A Study to Determine the Effect of Nitroglycerin Ointment 0.4% (Cellegesic) on the Pain Associated With Chronic Anal Fissures

Study Overview
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Brief Summary
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Anal fissure is a solitary ulcer in the squamous epithelium of the anus causing intense anal pain especially during defecation and for 1 or 2 hours afterwards. There are no approved drugs in the United States (US) for this condition and surgery is often the treatment choice. Strakan is conducting this confirmatory study so the product can be submitted for regulatory approval in the US. Strakan currently markets this product throughout Europe. The objective of this study is to determine the effect of nitroglycerin ointment 0.4% (Cellegesic) versus placebo on average pain intensity over every 24 hour period for up to 21 days of treatment in 250 patients.

Official Title
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A Randomized. Double-blind, Placebo-controlled, Multi-national Study to Determine the Effect of Cellegesic Nitroglycerin Ointment 0.4% (Cellegesic) on the Pain Associated With a Chronic Anal Fissure

Conditions
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Fissure in Ano, Pain

Intervention / Treatment
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* Drug: Cellegesic
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consenting patients of either sex. Between 18 and 75 years of age. With a single, chronic, posterior midline anal fissure. Defined as having anal pain for the 6 weeks prior to Screening. Exclusion Criteria: More than one anal fissure. A fistula-in-ano or anal abscess. Inflammatory bowel disease. Fibrotic anal stenosis. Anal fissure secondary to an underlying condition. Any anal surgery. Concomitant medication that may interfere with study evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cellegesic (nitroglycerin 0.4%)<br>Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days. | Drug: Cellegesic<br>* Cellegesic was supplied as an ointment containing 0.4% w/w nitroglycerin.<br>* Other names: Rectogesic;|
| Placebo Comparator: Placebo 375 mg<br>Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days. | Drug: Placebo<br>* Placebo was supplied as an ointment identical to Cellegesic ointment except that it contained no nitroglycerin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pain Intensity at Days 14-18 | Participants rated the pain associated with their chronic anal fissure over the preceding 24 hours on a 100 mm visual analog scale at Baseline and on Days 14 through 18. The average pain rating on Days 14 through 18 was calculated and used to determine the change from Baseline. The left-end of the visual analog scale was labelled least possible pain and the right-end of the visual analog scale was labelled worst possible pain. The pain rating ranged from 0 to 100, with a higher score indicating more pain. A negative change score indicated improvement. | Baseline to Day 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to an Improvement in Pain Intensity | Participants rated the pain associated with their chronic anal fissure over the preceding 24 hours on a 100 mm visual analog scale (VAS) at Baseline and on each of the 21 treatment days of the study. The left-end of the visual analog scale was labelled least possible pain and the right-end of the visual analog scale was labelled worst possible pain. The pain rating ranged from 0 to 100, with a higher score indicating more pain. Improvement was defined as either a ≥ 50% decrease or a ≥ 10 mm decrease from Baseline in rated pain intensity. | Baseline to Day 21 | 
| Percentage of Responders | Participants rated the pain associated with their chronic anal fissure over the preceding 24 hours on a 100 mm visual analog scale at Baseline and on Days 14 through 18. The average pain rating on Days 14 through 18 was calculated. The left-end of the visual analog scale was labelled least possible pain and the right-end of the visual analog scale was labelled worst possible pain. The pain rating ranged from 0 to 100, with a higher score indicating more pain. A responder was defined as a participant with either a ≥ 50% decrease or a ≥ 10 mm decrease from Baseline in the 24 hour average pain intensity averaged over Days 14 to 18. | Baseline to Day 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain associated with chronic anal fissure