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

Primary Purpose

Anal Fissure

Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Nitroglycerin Ointment 0.4%
Sponsored by
Forest Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anal Fissure focused on measuring Anal Fissure, Nitroglycerin, Pediatrics, RECTIV®, Pediatric Research Equity Act

Eligibility Criteria

12 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital
  • Advanced Medical Research Center
  • Arnold Palmer Hospital for Children
  • Willis-Knighton Pediatric GI Specialist
  • Children's Mercy Hospital
  • Sealy Urgent Care Center and Medical Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rectiv

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

• 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

Full Information

First Posted
August 7, 2013
Last Updated
May 1, 2015
Sponsor
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01920074
Brief Title
Pharmacokinetic,Safety and Exploratory Efficacy of RECTIV® in Adolescents With Chronic Anal Fissure
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Study stopped due to study enrollment challenges that impacted the feasibility of conducting the study.
Study Start Date
June 2013 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forest Laboratories

4. Oversight

Data Monitoring Committee
No

5. Study Description

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
Detailed 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anal Fissure
Keywords
Anal Fissure, Nitroglycerin, Pediatrics, RECTIV®, Pediatric Research Equity Act

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rectiv
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nitroglycerin Ointment 0.4%
Primary Outcome Measure Information:
Title
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
Description
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)
Time Frame
Day 5
Secondary Outcome Measure Information:
Title
• 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
Time Frame
Day 5
Other Pre-specified Outcome Measures:
Title
To assess the safety of Rectiv® in adolescents (age ≥12 to <17 years)
Description
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).
Time Frame
Screening through the completion of study participation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Hyman, MD
Organizational Affiliation
Children's Hospital New Orleans, LA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Taryn Weissman, MD
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Advanced Medical Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
Arnold Palmer Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Willis-Knighton Pediatric GI Specialist
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71118
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Sealy Urgent Care Center and Medical Clinic
City
Sealy
State/Province
Texas
ZIP/Postal Code
77474
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15949202
Citation
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.
Results Reference
result
PubMed Identifier
11668104
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. doi: 10.1136/adc.85.5.404.
Results Reference
result
PubMed Identifier
17096178
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 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.
Results Reference
result

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

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