Pharmacokinetic,Safety and Exploratory Efficacy of RECTIV® in Adolescents With Chronic Anal Fissure

Study Overview
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Brief Summary
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RECTIV® is an ointment containing 0.4% nitroglycerin (NTG) for the treatment of moderate to severe pain associated with chronic anal fissure approved in June 2011 by the US Food and Drug Administration (FDA) for adults. The purpose of this study is to assess the safety, pharmacokinetics, and exploratory efficacy of RECTIV® in adolescents

Detailed Description
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This is an open-label, multicenter study conducted in up to 10 sites in the United States. A total of 13 pediatric male or female patients age ≥12 to <17 years will be enrolled. The patients will administer a dose of Rectiv® twice daily to characterize the safety, pharmacokinetics , and exploratory efficacy of Nitroglycerin Ointment 0.4% (RECTIV® )over 5 days

Official Title
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A Phase 4, Multiple-dose, Pharmacokinetic, Safety, and Exploratory Efficacy Study of Nitroglycerin Ointment 0.4% (RECTIV®) in Adolescents (Age ≥12 to <17 Years) With Moderate to Severe Pain Due to Chronic Anal Fissure

Conditions
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Anal Fissure

Intervention / Treatment
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* Drug: Nitroglycerin Ointment 0.4%


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female ≥12 and <17 years of age At least 1 anal fissure for a minimum of 3 weeks in duration Anal fissure pain experienced over the last 24 hours at Screening and before enrollment Patient (and parent or caregiver as appropriate) has provided written informed consent Key Exclusion Criteria: Current diagnosis of hemorrhoids Hypersensitivity, allergy, or contraindication to nitroglycerin History of hypertension and/or cardiovascular disease History or current diagnosis of inflammatory bowel disease History or current diagnosis of fistula(e)-in-ano or an anal abscess Fibrotic anal stenosis Previous anal surgery Diagnosis of cancer History of migraine or chronic headaches requiring treatment with analgesics Pregnant or lactating female patients Weight <36 kg

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rectiv<br> | Drug: Nitroglycerin Ointment 0.4%<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Noncompartmental pharmacokinetic (PK) analyses will be performed on the full pharmacokinetic curves for NTG and its metabolites (1,2 glyceryl dinitrate and 1,3 glyceryl dinitrate) on Day 5 | The following PK parameters will be calculated as data permit: Maximum observed concentration (Cmax) Time of the maximum observed plasma concentration (Tmax) Area under the concentration time curve from dosing up to the last quantifiable concentration (AUC0-last). Area under the concentration time curve from dosing up to 480 minutes (AUC0-480) The extrapolated area under the concentration time curve from dosing up to 12 hours (AUC0-12h) also will be calculated if quantifiable concentrations are observed during the entire dose interval. Terminal elimination half-life (t1/2) On the basis of the results of the study, additional noncompartmental PK parameters may be calculated and reported. In addition, a population PK model for NTG will be developed based on the PK data from Day 5. By using this model, the following additional PK parameters may be reported: Apparent volume of distribution (V/F) Apparent clearance (CL/F) | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Absolute change from baseline in 24-hour average anal fissure pain scores assessed by the Wong-Baker FACES® and the Numerical Rating Scale for pain after each evening dose over days 1 through 4 |  | Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anal Fissure, Nitroglycerin, Pediatrics, RECTIV®, Pediatric Research Equity Act