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Open-label Extension Study of the Phase 3 VRX-RET-E22-301 Double-Blind Trial

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ClinicalTrials.gov Identifier: NCT00310375
Recruitment Status : Completed
First Posted : April 3, 2006
Results First Posted : November 25, 2016
Last Update Posted : April 9, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Epilepsy
Intervention: Drug: Ezogabine: USAN Retigabine (International Nonproprietary Name)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Eligible Participants (Par) who completed the Maintenance and Transition Phases of the parent study were enrolled in this open-label extension study. Par received 600-1200 mg/day retigabine as an adjunct therapy to current antiepileptic medication or vagal nerve stimulation until Par was withdrawn or withdrew consent or until study was terminated.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All participants who completed Study VRX-RET-E22-301(parent study) and did not have an ongoing serious adverse event (SAE) were eligible to participate in the study.

Reporting Groups
  Description
Placebo in Parent Study Participants received retigabine tablets as a total dose of between 600 to 1200 mg/day (dose administered twice daily or TID) as an adjunct therapy to their ongoing antiepileptic drugs with or without vagal nerve stimulation until withdrawal, withdrawn consent or switched to commercial product. Participants who received placebo in parent study are included in this arm.
Retigabine in Parent Study Participants received retigabine tablets as a total dose of between 600 to 1200 mg/day (dose administered twice daily or TID) as an adjunct therapy to their ongoing antiepileptic drugs with or without vagal nerve stimulation until withdrawal, withdrawn consent or switched to commercial product. Participants who received retigabine in parent study are included in this arm.
Safety Follow-up Continuation Phase (SFUCP) Participants who withdraw from retigabine and who were found to have abnormal pigmentation of the retina or unexplained vision loss, pigmentation of non-retinal ocular tissue or discoloration of skin, lips, nails or mucosa entered the SFUCP. During the SFUCP, participants underwent 6-monthly comprehensive eye examinations and/or skin assessments by the investigator, ophthalmologist, retinal specialist or dermatologist as appropriate. Participants were followed up in the SFUCP until the dermatology/ophthalmology finding(s) either resolved or stabilized. Stabilization was defined in the protocol as no changes on two consecutive 6-monthly assessments over at least over 12 months after discontinuation of retigabine.

Participant Flow for 2 periods

Period 1:   Primary Reporting Phase
    Placebo in Parent Study   Retigabine in Parent Study   Safety Follow-up Continuation Phase (SFUCP)
STARTED   102   79   0 
COMPLETED   11   11   0 
NOT COMPLETED   91   68   0 
Adverse Event                28                22                0 
Lack of Efficacy                24                19                0 
Pregnancy                2                2                0 
Withdrawal by Subject                10                7                0 
Protocol Violation                8                5                0 
Change in Par medical condition                2                0                0 
Transaminase >5 upper limit of normal                2                1                0 
Physician Decision                5                3                0 
Request of the sponsor                2                2                0 
Failed to return                1                3                0 
Participant request unrelated to study                1                2                0 
Going for temporal lobectomy                1                0                0 
Missed study drug >5 days                1                0                0 
Site closure                3                0                0 
Missed study drug for 2 months                1                0                0 
Par. switched to commercial product                0                1                0 
Request of Ethics Committee                0                1                0 

Period 2:   Safety Follow-up Continuation Phase
    Placebo in Parent Study   Retigabine in Parent Study   Safety Follow-up Continuation Phase (SFUCP)
STARTED   0   0   19 
COMPLETED   0   0   18 [1] 
NOT COMPLETED   0   0   1 
Lost to Follow-up                0                0                1 
[1] Met the protocol defined stopping criteria



  Baseline Characteristics

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
Placebo in Parent Study Participants received retigabine tablets as a total dose of between 600 to 1200 mg/day (dose administered twice daily or TID) as an adjunct therapy to their ongoing antiepileptic drugs with or without vagal nerve stimulation until withdrawal, withdrawn consent or switched to commercial product. Participants who received placebo in parent study are included in this arm.
Retigabine in Parent Study Participants received retigabine tablets as a total dose of between 600 to 1200 mg/day (dose administered twice daily or TID) as an adjunct therapy to their ongoing antiepileptic drugs with or without vagal nerve stimulation until withdrawal, withdrawn consent or switched to commercial product. Participants who received retigabine in parent study are included in this arm.
Total Total of all reporting groups

