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

Anal Fissure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01920074
• Other study ID #: APT-NIT_S-PRO-M_PEDKPK1_E
• Status: Withdrawn
• Phase: Phase 4
• First received: August 7, 2013
• Last updated: May 1, 2015
• Start date: June 2013
• Est. completion date: April 2015

Study information

• Verified date: May 2015
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 16 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anal Fissure
• Fissure in Ano

Intervention

Drug:
• Nitroglycerin Ointment 0.4%

Locations

Country	Name	City	State
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Hospital	Los Angeles	California
United States	Advanced Medical Research Center	Miami	Florida
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Sealy Urgent Care Center and Medical Clinic	Sealy	Texas
United States	Willis-Knighton Pediatric GI Specialist	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Country where clinical trial is conducted

United States, 

References & Publications (3)

Demirbag S, Tander B, Atabek C, Surer I, Oztürk 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. — View Citation

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. — View Citation

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 t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess the safety of Rectiv® in adolescents (age =12 to <17 years)	Safety and tolerability are assessed through adverse events (AEs), clinical laboratory test results (hematology, serum biochemistry, and urinalysis), vital sign measurements (heart rate, supine and orthostatic blood pressure, oral temperature, and respiratory rate), 12-lead ECG results, anal area assessment, physical examination findings (including body weight), and concomitant medications (including the use of rescue acetaminophen for headaches).	Screening through the completion of study participation	Yes
Primary	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	No
Secondary	• 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	No