Last updated: 11/20/2020 19:50:05

Study in pediatric subjects with epilepsy

GSK study ID
113284
See study documents
Clinicaltrials.gov ID
NCT01494584
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:

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

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

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

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:

Number of participants with any adverse event (AE)

Timeframe: From the start of the first titration until follow-up (assessed up to 46 days)

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

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

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

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

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

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

Change from baseline in hematocrit at Day 7 post each up-titration

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Change from baseline in mean corpuscle hemoglobin at Day 7 post each up-titration

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Change from baseline in mean corpuscle volume at Day 7 post each up-titration

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

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

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)

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)

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

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

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

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

Number of participants with abnormal electrocardiogram (ECG) findings

Timeframe: Baseline (Screening) and Day 7 post up-titration, up to Day 35

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

Change from Baseline in heart rate (HR)

Timeframe: Baseline (Screening) and Day 7 post up-titration, up to Day 35

Change from baseline in post void residual ultrasound at Day 21

Timeframe: Screening and Day 7 of Titration 3 (Day 21)

Number of participants with the indicated neurological abnormality

Timeframe: Screening and Day 7 of Titration 3 (Day 21)

Interventions:
  • Drug: ezogabine/retigabine
    • Enrollment:
    5
    Primary completion date:
    2013-29-04
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Debra J. Tompson, Mauro Buraglio, Susan M. Andrews, and James W. Wheless. Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability. The Journal of Pediatric Pharmacology and Therapeutics. 2016;21(5):404-412.
    Medical condition
    Epilepsy
    Product
    retigabine
    Collaborators
    Valeant
    Study date(s)
    July 2012 to April 2013
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    12 - 17 years
    Accepts healthy volunteers
    No
    • Between 12 and 18 years of age.
    • Diagnosis of uncontrolled partial onset seizures (with or without secondarily generalized seizures) or Lennox-Gastaut syndrome.
    • Epilepsy secondary to progressive cerebral disease, tumor or any progressive neurodegenerative disease.
    • History of status epilepticus in the last six months.
    Inclusion and exclusion 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.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Dallas, Texas, United States, 75230-2507
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Los Angeles, California, United States, 90027
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Memphis, Tennessee, United States, 38105
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Wellington, Florida, United States, 33414
    Status
    Study Complete
    Contact us

    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2013-29-04
    Actual study completion date
    2013-29-04

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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