICSI score range from 0 (Not at all) to 5 (Almost always) for the first 3 items and a score of 0 (Not at all) to 4 (Almost always) for the last item, with an index score range of 0-19. Higher scores indicate more severe BPS. The analysis was conducted using one-way ANCOVA model to calculate the LS mean change from baseline ICSI total score and associated SE at Week 4 for each treatment arm. Negative values indicate decrease in severity of BPS. | Baseline and Week 4 |