A Long-term, Safety, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01777139
• Collaborator: (none)
• Enrollment: 30
• Locations: 12
• Arm: 1
• Actual Duration (Months): 53.1
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a multicentre, long-term, open-label extension (OLE) study to assess the long-term safety, tolerability and efficacy of retigabine immediate-release (IR) as adjunctive therapy in adult Asian subjects with drug-resistant partial-onset seizures (POS).

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Retigabine IR	Phase 3

Detailed Description

Subjects who successfully complete the Maintenance Phase of Study RTG114855 (parent study) and are expected to benefit from therapy with retigabine IR will be eligible for this OLE study. The study will consist of Screening (1 day), Open-Label Treatment and Follow-up (3 weeks) phase. Subjects will initially receive a starting dose of retigabine IR at 900 milligram (mg)/day and the same concurrent antiepileptic drug (AED) regimen that they were receiving at the final visit of the Transition Phase of the parent study. After the first week of the OLE study, the dose of retigabine IR may be adjusted to between 600 and 1200 mg/day, with dose adjustments in increments or decrements of 150 mg/week, based on efficacy and tolerability. In addition, the dose and number of concurrent AEDs may also be adjusted to meet each individual subject's needs. The efficacy and safety issues will be assessed throughout the study; subjects will be instructed to call the investigator if they experience any efficacy or tolerability issues between the study visits. As the duration of the study will be determined based on the following four conditions: 1) regulatory approval and commercialisation of retigabine IR; 2) retigabine IR is not approved by the regulatory authorities; 3) the study is terminated by the Sponsor for reasons including, but not limited to, safety issues; or 4) the subject is withdrawn or withdraws consent, 4 years will be considered as a guide to the duration of the study. The safety and tolerability endpoints are incidence and severity of adverse events (AEs); proportion of subjects with AEs leading to discontinuation; change from Baseline in vital sign measurements and weight; change from Baseline in electrocardiogram parameters; change from Baseline in haematology, chemistry, and urinalysis parameters; changes from Baseline in American Urological Association Symptom Index and post-void residual bladder ultrasound volumes; and summary of the Columbia-Suicide Severity Rating Scale. Efficacy will be assessed by calculating the percent change from Baseline (parent study) in 28-day total POS frequency for the entire open-label Treatment Phase of this OLE study. This will also be calculated based on duration of exposure. Responder rate (defined as a >/=50% reduction from Baseline in 28-day total POS frequency) will also be summarised for the entire open-label Treatment Phase and by duration of exposure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures (Extension of Study RTG114855)
• Actual Study Start Date: Apr 11, 2013
• Actual Primary Completion Date: Dec 14, 2016
• Actual Study Completion Date: Sep 13, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Retigabine IR All subjects will initially receive a starting dose of retigabine IR at 900 mg/day and after the first week of the OLE study, the dose of retigabine IR may be increased or decreased in increments or decrements of decrements of 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of retigabine IR must be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.

Drug: Retigabine IR; Retigabine IR tablets will be available in 5 strengths: 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent (TE) Serious Adverse Events (SAEs) and Non-SAEs [Up to 4 years]

   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. 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, other situations and is associated with liver injury or impaired liver function is SAE. TEAE refers to an AE for which the onset was on or after the date of the first RTG dose in this study and on or before 30 days after the last RTG dose date. AEs that started in the parent study that worsened in this study were also considered as TEAEs. Safety population comprised of participants who take at least 1 dose of study medication after they have enrolled into this OLE study. Number of participants with TE-SAEs and non-SAEs (with incidence >= 5%) have been presented.

2. Percentage of Participants With TEAEs Leading to Study Discontinuation [Up to 4 years]

   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. TEAE refers to an AE for which the onset was on or after the date of the first RTG dose in this study and on or before 30 days after the last RTG dose date. Percentage of participants with TEAEs leading to study discontinuation were presented.

3. Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs [Baseline and up to 4 years]

   The vital signs were evaluated as per PCC Criteria. The vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The vital signs were measured in a seated position after 5 minutes of rest. PCC range for DBP was increase or decrease of >=20, for SBP was increase or decrease of >=15 and for heart rate was increase or decrease of >=15. A Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. Change from Baseline was defined as post-Baseline value minus Baseline value. Number of participants with vital sign values of PCC at any Post-Baseline visit were presented.

4. Number of Participants With PCC Values of Change From Baseline for Body Weight [Baseline and up to 4 years]

   Body weight of participants were measured as a measure of safety. PCC range for body weight was increase or decrease of >=7 percent. A Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. Change from Baseline was defined as post-Baseline value minus Baseline value. Number of participants with PCC values of body weight at any Post-Baseline visit were presented.

5. Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters [Baseline and up to 4 years]

   Single measurements of 12-lead ECGs were obtained in a supine position after at least 10 minutes of rest using an ECG machine that automatically calculates the heart rate (HR) as beats per minute (bpm) and measures PR, QRS, Bazett's correction QT interval (QTcB) and Friedericia's correction QT interval (QTcF) in milliseconds (msec). A Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. Change from Baseline was defined as post-Baseline value minus Baseline value. Number of participants with PCC values of ECG parameters at any Post-Baseline visit were presented. For the 'Any Post Baseline' value, only the worst case finding was counted for each participant.

6. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) [Baseline and up to 4 years]

   Blood samples were collected from participants for evaluation of change from Baseline in hematology parameters including basophils, eosinophils, lymphocytes,monocytes, platelet count, total neutrophils, and WBC. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and standard deviation (SD) were calculated.

7. Change From Baseline in Hematocrit [Baseline and up to 4 years]

   Blood samples were collected from participants for evaluation of hematocrit. Hematocrit is a ratio of red blood cells to the total volume of blood. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

8. Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) [Baseline and up to 4 years]

   Blood samples were collected from participants to evaluate change from Baseline in hemoglobin and MCHC levels. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

9. Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level [Baseline and up to 4 years]

   Blood samples were collected from participants to evaluate change from Baseline in MCH levels. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

10. Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in MCV and MPV levels. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

11. Change From Baseline in Red Blood Cell (RBC) Count [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in RBC count. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

12. Change From Baseline in Red Cell Distribution Width (RDW) [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in RDW. RDW is a parameter that measures variation in red blood cell size or red blood cell volume. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

13. Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (Alk. Phosph.), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LD) [Baseline and up to 4 years]

    Blood samples collected from participants to evaluate change from Baseline in clinical chemistry parameters included ALT, Alk. phosph., AST,CK, GGT and LD. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

14. Change From Baseline in Albumin and Total Protein [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in albumin and total protein. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

15. Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in BUN/creatinine. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

16. Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in calcium, CO2 content/Bicarb, chloride, glucose, magnesium, potassium, sodium, and urea/BUN. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

17. Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid [Baseline and up to 4 years]

    Blood samples were collected from participants to evaluate change from Baseline in creatinine, direct bilirubin, total bilirubin, and uric acid. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

18. Change From Baseline in Urine Albumin/Creatinine Ratio [Baseline and up to 4 years]

    Urine samples were collected from participants to evaluate change from Baseline in urine albumin/creatinine ratio. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated. NA indicates data was not available as standard deviation could not be calculated for single participant.

19. Number of Participants With Abnormal Urinalysis Values (Categorical Data) [Up to 4 years]

    Urine samples were collected from participants to analyze presence of abnormal urinalysis parameters including glucose, ketones, RBC, WBC, occult blood and protein. Abnormal urinalysis values have been presented for all parameters. Only those participants with data available at specific time points were analyzed (represented by n= X in the category titles).

20. Specific Gravity of Urine at Indicated Time Points [Up to 4 years]

    Urine samples were collected to analyze specific gravity of urine. Specific gravity, is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

21. Potential of Hydrogen (pH) of Urine at Indicated Time Points [Up to 4 years]

    Urine Samples were collected to analyze pH. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH scale ranges from 0 to 14. A neutral pH is 7.0. The higher number indicates the more basic (alkaline) nature of urine and lower the number indicates the more acidic urine. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

22. Change From Baseline in Urine Creatinine Concentration [Baseline and up to 4 years]

    Urine samples were collected from participants to evaluate change from Baseline in Urine creatinine concentration. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

23. Change From Baseline in American Urological Association (AUA) Symptom Scale Scores [Baseline and up to 4 years]

    The effect of RTG on bladder function was assessed using AUA symptom index. It is a 7-item Likert-scored scale with seven questions, each with six potential responses. Responses to each of 7 questions were scored from 0 (no symptom at all) to 5 (almost always symptoms present) which were summmed to get total possible score ranging from 0 to 35 with higher scores indicating worse symptom severity. The total score for all questions was classified as mild (0-7), moderate (8-19) or severe (>19). Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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).

24. Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes [Baseline and up to 4 years]

    The PVR bladder ultrasound was used to assess the effects of RTG on bladder function. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.

25. Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) [Up to 4 years]

    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. It consists of an assessment of suicidal ideation (ranging from "desire to be dead" to "active suicidal ideation with specific plan and intent") and an assessment of suicidal behavior (ranging from "preparatory acts or behavior" to "completed suicide").

26. Number of Participants Who Discontinued From RTG [Up to 4 years]

    The number of participants who discontinued from RTG treatment has been presented.

27. Percentage of Participants With Retinal Pigmentary Abnormalities [Up to 4 years]

    Percentage of participants with abnormal findings after eye examination were evaluated. Abnormalities detected on-treatment in study RTG114873 were presented. Retinal pigmentary abnormalities included abnormalities in the macula, peripheral retina and unspecified location.

28. Percentage of Participants With Pigmentation of Non-retinal Ocular Tissues [Up to 4 years]

    Percentage of participants with abnormal findings after eye examination were evaluated. Abnormalities detected on-treatment in study RTG114873 were presented. Pigmentation of non-retinal ocular tissues included pigmentation of the sclera and/or conjunctiva, cornea, iris and lens.

29. Percentage of Participants With Dermatologist-confirmed Abnormal Discoloration [Up to 4 years]

    Percentage of participants with abnormal findings after skin examination (including the skin around the eyes and the eyelids, lips, nails, or mucosa) were evaluated.

30. Percentage of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination [Up to 4 years]

    Percentage of participants with a clinically significant decrease in visual acuity from initial examination were evaluated. Only abnormalities occurring on-treatment in study RTG114873 were presented.

31. Percentage of Participants With Decrease in Confrontational Visual Field From Initial Examination [Up to 4 years]

    Percentage of participants with decrease in confrontational visual field from initial examination were evaluated. Only abnormalities occurring on-treatment in study RTG114873 were presented.

32. Percentage of Responders to POS Frequency [Up to 4 years]

    A responder was defined as a participant experiencing a >=50 percent reduction in 28 day total POS frequency from Baseline. A responder rate was calculated overall and based on duration of exposure. As this was an OLE study, Baseline was defined by the parent study Baseline period. Percentage of responders were evaluated from study RTG114873 Day 1 through the last dosing day, excluding the Taper Phase.

33. Percent Change From Baseline in 28-day Total POS Frequency [Baseline and up to 4 years]

    The 28-day total POS frequency was calculated as the number of total POS reported during the treatment phase, divided by the number of applicable days in the treatment phase, then multiplying this ratio by 28. In this formula, innumerable seizures were counted as 10 seizures and status epilepticus was counted as 1 seizure. As this was an OLE study, Baseline was defined by the parent study Baseline period. The percent change from Baseline was calculated as the 28-day total POS on-treatment frequency (during dosing in this study, not including the taper phase) minus the Baseline 28-day total POS frequency, with this difference being divided by the Baseline 28-day partial seizure rate, and the resulting quantity multiplied by 100. It was calculated as overall and by duration of exposure. Mean and SD were presented.

34. Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of RTG [Up to 1.4 years]

    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. This analysis was performed on the All SFUCP Subjects population which comprised of all participants who enter the SFUCP.

35. Number of Participants With Resolution of Dermatologist-confirmed Abnormal Discoloration After Discontinuation of RTG [Up to 1.4 years]

    The skin examination included assessment of the skin around the eyes and the eye lids, lips, nails, and mucosa. Participants who enter the SFUCP who had on-treatment finding(s) of abnormal discoloration of skin, lips, nails or mucosa confirmed by a dermatologist, underwent assessments performed by a dermatologist at 6-monthly intervals.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject has successfully completed the Maintenance Phase and Transition Phase of Study RTG114855.

• The subject is expected, in the opinion of the investigator, to benefit from participation in this OLE study.

• The subject or the caregiver is able and willing to maintain an accurate and complete written daily 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 enrol and participate in the study if she is of: nonchildbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is premenarchal or postmenopausal), premenopausal females with a documented (medical report verification) hysterectomy with or without oophorectomy, or bilateral oophorectomy when reproductive status has been confirmed by hormone level assessment, and postmenopausal females defined as being amenorrhoeic for

1 year with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by oestradiol and follicle stimulating hormone levels consistent with menopause (according to local laboratory ranges). Women who have not been confirmed as postmenopausal should be advised to use contraception.

• Childbearing potential, has a negative urine or serum pregnancy test at Screening.

• Is not pregnant or lactating or planning to become pregnant during the study.

Exclusion Criteria:

• Has met any of the withdrawal criteria in the parent study (RTG114855) or has, in the opinion of the investigator, clinically significant abnormal laboratory or ECG findings that preclude entry into RTG114873.

• Is planning to begin treatment with an investigational drug (other than retigabine) and/or an experimental device for the treatment of epilepsy or any other medical condition.

• Has any medical condition that, in the investigator's judgement, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to clinically significant cardiac, renal, or hepatic condition; or a condition that affects the absorption, distribution, metabolism, or excretion of drugs.

• Is unwilling or unable to follow the study procedures or reporting of AEs.

• Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months or has history of suicide attempt in the last 2 years or >1 lifetime suicide attempt.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Busan		Korea, Republic of	602-715
2	GSK Investigational Site	Busan		Korea, Republic of	612-865
3	GSK Investigational Site	Daegu		Korea, Republic of	700-712
4	GSK Investigational Site	Daejeon		Korea, Republic of	301-721
5	GSK Investigational Site	Gyeonggi-do		Korea, Republic of	463-707
6	GSK Investigational Site	Seoul		Korea, Republic of	110-744
7	GSK Investigational Site	Seoul		Korea, Republic of	135-720
8	GSK Investigational Site	Seoul		Korea, Republic of	138-736
9	GSK Investigational Site	Seoul		Korea, Republic of	143-729
10	GSK Investigational Site	Kuala Lumpur		Malaysia	59100
11	GSK Investigational Site	Bangkok		Thailand	10400
12	GSK Investigational Site	Khon Kaen		Thailand	40002

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01777139
• Other Study ID Numbers: 114873
• First Posted: Jan 28, 2013
• Last Update Posted: Mar 11, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Retigabine; Drug-Resistant; Epilepsy; Partial-Onset Seizures; Safety and Tolerability; Immediate Release; Long-Term; Adjunctive Therapy; Asian Subjects; Efficacy; GW582892
• Additional relevant MeSH terms: Epilepsy; Seizures; Ezogabine

Study Results

Participant Flow

Recruitment Details	Participants with partial-onset seizures (POS) who successfully completed the maintenance phase of study RTG114855 (NCT01648101) were recruited in this open-label extension (OLE) study.
Pre-assignment Detail	All the participants received at least 1 dose of retigabine (RTG) immediate release (IR). Screening was performed on the day of final visit of the parent study. A total of 30 participants, 12 from placebo and 18 from RTG group who completed the treatment and transition phases of the parent study were included in this OLE study.

Arm/Group Title	RTG IR	RTG in Safety Follow-up Continuation Phase (SFUCP)
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.	Participants who withdraw from the Open-Label Treatment Phase and who had retinal pigmentation or unexplained vision loss, pigmentation of non-retinal ocular tissue or abnormal discoloration of nails, lips, skin or mucosa were followed-up in SFUCP which was the final reporting phase of the study. During SFUCP, participants underwent six monthly comprehensive eye examinations and/or dermatological assessments. Participants were followed-up until the discoloration /pigmentation either resolves or stabilizes, as defined by no change over two consecutive six monthly assessments over at least 12 months after discontinuation of RTG IR.
Period Title: Primary Reporting Phase (Up to 4 Years)
STARTED	30	0
COMPLETED	0	0
NOT COMPLETED	30	0
Period Title: Primary Reporting Phase (Up to 4 Years)
STARTED	0	4
COMPLETED	0	0
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Overall Participants	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.0 (9.25)
Sex: Female, Male (Count of Participants)
Female	10 33.3%
Male	20 66.7%
Race/Ethnicity, Customized (Count of Participants)
Asian-East Asian Heritage	17 56.7%
Asian-South East Asian Heritage	12 40%
Asian-Mixed Race	1 3.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent (TE) Serious Adverse Events (SAEs) and Non-SAEs
Description	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. 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, other situations and is associated with liver injury or impaired liver function is SAE. TEAE refers to an AE for which the onset was on or after the date of the first RTG dose in this study and on or before 30 days after the last RTG dose date. AEs that started in the parent study that worsened in this study were also considered as TEAEs. Safety population comprised of participants who take at least 1 dose of study medication after they have enrolled into this OLE study. Number of participants with TE-SAEs and non-SAEs (with incidence >= 5%) have been presented.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Any non-SAE	23 76.7%
Any SAE	5 16.7%

2. Primary Outcome

Title	Percentage of Participants With TEAEs Leading to Study Discontinuation
Description	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. TEAE refers to an AE for which the onset was on or after the date of the first RTG dose in this study and on or before 30 days after the last RTG dose date. Percentage of participants with TEAEs leading to study discontinuation were presented.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Number [Percentage of Participants]	17 56.7%

3. Primary Outcome

Title	Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs
Description	The vital signs were evaluated as per PCC Criteria. The vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The vital signs were measured in a seated position after 5 minutes of rest. PCC range for DBP was increase or decrease of >=20, for SBP was increase or decrease of >=15 and for heart rate was increase or decrease of >=15. A Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. Change from Baseline was defined as post-Baseline value minus Baseline value. Number of participants with vital sign values of PCC at any Post-Baseline visit were presented.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
DBP; increase by >=20	4 13.3%
DBP; decrease by >=20	9 30%
SBP; increase by >=15	5 16.7%
SBP; decrease by >=15	5 16.7%
HR; increase by >=15	9 30%
HR; decrease by >=15	5 16.7%

4. Primary Outcome

Title	Number of Participants With PCC Values of Change From Baseline for Body Weight
Description	Body weight of participants were measured as a measure of safety. PCC range for body weight was increase or decrease of >=7 percent. A Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. Change from Baseline was defined as post-Baseline value minus Baseline value. Number of participants with PCC values of body weight at any Post-Baseline visit were presented.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Body weight;increase by >=7 percent	11 36.7%
Body weight; decrease by >=7 percent	4 13.3%

5. Primary Outcome

Title	Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters
Description	Single measurements of 12-lead ECGs were obtained in a supine position after at least 10 minutes of rest using an ECG machine that automatically calculates the heart rate (HR) as beats per minute (bpm) and measures PR, QRS, Bazett's correction QT interval (QTcB) and Friedericia's correction QT interval (QTcF) in milliseconds (msec). A Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. Change from Baseline was defined as post-Baseline value minus Baseline value. Number of participants with PCC values of ECG parameters at any Post-Baseline visit were presented. For the 'Any Post Baseline' value, only the worst case finding was counted for each participant.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
HR <50 bpm, decreased from Baseline>=15 bpm	1 3.3%
HR >100 bpm, increased from Baseline >=15 bpm	0 0%
PR interval >=210 msec, increased from Baseline	1 3.3%
QRS interval >=120 msec, increased from Baseline	0 0%
QTcB:Post-Baseline QTc>=450, Baseline<450 msec	5 16.7%
QTcB:Post-Baseline QTc>=480, Baseline < 480 msec	0 0%
QTcB:Post-Baseline QTc>500 msec	0 0%
QTcB:Post-Baseline QTc>=500, Baseline <500msec	0 0%
QTcB:Increase in QTc of >30 msec from Baseline	3 10%
QTcB:Increase in QTc of >30,<=60 msecfrom Baseline	3 10%
QTcB:Increase in QTc of >60 msec from Baseline	0 0%
QTcF:Post-Baseline QTc>=450, Baseline<450 msec	1 3.3%
QTcF:Post-Baseline QTc>=480, Baseline<480 msec	0 0%
QTcF: Post-Baseline QTc>500 msec	0 0%
QTcF:Post-Baseline QTc>=500, Baseline<500 msec	0 0%
QTcF:Increase in QTc of >30 msec from Baseline	3 10%
QTcF:Increase in QTcof >30,<=60 msec from Baseline	3 10%
QTcF:Increase in QTc of >60 msec from Baseline	0 0%

