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

A Multicenter, Open-label, Long-term, Safety, Tolerability and Efficacy Study of Retigabine in Adult Epilepsy Patients With Partial-onset Seizures (Extension of Study VRX-RET-E22-301)

The purpose of this study is to evaluate the safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy patients with partial-onset seizures, who completed the VRX-RET-E22-301 double-blind study. The efficacy of long-term treatment with retigabine and patient quality of life will also be assessed.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Ezogabine: USAN Retigabine (International Nonproprietary Name)

Detailed Description

This Phase 3 trial is an open-label extension study of the placebo-controlled, double-blind VRX-RET-E22-301 trial. Patients who have completed the VRX-RET-E22-301 trial and who meet inclusion and exclusion criteria will be treated with 600-1200 mg/day of retigabine as an adjunct therapy to their current antiepileptic drugs (AEDs) or vagal nerve stimulation. Treatment will be continued until retigabine is commercially available, or until the program is discontinued. Patients will be recruited from 45-50 sites in the United States, Canada, Mexico, Brazil, and Argentina. The safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy patients with partial-onset seizures will be evaluated. In addition, the efficacy of long-term treatment with retigabine and patient quality of life will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CBA
    • Capital Federal, CBA, Argentina, C1181ACH
      • Hospital Italiano de Buenos Aires
    • Capital Federal, CBA, Argentina
      • Hospital General de Agudos "Dr. J.M. Ramos Mejia"
    • Capital Federal, CBA, Argentina
      • Hospital General de Agudos "Dr. Teodoro Alvarez"
  • CRD
    • Cordoba, CRD, Argentina, 5000
      • Fundacion Lennox
    • Cordoba, CRD, Argentina, 5000
      • Sanatorio del Salvador II
    • Cordoba, CRD, Argentina, X5016KEH
      • Hospital Privado Centro Medico de Cordoba
• Brazil
  • BA
    • Salvador, BA, Brazil, 40110-060
      • Hospital Universitario Prof Edgard Santos -- UFBA
  • SP
    • Ribeirao Preto, SP, Brazil, 14048-900
      • Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
    • Sao Paulo, SP, Brazil, 04024 002
      • Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
    • Sao Paulo, SP, Brazil, 05403-900
      • Hospital das Clinicas da Fac de Medicina de Sao Paulo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Center
    • Edmonton, Alberta, Canada, T5G 0B7
      • Glenrose Rehabilitation Center
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Health Sciences Centre
  • Quebec
    • Montréal, Quebec, Canada, H2L 4M1
      • CHUM -- Hôpital Notre-Dame
• Mexico
  • DF
    • La Fama, DF, Mexico, 42690
      • Instituto Nacional de Neurologia y Neurocirugia
    • Mexico, DF, Mexico, 03229
      • Centro Medico
    • Mexico, DF, Mexico, 14050
      • Hospital de Psiquiatria San Fernando, IMSS
    • Tlalpan, DF, Mexico, 14050
      • CIF BIOTEC, Medica Sur
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Antiguo Hospital Civil de Guadalajara
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64000
      • Hospital y Clinica OCA S.A. de C.V.
  • SLP
    • San Luis Potosi, SLP, Mexico, 78250
      • Hospital Central Dr. Ignacio Morones Prieto
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama -- Department of Neurology/Epilepsy Center
    • Huntsville, Alabama, United States, 35801
      • North Alabama Neuroscience Research Associates
    • Northport, Alabama, United States, 35476
      • Neurology Clinic
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials Inc.
  • California
    • La Jolla, California, United States, 92037
      • UCSD Thornton Hospital
    • Los Angeles, California, United States, 90073
      • West Los Angeles VA Healthcare Center
    • Los Angeles, California, United States, 90033
      • University of Southern California -- Keck School of Medicine
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves
    • Denver, Colorado, United States, 80010
      • University of Colorado Department Of Neurology
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida -- Shands Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
    • Sarasota, Florida, United States, 34233
      • Lovelace Scientific Resources
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Epilepsy Group, P.A.
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Comprehensive Epilepsy Care Center for Children and Adults
  • New York
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Neurology Specialists
  • Ohio
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio at Toledo
  • Oregon
    • Tualatin, Oregon, United States, 97062
      • Oregon Neurology PC
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Milton S. Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75230
      • Neurological Clinic of Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Comprehensive Epilepsy Program
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient has successfully completed the Maintenance and Transition phases of Study VRX-RET-E22-301 for the treatment of partial-onset seizures
• Patient is expected to benefit from participation in the study in the opinion of the Investigator.

