Clinical trial NCT01494584: Study in Pediatric Subjects With Epilepsy
Official title: Open-label, Multiple Dose Study to Evaluate the Parmacokinetics, Safety and Tolerability of Ezogabine/Retigabine as Adjunctive Treatment in Subjects Aged From 12 Years to Less Than 18 Years With Partial Onset Seizures or Lennox-Gastaut Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Epilepsy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Bausch Health Americas, Inc.
First posted: 2011-12-19
Enrollment: 5
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label study to evaluate the pharmacokinetics, safety and tolerability of ezogabine/retigabine in subjects aged 12 years to less than 18 years with uncontrolled partial onset seizures or Lennos-Gastaut syndrome.


Eligibility criteria: Inclusion Criteria:

* Between 12 and 18 years of age.
* Diagnosis of uncontrolled partial onset seizures (with or without secondarily generalized seizures) or Lennox-Gastaut syndrome.
* Taking between one and three antiepileptic drugs.
* Able to swallow tablets.
* Females must be of : (1) Non-childbearing potential or (2) Child-bearing potential and agrees to use acceptable contraception.

Exclusion Criteria:

* Epilepsy secondary to progressive cerebral disease, tumor or any progressive neurodegenerative disease.
* History of status epilepticus in the last six months.
* Currently treated with felbamate or has been treated with vigabatrin within the past 6 months.
* Following the ketogenic diet.
* Suicidal intent or history of suicide attempt in the last 2 years.
* Elevated liver enzymes or abnormal kidney function.
* Current disturbance of micturition or known urinary obstructions.
* History of vesicoureteric reflux.
* Abnormal post-void residual bladder ultrasound.
* Urinary retention and/or required urinary catheterization in the preceding 6 months.
* Abnormal urine sample at screening/.baseline.
* Abnormal blood sample at screening.
* Clinically significant arrhythmias.
* Abnormal ECG at screening.
* BMI lower than the 10th percentile for age and gender or subject weighs less than 30kg.

Primary outcomes:
measure: The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Secondary outcomes:
measure: Number of Participants With Any Adverse Event (AE)
timeFrame: From the start of the first titration until follow-up (assessed up to 46 days)
measure: Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (BUN) at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC [Total Absolute Neutrophil Count]), Platelet Count, and White Blood Cell Count at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Hematocrit at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration
timeFrame: Baseline (Screening), Day 7, Day 21, and Day 35
measure: Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up
timeFrame: Screening, Day 1 (D1), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), Day 35 (D35), and at the Follow-up Visit (up to Day 46)
measure: Percent Change From Baseline in 28-day Seizure Frequency Rate
timeFrame: Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)
measure: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t]) for the N-acetyl Metabolite of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) for the N-acetyl Metabolite of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Time to Maximum Concentration (Tmax) Following Oral Administration of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Baseline (Screening) and Day 7 post up-titration, up to Day 35
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
timeFrame: Baseline (Screening) and Day 7 post up-titration, up to Day 35
measure: Change From Baseline in Heart Rate (HR)
timeFrame: Baseline (Screening) and Day 7 post up-titration, up to Day 35
measure: Change From Baseline in Post Void Residual Ultrasound at Day 21
timeFrame: Screening and Day 7 of Titration 3 (Day 21)
measure: Number of Participants With the Indicated Neurological Abnormality
timeFrame: Screening and Day 7 of Titration 3 (Day 21)
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:
citation: Tompson DJ, Buraglio M, Andrews SM, Wheless JW. Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability. J Pediatr Pharmacol Ther. 2016 Sep-Oct;21(5):404-412. doi: 10.5863/1551-6776-21.5.404.