Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects (>= 12 Years Old) With POS or LGS

This study has been terminated.
(FDA placed a clinical hold on the Pediatric Program requiring retigabine discontinuation in subjects; early termination allows for timely reporting of results.)
Sponsor:
Collaborator:
Valeant Pharmaceuticals International, Inc.
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01668654
First received: May 17, 2012
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the long-term safety and tolerability of retigabine/ezogabine as an adjunctive treatment in subjects with either partial onset seizures (12 to < 18 years old) or Lennox-Gastaut Syndrome (12 to <30 years old) who have participated in a previous ("parent") study.


Condition Intervention Phase
Epilepsy
Drug: retigabine/ezogabine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RTG113388, a Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects With Partial Onset Seizures (>= 12 Years Old) and Subjects With Lennox-Gastaut Syndrome (>=12 Years Old)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects with at least one

  • Incidence of serious adverse events (SAEs) [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects with at least one

  • Incidence of AEs leading to withdrawal [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects with at least one

  • Incidence of vital signs outside normal ranges and pre-determined clinically important findings [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects with at least one

  • Summary and change from baseline in vital signs, height, weight, and body mass index [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximum, estimations of variance

  • Summary and change from baseline of ECG parameters [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximum, estimations of variance

  • Summary of ECG assessment and interpretation of clinical significance based on investigator judgment [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects by category (not abnormal; abnormal, not clinically significant; abnormal, clinically significant

  • Changes from baseline in hematology, chemistry, and urinalysis parameters [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximum, estimations of variance

  • Incidence of hematology, chemistry and urinalysis parameters outside normal ranges and pre-determined clinically important ranges [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects with at least one

  • Changes from baseline in bladder volume as assessed by the post-void residual ultrasound [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximum, estimations of variance

  • Changes from baseline in cognition, behavior and learning, as measured by the Leiter-R, Child Behavior Checklist, and Wide Range Assessment of Memory and Learning 2nd Edition, respectively [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximum, estimations of variance by domain

  • Summary of sexual maturation over time based on the Tanner Stages of Puberty in subjects <= 18 years old [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    number and percent of subjects by stage

  • Time to withdrawal [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximum, estimations of variance


Secondary Outcome Measures:
  • percent change from baseline in seizure frequency [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    baseline from the "parent" study; means, medians, minimum, maximum, estimations of variance

  • percentage of responders [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    >=50% reduction from baseline ("parent" study) in seizure frequency

  • clinical global impression of severity (CGI-S) [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximimum, estimations of variance

  • clinical global impression of improvement (CGI-I) [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximimum, estimations of variance

  • summary of change from baseline in child health status (Child Health Questionnaire in subjects < 18 years old) [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximimum, estimations of variance

  • summary of pharmacokinetic AUC [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximimum, estimations of variance

  • summary of pharmacokinetic Cl/F [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    means, medians, minimum, maximimum


Enrollment: 4
Study Start Date: September 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: retigabine/ezogabine
retigabine/ezogabine will be administered three times a day (TID) as add-on therapy based on weight
Drug: retigabine/ezogabine
retigabine/ezogabine will be administered three times a day (TID) as add-on therapy based on weight

Detailed Description:

Epilepsy is among the most common serious neurologic disorders in childhood. Medicines with novel actions of mechanisms of action are needed to try to address the unmet clinical need for seizure control in patients with treatment-resistant epilepsy. The purpose of this study is to evaluate the long-term safety and tolerability of retigabine/ezogabine as an adjunctive treatment in subjects with either partial onset seizures (12 to < 18 years old) or Lennox-Gastaut Syndrome (12 to <30 years old) who have participated in a previous ("parent") study.

  Eligibility

Ages Eligible for Study:   12 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has participated in either a Phase II or Phase III retigabine/ezogabine clinical trial evaluating partial onset seizures or seizures comprising Lennox-Gastaut syndrome and met the requirements defined in the parent study to transition into the open-label extension study
  • Investigator and caregiver consider it beneficial for the patient to continue treatment with retigabine/ezogabine
  • Female subjects of child-bearing potential (after menarche) must either not be sexually active or must be practicing an acceptable method of contraception (documented in the medical chart) from two weeks prior to administration of study medication and for 28 days after completion or premature discontinuation from the study
  • Subject is living with his/her custodial parent(s) or legal guardian(s) and has contact with them on a daily basis
  • Written informed consent is obtained from the subjects parent/guardian and accompanying assent from subject. The subject, and/or his/her custodial parents(s) or legal guardian(s) have the ability to comprehend the key components of the informed consent form

Exclusion Criteria:

  • Has insufficient ability to articulate the presence or absence of urinary tract symptoms
  • Has experienced an adverse event, clinically significant laboratory abnormality or was discontinued from the parent study due to a reason that in the investigator's judgment would preclude enrollment to the study
  • Has a urine sample with: Urine specific gravity >1.035, Urine pH <4.6 or >8.0, ≥2+ proteinuria, Casts or crystals (any type), >5 RBC/HPF, unrelated to menses
  • Has a blood sample with: BUN >21 mg/dl for 12 year old, or >25 mg/dl for >12 year old, Creatinine >1.03 mg/dl (F), or >1.3 mg/dl (M), Uric acid >7.5 mg/dl (F), or >8.5 mg/dl (M), Chloride >108 mEq/L, parameters for calcium, inorganic phosphorous or CO2 that are clinically significant as judged by the investigator
  • Has presence of clinically significant hepatic laboratory values: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2x upper limit of normal (ULN); alkaline phosphatase and bilirubin ≥1.5xULN (isolated bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%
  • Has presence of clinically significant cardiac arrhythmias
  • Has any abnormality on 12-lead ECG which is clinically significant in the opinion of the investigator, or has a corrected QT interval (using either Bazett's or Fridericia's) >500msec ( >530 msec for subjects with Bundle Branch Block), uncorrected QT interval >600msec, or change from baseline QTc >60msec
  • Has a history of one or more renal calculi
  • Has disturbances of micturition or known urinary obstructions, including renal calculi
  • Has a documented anatomical stricture or other anatomical abnormality of the urinary tract system that has the potential to interfere with urinary flow
  • Has experienced clinically significant urinary retention and/or required urinary catheterization in the preceding 6 months
  • Has experienced 2 or more objectively documented urinary tract infections in the preceding 12 months
  • Has a history of inadequate fluid intake and clinically significant dehydration in the preceding 6 months
  • Within the preceding month, has taken anti-cholinergic medication on an ongoing basis
  • Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months or has history of suicide attempt in the last 2 years or more than one lifetime suicide attempt
  • Is planning surgery or implantation of a vagus nerve stimulator to control seizures during the study
  • Is currently or has been abusing substance(s) or any medications in the 12 months prior to study entry
  • Has taken an investigational drug (exception retigabine/ezogabine), or used an investigational device, within the previous 30 days prior, or plans to take an investigational drug anytime during the study
  • Females who are lactating or are pregnant
  • Unwillingness or inability to follow the procedures outlined in the protocol
  • The subject is felt, by the investigator, to be unsuitable for inclusion in the study
  • Children in care
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01668654

Locations
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90027
United States, Florida
GSK Investigational Site
Gulf Breeze, Florida, United States, 32561
GSK Investigational Site
Port Charlotte, Florida, United States, 33952
GSK Investigational Site
Wellington, Florida, United States, 33414
United States, Minnesota
GSK Investigational Site
St. Paul, Minnesota, United States, 55102-2534
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27710
United States, Tennessee
GSK Investigational Site
Memphis, Tennessee, United States, 38105
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78723
GSK Investigational Site
Dallas, Texas, United States, 75230-2507
Sponsors and Collaborators
GlaxoSmithKline
Valeant Pharmaceuticals International, Inc.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01668654     History of Changes
Other Study ID Numbers: 113388
Study First Received: May 17, 2012
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Epilepsy
Partial Onset epilepsy
Lennox-Gastaut Syndrome
Open-label extension study

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
D 23129
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014