Exclusion Criteria:

• Patient meets any of the withdrawal criteria in the previous VRX-RET-E22-301 study or is experiencing an ongoing serious adverse event.
• Patient is receiving any investigational drug or using any experimental device in addition to Retigabine for treatment of epilepsy or any other medical condition.
• Patient has any other condition that would prevent compliance with the study procedures or proper reporting of adverse events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ezogabine: USAN Retigabine (International Nonproprietary Name); Film-coated tablets - 50mg, 100mg or 300mg

Drug: Ezogabine: USAN Retigabine (International Nonproprietary Name); Film-coated tablets containing 50 mg, 100 mg, or 300 mg of retigabine per tablet. Dosage and frequency will be specific to each patient so long as the patient receives between 600 and 1200 mg of retigabine per day. The duration will be until the trial concludes or the patient leaves the trial.; Other Names: GKE-841; D-23129; GW582892X

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Serious Adverse Event (SAE) and Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization (unplanned hospital stay) or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect. Treatment-emergent AE was defined as an AE with an onset on or after the day of first dose of the study medication and on or before 30 days after the last dose date. AEs reported during parent study and worsened after first dose of RTG in this OLE study were also reported.	Assessed up to a maximum of 9 years
Number of Participants With Treatment-emergent Adverse Events Leading to Withdrawal From Study Drug	Treatment-emergent AE was defined as an AE with an onset on or after the day of first dose of the study medication and on or before 30 days after the last dose date. AEs reported during parent study and worsened after first dose of RTG in this OLE study were also reported.	Assessed up to a maximum of 9 years
Kaplan-Meier Estimate of the Probability of Discontinuation (d/c) From Study Drug	The time frame of premature study discontinuation was defined as the time from the day of first the study medication to the time of withdrawal from study drug. For those who have a taper dose start date, the time of withdrawal was the day before the start of taper dose. For those without a taper dose start date, the time of withdrawal was the last dose date. Participants who switched to the commercial product were censored at the last dose of study drug in the Kaplan-Meier analysis. All participants who withdrew from study drug prematurely but didn't switch to commercial product were counted as "events". Kaplan-Meier estimate of the probability of discontinuation at the specified time or earlier. Number of Participants continuing on RTG at each time of withdrawal were analyzed (represented as n=X in category title).	Assessed up to a maximum of 9 years
Change From Baseline in Blood Pressure	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was obtained in supine (Su) position and again in standing (St) position after the participant was standing for approximately 2 minutes at each study visit (Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Not Applicable (NA) indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Heart Rate	Heart rate (HR) was measured in supine (Su) position and again in standing (St) position after the participant was standing for approximately 2 minutes at each study visit (Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Body Temperature	Body temperature was measured in degree Celsius at each study visit (Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available	Baseline and Up to Month 108
Change From Baseline in Weight	Weight was measured in ordinary indoor clothing (without shoes) and was recorded at each study visit (On Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
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)	A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. The following electrocardiogram parameters are presented PR Interval, QRS Duration, Uncorrected QT interval (uQT), Corrected QT (Bazett's correction) interval (QTcB), Corrected QT (Friedericia's correction) interval (QTcF). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in the 12-lead Electrocardiogram (ECG) Parameter-RR Interval	A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. The following electrocardiogram parameters are presented: RR Interval. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).	Baseline and Up to Month 108
Change From Baseline in Electrocardiogram (ECG) Parameter-QRS Axis	A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. ECG parameter QRS Axis is presented here. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).	Baseline and Up to Month 108
Change From Baseline in Hematology Parameters- Bands, Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets, White Blood Cells Count (WBC)	Following hematology parameters were assessed, Bands (Band neutrophils), Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets and WBC. Hematology parameters were assessed at Month 1, Month 2, Month 3, Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Hematology Parameter-Red Blood Cell Count	Red Blood Cell count (RBC) was assessed at Month 1, Month 2, Month 3, Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available..	Baseline and Up to Month 108
Change From Baseline in Haematocrit	Haematocrit was assessed at Month 1, Month 2, Month 3, Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).	Baseline and Up to Month 108
