Clinical trial NCT01668654: Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects (>= 12 Years Old) With POS or LGS
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Epilepsy
Partial Onset epilepsy
Lennox-Gastaut Syndrome
Open-label extension study
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Bausch Health Americas, Inc.
First posted: 2012-08-20
Enrollment: 4
Sex: ALL
Minimum age (years): 12
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Participants (Par.) With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period
timeFrame: From the start of study medication until the end of Follow-Up (up to 178 days)
measure: Number of Participants With AEs Leading to Withdrawal
timeFrame: From the start of study medication until the end of the Follow-Up Visit (up to 178 days)
measure: Number of Participants With Vital Signs Outside the Pre-determined Clinically Important Findings or Outside the Normal Ranges at Any Time During the Study
timeFrame: Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in SBP and DBP at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Heart Rate at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Body Temperature at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Body Height at Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Body Weight at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Electrocardiogram (ECG) at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), EW Visit (up to 178 days)
measure: Number of Participants With Abnormal Clinically Significant ECG Findings Based on Investigator Judgment at Anytime During the Study
timeFrame: Eligibility Assessment and EW Visit
measure: Change From Baseline in ALT, ALP, AST, CK, and LDH Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in the BUN/Creatinine and the Urine Albumin/Creatinine Ratios at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Calcium, Carbon Dioxide Content/Bicarbonate, Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorus, Potassium, Sodium, and Urea/BUN Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Uric Acid, and Urine Creatinine Concentration Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Thyroid Stimulating Hormone (TSH) and Urine Albumin Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, and White Blood Cell Count Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, and Red Cell Distribution Width (RDW) Percentages at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in the Hematocrit Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in the Mean Corpuscle Volume and Mean Platelet Volume Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Change From Baseline in the Red Blood Cell Count Measurements at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Number of Partcipants With Hematology, Chemistry and Urinalysis Parameters Outside the Normal Ranges and Pre-determined Clinically Important Ranges
timeFrame: Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)
measure: Changes From Baseline in Bladder Volume as Assessed by the Post Void Residual (PVR) Ultrasound at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1), Visit 6, EW Visit
measure: Changes From Baseline in Cognition as Measured by the Leiter-R at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1) up to 178 days
measure: Changes From Baseline in Behaviour as Measured by the Child Behavior Checklist (CBCL) at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1) up to 178 days
measure: Changes From Baseline in Learning as Measured by the Wide Range Assessment of Memory and Learning , 2nd Edition (WRAML2) at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1) up to 178 days
measure: Number of Participants With Sexual Maturation Based on the Tanner Stage I to Stage V of Puberty in Participants <=18 Years Old Throughout the Study
timeFrame: Eligibility Assessment (Visit 1) and EW Visit
measure: Number of Days of Exposure to Retigabine/Ezogabine TID by Individual Participant
timeFrame: Treatment Phase plus Taper Phase (up to 97 days)
Secondary outcomes:
measure: Percent Change From Baseline in the Seizure Frequency at the Indicated Time Points
timeFrame: Basline, Eligibility Assessment (Visit 1) up to 178 days
measure: Number of Participants Who Were Responders During the Treatment Period
timeFrame: Eligibility Assessment (Visit 1) up to 178 days
measure: Clinical Global Impression- Improvement (CGI-I) Assessment at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1) up to 178 days
measure: Clinical Global Impression-Severity of Illness (CGI-S) Assessment at the Indicated Time Points
timeFrame: Baseline, Eligibility Assessment (Visit 1) up to 178 days
measure: Change From Baseline in Child Health Status as Measured by the Child Health Questionnaire (CHQ) in Participants <18 Years Old at the Indicated Time Points
timeFrame: Baseline, Eligibilty Assessment (Visit 1), EW Visit and FU Visit (up to 178 days)
measure: Area Under the Plasma Concentration-time Curve (AUC) Following Oral Administration of Retigabine/Ezogabine at the Indicated Time Points
timeFrame: Eligibility Assessment (Visit 1) up to 178 days
measure: Apparent Clearance (CL/F) Following Oral Administration of Retigabine/Ezogabine at Indicated Time Points
timeFrame: Eligbility Assessment (Visit 1), up to 178 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Wellington
country: United States
facility: GSK Investigational Site
state: Florida
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: