Long-Term Safety Study of Retigabine Immediate Release (IR) as Adjunctive Therapy in the Treatment of Adults With Partial-Onset Seizures (POS) (IR)

A Multicentre, Open-Label, Long-Term, Safety and Tolerability Study of Retigabine Immediate Release (IR) in Adults With Partial-Onset Seizures (Extension of Study RGB113905)

The purpose of this Phase III study is to assess the long-term safety, tolerability and efficacy of flexibly dosed retigabine Immediate Release (IR) as adjunctive therapy in adult subjects with partial-onset seizures. In addition, those subjects who successfully completed 20 weeks of adjunctive treatment with retigabine IR in the parent study, RGB113905, and who were thought to have benefitted from treatment will be provided continued access to retigabine IR.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Retigabine IR

Detailed Description

RTG113413 is an open-label, multicentre extension study of RGB113905. This study will enroll adult subjects with partial-onset seizures (POS) who successfully completed 20 weeks of adjunctive treatment with retigabine IR (4-weeks Titration Phase and 16-weeks Flexible Dose Evaluation Phase) in the parent study, RGB113905 and who were thought to have benefitted from the treatment.

The Screening Visit (Visit 1) will be performed on the same day as the final visit of the parent study (Visit 7/Week 20). Subjects entering the extension study will initially receive the same dose of retigabine IR and concurrent antiepileptic drug (AED) as they were receiving on the final visit of the parent study. After the first week of the extension study, the subject's retigabine dose can be adjusted based on efficacy and tolerability. The overall daily dose of retigabine IR must be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). In addition, the dose and the number of concurrent AEDs can be adjusted to meet the individual needs of the subject. Retigabine IR monotherapy is not permitted. If concurrent AED therapy is removed, the subject must be withdrawn from the study.

Subjects in this study will be eligible to receive retigabine IR treatment until one of the following criteria have been met: 1) regulatory approval and commercial availability of retigabine IR or 2) retigabine IR is not approved by the regulatory authorities or 3) the study is terminated by the sponsor for reasons including, but not limited to, safety issues or 4) subject is withdrawn or withdraws consent or 5) subject has received retigabine IR treatment for a total of 3 years and options i-iv have not been met. After the Screening Visit, subjects will be required to attend 4 further clinic visits at Weeks 13, 26, 39, and 52 in the first year of the study and a total of 3 clinic visits at approximately 4-monthly intervals during each of the second and third year of study. Upon completion or early withdrawal, subjects will begin a 3-week taper period and then return for a follow-up visit.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • GSK Investigational Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • GSK Investigational Site
  • Sofia, Bulgaria, 1431
    • GSK Investigational Site
  • Sofia, Bulgaria, 1113
    • GSK Investigational Site
• France
  • Limoges, France, 87042
    • GSK Investigational Site
  • Strasbourg Cedex, France, 67098
    • GSK Investigational Site
• Germany
  • Nordrhein-Westfalen
    • Bielefeld, Nordrhein-Westfalen, Germany, 33617
      • GSK Investigational Site
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00163
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00185
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16153
      • GSK Investigational Site
  • Marche
    • Torrette Di Ancona, Marche, Italy, 60126
      • GSK Investigational Site
  • Puglia
    • Foggia, Puglia, Italy, 71100
      • GSK Investigational Site
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • GSK Investigational Site
• Netherlands
  • Heemstede, Netherlands, 2103 SW
    • GSK Investigational Site
• Poland
  • Warszawa, Poland, 00-453
    • GSK Investigational Site
• Russian Federation
  • Belgorod, Russian Federation, 308007
    • GSK Investigational Site
  • Kazan, Russian Federation, 420064
    • GSK Investigational Site
  • Krasnodar, Russian Federation, 350007
    • GSK Investigational Site
  • Moscow, Russian Federation, 117049
    • GSK Investigational Site
  • Moscow, Russian Federation, 107150
    • GSK Investigational Site
  • Samara, Russian Federation, 443095
    • GSK Investigational Site
  • Smolensk, Russian Federation, 214 019
    • GSK Investigational Site
  • St.-Petersburg, Russian Federation, 193019
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • GSK Investigational Site
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
• Ukraine
  • Dnepropetrovsk, Ukraine, 49005
    • GSK Investigational Site
  • Lugansk, Ukraine, 91045
    • GSK Investigational Site
  • Odesa, Ukraine, 65014
    • GSK Investigational Site
  • Oleksandrivka Village, Odesa, Ukraine, 67513
    • GSK Investigational Site
  • Poltava, Ukraine
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The subject has successfully completed the 20-weeks (4-weeks Titration and 16-weeks of Flexible Dose Evaluation Phases) of treatment with retigabine IR as adjunctive therapy to one of the pre-specified AEDs in the parent study RGB113905.
• The investigator and the subject, or caregiver, if applicable, should consider it beneficial for the subject to receive continued retigabine IR therapy.
• The subject is able and willing to maintain an accurate and complete daily written Seizure Calendar or has a caregiver who is able and willing to maintain an accurate and complete daily written Seizure Calendar for the entire duration of the study.
• The subject has given written informed consent, or has a legally authorized representative who has given written informed consent, prior to the performance of any study assessments.
• A female subject is eligible to enter and participate in the study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre- menarcheal or post menopausal).
• A female subject is eligible to enter and participate in the study if she is child-bearing potential and has a negative pregnancy test at Screening, and agrees to use one of the contraceptive methods listed in Appendix 3 of the protocol.
• A female subject is eligible to enter and participate in the study if she not pregnant or lactating or planning to become pregnant during the study.
• French subjects only: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• Has met any of the withdrawal criteria in the previous RGB113905 study or has clinically significant abnormal clinical laboratory or ECG findings not resolved prior to entry to the open-label extension study.
• Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that are likely to interfere with the study objectives.
• Has any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.
• Has any abnormality on 12-lead ECG at Screening which is clinically significant in the opinion of the investigator, or has QTc (either QTcB Bazett's correction or QTcF Fridericia's correction) >500 msec or >530 msec for subjects with Bundle Branch Block or an increase in QTc of >60 msec from Baseline in the parent study.
• Is unwilling or inability to follow the study procedures or reporting of AEs.
• Is planning on following a ketogenic diet or planning surgery or implantation of a Vagus Nerve Stimulator (VNS) to control seizures during the study. Note: Subjects who already have a VNS implanted which is functional may be permitted to enter the study.
• Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.

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: Retigabine IR; Open label flexible dose between 300 mg/day (Minimum) and 1200 mg/day (maximum).	Drug: Retigabine IR; Flexible dose between 300 mg/day (minimum) and 1200 mg/day (maximum)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (TESAEs): Safety Population	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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect or is associated with liver injury or impaired liver function. TEAE refers to an AE for which the onset was on or after the date of the first retigabine dose in this study and on or before 30 days after the last retigabine dose date. AEs that started in the parent study that increased in severity during this study were also considered treatment-emergent. The analysis was performed on Safety Population, which included participants who took at least one dose of study medication after they had enrolled into this OLE study.	Up to 5.8 years
Number of Participants With AEs and SAEs: All SFUCP Subjects	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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect or is associated with liver injury or impaired liver function. The following AEs were collected in the SFUCP: AEs related to the finding(s) of pigmentation/, discoloration of the eye/skin, AEs related to unexplained vision loss, SAEs, Deaths and Pregnancies. SFUCP collected AEs are those for which onset was 31 days or more after the last dose of retigabine. The analysis was performed on the All SFUCP Subjects population which comprised of all subjects who enter the SFUCP.	Up to 2.6 years
Number of Participants Withdrawn Due to TEAEs	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. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolonged existing hospitalization, results in disability, is a congenital anomaly/birth defect or is associated with liver injury or impaired liver function. TEAE refers to an AE for which the onset was on or after the date of the first retigabine dose and on or before 30 days after the last retigabine dose date.	Up to 5.8 years
Number of Participants With Retinal Pigmentary Abnormalities	Number of participants with abnormal findings after eye examination were evaluated. Only retinal pigmentary abnormalities detected on-treatment with retigabine were presented. Retinal pigmentary abnormalities included abnormalities in the macula, peripheral retina and unspecified location.	Up to 5.8 years
Number of Participants With Pigmentation of Non-retinal Ocular Tissue(s)	Number of participants with abnormal findings after eye examination were evaluated. Pigmentation of non-retinal ocular tissue (s) detected on-treatment with retigabine were presented. Non-retinal pigmentary abnormalities included abnormalities in the sclera and/ or conjunctiva, cornea, iris and lens.	Up to 5.8 years
Number of Participants With Abnormal Discoloration of Skin	Number of participants with Dermatologist-Confirmed abnormal discoloration of skin including skin around the eyes and eyelids, lips, nails, or mucosa were evaluated. Only abnormalities occurring on-treatment with retigabine were presented.	Up to 5.8 years
Number of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination	Number of participants with a clinically significant decrease in visual acuity from initial examination were evaluated. Only abnormalities occurring on-treatment with retigabine were presented.	Up to 5.8 years
Number of Participants With Decrease in Confrontational Visual Field From Initial Examination	Number of participants with a clinically significant decrease in confrontational visual field from initial examination were evaluated. Only abnormalities occurring on-treatment with retigabine were presented.	Up to 5.8 years
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline in Vital Signs and Weight	Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured after at least 5 minutes of rest. Body weight was measured without shoes and wearing light clothing. Baseline assessments in this OLE study were defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Increase or decrease of >=20 in SBP, increase or decrease of >=15 in DBP and HR were considered as PCC values. Number of participants with PCC values of vital signs for any visit post-Baseline are presented.	Up to 5.8 years
Change From Baseline in Electrocardiogram (ECG) Parameter Including HR	Single measurements of 12-lead ECG were obtained in supine position after at least 10 minutes of rest using an ECG machine to measure HR. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in ECG Parameter Including PR Interval, QRS Duration, Uncorrected QT Interval, Corrected QT by Bazett's Formula (QTcB), Corrected QT by Fridericia's Formula (QTcF) and RR Interval	Single measurements of 12-lead ECG were obtained in supine position after at least 10 minutes of rest using an ECG machine to measure parameters including PR interval, QRS duration, uncorrected QT interval, QTcB, QTcF and RR interval. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Number of Participants With Clinical Chemistry Parameters of PCC	Number of participants with chemistry parameters of PCC at 'any visit post-Baseline' are presented. Chemistry parameters for which PCC values were identified were alanine aminotransferase (ALT) (if value >=3 * upper limit of normal [ULN]), alkaline phosphatase (alk.phosphatase) (if value >=3*ULN), aspartate aminotransferase (AST) (if value >=3*ULN), calcium (if value <=1.8962 or >=2.8692), carbon-di-oxide (CO2) (if value <=18 or >=36), chloride (if value <=92 or >=112), creatine kinase (if value >=3*ULN), direct bilirubin (if value >=1.5*ULN), glucose (if value <=2.7755 or >=11.102), lactate dehydrogenase (LD) (if value >=3*ULN), magnesium (if value <0.36 or >2.50), potassium (if value <=3.0 or >=6.0), sodium (if value <=127 or >=153), total bilirubin (if value >=1.5*ULN), total protein (if value <45 or >100), blood urea nitrogen (BUN) (if value >=14.28). Only those participants with data available at specific time points were analyzed (represented by n=X in the category titles).	Up to 5.8 years
Number of Participants With Hematology Parameters of PCC	Blood samples were collected from participants to evaluate hematology parameters. Number of participants with clinical hematology parameters of PCC at 'any visit post-Baseline' are presented. Hematology parameters for which PCC values were identified were eosinophils (if value is >0.8), hematocrit (if value is <=0.32 for males and <=0.28 for females), platelet count (if value is <=100 or >=550), total neutrophils (if value is <=1.8), white blood cells (WBC) (if value is <=2.8 or >=16). Only those participants with data available at specific time points were analyzed (represented by n=X in the category titles).	Up to 5.8 years
Number of Participants With Urinalysis Parameters of PCC	Urine samples were collected from participants at specific time points. Number of participants with urinalysis parameters of PCC at 'any visit post-Baseline' are presented. Urinalysis parameters for which PCC values were identified were albumin/creatinine ratio (if value is >11.3), red blood cells (RBC) (if value is 3-5 or higher), WBC (if value is 5-10 or higher for male and 10-15 or higher for females), specific gravity (if value is <1.001 or >1.035) and potential of hydrogen (pH) (if value is <4.6 or >8.0). Only those participants with data available at specific time points were analyzed (represented by n=X in the category titles).	Up to 5.8 years
Change From Baseline in Albumin and Total Protein	Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including albumin and total protein. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Alk. Phosphatase, ALT, AST, Creatine Kinase and LD Levels	Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including alk. phosphatase, ALT, AST, creatine kinase and LD. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Direct Bilirubin, Total Bilirubin and Creatinine	Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including direct bilirubin, total bilirubin and creatinine. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in BUN/Creatinine Ratio	Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including BUN/creatinine ratio. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Calcium, Chloride, CO2, Glucose, Potassium, Magnesium, Sodium and BUN	Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including calcium, chloride, CO2, glucose, potassium, magnesium, sodium and BUN. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Absolute Basophils, Absolute Eosinophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Total Neutrophils, Platelet Count and WBC Count	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including absolute basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and WBC count. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Levels	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including hemoglobin and MCHC. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Hematocrit Levels	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including hematocrit. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Levels	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including MCH. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) Levels	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including MCV and MPV. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in RBC Count	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including RBC count. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Up to 5.8 years
Change From Baseline in Percent Basophils, Percent Eosinophils, Percent Lymphocytes, Percent Monocytes, Percent Neutrophils and RBC Distribution Width (RDW) Levels	Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including percent basophils, eosinophils, lymphocytes, monocytes, neutrophils and RDW. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Urine Albumin Creatinine Ratio	Urine samples were collected from participants for evaluation of change from Baseline in urinalysis parameters including albumin creatinine ratio. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Urine Albumin Levels	Urine samples were collected from participants for evaluation of change from Baseline in urinalysis parameters including albumin levels. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Urine Creatinine Levels	Urine samples were collected from participants for evaluation of change from Baseline in urinalysis parameters including creatinine levels. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Changes From Baseline in American Urological Association Symptom Scale (AUA SS) Score	The effect of retigabine on bladder function was assessed using AUA symptom index. It is a 7-item Likert-scored scale ranging from 0 (no symptom at all) to 5 (almost always symptoms present) with a total possible score of 35. AUA SS score is the sum of the responses to these seven questions. The total score for all questions was classified as mild (0 to 7), moderate (8 to 19), or severe (>19). Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Change From Baseline in Post-Void Residual (PVR) Bladder Ultrasound Urine Volume	The PVR bladder ultrasound was used to assess urinary retention. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).	Baseline and up to 5.8 years