6. Primary Outcome

Title	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC)
Description	Blood samples were collected from participants for evaluation of change from Baseline in hematology parameters including basophils, eosinophils, lymphocytes,monocytes, platelet count, total neutrophils, and WBC. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and standard deviation (SD) were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Basophils;Visit 1-Day 1;n=29	0.000 (0.0118)
Basophils;Visit 2 - Month 1;n=28	0.000 (0.0126)
Basophils;Visit 3 - Month 3;n=26	0.000 (0.0118)
Basophils;Visit 4 - Month 6;n=16	-0.003 (0.0184)
Basophils;Visit 5 - Month 9;n=16	0.001 (0.0178)
Basophils;Visit 6 - Month 12;n=13	0.003 (0.0132)
Basophils;Visit 7 (Month 16);n=12	-0.002 (0.0147)
Basophils;Visit 8 (Month 20);n=11	0.003 (0.0220)
Basophils;Visit 9 (Month 24);n=10	0.000 (0.0105)
Basophils;Visit 10 (Month 28);n=10	0.002 (0.0079)
Basophils;Visit 11 (Month 32);n=9	0.004 (0.0188)
Basophils;Visit 12 (Month 36);n=4	0.005 (0.0058)
Basophils;Study Conclusion/Withdrawal;n=28	-0.003 (0.0146)
Basophils;Follow-Up Visit;n=5	-0.008 (0.0130)
Eosinophils;Visit 1-Day 1; n=29	-0.012 (0.1152)
Eosinophils; Visit 2 - Month 1; n=28	-0.051 (0.1311)
Eosinophils; Visit 3 - Month 3; n=26	-0.070 (0.2813)
Eosinophils; Visit 4 - Month 6; n=16	-0.004 (0.1020)
Eosinophils; Visit 5 - Month 9; n=16	0.038 (0.1038)
Eosinophils; Visit 6 - Month 12; n=13	-0.014 (0.0846)
Eosinophils; Visit 7 (Month 16); n=12	0.010 (0.1135)
Eosinophils; Visit 8 (Month 20); n=11	0.008 (0.0908)
Eosinophils; Visit 9 (Month 24); n=10	-0.051 (0.0983)
Eosinophils; Visit 10 (Month 28); n=10	0.006 (0.1467)
Eosinophils; Visit 11 (Month 32); n=9	0.011 (0.0494)
Eosinophils; Visit 12 (Month 36); n=4	-0.025 (0.0900)
Eosinophils; Study Conclusion/Withdrawal; n=28	-0.026 (0.1085)
Eosinophils; Follow-Up Visit; n=5	-0.078 (0.1268)
Lymphocytes; Visit 1-Day 1; n= 29	-0.132 (0.5985)
Lymphocytes; Visit 2 - Month 1; n=28	-0.065 (0.5549)
Lymphocytes; Visit 3 - Month 3; n=26	-0.120 (0.4974)
Lymphocytes; Visit 4 - Month 6; n=16	0.024 (0.3740)
Lymphocytes; Visit 5 - Month 9; n=16	-0.032 (0.4358)
Lymphocytes; Visit 6 - Month 12; n= 13	-0.109 (0.3685)
Lymphocytes; Visit 7 (Month 16); n=12	0.007 (0.3039)
Lymphocytes; Visit 8 (Month 20); n=11	-0.037 (0.3250)
Lymphocytes; Visit 9 (Month 24); n=10	0.052 (0.4157)
Lymphocytes; Visit 10 (Month 28); n=10	0.108 (0.2986)
Lymphocytes; Visit 11 (Month 32); n=9	0.022 (0.4280)
Lymphocytes; Visit 12 (Month 36); n=4	-0.268 (0.3096)
Lymphocytes; Study Conclusion/Withdrawal; n=28	-0.068 (0.5778)
Lymphocytes; Follow-Up Visit; n=5	-0.070 (0.3466)
Monocytes; Visit 1-Day 1; n= 29	-0.018 (0.1204)
Monocytes; Visit 2 - Month 1; n=28	-0.028 (0.1357)
Monocytes; Visit 3 - Month 3; n=26	-0.044 (0.1350)
Monocytes; Visit 4 - Month 6; n=16	0.033 (0.1445)
Monocytes; Visit 5 - Month 9; n=16	-0.042 (0.1348)
Monocytes; Visit 6 - Month 12; n= 13	0.076 (0.1711)
Monocytes; Visit 7 (Month 16); n=12	-0.021 (0.1717)
Monocytes; Visit 8 (Month 20); n=11	0.129 (0.1936)
Monocytes; Visit 9 (Month 24); n=10	-0.021 (0.1358)
Monocytes; Visit 10 (Month 28); n=10	-0.022 (0.1781)
Monocytes; Visit 11 (Month 32); n=9	0.088 (0.1384)
Monocytes; Visit 12 (Month 36); n=4	0.035 (0.0823)
Monocytes; Study Conclusion/Withdrawal; n=28	0.014 (0.1809)
Monocytes; Follow-Up Visit; n=5	0.054 (0.1011)
Platelet count; Visit 1-Day 1; n=28	8.3 (25.26)
Platelet count; Visit 2 - Month 1; n=28	6.3 (24.01)
Platelet count; Visit 3 - Month 3; n=25	14.5 (26.01)
Platelet count; Visit 4 - Month 6; n=18	5.8 (37.84)
Platelet count; Visit 5 - Month 9; n=17	6.0 (29.90)
Platelet count; Visit 6 - Month 12; n=15	10.2 (35.51)
Platelet count; Visit 7 (Month 16); n=14	18.5 (23.65)
Platelet count; Visit 8 (Month 20); n=11	16.6 (39.64)
Platelet count; Visit 9 (Month 24); n=11	15.5 (22.98)
Platelet count; Visit 10 (Month 28); n=10	20.3 (40.66)
Platelet count; Visit 11 (Month 32); n=9	17.1 (50.38)
Platelet count; Visit 12 (Month 36); n=4	28.5 (13.53)
Platelet count; Study Conclusion/Withdrawal; n=28	17.0 (37.37)
Platelet count; Follow-Up Visit; n=5	-2.0 (26.93)
Total Neutrophils; Visit 1-Day 1; n=30	-0.099 (1.3450)
Total Neutrophils; Visit 2 - Month 1; n=28	-0.028 (1.1045)
Total Neutrophils; Visit 3 - Month 3; n=26	0.369 (1.7061)
Total Neutrophils; Visit 4 - Month 6; n=16	-0.318 (1.4286)
Total Neutrophils; Visit 5 - Month 9; n=16	-0.158 (1.6801)
Total Neutrophils; Visit 6 - Month 12; n=13	0.182 (0.9911)
Total Neutrophils; Visit 7 (Month 16); n=12	0.252 (0.9079)
Total Neutrophils; Visit 8 (Month 20); n=11	0.325 (1.0561)
Total Neutrophils; Visit 9 (Month 24); n=10	0.656 (1.0269)
Total Neutrophils; Visit 10 (Month 28); n=10	0.238 (0.8603)
Total Neutrophils; Visit 11 (Month 32); n=9	1.310 (2.2464)
Total Neutrophils; Visit 12 (Month 36); n=4	0.310 (0.6800)
Total Neutrophils;Study Conclusion/Withdrawal;n=28	0.086 (1.1378)
Total Neutrophils; Follow-Up Visit; n=5	-0.176 (1.4051)
WBC ; Visit 1-Day 1; n=30	-0.15 (1.417)
WBC ; Visit 2 - Month 1; n=28	-0.16 (1.182)
WBC; Visit 3 - Month 3; n=26	0.14 (1.501)
WBC; Visit 4 - Month 6; n=18	-0.42 (1.545)
WBC; Visit 5 - Month 9; n=17	-0.12 (1.630)
WBC; Visit 6 - Month 12; n=15	0.34 (1.330)
WBC ; Visit 7 (Month 16); n=14	0.20 (0.927)
WBC ; Visit 8 (Month 20); n=12	0.53 (1.127)
WBC ; Visit 9 (Month 24); n=11	0.64 (0.837)
WBC; Visit 10 (Month 28); n=10	0.33 (1.003)
WBC; Visit 11 (Month 32); n=9	1.43 (2.155)
WBC; Visit 12 (Month 36); n=4	0.08 (0.991)
WBC; Study Conclusion/Withdrawal;n=28	0.01 (1.212)
WBC; Follow-Up Visit; n=5	-0.28 (1.395)

7. Primary Outcome

Title	Change From Baseline in Hematocrit
Description	Blood samples were collected from participants for evaluation of hematocrit. Hematocrit is a ratio of red blood cells to the total volume of blood. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=30	-0.0035 (0.02749)
Visit 2 - Month 1; n=28	-0.0048 (0.02512)
Visit 3 - Month 3; n=26	-0.0033 (0.02175)
Visit 4 - Month 6; n=18	-0.0022 (0.01659)
Visit 5 - Month 9; n=17	-0.0004 (0.01790)
Visit 6 - Month 12; n=15	-0.0014 (0.01883)
Visit 7 (Month 16); n=14	0.0027 (0.01887)
Visit 8 (Month 20); n=12	0.0105 (0.01857)
Visit 9 (Month 24); n=11	0.0174 (0.02331)
Visit 10 (Month 28); n=10	0.0189 (0.01987)
Visit 11 (Month 32); n=9	0.0344 (0.02959)
Visit 12 (Month 36); n=4	0.0408 (0.02608)
Study Conclusion/Withdrawal;n=28	0.0055 (0.02345)
Follow-Up Visit; n=5	0.0048 (0.02100)

8. Primary Outcome

Title	Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
Description	Blood samples were collected from participants to evaluate change from Baseline in hemoglobin and MCHC levels. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Hemoglobin; Visit 1-Day 1; n=30	-2.6 (8.23)
Hemoglobin; Visit 2 - Month 1; n=28	-2.8 (7.75)
Hemoglobin; Visit 3 - Month 3; n=26	-2.2 (6.83)
Hemoglobin; Visit 4 - Month 6; n=18	-0.2 (5.33)
Hemoglobin; Visit 5 - Month 9; n=17	-0.8 (5.96)
Hemoglobin; Visit 6 - Month 12; n=15	-1.9 (6.28)
Hemoglobin; Visit 7 (Month 16); n=14	-1.5 (6.00)
Hemoglobin; Visit 8 (Month 20); n=12	2.3 (5.10)
Hemoglobin; Visit 9 (Month 24); n=11	2.6 (6.55)
Hemoglobin; Visit 10 (Month 28); n=10	1.9 (6.12)
Hemoglobin; Visit 11 (Month 32); n=9	9.1 (9.84)
Hemoglobin; Visit 12 (Month 36); n=4	8.0 (6.98)
Hemoglobin; Study Conclusion/Withdrawal;n=28	1.3 (6.31)
Hemoglobin; Follow-Up Visit; n=5	1.8 (7.92)
MCHC; Visit 1-Day 1; n=30	-3.1 (8.45)
MCHC; Visit 2 - Month 1; n=28	-2.9 (7.92)
MCHC; Visit 3 - Month 3; n=26	-2.4 (9.27)
MCHC; Visit 4 - Month 6; n=18	1.2 (7.31)
MCHC; Visit 5 - Month 9; n=17	-1.1 (4.61)
MCHC; Visit 6 - Month 12; n=15	-2.6 (7.21)
MCHC; Visit 7 (Month 16); n=14	-5.1 (9.63)
MCHC; Visit 8 (Month 20); n=12	-2.3 (7.80)
MCHC; Visit 9 (Month 24); n=11	-6.4 (8.56)
MCHC; Visit 10 (Month 28); n=10	-9.9 (8.24)
MCHC; Visit 11 (Month 32); n=9	-4.6 (6.31)
MCHC; Visit 12 (Month 36); n=4	-12.8 (4.19)
MCHC; StudyConclusion/Withdrawal;n=28	-1.3 (8.47)
MCHC; Follow-Up Visit; n=5	0.8 (10.43)

9. Primary Outcome

Title	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level
Description	Blood samples were collected from participants to evaluate change from Baseline in MCH levels. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=30	-0.30 (0.539)
Visit 2 - Month 1; n=28	-0.16 (0.807)
Visit 3 - Month 3; n=26	-0.23 (0.759)
Visit 4 - Month 6; n=18	-0.14 (0.731)
Visit 5 - Month 9; n=17	-0.46 (0.600)
Visit 6 - Month 12; n=15	-0.65 (0.588)
Visit 7 (Month 16); n=14	-0.56 (0.717)
Visit 8 (Month 20); n=12	-0.73 (0.574)
Visit 9 (Month 24); n=11	-0.87 (0.461)
Visit 10 (Month 28); n=10	-0.76 (0.435)
Visit 11 (Month 32); n=9	-0.73 (0.391)
Visit 12 (Month 36); n=4	-1.53 (0.506)
StudyConclusion/Withdrawal; n=28	-0.52 (0.731)
Follow-Up Visit; n=5	-0.64 (0.611)

10. Primary Outcome

Title	Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV)
Description	Blood samples were collected from participants to evaluate change from Baseline in MCV and MPV levels. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
MCV; Visit 1-Day 1; n=30	0.1 (2.15)
MCV; Visit 2 - Month 1; n=28	0.4 (2.35)
MCV; Visit 3 - Month 3; n=26	0.1 (2.42)
MCV; Visit 4 - Month 6; n=18	-0.7 (1.75)
MCV; Visit 5 - Month 9; n=17	-1.1 (1.52)
MCV; Visit 6 - Month 12; n=15	-1.2 (2.08)
MCV; Visit 7-(Month 16); n=14	-0.1 (2.06)
MCV; Visit 8-(Month 20); n=12	-1.3 (2.01)
MCV; Visit 9-(Month 24); n=11	-0.7 (1.85)
MCV; Visit 10-(Month 28); n=10	0.8 (2.44)
MCV; Visit 1- (Month 32); n=9	-0.8 (2.05)
MCV; Visit 12- (Month 36); n=4	-0.8 (1.26)
MCV; StudyConclusion/Withdrawal; n=28	-1.0 (2.16)
MCV; Follow-Up Visit; n=5	-2.2 (1.64)
MPV; Visit 1- Day 1; n=28	-0.43 (0.526)
MPV; Visit 2 - Month 1; n=28	-0.41 (0.610)
MPV; Visit 3 - Month 3; n=25	-0.34 (0.579)
MPV; Visit 4 - Month 6; n=18	-0.07 (0.642)
MPV; Visit 5 - Month 9; n=17	-0.32 (0.645)
MPV; Visit 6 - Month 12; n=15	-0.19 (0.678)
MPV; Visit 7-(Month 16); n=14	-0.36 (0.624)
MPV; Visit 8-(Month 20); n=11	-0.15 (0.658)
MPV; Visit 9-(Month 24); n=11	0.07 (0.629)
MPV; Visit 10-(Month 28); n=10	-0.14 (0.435)
MPV; Visit 11- (Month 32); n=9	0.21 (0.933)
MPV; Visit 12- (Month 36); n=4	-0.73 (0.386)
MPV; StudyConclusion/Withdrawal; n=28	-0.18 (0.572)
MPV; Follow-Up Visit; n=5	0.28 (0.349)

11. Primary Outcome

Title	Change From Baseline in Red Blood Cell (RBC) Count
Description	Blood samples were collected from participants to evaluate change from Baseline in RBC count. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1- Day 1; n=30	-0.03 (0.266)
Visit 2 - Month 1; n=28	-0.06 (0.256)
Visit 3 - Month 3; n=26	-0.03 (0.241)
Visit 4 - Month 6; n=18	0.01 (0.227)
Visit 5 - Month 9; n=17	0.05 (0.218)
Visit 6 - Month 12; n=15	0.04 (0.188)
Visit 7 - (Month 16); n=14	0.04 (0.198)
Visit 8 - (Month 20); n=12	0.19 (0.207)
Visit 9 - (Month 24); n=11	0.22 (0.214)
Visit 10 -(Month 28); n=10	0.17 (0.200)
Visit 11- (Month 32); n=9	0.41 (0.322)
Visit 12- (Month 36); n=4	0.45 (0.265)
StudyConclusion/Withdrawal; n=28	0.13 (0.229)
Follow-Up Visit; n=5	0.16 (0.241)

12. Primary Outcome

Title	Change From Baseline in Red Cell Distribution Width (RDW)
Description	Blood samples were collected from participants to evaluate change from Baseline in RDW. RDW is a parameter that measures variation in red blood cell size or red blood cell volume. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1- Day 1; n=30	0.31 (0.887)
Visit 2 - Month 1; n=28	0.43 (0.716)
Visit 3 - Month 3; n=26	0.18 (1.016)
Visit 4 - Month 6; n=18	-0.33 (0.806)
Visit 5 - Month 9; n=17	-0.03 (1.025)
Visit 6 - Month 12; n=15	0.01 (0.684)
Visit 7 - (Month 16); n=14	0.13 (0.685)
Visit 8 - (Month 20); n=12	-0.33 (0.735)
Visit 9 - (Month 24); n=11	-0.01 (0.468)
Visit 10 -(Month 28); n=10	0.35 (0.665)
Visit 11- (Month 32); n=9	-0.36 (0.814)
Visit 12- (Month 36); n=4	-0.33 (0.690)
Study Conclusion/Withdrawal; n=28	-0.01 (1.009)
Follow-Up Visit; n=5	-0.14 (0.885)

13. Primary Outcome

Title	Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (Alk. Phosph.), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LD)
Description	Blood samples collected from participants to evaluate change from Baseline in clinical chemistry parameters included ALT, Alk. phosph., AST,CK, GGT and LD. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
ALT; Visit 1-Day 1; n= 28	0.8 (4.78)
ALT; Visit 2 - Month 1; n=27	3.3 (14.86)
ALT; Visit 3 - Month 3; n=24	0.3 (5.44)
ALT; Visit 4 - Month 6; n=19	0.9 (6.20)
ALT; Visit 5 - Month 9; n=17	0.6 (4.17)
ALT; Visit 6 - Month 12; n=15	1.5 (6.41)
ALT; Visit 7 (Month 16); n=14	0.3 (4.61)
ALT; Visit 8 (Month 20); n=12	0.4 (4.62)
ALT; Visit 9 (Month 24); n=11	0.8 (8.59)
ALT; Visit 10 (Month 28); n=10	1.6 (6.00)
ALT; Visit 11 (Month 32); n=9	7.4 (13.57)
ALT; Visit 12 (Month 36); n=4	0.0 (5.29)
ALT; Study Conclusion/Withdrawal; n=27	1.1 (6.05)
ALT ; Follow-Up Visit; n=4	9.8 (15.65)
Alk. Phosph.; Visit 1-Day 1; n= 28	-1.5 (13.64)
Alk. Phosph; Visit 2 - Month 1; n=27	-2.2 (12.43)
Alk. Phosph; Visit 3 - Month 3; n=24	-2.5 (17.09)
Alk. Phosph; Visit 4 - Month 6; n=19	-5.1 (13.82)
Alk. Phosph; Visit 5 - Month 9; n=17	-4.7 (14.50)
Alk. Phosph; Visit 6 - Month 12; n=15	-2.5 (18.28)
Alk. Phosph; Visit 7 (Month 16); n=14	0.2 (20.10)
Alk. Phosph; Visit 8 (Month 20); n=12	0.5 (19.15)
Alk. Phosph; Visit 9 (Month 24); n=11	-3.5 (16.42)
Alk. Phosph; Visit 10 (Month 28); n=10	-5.3 (12.68)
Alk. Phosph; Visit 11 (Month 32); n=9	5.8 (15.91)
Alk. Phosph; Visit 12 (Month 36); n=4	7.8 (18.03)
Alk. Phosph; Study Conclusion/Withdrawal; n=27	-2.7 (16.65)
Alk. Phosph ; Follow-Up Visit; n=4	-21.3 (19.69)
AST; Visit 1-Day 1; n= 27	0.5 (6.35)
AST; Visit 2 - Month 1; n=26	2.0 (10.61)
AST; Visit 3 - Month 3; n=24	0.0 (4.57)
AST; Visit 4 - Month 6; n=19	1.3 (4.13)
AST; Visit 5 - Month 9; n=17	2.6 (6.02)
AST; Visit 6 - Month 12; n=15	2.1 (5.42)
AST; Visit 7 (Month 16); n=14	1.8 (3.17)
AST; Visit 8 (Month 20); n=12	1.6 (3.32)
AST; Visit 9 (Month 24); n=11	2.5 (4.30)
AST; Visit 10 (Month 28); n=9	2.9 (4.88)
AST; Visit 11 (Month 32); n=9	4.7 (4.58)
AST; Visit 12 (Month 36); n=4	0.8 (2.50)
AST; Study Conclusion/Withdrawal; n=27	1.5 (6.08)
AST; Follow-Up Visit; n=4	7.5 (10.34)
CK; Visit 1-Day 1; n= 28	-103.3 (483.91)
CK; Visit 2 - Month 1; n=27	-72.5 (414.16)
CK; Visit 3 - Month 3; n=24	-88.8 (461.41)
CK; Visit 4 - Month 6; n=19	-10.3 (56.38)
CK; Visit 5 - Month 9; n=17	-10.9 (63.16)
CK; Visit 6 - Month 12; n=15	11.9 (62.40)
CK; Visit 7-(Month 16); n=14	9.2 (23.66)
CK; Visit 8 -(Month 20); n=12	1.3 (21.83)
CK; Visit 9 -(Month 24); n=11	4.8 (35.02)
CK; Visit 10-(Month 28); n=10	2.6 (27.47)
CK; Visit 11-(Month 32); n=9	93.7 (185.31)
CK; Visit 12-(Month 36); n=4	26.3 (51.06)
CK; Study Conclusion/Withdrawal; n=27	24.7 (658.19)
CK; Follow-Up Visit; n=4	261.0 (553.52)
GGT; Visit 1-Day 1; n= 28	4.6 (21.15)
GGT; Visit 2 - Month 1; n=27	4.2 (37.01)
GGT; Visit 3 - Month 3; n=24	-4.5 (24.84)
GGT; Visit 4 - Month 6; n=19	-2.7 (18.93)
GGT; Visit 5 - Month 9; n=17	-2.5 (31.07)
GGT; Visit 6 - Month 12; n=15	-4.7 (21.26)
GGT; Visit 7-(Month 16); n=14	-3.6 (20.89)
GGT; Visit 8 - (Month 20); n=12	-13.1 (29.03)
GGT; Visit 9 - (Month 24); n=11	-6.0 (29.25)
GGT; Visit 10-(Month 28); n=10	8.3 (23.32)
GGT; Visit 11-(Month 32); n=9	24.3 (32.31)
GGT; Visit 12-(Month 36); n=4	10.0 (27.48)
GGT; StudyConclusion/Withdrawal; n=27	2.1 (33.39)
GGT; Follow-Up Visit; n=4	-3.8 (9.03)
LD; Visit 1-Day 1; n=27	-1.4 (20.13)
LD; Visit 2 - Month 1; n=26	0.8 (22.57)
LD; Visit 3 - Month 3; n=24	1.7 (17.96)
LD; Visit 4 - Month 6; n=19	-8.5 (19.35)
LD; Visit 5 - Month 9; n=17	1.9 (17.71)
LD; Visit 6 - Month 12; n=15	-1.6 (22.21)
LD; Visit 7-(Month 16); n=14	1.3 (21.21)
LD; Visit 8 - (Month 20); n=12	-0.5 (12.08)
LD; Visit 9 - (Month 24); n=11	12.2 (8.40)
LD; Visit 10-(Month 28); n=9	8.3 (16.65)
LD; Visit 11-(Month 32); n=9	18.8 (18.98)
LD; Visit 12-(Month 36); n=4	8.5 (7.90)
LD; Study Conclusion/Withdrawal; n=27	2.6 (23.41)
LD; Follow-Up Visit; n=4	2.5 (8.19)

14. Primary Outcome

Title	Change From Baseline in Albumin and Total Protein
Description	Blood samples were collected from participants to evaluate change from Baseline in albumin and total protein. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Albumin; Visit 1-Day 1; n=28	-0.9 (2.03)
Albumin; Visit 2 - Month 1; n=27	-0.3 (2.22)
Albumin; Visit 3 - Month 3; n=24	-0.3 (1.85)
Albumin; Visit 4 - Month 6; n=19	0.1 (2.41)
Albumin; Visit 5 - Month 9; n=17	-0.3 (2.34)
Albumin; Visit 6 - Month 12; n=15	-1.1 (3.02)
Albumin; Visit 7-(Month 16); n=14	-0.7 (2.97)
Albumin; Visit 8 - (Month 20); n=12	-0.6 (2.02)
Albumin; Visit 9 - (Month 24); n=11	-0.3 (2.33)
Albumin; Visit 10-(Month 28); n=10	-0.2 (2.66)
Albumin; Visit 11-(Month 32); n=9	1.2 (3.77)
Albumin; Visit 12-(Month 36); n=4	-0.3 (0.96)
Albumin; Study Conclusion/Withdrawal; n=27	-0.6 (2.48)
Albumin; Follow-Up Visit; n=4	-0.3 (2.87)
Total protein; Visit 1-Day 1; n=28	-0.7 (2.84)
Total protein; Visit 2 - Month 1; n=27	-0.7 (4.08)
Total protein; Visit 3 - Month 3; n=24	0.1 (3.35)
Total protein; Visit 4 - Month 6; n=19	0.5 (3.66)
Total protein; Visit 5 - Month 9; n=17	-0.4 (3.87)
Total protein; Visit 6 - Month 12; n=15	-0.3 (5.23)
Total protein; Visit 7-(Month 16); n=14	0.6 (5.36)
Total protein; Visit 8 - (Month 20); n=12	1.3 (4.41)
Total protein; Visit 9 - (Month 24); n=11	2.4 (4.37)
Total protein; Visit 10-(Month 28); n=10	2.5 (4.86)
Total protein; Visit 11-(Month 32); n=9	3.8 (6.63)
Total protein; Visit 12-(Month 36); n=4	1.8 (2.22)
Total protein; Study Conclusion/Withdrawal; n=27	0.7 (3.52)
Total protein; Follow-Up Visit; n=4	0.5 (3.00)

15. Primary Outcome

Title	Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio
Description	Blood samples were collected from participants to evaluate change from Baseline in BUN/creatinine. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=28	4.2 (21.83)
Visit 2 - Month 1; n=27	6.2 (20.92)
Visit 3 - Month 3; n=24	7.0 (22.03)
Visit 4 - Month 6; n=19	7.0 (18.11)
Visit 5 - Month 9; n=17	18.11 (16.40)
Visit 6 - Month 12; n=15	5.5 (13.43)
Visit 7-(Month 16); n=14	4.2 (24.49)
Visit 8 - (Month 20); n=12	12.8 (21.46)
Visit 9 - (Month 24); n=11	7.0 (16.25)
Visit 10-(Month 28); n=10	1.9 (21.97)
Visit 11-(Month 32); n=9	13.8 (25.29)
Visit 12-(Month 36); n=4	30.0 (24.04)
Study Conclusion/Withdrawal; n=27	3.1 (24.50)
Follow-Up Visit; n=4	1.0 (29.39)

16. Primary Outcome

Title	Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN
Description	Blood samples were collected from participants to evaluate change from Baseline in calcium, CO2 content/Bicarb, chloride, glucose, magnesium, potassium, sodium, and urea/BUN. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Calcium; Visit 1-Day 1; n=27	-0.015 (0.0759)
Calcium; Visit 2 - Month 1; n=26	-0.009 (0.0813)
Calcium; Visit 3 - Month 3; n=24	0.017 (0.0586)
Calcium; Visit 4 - Month 6; n=19	0.009 (0.0819)
Calcium; Visit 5 - Month 9; n=17	0.020 (0.0742)
Calcium; Visit 6 - Month 12; n=15	-0.013 (0.0786)
Calcium; Visit 7-(Month 16); n=14	0.009 (0.0809)
Calcium; Visit 8 - (Month 20); n=12	0.013 (0.0628)
Calcium; Visit 9 - (Month 24); n=11	0.006 (0.0543)
Calcium; Visit 10-(Month 28); n=9	0.012 (0.0602)
Calcium; Visit 11-(Month 32); n=9	0.026 (0.0915)
Calcium; Visit 12-(Month 36); n=4	0.013 (0.0171)
Calcium; StudyConclusion/Withdrawal; n=27	0.015 (0.0820)
Calcium; Follow-Up Visit; n=4	0.068 (0.0634)
CO2 content/Bicarb; Visit 1-Day 1; n=27	-0.3 (2.11)
CO2 content/Bicarb; Visit 2 - Month 1; n=26	-0.3 (2.94)
CO2 content/Bicarb; Visit 3 - Month 3; n=24	-0.3 (3.52)
CO2 content/Bicarb; Visit 4 - Month 6; n=19	-0.6 (2.80)
CO2 content/Bicarb; Visit 5 - Month 9; n=17	-0.5 (2.70)
CO2 content/Bicarb; Visit 6 - Month 12; n=15	-0.9 (1.44)
CO2 content/Bicarb; Visit 7-(Month 16); n=14	-0.1 (2.59)
CO2 content/Bicarb; Visit 8 - (Month 20); n=12	-0.8 (1.96)
CO2 content/Bicarb; Visit 9 - (Month 24); n=11	-1.5 (2.58)
CO2 content/Bicarb; Visit 10-(Month 28); n=9	-1.8 (1.39)
CO2 content/Bicarb; Visit 11-(Month 32); n=9	2.4 (1.94)
CO2 content/Bicarb; Visit 12-(Month 36); n=4	-1.5 (1.91)
CO2content/Bicarb;Study Conclusion/Withdrawal;n=27	-1.0 (2.72)
CO2 content/Bicarb; Follow-Up Visit; n=4	0.8 (2.36)
Chloride; Visit 1-Day 1; n=28	-0.4 (2.97)
Chloride; Visit 2 - Month 1; n=27	-0.2 (3.32)
Chloride; Visit 3 - Month 3; n=24	-0.2 (2.91)
Chloride; Visit 4 - Month 6; n=19	-0.3 (2.89)
Chloride; Visit 5 - Month 9; n=17	0.1 (3.22)
Chloride; Visit 6 - Month 12; n=15	0.6 (3.54)
Chloride; Visit 7-(Month 16); n=14	0.7 (3.73)
Chloride; Visit 8 - (Month 20); n=12	1.3 (3.70)
Chloride; Visit 9 - (Month 24); n=11	1.0 (3.32)
Chloride; Visit 10-(Month 28); n=10	0.9 (3.87)
Chloride; Visit 11-(Month 32); n=9	1.3 (5.32)
Chloride; Visit 12-(Month 36); n=4	-1.5 (3.87)
Chloride; StudyConclusion/Withdrawal;n=27	-0.4 (3.67)
Chloride; Follow-Up Visit; n=4	-0.8 (2.22)
Glucose; Visit 1-Day 1; n=28	-0.42 (1.458)
Glucose; Visit 2 - Month 1; n=27	0.13 (1.554)
Glucose; Visit 3 - Month 3; n=24	0.12 (1.426)
Glucose; Visit 4 - Month 6; n=19	0.55 (1.094)
Glucose; Visit 5 - Month 9; n=17	0.32 (1.709)
Glucose; Visit 6 - Month 12; n=15	0.05 (1.477)
Glucose; Visit 7-(Month 16); n=14	1.97 (6.817)
Glucose; Visit 8 - (Month 20); n=12	0.08 (1.298)
Glucose; Visit 9 - (Month 24); n=11	0.49 (1.713)
Glucose; Visit 10-(Month 28); n=10	1.14 (2.303)
Glucose; Visit 11-(Month 32); n=9	1.13 (0.892)
Glucose; Visit 12-(Month 36); n=4	1.75 (2.533)
Glucose; StudyConclusion/Withdrawal;n=27	0.72 (2.312)
Glucose; Follow-Up Visit; n=4	-0.30 (1.152)
Magnesium; Visit 1-Day 1; n=28	-0.004 (0.0522)
Magnesium; Visit 2 - Month 1; n=27	-0.017 (0.0716)
Magnesium; Visit 3 - Month 3; n=24	-0.019 (0.0733)
Magnesium; Visit 4 - Month 6; n=19	-0.016 (0.0565)
Magnesium; Visit 5 - Month 9; n=17	0.006 (0.0662)
Magnesium; Visit 6 - Month 12; n=15	0.027 (0.0640)
Magnesium; Visit 7-(Month 16); n=14	0.041 (0.0434)
Magnesium; Visit 8 - (Month 20); n=12	0.040 (0.0628)
Magnesium; Visit 9 - (Month 24); n=11	0.035 (0.0520)
Magnesium; Visit 10-(Month 28); n=10	0.058 (0.0692)
Magnesium; Visit 11-(Month 32); n=9	0.050 (0.0585)
Magnesium; Visit 12-(Month 36); n=4	0.020 (0.0606)
Magnesium; Study Conclusion/Withdrawal;n=27	0.016 (0.0582)
Magnesium; Follow-Up Visit; n=4	0.053 (0.1424)
Potassium; Visit 1-Day 1; n=27	0.01 (0.277)
Potassium; Visit 2 - Month 1; n=26	-0.05 (0.258)
Potassium; Visit 3 - Month 3; n=24	0.00 (0.227)
Potassium; Visit 4 - Month 6; n=19	0.07 (0.341)
Potassium; Visit 5 - Month 9; n=17	0.01 (0.398)
Potassium; Visit 6 - Month 12; n=15	0.10 (0.321)
Potassium; Visit 7-(Month 16); n=14	0.06 (0.247)
Potassium; Visit 8 - (Month 20); n=12	0.09 (0.215)
Potassium; Visit 9 - (Month 24); n=11	0.08 (0.264)
Potassium; Visit 10-(Month 28); n=9	0.21 (0.318)
Potassium; Visit 11-(Month 32); n=9	-0.02 (0.367)
Potassium; Visit 12-(Month 36); n=4	0.18 (0.222)
Potassium; Study Conclusion/Withdrawal;n=27	-0.02 (0.275)
Potassium; Follow-Up Visit; n=4	0.20 (0.163)
Sodium; Visit 1-Day 1; n=28	-0.9 (3.37)
Sodium; Visit 2 - Month 1; n=27	-0.3 (3.48)
Sodium; Visit 3 - Month 3; n=24	0.8 (3.00)
Sodium; Visit 4 - Month 6; n=19	-0.3 (2.79)
Sodium; Visit 5 - Month 9; n=17	0.7 (2.52)
Sodium; Visit 6 - Month 12; n=15	0.7 (3.58)
Sodium; Visit 7-(Month 16); n=14	0.2 (4.21)
Sodium; Visit 8 - (Month 20); n=12	0.8 (4.13)
Sodium; Visit 9 - (Month 24); n=11	1.1 (2.07)
Sodium; Visit 10-(Month 28); n=10	1.3 (3.53)
Sodium; Visit 11-(Month 32); n=9	1.2 (4.74)
Sodium; Visit 12-(Month 36); n=4	-2.0 (4.76)
Sodium; StudyConclusion/Withdrawal;n=27	0.2 (3.14)
Sodium; Follow-Up Visit; n=4	0.5 (2.08)
Urea/BUN; Visit 1-Day 1; n=28	0.14 (1.176)
Urea/BUN; Visit 2 - Month 1; n=27	0.36 (1.239)
Urea/BUN; Visit 3 - Month 3; n=24	0.46 (1.353)
Urea/BUN; Visit 4 - Month 6; n=19	0.37 (1.180)
Urea/BUN; Visit 5 - Month 9; n=17	0.62 (0.884)
Urea/BUN; Visit 6 - Month 12; n=15	0.51 (0.877)
Urea/BUN; Visit 7-(Month 16); n=14	0.25 (1.260)
Urea/BUN; Visit 8 - (Month 20); n=12	0.91 (1.372)
Urea/BUN; Visit 9 - (Month 24); n=11	0.46 (1.016)
Urea/BUN; Visit 10-(Month 28); n=10	0.39 (1.325)
Urea/BUN; Visit 11-(Month 32); n=9	0.77 (1.578)
Urea/BUN; Visit 12-(Month 36); n=4	1.90 (1.971)
Urea/BUN; Study Conclusion/Withdrawal;n=27	0.18 (1.409)
Urea/BUN; Follow-Up Visit; n=4	0.25 (1.287)

17. Primary Outcome

Title	Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid
Description	Blood samples were collected from participants to evaluate change from Baseline in creatinine, direct bilirubin, total bilirubin, and uric acid. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Creatinine; Visit 1-Day 1; n=28	-2.18 (5.860)
Creatinine; Visit 2 - Month 1; n=27	-0.79 (6.450)
Creatinine; Visit 3 - Month 3; n=24	-0.35 (5.360)
Creatinine; Visit 4 - Month 6; n=19	-1.39 (6.575)
Creatinine; Visit 5 - Month 9; n=17	0.32 (4.770)
Creatinine; Visit 6 - Month 12; n=15	0.61 (4.837)
Creatinine; Visit 7-(Month 16); n=14	-0.94 (6.951)
Creatinine; Visit 8 - (Month 20); n=12	-0.05 (5.970)
Creatinine; Visit 9 - (Month 24); n=11	-0.15 (5.095)
Creatinine; Visit 10-(Month 28); n=10	4.31 (8.665)
Creatinine; Visit 11-(Month 32); n=9	-3.30 (4.268)
Creatinine; Visit 12-(Month 36); n=4	-2.73 (11.099)
Creatinine; Study Conclusion/Withdrawal;n=27	-0.08 (5.467)
Creatinine; Follow-Up Visit; n=4	4.30 (20.628)
Direct Bilirubin; Visit 1-Day 1; n=28	-0.2 (0.67)
Direct Bilirubin; Visit 2 - Month 1; n=27	0.0 (0.65)
Direct Bilirubin; Visit 3 - Month 3; n=24	0.0 (0.46)
Direct Bilirubin; Visit 4 - Month 6; n=19	0.0 (0.58)
Direct Bilirubin; Visit 5 - Month 9; n=17	-0.2 (0.64)
Direct Bilirubin; Visit 6 - Month 12; n=15	-0.1 (0.35)
Direct Bilirubin; Visit 7-(Month 16); n=14	-0.1 (0.53)
Direct Bilirubin; Visit 8 - (Month 20); n=12	-0.1 (0.51)
Direct Bilirubin; Visit 9 - (Month 24); n=11	-0.2 (0.75)
Direct Bilirubin; Visit 10-(Month 28); n=10	-0.1 (0.32)
Direct Bilirubin; Visit 11-(Month 32); n=9	-0.2 (0.44)
Direct Bilirubin; Visit 12-(Month 36); n=4	0.0 (0.82)
Direct Bilirubin; Study Conclusion/Withdrawal;n=27	0.0 (0.59)
Direct Bilirubin; Follow-Up Visit; n=4	0.3 (1.26)
Total Bilirubin; Visit 1-Day 1; n=28	3.0 (2.57)
Total Bilirubin; Visit 2 - Month 1; n=27	3.7 (2.69)
Total Bilirubin; Visit 3 - Month 3; n=24	3.8 (2.14)
Total Bilirubin; Visit 4 - Month 6; n=19	3.7 (2.87)
Total Bilirubin; Visit 5 - Month 9; n=17	2.8 (1.85)
Total Bilirubin; Visit 6 - Month 12; n=15	3.1 (3.03)
Total Bilirubin; Visit 7-(Month 16); n=14	3.5 (1.65)
Total Bilirubin; Visit 8 - (Month 20); n=12	2.8 (1.90)
Total Bilirubin; Visit 9 - (Month 24); n=11	2.7 (1.95)
Total Bilirubin; Visit 10-(Month 28); n=10	3.0 (2.11)
Total Bilirubin; Visit 11-(Month 32); n=9	2.6 (1.51)
Total Bilirubin; Visit 12-(Month 36); n=4	4.5 (2.65)
Total Bilirubin; Study Conclusion/Withdrawal;n=27	2.9 (2.83)
Total Bilirubin; Follow-Up Visit; n=4	2.3 (4.99)
Uric acid; Visit 1-Day 1; n=28	-0.6 (31.72)
Uric acid; Visit 2 - Month 1; n=27	6.3 (33.86)
Uric acid; Visit 3 - Month 3; n=24	-5.8 (31.63)
Uric acid; Visit 4 - Month 6; n=19	0.3 (32.18)
Uric acid; Visit 5 - Month 9; n=17	4.3 (25.30)
Uric acid; Visit 6 - Month 12; n=15	-5.5 (38.81)
Uric acid; Visit 7-(Month 16); n=14	-15.0 (51.93)
Uric acid; Visit 8 - (Month 20); n=12	-10.5 (45.12)
Uric acid; Visit 9 - (Month 24); n=11	8.6 (51.81)
Uric acid; Visit 10-(Month 28); n=10	6.3 (64.91)
Uric acid; Visit 11-(Month 32); n=9	-5.2 (66.94)
Uric acid; Visit 12-(Month 36); n=4	-30.3 (46.50)
Uric acid; Study Conclusion/Withdrawal;n=26	9.7 (46.87)
Uric acid; Follow-Up Visit; n=4	15.8 (62.74)

18. Primary Outcome

Title	Change From Baseline in Urine Albumin/Creatinine Ratio
Description	Urine samples were collected from participants to evaluate change from Baseline in urine albumin/creatinine ratio. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated. NA indicates data was not available as standard deviation could not be calculated for single participant.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=22	-0.05 (1.603)
Visit 2 - Month 1; n=19	0.16 (0.932)
Visit 3 - Month 3; n=18	1.51 (5.755)
Visit 4 - Month 6; n=14	-0.32 (1.342)
Visit 5 - Month 9; n=12	-0.26 (1.006)
Visit 6 - Month 12; n=10	9.80 (31.071)
Visit 7-(Month 16); n=8	0.69 (1.733)
Visit 8 - (Month 20); n=7	-0.24 (0.547)
Visit 9 - (Month 24); n=7	-0.34 (2.070)
Visit 10-(Month 28); n=6	0.38 (1.450)
Visit 11-(Month 32); n=6	0.87 (1.519)
Visit 12-(Month 36); n=1	0.80 (NA)
Study Conclusion/Withdrawal;n=17	0.51 (1.715)
Follow-Up Visit; n=5	3.30 (7.044)

