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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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 P

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 Summary: 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
Sponsor: Forest Laboratories

Current Primary Outcome: 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 [ Time Frame: 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)


Original Primary Outcome: Noncompartmental pharmacokinetic analyses will be performed on the full PK curves for NTG and its metabolites (1,2 glyceryl dinitrate and 1,3 glyceryl dinitrate) on Day 5 [ Time Frame: 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)


Current Secondary Outcome: • 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 ]

Original Secondary Outcome: Same as current

Information By: Forest Laboratories

Dates:
Date Received: August 7, 2013
Date Started: June 2013
Date Completion:
Last Updated: May 1, 2015
Last Verified: May 2015