Number of Participants With Suicidal Ideation or Behavior Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Score	Number of participants with suicidal ideation or behavior during treatment were assessed using the C-SSRS score scale. It is a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. Participants are classified with respect to extent of suicidal ideation, extent of suicidal behavior, and with respect to self-injurious behavior.	Up to 5.8 years
Number of Participants Experiencing New Seizure Types	Number of participants experiencing new seizure type that is seizure not experienced before were summarized. New seizure types were classified into 5 classes including type A (simple partial seizure), type B (complex partial seizure), type C (Partials, evolving to Secondary Generalized Seizures), type D (Generalized, excluding Myoclonic Seizures), type D2 (Myoclonic Seizures) and type E (Unclassified Seizures).	Up to 5.8 years
Number of Participants Experiencing Worsening of Seizures	Worsening of seizures was defined as an increase in seizure frequency or the occurrence of a new, more severe seizure type, or status epilepticus occurring in a participant without a history of status epilepticus. An increase in seizure frequency was defined as doubling of the 28-day seizure frequency compared to the 28-day Baseline seizure frequency established in the parent study. Number of participants experiencing worsening of seizure during study period are presented.	Up to 5.8 years
Duration of Retigabine Exposure	Duration of exposure was calculated from the first dose through the last dose during study including the Taper Phase and presented using median and full range.	Up to 5.8 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.	Up to 2.6 years
Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine	Participants who enter the SFUCP who had an on-treatment finding(s) of abnormal discoloration of skin, lips, nails or mucosa confirmed by a dermatologist entered the SFUCP and underwent assessments performed by a dermatologist at 6-monthly intervals. The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa.	Up to 2.6 years
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 abnormality of macula, peripheral retina and unspecified location. 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 one location (conjunctiva, sclera, cornea, iris or lens), all should be resolved for non-retinal pigmentary abnormality to be considered resolved.	Up to 2.6 years
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.	Up to 2.6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing a 0 to <25, 25 to <50, 50 to <75 and 75 to 100 Percent Reduction in 28 Day POS Frequency From Baseline	The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Baseline assessments in this OLE study are defined by and taken directly from the Baseline assessments in the parent study NCT01336621.	Baseline and up to 5.8 years
Percent Change From Baseline in 28-day Partial-onset Seizure Frequency	The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Percent change from Baseline in 28-day partial onset seizure frequency was presented as mean and standard deviation (SD). Baseline assessments in this OLE study are defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Percent change from Baseline was calculated as post-Baseline value minus Baseline value divided by Baseline value into 100.	Baseline and up to 5.8 years
Number of Participants Experiencing an Increase in 28-day Partial-onset Seizure Frequency From Baseline	The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Baseline assessments in this OLE study are defined by and taken directly from the Baseline assessments in the parent study NCT01336621.	Baseline and up to 5.8 years
Number of Participants Who Remained Seizure-free	The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Number of participants who were treated retigabine for at least 6 months and who remained seizure free for any 6 continuous months as well as number of participants who were treated with retigabine for at least 12 months and who remained seizure free for any 12 continuous months are presented.	Up to 5.8 years

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2011
• Primary Completion (Actual): December 14, 2016
• Study Completion (Actual): September 13, 2017

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 18, 2011

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Epilepsy; GW582892; Open Label Extension; Partial-onset seizures; retigabine IR
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Ezogabine
• Other Study ID Numbers: 113413; 2010-022777-34 (EudraCT Number)

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)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes