Study in Pediatric Subjects With Epilepsy

NCT01494584 | Terminated Phase 2 Results

• 1 other identifier: 113284
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

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.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (4)

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

  The steady state pharmacokinetic profile following oral administration of ezogabine/retigabine included determining the area under the curve over the dosing interval (AUC\[0-tau\]). The area under the plasma concentration-time curve over the dosing interval (AUC\[0-tau\]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate AUC(0-tau).

  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

  Clearance (CL/F) is defined as dose/AUC(0-tau). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate CL/F.

  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

  Cmax is defined as the first occurrence of the maximum observed plasma concentration. Ctau refers to the pre-dose (trough) concentration after the dosing interval which is equal to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate Cmax and Ctau.

  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

  The volume of distribution (Vd/F) is defined as MRT\*CL/F, where MRT is the mean residence time (calculated as AUMC\[0-tau\]/AUC\[0-tau\], where AUMC\[0-tau\] is the area under the first moment curve determined as the area under the concentration\*time versus time curve). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate the apparent volume of distribution.

  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 (22)

• Number of Participants With Any Adverse Event (AE)

  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

  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

  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

  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

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

Study Arms (1)

ezogabine/retigabine

EXPERIMENTAL

ezogabine dose escalation

Drug: ezogabine/retigabine

Interventions

ezogabine/retigabine DRUG

ezogabine dose escalation

ezogabine/retigabine

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (4)

GSK Investigational Site

Los Angeles, California, 90027, United States

Location

GSK Investigational Site

Wellington, Florida, 33414, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38105, United States

Location

GSK Investigational Site

Dallas, Texas, 75230-2507, United States

Location

Related Publications (1)

• 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.

  PMID: 27877093 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Interventions

ezogabine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 19, 2011
• Study Start: July 25, 2012
• Primary Completion: April 29, 2013
• Study Completion: April 29, 2013
• Last Updated: November 30, 2020
• Results First Posted: September 4, 2014

Record last verified: 2020-11

Locations

US (4)