Change From Baseline in Haemoglobin	Haemoglobin was assessed at Month 1, Month 2, Month 3, , Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available..	Baseline and Up to Month 108
Change From Baseline in Chemistry Parameters-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)	Alkaline phosphatase (AP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) were assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Chemistry Parameters-Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium, Urea	Bicarbonate (Bic.), BUN, Calcium (Ca), Chloride (Cl), Cholesterol (Cho.), Non-fasting glucose (NFG), Phosphorus (P), Potassium (Ka), Sodium (Na), Urea were assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Chemistry Parameters -Creatinine, Total Bilirubin (TB), Uric Acid (UA)	Creatinine, Total bilirubin (TB), Uric acid (UA) were assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Chemistry Parameter-Total Protein	Total Protein (TP) was assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)	Baseline and Up to Month 108
Change From Baseline in Urine Specific Gravity	Urine Specific gravity (USG) was assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Urine Power of Hydrogen (pH)	Urine pH was assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.	Baseline and Up to Month 108
Change From Baseline in Post-void Residual Bladder Ultrasound Volume	Post-void residual (PVR) bladder was assessed using ultrasound scan to assess urinary retention at Month 1, Month 3, Month 12 and annually after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)	Baseline and Up to Month 108
Change From Baseline in Overall American Urological Association (AUA) Symptom Index Score	An AUA Symptom Index is a 7-item Likert-scored scale describing urinary bladder function and was completed by the Investigator to assess the participant's urinary voiding function at Month 1, Month 3, Month 12 and annually after Month 12. The index scale ranges from 0-35, where higher scores are indicative of a worse issue. Scores are categorized as 0-7 mild, 8-19 moderate and >19 severe. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)	Baseline and Up to Month 108
Number of Participants With Abnormal Results in Physical Examination	A complete physical examination was performed at the end of each 12 month study cycle. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). If a participant had an abnormal result for at least one body system of exam, that participant was included in the 'Abnormal' category	Up to Month 108
Number of Participants With Abnormal Results of Neurological Examination	Participants were assessed at Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12. Participants in the worst category among the results of all neurological examination parameters are presented. Abnormal results were categorised as Abnormal not Clinically Significant (AbNCS)and Abnormal and Clinically Significant (AbCS). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)	Up to Month 108
Number of Participants With Pigmentation of Non-retinal Ocular Tissue	The ophthalmologist/retina specialist determined the presence or absence of abnormal discoloration of all non-retinal ocular tissues. Only those participants available at the specified time points were analyzed.	Assessed up to a maximum of 9 years
Number of Participants With Pigmentation of Retinal Ocular Tissue	The ophthalmologist/retina specialist determined the presence or absence of abnormal discoloration of retinal ocular tissues. It included Pigmentary abnormalities in the macula, of peripheral retina as well as in both of them.. Only those participants available at the specified time points were analyzed.	Assessed up to a maximum of 9 years
Number of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa	An assessment of the participant's nails, lips, skin and mucosa was completed by the investigator at the 4 monthly study visits. The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids,lips, nails, and mucosa	Assessed up to a maximum of 9 years
Number of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination	A comprehensive eye examination was conducted by retina specialist or general ophthalmologist to assess best corrected visual acuity. An initial comprehensive eye examination was completed by an ophthalmologist for all participants. This exam was not associated with a specific visit. Thereafter, eye examinations was performed approximately every 6 months. Eye examination was introduced following protocol amendment and was conducted in all participants. Participants discontinued before implementation of this amendment and who have not had a comprehensive eye examination and skin examination (and follow-up by a dermatologist, if clinically indicated) were asked to return to the clinic for an evaluation of their skin (and follow-up dermatology examination, if clinically indicated) and for a comprehensive eye examination. Number of Par. with both initial and at least one follow-up exam while on RTG treatment were analyzed.	Assessed up to a maximum of 9 years
Number of Participants With a Decrease in Confrontational Visual Field From Initial Examination	Decrease in confrontation visual field is defined as a participant having a normal initial exam and an abnormal exam thereafter or, a response of clinically significant worsening in either eye since the last assessment.	Assessed up to a maximum of 9 years
Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine	The ophthalmologist/retina specialist determined the presence or absence of retinal and non-retinal ocular abnormalities. Retinal abnormalities included abnormalities in the macula and/or the peripheral retina and non-retinal ocular pigmentary abnormality.	2 years and 9 months
Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine	An assessment of the participant's nails, lips, skin and mucosa was completed by the investigator at the 6 monthly SFUCP study visits. The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa.	2 years 9 months
Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation	Retinal pigmentary abnormality was determined by either an ophthalmologist or retina specialist. Retinal pigmentary abnormality included pigmentary abnormality of macula, pigmentary abnormality of the peripheral retina and non-retinal ocular pigmentary abnormality. If a participant had pigmentary abnormality of macula and pigmentary abnormality of the peripheral retina both should be resolved in order for retinal pigmentary abnormality to be considered resolved. If a participant had non-retinal ocular pigmentary abnormality in more than location (conjunctiva, sclera, cornea, iris or lens), all should be resolved for non-retinal pigmentary abnormality to be considered resolved. Only participants with resolution of the specified pigmentation are included in this analysis.	2 years 9 months
Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration	Assessments were at approximately 6-monthly intervals (timed relative to the participants previous dermatology assessment) until the abnormal discoloration either resolved or stabilized (as defined by no changes over 2 consecutive 6-monthly assessments performed by the dermatologist over at least 12 months after discontinuation of retigabine). The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa. Only participants with resolution of the specified tissue are included in this analysis.	2 years 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in the 28-day Partial Seizure	Twenty-eight-day total partial seizure frequency during the study is defined as the sum of total partial seizures from First date (Baseline visit date +1 if no seizures on Baseline or Baseline visit date if seizures reported on the Baseline) to Last date (last visit date for seizure record with non-missing response), divided by applicable days, standardized by 28 days. The applicable days are the days in which the subject had non-missing seizure data. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed.	Assessed up to a maximum of 9 years
Number of Responders	A participant was classified as a responder if there is an at least 50% reduction from Baseline in the 28-day total Partial Seizure frequency. Baseline was defined as the parent study Baseline. Only those participants available at the specified time points were analyzed.	Assessed up to a maximum of 9 years
Number of Participants Who Were Seizure Free for Any 6 Continuous Months	Number of seizure free days is defined as the number of applicable days without any seizures (partial, generalized or unclassified). Only the days in which a subject had non-missing seizure data were considered as applicable days. Duration of exposure is defined using a window range allowed for each scheduled visit. At least 6 months of exposure is defined as >= 173 days of exposure since the window range for Month 6 visit is +/- 7 days. Only those participants available at the specified time points were analyzed.	Assessed up to a maximum of 9 years
Number of Participants Who Were Seizure Free for Any 12 Continuous Months	Duration of exposure is defined using a window range allowed for each scheduled visit. At least 12 months of exposure is defined as >= 353 days of exposure since the window range for Month 12 visit is +/- 7 days. Only those participants available at the specified time points were analyzed.	Assessed up to a maximum of 9 years
Percentage of Seizure-free Days	Number of seizure free days is defined as the number of applicable days without any seizures (partial, generalized or unclassified). Only the days in which a participant had non-missing seizure data was considered as applicable days	Assessed up to a maximum of 9 years
Change From Baseline in Quality of Life in Epilepsy (QOLIE)-31-P Questionnaire	The QOLIE-31-P (Version 2.0) was utilized to assess quality of life. The QOLIE-31-P assessment was completed by the participants at Baseline, Month 3, Month 6, Month 9, Month 12 and annually after Month 12. The QOLIE has 7 sub scales as energy fatigue, emotional well being, social functioning, cognitive, medication effects, seizure worry and overall QOL. The assessment range for the overall score and the sub-scales is 0-100, where higher scores indicate greater well being. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)	Assessed up to a maximum of 9 years

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2006
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): March 15, 2017

Study Registration Dates

• First Submitted: March 30, 2006
• First Submitted That Met QC Criteria: March 30, 2006
• First Posted (Estimate): April 3, 2006

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Epilepsy; Anticonvulsant; Epilepsies, Partial; Partial Seizures; Potassium Channels; Complex Partial Seizures; RTG115098
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Ezogabine
• Other Study ID Numbers: VRX-RET-E22-303; RTG115098 (Other Identifier: GlaxoSmithKline)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)