Baseline Measures
   Placebo in Parent Study   Retigabine in Parent Study   Total 
Overall Participants Analyzed 
[Units: Participants]
 102   79   181 
Age 
[Units: Years]
Mean (Standard Deviation)
 38.0  (11.74)   37.1  (12.20)   37.6  (11.92) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      55  53.9%      39  49.4%      94  51.9% 
Male      47  46.1%      40  50.6%      87  48.1% 
Race/Ethnicity, Customized 
[Units: Participants]
     
Caucasian   54   40   94 
Hispanic   30   26   56 
African-American (black)   7   7   14 
Other   11   6   17 
Number of Participants with Vagal nerve stimulator (VNS) use 
[Units: Participants]
     
No   89   74   163 
Yes   13   5   18 
Number of background AEDs 
[Units: Participants]
     
AED=1   12   18   30 
AED=2   47   41   88 
AED=3   43   20   63 
Mean Duration of Partial seizures [1] 
[Units: Years]
Mean (Standard Deviation)
 24.1  (13.06)   23.7  (12.88)   23.9  (12.95) 
[1] For this study specific outcome measure, Placebo in Parent Study N=101 and Retigabine in parent study N=79
Mean Duration of Generalized Seizure [1] 
[Units: Years]
Mean (Standard Deviation)
 18.6  (12.45)   25.8  (13.25)   21.5  (12.94) 
[1] For this study specific outcome measure, Placebo in Parent Study N=12 and Retigabine in parent study N=8
Clinical Global Impression (CGI) at Baseline 
[Units: Participants]
     
Not Assessed   0   0   0 
No Seizures   0   0   0 
Very Mild Severity   2   0   2 
Mild Severity   9   8   17 
Moderate Severity   49   40   89 
Marked Severity   36   26   62 
Very Severe   6   5   11 
Among the Most Extremely Severe   0   0   0 


  Outcome Measures

1.  Primary:   Number of Participants With Treatment-emergent Serious Adverse Event (SAE) and Adverse Event (AE)   [ Time Frame: Assessed up to a maximum of 9 years ]

2.  Primary:   Number of Participants With Treatment-emergent Adverse Events Leading to Withdrawal From Study Drug   [ Time Frame: Assessed up to a maximum of 9 years ]

3.  Primary:   Kaplan-Meier Estimate of the Probability of Discontinuation (d/c) From Study Drug   [ Time Frame: Assessed up to a maximum of 9 years ]

4.  Primary:   Change From Baseline in Blood Pressure   [ Time Frame: Baseline and Up to Month 108 ]

5.  Primary:   Change From Baseline in Heart Rate   [ Time Frame: Baseline and Up to Month 108 ]

6.  Primary:   Change From Baseline in Body Temperature   [ Time Frame: Baseline and Up to Month 108 ]

7.  Primary:   Change From Baseline in Weight   [ Time Frame: Baseline and Up to Month 108 ]

8.  Primary:   Change From Baseline in the 12-lead Electrocardiogram (ECG) Parameters-PR Interval, QRS Duration, Uncorrected QT (uQT) Interval, Corrected QT (Bazett's Correction) Interval (QTcB), Corrected QT (Friedericia's Correction) Interval (QTcF)   [ Time Frame: Baseline and Up to Month 108 ]

9.  Primary:   Change From Baseline in the 12-lead Electrocardiogram (ECG) Parameter-RR Interval   [ Time Frame: Baseline and Up to Month 108 ]

10.  Primary:   Change From Baseline in Electrocardiogram (ECG) Parameter-QRS Axis   [ Time Frame: Baseline and Up to Month 108 ]

11.  Primary:   Change From Baseline in Hematology Parameters- Bands, Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets, White Blood Cells Count (WBC)   [ Time Frame: Baseline and Up to Month 108 ]

12.  Primary:   Change From Baseline in Hematology Parameter-Red Blood Cell Count   [ Time Frame: Baseline and Up to Month 108 ]

13.  Primary:   Change From Baseline in Haematocrit   [ Time Frame: Baseline and Up to Month 108 ]

14.  Primary:   Change From Baseline in Haemoglobin   [ Time Frame: Baseline and Up to Month 108 ]

15.  Primary:   Change From Baseline in Chemistry Parameters-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)   [ Time Frame: Baseline and Up to Month 108 ]

16.  Primary:   Change From Baseline in Chemistry Parameters-Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium, Urea   [ Time Frame: Baseline and Up to Month 108 ]

17.  Primary:   Change From Baseline in Chemistry Parameters -Creatinine, Total Bilirubin (TB), Uric Acid (UA)   [ Time Frame: Baseline and Up to Month 108 ]

18.  Primary:   Change From Baseline in Chemistry Parameter-Total Protein   [ Time Frame: Baseline and Up to Month 108 ]

19.  Primary:   Change From Baseline in Urine Specific Gravity   [ Time Frame: Baseline and Up to Month 108 ]

20.  Primary:   Change From Baseline in Urine Power of Hydrogen (pH)   [ Time Frame: Baseline and Up to Month 108 ]

21.  Primary:   Change From Baseline in Post-void Residual Bladder Ultrasound Volume   [ Time Frame: Baseline and Up to Month 108 ]

22.  Primary:   Change From Baseline in Overall American Urological Association (AUA) Symptom Index Score   [ Time Frame: Baseline and Up to Month 108 ]

23.  Primary:   Number of Participants With Abnormal Results in Physical Examination   [ Time Frame: Up to Month 108 ]

24.  Primary:   Number of Participants With Abnormal Results of Neurological Examination   [ Time Frame: Up to Month 108 ]

25.  Primary:   Number of Participants With Pigmentation of Non-retinal Ocular Tissue   [ Time Frame: Assessed up to a maximum of 9 years ]

26.  Primary:   Number of Participants With Pigmentation of Retinal Ocular Tissue   [ Time Frame: Assessed up to a maximum of 9 years ]

27.  Primary:   Number of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa   [ Time Frame: Assessed up to a maximum of 9 years ]

28.  Primary:   Number of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination   [ Time Frame: Assessed up to a maximum of 9 years ]

29.  Primary:   Number of Participants With a Decrease in Confrontational Visual Field From Initial Examination   [ Time Frame: Assessed up to a maximum of 9 years ]

30.  Primary:   Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine   [ Time Frame: 2 years and 9 months ]

31.  Primary:   Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine   [ Time Frame: 2 years 9 months ]

32.  Primary:   Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation   [ Time Frame: 2 years 9 months ]

33.  Primary:   Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration   [ Time Frame: 2 years 9 months ]

34.  Secondary:   Percentage Change From Baseline in the 28-day Partial Seizure   [ Time Frame: Assessed up to a maximum of 9 years ]

35.  Secondary:   Number of Responders   [ Time Frame: Assessed up to a maximum of 9 years ]

36.  Secondary:   Number of Participants Who Were Seizure Free for Any 6 Continuous Months   [ Time Frame: Assessed up to a maximum of 9 years ]

37.  Secondary:   Number of Participants Who Were Seizure Free for Any 12 Continuous Months   [ Time Frame: Assessed up to a maximum of 9 years ]

38.  Secondary:   Percentage of Seizure-free Days   [ Time Frame: Assessed up to a maximum of 9 years ]

39.  Secondary:   Change From Baseline in Quality of Life in Epilepsy (QOLIE)-31-P Questionnaire   [ Time Frame: Assessed up to a maximum of 9 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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

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



Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00310375     History of Changes
Other Study ID Numbers: VRX-RET-E22-303
RTG115098 ( Other Identifier: GlaxoSmithKline )
First Submitted: March 30, 2006
First Posted: April 3, 2006
Results First Submitted: July 27, 2016
Results First Posted: November 25, 2016
Last Update Posted: April 9, 2018