19. Primary Outcome

Title	Number of Participants With Abnormal Urinalysis Values (Categorical Data)
Description	Urine samples were collected from participants to analyze presence of abnormal urinalysis parameters including glucose, ketones, RBC, WBC, occult blood and protein. Abnormal urinalysis values have been presented for all parameters. Only those participants with data available at specific time points were analyzed (represented by n= X in the category titles).
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1 Day1, Glucose, 4+or 2 or more g/dL,n=30	2 6.7%
Visit 1 Day 1, RBC, 1-3,n=29	4 13.3%
Visit 1 Day 1, RBC, 3-5, n=29	4 13.3%
Visit 1 Day 1, RBC, 5-10, n=29	6 20%
Visit 1 Day 1, RBC, 10-15, n=29	1 3.3%
Visit 1 Day 1, RBC, 15-25, n=29	6 20%
Visit 1 Day 1, RBC, 25-50, n=29	2 6.7%
Visit 1 Day 1, RBC, 50-100, n=29	1 3.3%
Visit 1 Day 1, WBC,1-3, n=29	3 10%
Visit 1 Day 1, WBC,3-5, n=29	1 3.3%
Visit 1 Day 1, WBC,5-10, n=29	2 6.7%
Visit 1 Day 1, Occult Blood,1+, n=30	1 3.3%
Visit 1 Day 1, Occult Blood,4+, n=30	1 3.3%
Visit 1 Day 1, protein, 1+, n=30	5 16.7%
Visit 2 Month 1, Glucose,1+ or 1/4 g/dL, n=28	1 3.3%
Visit 2 Month 1, Glucose,4+or 2 or more g/dL,n=28	1 3.3%
Visit 2 Month 1, Ketone 1+, n=28	1 3.3%
Visit 2 Month 1, RBC, 1-3, n=27	7 23.3%
Visit 2 Month 1, RBC, 3-5, n=27	4 13.3%
Visit 2 Month 1, RBC, 5-10, n=27	4 13.3%
Visit 2 Month 1, RBC, 10-15, n=27	4 13.3%
Visit 2 Month 1, RBC, 15-25, n=27	1 3.3%
Visit 2 Month 1, RBC, 50-100, n=27	1 3.3%
Visit 2 Month 1,WBC,1-3, n=27	5 16.7%
Visit 2 Month 1, WBC,3-5, n=27	1 3.3%
Visit 2 Month 1, Occult Blood,1+, n=28	1 3.3%
Visit 2 Month 1, protein, 1+, n=28	5 16.7%
Visit 3 Month 3, Ketones,1+, n=26	1 3.3%
Visit 3 Month 3, RBC, 1-3, n=26	5 16.7%
Visit 3 Month 3, RBC, 3-5, n=26	3 10%
Visit 3 Month 3, RBC, 5-10, n=26	6 20%
Visit 3 Month 3, RBC, 10-15, n=26	3 10%
Visit 3 Month 3, RBC, 15-25, n=26	2 6.7%
Visit 3 Month 3, RBC, 25-50, n=26	2 6.7%
Visit 3 Month 3, RBC,innumerable, n=26	1 3.3%
Visit 3 Month 3, WBC,1-3, n=26	4 13.3%
Visit 3 Month 3, WBC,15-25, n=26	3 10%
Visit 3 Month 3, WBC,innumerable, n=26	1 3.3%
Visit 3 Month 3, Occult Blood,1+, n=26	3 10%
Visit 3 Month 3, Occult Blood,4+, n=26	1 3.3%
Visit 3 Month 3, protein, 1+, n=26	6 20%
Visit 4 Month 6, Glucose,3+ or 1 g/dL, n=19	2 6.7%
Visit 4 Month 6, RBC, 1-3, n=19	5 16.7%
Visit 4 Month 6, RBC, 3-5, n=19	3 10%
Visit 4 Month 6, RBC, 5-10, n=19	3 10%
Visit 4 Month 6 RBC, 10-15,n=19	1 3.3%
Visit 4 Month 6, RBC, 15-25, n=19	2 6.7%
Visit 4 Month 6, RBC, 25-50, n=19	1 3.3%
Visit 4 Month 6, RBC, 50-100, n=19	1 3.3%
Visit 4 Month 6, WBC,1-3, n=19	1 3.3%
Visit 4 Month 6, WBC,3-5, n=19	1 3.3%
Visit 4 Month 6, Occult Blood,1+, n=19	2 6.7%
Visit 4 Month 6, protein, 1+,n=19	3 10%
Visit 5 Month 9, Glucose,2+ or 1/2 g/dL, n=17	1 3.3%
Visit 5 Month 9, Glucose,3+ or 1 g/dL, n=17	1 3.3%
Visit 5 Month 9, RBC, 1-3, n=17	1 3.3%
Visit 5 Month 9, RBC, 3-5, n=17	5 16.7%
Visit 5 Month 9, RBC, 5-10, n=17	3 10%
Visit 5 Month 9, RBC, 10-15, n=17	3 10%
Visit 5 Month 9, RBC, 15-25, n=17	1 3.3%
Visit 5 Month 9, RBC, 25-50, n=17	1 3.3%
Visit 5 Month 9, RBC, innumerable, n=17	1 3.3%
Visit 5 Month 9, WBC,1-3, n=17	4 13.3%
Visit 5 Month 9, WBC,15-25, n=17	1 3.3%
Visit 5 Month 9, WBC, innumerable, n=17	1 3.3%
Visit 5 Month 9,Occult Blood,1+, n=17	1 3.3%
Visit 5 Month 9, Occult Blood,4+, n=17	2 6.7%
Visit 5 Month 9, protein, 1+, n=17	1 3.3%
Visit 6 Month 12, RBC, 1-3, n= 15	4 13.3%
Visit 6 Month 12, RBC, 3-5, n= 15	3 10%
Visit 6 Month 12, RBC, 5-10, n= 15	5 16.7%
Visit 6 Month 12, RBC, 10-15, n= 15	2 6.7%
Visit 6 Month 12, RBC, 15-25, n= 15	1 3.3%
Visit 6, Month 12, WBC, 1-3, n= 15	5 16.7%
Visit 6, Month 12, WBC, 3-5, n= 15	2 6.7%
Visit 6, Month 12, Occult blood, 1+, n= 15	4 13.3%
Visit 6, Month 12, Protein, 1+, n= 15	2 6.7%
Visit 6, Month 12, Protein, 2+, n= 15	1 3.3%
Visit 7,Month16,Glucose, 4+ or 2 or more g/dL,n=14	1 3.3%
Visit 7, Month 16, Ketone, 1+, n= 14	1 3.3%
Visit 7, Month 16, RBC, 1-3, n= 13	2 6.7%
Visit 7, Month 16, RBC, 3-5, n= 13	2 6.7%
Visit 7, Month 16, RBC, 5-10, n= 13	3 10%
Visit 7, Month 16, RBC, 10-15, n= 13	2 6.7%
Visit 7, Month 16, RBC, 25-50, n= 13	2 6.7%
Visit 7, Month 16, WBC, 1-3, n= 13	2 6.7%
Visit 7, Month 16, WBC, 3-5, n= 13	1 3.3%
Visit 7, Month 16, Occult blood, 1+, n= 14	1 3.3%
Visit 7, Month 16, Occult blood, 4+, n= 14	1 3.3%
Visit 7, Month 16, Protein, 1+, n= 14	3 10%
Visit 8, Month 20, RBC, 1-3, n= 12	3 10%
Visit 8, Month 20, RBC, 3-5, n= 12	2 6.7%
Visit 8, Month 20, RBC, 10-15, n= 12	2 6.7%
Visit 8, Month 20, RBC, 15-25, n= 12	1 3.3%
Visit 8, Month 20, RBC, 25-50, n= 12	1 3.3%
Visit 8, Month 20, WBC, 1-3, n= 12	2 6.7%
Visit 8, Month 20, WBC, 3-5, n= 12	1 3.3%
Visit 8, Month 20, Occult blood, 1+, n= 12	2 6.7%
Visit 9,Month24,Glucose,4+ or 2 or more g/dL,n=11	1 3.3%
Visit 9, Month 24, RBC, 1-3, n= 11	3 10%
Visit 9, Month 24, RBC, 3-5, n= 11	1 3.3%
Visit 9, Month 24, RBC, 5-10, n= 11	2 6.7%
Visit 9, Month 24, RBC, 10-15, n= 11	1 3.3%
Visit 9, Month 24, RBC, 50-100, n= 11	1 3.3%
Visit 9, Month 24, WBC, 3-5, n= 11	1 3.3%
Visit 9, Month 24, WBC, Innumerable, n= 11	1 3.3%
Visit 9, Month 24, Occult blood, 1+, n= 11	1 3.3%
Visit 9, Month 24, Occult blood, 4+, n= 11	2 6.7%
Visit 9, Month 24, Protein, 1+, n= 11	1 3.3%
Visit 9, Month 24, Protein, 2+, n= 11	1 3.3%
Visit 10,Month28,Glucose,4+ or 2 or more g/dL,n=10	1 3.3%
Visit 10, Month 28, RBC, 1-3, n= 9	2 6.7%
Visit 10, Month 28, RBC, 3-5, n= 9	2 6.7%
Visit 10, Month 28, RBC, 5-10, n= 9	2 6.7%
Visit 10, Month 28, RBC, 25-50, n= 9	1 3.3%
Visit 10, Month 28, WBC, 1-3, n= 9	1 3.3%
Visit 10, Month 28, Occult blood, 1+, n= 10	1 3.3%
Visit 10, Month 28, Protein, 1+, n= 10	2 6.7%
Visit 11,Month 32,Glucose,4+ or 2 or more g/dL,n=9	1 3.3%
Visit 11, Month 32, RBC, 3-5, n= 9	1 3.3%
Visit 11, Month 32, RBC, 5-10, n= 9	2 6.7%
Visit 11, Month 32, RBC, 10-15, n= 9	2 6.7%
Visit 11, Month 32, RBC, 25-50, n= 9	1 3.3%
Visit 11, Month 32, RBC, 50-100, n= 9	1 3.3%
Visit 11, Month 32, WBC, 1-3, n= 9	1 3.3%
Visit 11, Month 32, WBC, 10-15, n= 9	1 3.3%
Visit 11, Month 32, WBC, innumerable, n= 9	1 3.3%
Visit 11, Month 32, Occult blood, 1+, n= 9	1 3.3%
Visit 11, Month 32, Occult blood, 2+, n= 9	1 3.3%
Visit 11, Month 32, Occult blood, 4+, n= 9	1 3.3%
Visit 12,Month 36,Glucose,4+ or 2 or more g/dL,n=4	1 3.3%
Visit 12, Month 36, RBC, 3-5, n= 4	2 6.7%
Visit 12, Month 36, RBC, 5-10, n= 4	1 3.3%
Visit 12, Month 36, Occult blood, 1+, n= 4	1 3.3%
Study conclusion/Withdrawal,Glucose,3+or1g/dL,n=28	1 3.3%
Study conclusion/Withdrawal,Glucose,4+or2g/dL,n=28	2 6.7%
Study conclusion/Withdrawal, Ketones, trace, n= 28	1 3.3%
Study conclusion/Withdrawal, RBC, 1-3, n= 28	5 16.7%
Study conclusion/Withdrawal, RBC, 3-5, n= 28	2 6.7%
Study conclusion/Withdrawal, RBC, 5-10, n= 28	7 23.3%
Study conclusion/Withdrawal, RBC, 10-15, n= 28	4 13.3%
Study conclusion/Withdrawal, RBC, 15-25, n= 28	2 6.7%
Study conclusion/Withdrawal, RBC, 25-50, n= 28	2 6.7%
Study conclusion/Withdrawal, WBC, 1-3, n= 28	4 13.3%
Study conclusion/Withdrawal, WBC, 3-5, n= 28	2 6.7%
Study conclusion/Withdrawal, WBC, 5-10, n= 28	1 3.3%
Study conclusion/Withdrawal, WBC 10-15, n= 28	1 3.3%
Study conclusion/Withdrawal, WBC 15-25, n= 28	1 3.3%
Study conclusion/Withdrawal, Occult blood,1+ n= 28	2 6.7%
Study conclusion/Withdrawal, Occult blood,2+ n= 28	1 3.3%
Study conclusion/Withdrawal, Occult blood,4+ n= 28	2 6.7%
Study conclusion/Withdrawal, Protein, trace, n= 28	1 3.3%
Study conclusion/Withdrawal, Protein, 1+, n= 28	5 16.7%
Follow up, Ketones, trace, n= 5	1 3.3%
Follow up, RBC, 1-3, n= 5	1 3.3%
Follow up, RBC, 5-10, n= 5	2 6.7%
Follow up, WBC, 1-3, n= 5	3 10%
Follow up, WBC, 10-15, n= 5	1 3.3%
Follow up, Protein, 1+, n= 5	1 3.3%

20. Primary Outcome

Title	Specific Gravity of Urine at Indicated Time Points
Description	Urine samples were collected to analyze specific gravity of urine. Specific gravity, is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=30	1.0160 (0.00423)
Visit 2 - Month 1; n=28	1.0157 (0.00522)
Visit 3 - Month 3; n=26	1.0187 (0.00437)
Visit 4 - Month 6; n=19	1.0161 (0.00542)
Visit 5 - Month 9; n=17	1.0153 (0.00413)
Visit 6 - Month 12; n=15	1.0157 (0.00458)
Visit 7-(Month 16); n=14	1.0146 (0.00414)
Visit 8 - (Month 20); n=12	1.0158 (0.00359)
Visit 9 - (Month 24); n=11	1.0145 (0.00350)
Visit 10-(Month 28); n=10	1.0140 (0.00459)
Visit 11-(Month 32); n=9	1.0139 (0.00486)
Visit 12-(Month 36); n=4	1.0150 (0.00408)
Study Conclusion/Withdrawal;n=28	1.0166 (0.00409)
Follow-Up Visit; n=5	1.0198 (0.00476)

21. Primary Outcome

Title	Potential of Hydrogen (pH) of Urine at Indicated Time Points
Description	Urine Samples were collected to analyze pH. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH scale ranges from 0 to 14. A neutral pH is 7.0. The higher number indicates the more basic (alkaline) nature of urine and lower the number indicates the more acidic urine. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=30	6.68 (0.771)
Visit 2 - Month 1; n=28	6.48 (0.659)
Visit 3 - Month 3; n=26	6.35 (0.784)
Visit 4 - Month 6; n=19	6.39 (0.756)
Visit 5 - Month 9; n=17	6.74 (0.640)
Visit 6 - Month 12; n=15	6.40 (0.828)
Visit 7-(Month 16); n=14	6.54 (0.746)
Visit 8 - (Month 20); n=12	6.71 (0.620)
Visit 9 - (Month 24); n=11	6.86 (1.051)
Visit 10-(Month 28); n=10	6.80 (0.919)
Visit 11-(Month 32); n=9	6.78 (0.667)
Visit 12-(Month 36); n=4	6.88 (0.250)
Study Conclusion/Withdrawal;n=28	6.52 (0.687)
Follow-Up Visit; n=5	6.10 (0.548)

22. Primary Outcome

Title	Change From Baseline in Urine Creatinine Concentration
Description	Urine samples were collected from participants to evaluate change from Baseline in Urine creatinine concentration. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=30	-1803.3 (6012.94)
Visit 2 - Month 1; n=27	-1725.9 (6632.88)
Visit 3 - Month 3; n=25	-508.0 (6155.28)
Visit 4 - Month 6; n=19	-94.7 (7902.92)
Visit 5 - Month 9; n=17	-58.8 (6676.18)
Visit 6 - Month 12; n=15	-286.7 (3000.21)
Visit 7-(Month 16); n=14	-235.7 (3996.27)
Visit 8 - (Month 20); n=12	-341.7 (7648.46)
Visit 9 - (Month 24); n=11	-81.8 (5230.07)
Visit 10-(Month 28); n=10	4940.0 (9857.11)
Visit 11-(Month 32); n=9	2944.4 (6495.98)
Visit 12-(Month 36); n=3	1000.0 (11887.39)
Study Conclusion/Withdrawal;n=27	-1781.5 (5805.11)
Follow-Up Visit; n=5	7100.0 (4959.33)

