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Study in Pediatric Subjects With Epilepsy

This study has been terminated.
(Terminated after placing the study on hold at the request of the FDA)
Sponsor:
Collaborator:
Valeant Pharmaceuticals International, Inc.
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01494584
First received: December 1, 2011
Last updated: September 25, 2014
Last verified: September 2014
Results First Received: July 10, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Epilepsy
Intervention: Drug: ezogabine/retigabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrolled participants (par.) were aged 12 years to less than 18 years with partial onset seizures or Lennox-Gastaut syndrome (LGS), and were required to be on at least 1 but not more than 3 anti-epileptic therapies without achieving complete control of their seizures.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 5 par. who met the eligibility criteria were assigned to Regimen A (>50 kilograms [kg]) or B (30 to <=50 kg) based on body weight and entered a 2-week Screening phase, followed by a dosing phase (up to 5 weeks). Upon completion of the dosing phase, par. either entered a follow-up phase or a separate extension study.

Reporting Groups
  Description
Ezogabine/Retigabine Participants recieved an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.

Participant Flow:   Overall Study
    Ezogabine/Retigabine  
STARTED     5  
COMPLETED     4  
NOT COMPLETED     1  
Study Closed/Terminated                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ezogabine/Retigabine Participants received an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.

Baseline Measures
    Ezogabine/Retigabine  
Number of Participants  
[units: participants]
  5  
Age  
[units: Years]
Mean ± Standard Deviation
  14.6  ± 1.34  
Gender  
[units: Participants]
 
Female     1  
Male     4  
Race/Ethnicity, Customized  
[units: Participants]
 
White-White/Caucasian/European Heritage     5  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   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 ]

5.  Secondary:   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) ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Secondary:   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 ]

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

13.  Secondary:   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 ]

14.  Secondary:   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 ]

15.  Secondary:   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 ]

16.  Secondary:   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) ]

17.  Secondary:   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) ]

18.  Secondary:   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 ]

19.  Secondary:   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 ]

20.  Secondary:   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 ]

21.  Secondary:   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 ]

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

23.  Secondary:   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 ]

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

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

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01494584     History of Changes
Other Study ID Numbers: 113284
Study First Received: December 1, 2011
Results First Received: July 10, 2014
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration