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.

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. 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.

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 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.

Safety Population

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.

Safety Population. Only those participants with >=1 ophthalmology exam on or before last dose of RTG are presented.

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.

Safety Population. Only those participants with >=1 ophthalmology exam on or before last dose of RTG are presented.

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.

Safety Population. Only those participants who had at least one skin exam by the investigator or dermatologist on or before the last dose of RTG or dermatologist-confirmed discoloration with start date on or before the date of last dose of RTG are presented.

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.

Safety Population. Only those participants with both initial and at least 1 follow-up exam while on RTG treatment are presented.

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.

Safety Population. Only those subjects with both initial and at least 1 follow-up exam while on RTG treatment are presented.

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.

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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).

Safety Population

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.

Safety Population

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).

Safety Population

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.

Safety Population

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.

Safety Population

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.

All SFUCP Subjects

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.

All SFUCP Subjects

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.

All SFUCP Subjects

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.

All SFUCP Subjects

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.

Safety Population

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.

Safety Population

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.

Safety Population

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.

Safety population