23. Primary Outcome

Title	Change From Baseline in American Urological Association (AUA) Symptom Scale Scores
Description	The effect of RTG on bladder function was assessed using AUA symptom index. It is a 7-item Likert-scored scale with seven questions, each with six potential responses. Responses to each of 7 questions were scored from 0 (no symptom at all) to 5 (almost always symptoms present) which were summmed to get total possible score ranging from 0 to 35 with higher scores indicating worse symptom severity. The total score for all questions was classified as mild (0-7), moderate (8-19) or severe (>19). Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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).
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Retigabine IR
Arm/Group Description	All subjects will initially receive a starting dose of retigabine IR at 900 mg/day and after the first week of the OLE study, the dose of retigabine IR may be increased or decreased in increments or decrements of decrements of 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of retigabine IR must be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=29	-0.5 (2.68)
Visit 2-Month 1; n=28	0.3 (2.37)
Visit 3 - Month 3; n=25	-0.3 (2.41)
Visit 6 - Month 12; n=15	-0.7 (1.58)
Visit 7-(Month 16); n=1	-2.0 (NA)
Visit 9 - (Month 24); n=10	-0.1 (5.20)
Visit 12-(Month 36); n=4	3.0 (5.48)
Visit 13 (Month 40); n=1	0.0 (NA)
Study Conclusion/Withdrawal;n=29	1.1 (4.45)
Follow-Up Visit; n=5	1.2 (3.56)

24. Primary Outcome

Title	Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes
Description	The PVR bladder ultrasound was used to assess the effects of RTG on bladder function. Baseline was defined as the last assessment of that endpoint in parent study RTG114855 taken prior to the first active treatment with RTG IR. 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). Mean and SD were calculated.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Visit 1-Day 1; n=29	-3.4 (36.38)
Visit 2 - Month 1; n=28	9.2 (24.66)
Visit 3 - Month 3; n=25	2.0 (39.72)
Visit 6 - Month 12; n=15	1.7 (30.67)
Visit 7-(Month 16); n=1	-8.0 (NA)
Visit 9 - (Month 24); n=10	-8.2 (36.79)
Visit 12-(Month 36); n=4	-13.1 (31.50)
Visit 13 (Month 40); n=1	35.0 (NA)
Study Conclusion/Withdrawal;n=29	-1.7 (31.01)
Follow-Up Visit; n=3	-22.0 (53.70)

25. Primary Outcome

Title	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	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. It consists of an assessment of suicidal ideation (ranging from "desire to be dead" to "active suicidal ideation with specific plan and intent") and an assessment of suicidal behavior (ranging from "preparatory acts or behavior" to "completed suicide").
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Suicidal ideation	1 3.3%
Suicidal behavior	0 0%

26. Primary Outcome

Title	Number of Participants Who Discontinued From RTG
Description	The number of participants who discontinued from RTG treatment has been presented.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Day 0	0 0%
Day 3	1 3.3%
Day 17	1 3.3%
Day 62	1 3.3%
Day 66	1 3.3%
Day 98	1 3.3%
Day 111	1 3.3%
Day 126	1 3.3%
Day 163	1 3.3%
Day 168	2 6.7%
Day 169	1 3.3%
Day 229	1 3.3%
Day 240	1 3.3%
Day 287	1 3.3%
Day 339	1 3.3%
Day 413	1 3.3%
Day 498	1 3.3%
Day 559	1 3.3%
Day 650	1 3.3%
Day 781	1 3.3%
Day 852	1 3.3%
Day 927	1 3.3%
Day 930	0 0%
Day 943	0 0%
Day 1007	1 3.3%
Day 1008	1 3.3%
Day 1098	0 0%
Day 1169	0 0%
Day 1233	0 0%

27. Primary Outcome

Title	Percentage of Participants With Retinal Pigmentary Abnormalities
Description	Percentage of participants with abnormal findings after eye examination were evaluated. Abnormalities detected on-treatment in study RTG114873 were presented. Retinal pigmentary abnormalities included abnormalities in the macula, peripheral retina and unspecified location.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	22
Number [Percentage of participants]	18 60%

28. Primary Outcome

Title	Percentage of Participants With Pigmentation of Non-retinal Ocular Tissues
Description	Percentage of participants with abnormal findings after eye examination were evaluated. Abnormalities detected on-treatment in study RTG114873 were presented. Pigmentation of non-retinal ocular tissues included pigmentation of the sclera and/or conjunctiva, cornea, iris and lens.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	22
Number [Percentage of participants]	32 106.7%

29. Primary Outcome

Title	Percentage of Participants With Dermatologist-confirmed Abnormal Discoloration
Description	Percentage of participants with abnormal findings after skin examination (including the skin around the eyes and the eyelids, lips, nails, or mucosa) were evaluated.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	25
Number [Percentage of participants]	0 0%

30. Primary Outcome

Title	Percentage of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination
Description	Percentage of participants with a clinically significant decrease in visual acuity from initial examination were evaluated. Only abnormalities occurring on-treatment in study RTG114873 were presented.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	19
Number [Percentage of participants]	16 53.3%

31. Primary Outcome

Title	Percentage of Participants With Decrease in Confrontational Visual Field From Initial Examination
Description	Percentage of participants with decrease in confrontational visual field from initial examination were evaluated. Only abnormalities occurring on-treatment in study RTG114873 were presented.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	19
Number [Percentage of participants]	21 70%

32. Primary Outcome

Title	Percentage of Responders to POS Frequency
Description	A responder was defined as a participant experiencing a >=50 percent reduction in 28 day total POS frequency from Baseline. A responder rate was calculated overall and based on duration of exposure. As this was an OLE study, Baseline was defined by the parent study Baseline period. Percentage of responders were evaluated from study RTG114873 Day 1 through the last dosing day, excluding the Taper Phase.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Number [Percentage of responders]	23

33. Primary Outcome

Title	Percent Change From Baseline in 28-day Total POS Frequency
Description	The 28-day total POS frequency was calculated as the number of total POS reported during the treatment phase, divided by the number of applicable days in the treatment phase, then multiplying this ratio by 28. In this formula, innumerable seizures were counted as 10 seizures and status epilepticus was counted as 1 seizure. As this was an OLE study, Baseline was defined by the parent study Baseline period. The percent change from Baseline was calculated as the 28-day total POS on-treatment frequency (during dosing in this study, not including the taper phase) minus the Baseline 28-day total POS frequency, with this difference being divided by the Baseline 28-day partial seizure rate, and the resulting quantity multiplied by 100. It was calculated as overall and by duration of exposure. Mean and SD were presented.
Time Frame	Baseline and up to 4 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	RTG IR
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Measure Participants	30
Mean (Standard Deviation) [Percent change]	-29.37 (58.363)

34. Primary Outcome

Title	Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of RTG
Description	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. This analysis was performed on the All SFUCP Subjects population which comprised of all participants who enter the SFUCP.
Time Frame	Up to 1.4 years

Outcome Measure Data

Analysis Population Description

All SFUCP Subjects

Arm/Group Title	RTG in SFUCP
Arm/Group Description	Participants who withdraw from the Open-Label Treatment Phase (i.e., discontinue RTG IR including any dose taper), and who were found to have retinal pigmentation or unexplained vision loss, pigmentation of non-retinal ocular tissue or abnormal discoloration of nails, lips, skin or mucosa were followed-up in SFUCP which was the final reporting phase of the study. During SFUCP, participants underwent six monthly comprehensive eye examinations and/or dermatological assessments. Participants were followed-up until the discoloration /pigmentation either resolves or stabilizes, as defined by no change over two consecutive six monthly assessments over at least 12 months after discontinuation of RTG IR.
Measure Participants	4
Retinal pigmentary abnormality	0 0%
Non-retinal ocular pigmentary abnormality	0 0%

35. Primary Outcome

Title	Number of Participants With Resolution of Dermatologist-confirmed Abnormal Discoloration After Discontinuation of RTG
Description	The skin examination included assessment of the skin around the eyes and the eye lids, lips, nails, and mucosa. Participants who enter the SFUCP who had on-treatment finding(s) of abnormal discoloration of skin, lips, nails or mucosa confirmed by a dermatologist, underwent assessments performed by a dermatologist at 6-monthly intervals.
Time Frame	Up to 1.4 years

Outcome Measure Data

Analysis Population Description

All SFUCP Subjects

Arm/Group Title	RTG in SFUCP
Arm/Group Description	Participants who withdraw from the Open-Label Treatment Phase (i.e., discontinue RTG IR including any dose taper), and who were found to have retinal pigmentation or unexplained vision loss, pigmentation of non-retinal ocular tissue or abnormal discoloration of nails, lips, skin or mucosa were followed-up in SFUCP which was the final reporting phase of the study. During SFUCP, participants underwent six monthly comprehensive eye examinations and/or dermatological assessments. Participants were followed-up until the discoloration /pigmentation either resolves or stabilizes, as defined by no change over two consecutive six monthly assessments over at least 12 months after discontinuation of RTG IR.
Measure Participants	4
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected from the start of the study treatment up to 4 years.
Adverse Event Reporting Description	AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Arm/Group Title	RTG IR		RTG in SFUCP
Arm/Group Description	Eligible participants initially received a starting dose of RTG IR 900 milligrams per day (mg/day) and the same doses of the same concurrent anti-epileptic drugs (AEDs) that they were receiving at the final visit of the transition phase of the parent study. After the first week of the OLE study, the dose of RTG IR could be increased or decreased in increments or decrements 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of RTG IR was to be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.		Participants who withdraw from the Open-Label Treatment Phase and who had retinal pigmentation or unexplained vision loss, pigmentation of non-retinal ocular tissue or abnormal discoloration of nails, lips, skin or mucosa were followed-up in SFUCP which was the final reporting phase of the study. During SFUCP, participants underwent six monthly comprehensive eye examinations and/or dermatological assessments. Participants were followed-up until the discoloration /pigmentation either resolves or stabilizes, as defined by no change over two consecutive six monthly assessments over at least 12 months after discontinuation of RTG IR.
All Cause Mortality
	RTG IR		RTG in SFUCP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/4 (0%)
Serious Adverse Events
	RTG IR		RTG in SFUCP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)		0/4 (0%)
Eye disorders
Diabetic retinopathy	1/30 (3.3%)	1	0/4 (0%)	1
Vitreous haemorrhage	1/30 (3.3%)	1	0/4 (0%)	1
Infections and infestations
Endophthalmitis	1/30 (3.3%)	1	0/4 (0%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/30 (3.3%)	1	0/4 (0%)	1
Nervous system disorders
Postictal state	1/30 (3.3%)	2	0/4 (0%)	2
Cerebral haematoma	1/30 (3.3%)	1	0/4 (0%)	1
Dizziness	1/30 (3.3%)	1	0/4 (0%)	1
Headache	1/30 (3.3%)	1	0/4 (0%)	1
Other (Not Including Serious) Adverse Events
	RTG IR		RTG in SFUCP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)		0/4 (0%)
Eye disorders
Retinal pigmentation	2/30 (6.7%)	2	0/4 (0%)	2
Vision blurred	2/30 (6.7%)	2	0/4 (0%)	2
General disorders
Fatigue	2/30 (6.7%)	2	0/4 (0%)	2
Asthenia	3/30 (10%)	3	0/4 (0%)	3
Infections and infestations
Upper respiratory tract infection	2/30 (6.7%)	2	0/4 (0%)	2
Nasopharyngitis	3/30 (10%)	3	0/4 (0%)	3
Nervous system disorders
Memory impairment	3/30 (10%)	3	0/4 (0%)	3
Headache	4/30 (13.3%)	4	0/4 (0%)	4
Somnolence	9/30 (30%)	10	0/4 (0%)	10
Dizziness	11/30 (36.7%)	16	0/4 (0%)	16
Skin and subcutaneous tissue disorders
Rash macular	2/30 (6.7%)	2	0/4 (0%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.