Study in Pediatric Subjects With Epilepsy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01494584
• Date of registration: 01/12/2011
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Study in Pediatric Subjects With Epilepsy
• Scientific 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
• Date of first enrolment: July 25, 2012
• Target sample size: 5
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01494584
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & 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.



Age minimum: 12 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Epilepsy

Intervention(s)

Drug: ezogabine/retigabine

Primary Outcome(s)

Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine [Time Frame: 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 [Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine [Time Frame: 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 [Time Frame: 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 Outcome(s)

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 [Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on 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 [Time Frame: Baseline (Screening), Day 7, Day 21, and Day 35]

Change From Baseline in Hematocrit at Day 7 Post Each Up-titration [Time Frame: Baseline (Screening), Day 7, Day 21, and Day 35]

Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration [Time Frame: 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 [Time Frame: Baseline (Screening), Day 7, Day 21, and Day 35]

Change From Baseline in Post Void Residual Ultrasound at Day 21 [Time Frame: Screening and Day 7 of Titration 3 (Day 21)]

Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration [Time Frame: Baseline (Screening), Day 7, Day 21, and Day 35]

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points [Time Frame: Baseline (Screening) and Day 7 post up-titration, up to Day 35]

Number of Participants With the Indicated Neurological Abnormality [Time Frame: Screening and Day 7 of Titration 3 (Day 21)]

Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Time Frame: Baseline (Screening) and Day 7 post up-titration, up to Day 35]

Number of Participants With Any Adverse Event (AE) [Time Frame: From the start of the first titration until follow-up (assessed up to 46 days)]

Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up [Time Frame: 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)]

Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration [Time Frame: Baseline (Screening), Day 7, Day 21, and Day 35]

Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine [Time Frame: 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 [Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration [Time Frame: Baseline (Screening), 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 [Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration [Time Frame: 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 [Time Frame: 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 [Time Frame: Baseline (Screening), Day 7, Day 21, and Day 35]

Change From Baseline in Heart Rate (HR) [Time Frame: Baseline (Screening) and Day 7 post up-titration, up to Day 35]

Percent Change From Baseline in 28-day Seizure Frequency Rate [Time Frame: Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)]

Secondary ID(s)

113284

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bausch Health Americas, Inc.

Results

• Results available: Yes
• Date Posted: 04/09/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01494584