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

NCT01920074 | Withdrawn Phase 4

• 1 other identifier: APT-NIT_S-PRO-M_PEDKPK1_E
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Anal Fissure

Keywords

Anal Fissure; Nitroglycerin; Pediatrics; RECTIV®; Pediatric Research Equity Act

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• • 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

Other Outcomes (1)

• To assess the safety of Rectiv® in adolescents (age ≥12 to <17 years)

  Screening through the completion of study participation

Study Arms (1)

Rectiv

EXPERIMENTAL

Drug: Nitroglycerin Ointment 0.4%

Interventions

Nitroglycerin Ointment 0.4% DRUG

Rectiv

Eligibility Criteria

• Age: 12 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead

Study Sites (6)

Children's Hospital

Los Angeles, California, 90027, United States

Location

Advanced Medical Research Center

Miami, Florida, 33135, United States

Location

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

Willis-Knighton Pediatric GI Specialist

Shreveport, Louisiana, 71118, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Sealy Urgent Care Center and Medical Clinic

Sealy, Texas, 77474, United States

Location

Related Publications (3)

• Demirbag S, Tander B, Atabek C, Surer I, Ozturk H, Cetinkursun S. Long-term results of topical glyceryl trinitrate ointment in children with anal fissure. Ann Trop Paediatr. 2005 Jun;25(2):135-7. doi: 10.1179/146532805X45737.

  PMID: 15949202 RESULT

• Kenny SE, Irvine T, Driver CP, Nunn AT, Losty PD, Jones MO, Turnock RR, Lamont GL, Lloyd DA. Double blind randomised controlled trial of topical glyceryl trinitrate in anal fissure. Arch Dis Child. 2001 Nov;85(5):404-7. doi: 10.1136/adc.85.5.404.

  PMID: 11668104 RESULT

• Schiano di Visconte M, Di Bella R, Munegato G. Randomized, prospective trial comparing 0.25 percent glycerin trinitrate ointment and anal cryothermal dilators only with 0.25 percent glycerin trinitrate ointment and only with anal cryothermal dilators in the treatment of chronic anal fissure: a two-year follow-up. Dis Colon Rectum. 2006 Dec;49(12):1822-30. doi: 10.1007/s10350-006-0731-y.

  PMID: 17096178 RESULT

MeSH Terms

Conditions

Fissure in Ano

Condition Hierarchy (Ancestors)

Anus Diseases; Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Paul Hyman, MD

  Children's Hospital New Orleans, LA

  PRINCIPAL INVESTIGATOR

• Taryn Weissman, MD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 9, 2013
• Study Start: June 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 4, 2015

Record last verified: 2015-05

Locations

US (6)