Trial Outcomes & Findings for A Long-term, Safety, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures (NCT NCT01777139)

Last Updated: 2020-03-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

Baseline and up to 4 years

Results posted on

2020-03-11

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	RTG IR 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.	RTG in Safety Follow-up Continuation Phase (SFUCP) 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.
Primary Reporting Phase (Up to 4 Years) STARTED	30	0
Primary Reporting Phase (Up to 4 Years) COMPLETED	0	0
Primary Reporting Phase (Up to 4 Years) NOT COMPLETED	30	0
SFUCP (Up to 1.4 Years) STARTED	0	4
SFUCP (Up to 1.4 Years) COMPLETED	0	0
SFUCP (Up to 1.4 Years) NOT COMPLETED	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	RTG IR 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.	RTG in Safety Follow-up Continuation Phase (SFUCP) 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.
Primary Reporting Phase (Up to 4 Years) Adverse Event	7	0
Primary Reporting Phase (Up to 4 Years) Lack of Efficacy	6	0
Primary Reporting Phase (Up to 4 Years) Withdrawal by Subject	8	0
Primary Reporting Phase (Up to 4 Years) Other (Study drug discontinued)	3	0
Primary Reporting Phase (Up to 4 Years) Other (Reached stopping criteria)	2	0
Primary Reporting Phase (Up to 4 Years) Other (Subjects entered SFUCP)	4	0
SFUCP (Up to 1.4 Years) Withdrawal by Subject	0	1
SFUCP (Up to 1.4 Years) Other-Study drug discontinued	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RTG IR n=30 Participants 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.
Age, Continuous	36.0 Years STANDARD_DEVIATION 9.25 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	17 Participants n=5 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Mixed Race	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants With Treatment Emergent (TE) Serious Adverse Events (SAEs) and Non-SAEs Any non-SAE	23 Participants
Number of Participants With Treatment Emergent (TE) Serious Adverse Events (SAEs) and Non-SAEs Any SAE	5 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Percentage of Participants With TEAEs Leading to Study Discontinuation	17 Percentage of Participants

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs DBP; increase by >=20	4 Participants
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs DBP; decrease by >=20	9 Participants
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs SBP; increase by >=15	5 Participants
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs SBP; decrease by >=15	5 Participants
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs HR; increase by >=15	9 Participants
Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs HR; decrease by >=15	5 Participants

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants With PCC Values of Change From Baseline for Body Weight Body weight;increase by >=7 percent	11 Participants
Number of Participants With PCC Values of Change From Baseline for Body Weight Body weight; decrease by >=7 percent	4 Participants

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Post-Baseline QTc>=500, Baseline <500msec	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters HR <50 bpm, decreased from Baseline>=15 bpm	1 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters HR >100 bpm, increased from Baseline >=15 bpm	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters PR interval >=210 msec, increased from Baseline	1 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QRS interval >=120 msec, increased from Baseline	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Post-Baseline QTc>=450, Baseline<450 msec	5 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Post-Baseline QTc>=480, Baseline < 480 msec	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Post-Baseline QTc>500 msec	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Increase in QTc of >30 msec from Baseline	3 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Increase in QTc of >30,<=60 msecfrom Baseline	3 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcB:Increase in QTc of >60 msec from Baseline	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF:Post-Baseline QTc>=450, Baseline<450 msec	1 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF:Post-Baseline QTc>=480, Baseline<480 msec	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF: Post-Baseline QTc>500 msec	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF:Post-Baseline QTc>=500, Baseline<500 msec	0 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF:Increase in QTc of >30 msec from Baseline	3 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF:Increase in QTcof >30,<=60 msec from Baseline	3 Participants
Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters QTcF:Increase in QTc of >60 msec from Baseline	0 Participants

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 3 - Month 3; n=26	0.14 Giga unit per liter (GI/L) Standard Deviation 1.501
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 11 (Month 32); n=9	1.310 Giga unit per liter (GI/L) Standard Deviation 2.2464
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 12 (Month 36); n=4	0.310 Giga unit per liter (GI/L) Standard Deviation 0.6800
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils;Study Conclusion/Withdrawal;n=28	0.086 Giga unit per liter (GI/L) Standard Deviation 1.1378
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Follow-Up Visit; n=5	-0.176 Giga unit per liter (GI/L) Standard Deviation 1.4051
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC ; Visit 1-Day 1; n=30	-0.15 Giga unit per liter (GI/L) Standard Deviation 1.417
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC ; Visit 2 - Month 1; n=28	-0.16 Giga unit per liter (GI/L) Standard Deviation 1.182
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 1-Day 1;n=29	0.000 Giga unit per liter (GI/L) Standard Deviation 0.0118
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 2 - Month 1;n=28	0.000 Giga unit per liter (GI/L) Standard Deviation 0.0126
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 3 - Month 3;n=26	0.000 Giga unit per liter (GI/L) Standard Deviation 0.0118
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 4 - Month 6;n=16	-0.003 Giga unit per liter (GI/L) Standard Deviation 0.0184
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 5 - Month 9;n=16	0.001 Giga unit per liter (GI/L) Standard Deviation 0.0178
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 6 - Month 12;n=13	0.003 Giga unit per liter (GI/L) Standard Deviation 0.0132
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 7 (Month 16);n=12	-0.002 Giga unit per liter (GI/L) Standard Deviation 0.0147
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 8 (Month 20);n=11	0.003 Giga unit per liter (GI/L) Standard Deviation 0.0220
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 9 (Month 24);n=10	0.000 Giga unit per liter (GI/L) Standard Deviation 0.0105
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 10 (Month 28);n=10	0.002 Giga unit per liter (GI/L) Standard Deviation 0.0079
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 11 (Month 32);n=9	0.004 Giga unit per liter (GI/L) Standard Deviation 0.0188
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Visit 12 (Month 36);n=4	0.005 Giga unit per liter (GI/L) Standard Deviation 0.0058
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Study Conclusion/Withdrawal;n=28	-0.003 Giga unit per liter (GI/L) Standard Deviation 0.0146
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Basophils;Follow-Up Visit;n=5	-0.008 Giga unit per liter (GI/L) Standard Deviation 0.0130
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils;Visit 1-Day 1; n=29	-0.012 Giga unit per liter (GI/L) Standard Deviation 0.1152
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 2 - Month 1; n=28	-0.051 Giga unit per liter (GI/L) Standard Deviation 0.1311
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 3 - Month 3; n=26	-0.070 Giga unit per liter (GI/L) Standard Deviation 0.2813
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 4 - Month 6; n=16	-0.004 Giga unit per liter (GI/L) Standard Deviation 0.1020
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 5 - Month 9; n=16	0.038 Giga unit per liter (GI/L) Standard Deviation 0.1038
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 6 - Month 12; n=13	-0.014 Giga unit per liter (GI/L) Standard Deviation 0.0846
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 7 (Month 16); n=12	0.010 Giga unit per liter (GI/L) Standard Deviation 0.1135
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 8 (Month 20); n=11	0.008 Giga unit per liter (GI/L) Standard Deviation 0.0908
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 9 (Month 24); n=10	-0.051 Giga unit per liter (GI/L) Standard Deviation 0.0983
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 10 (Month 28); n=10	0.006 Giga unit per liter (GI/L) Standard Deviation 0.1467
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 11 (Month 32); n=9	0.011 Giga unit per liter (GI/L) Standard Deviation 0.0494
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Visit 12 (Month 36); n=4	-0.025 Giga unit per liter (GI/L) Standard Deviation 0.0900
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Study Conclusion/Withdrawal; n=28	-0.026 Giga unit per liter (GI/L) Standard Deviation 0.1085
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Eosinophils; Follow-Up Visit; n=5	-0.078 Giga unit per liter (GI/L) Standard Deviation 0.1268
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 1-Day 1; n= 29	-0.132 Giga unit per liter (GI/L) Standard Deviation 0.5985
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 2 - Month 1; n=28	-0.065 Giga unit per liter (GI/L) Standard Deviation 0.5549
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 3 - Month 3; n=26	-0.120 Giga unit per liter (GI/L) Standard Deviation 0.4974
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 4 - Month 6; n=16	0.024 Giga unit per liter (GI/L) Standard Deviation 0.3740
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 5 - Month 9; n=16	-0.032 Giga unit per liter (GI/L) Standard Deviation 0.4358
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 6 - Month 12; n= 13	-0.109 Giga unit per liter (GI/L) Standard Deviation 0.3685
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 7 (Month 16); n=12	0.007 Giga unit per liter (GI/L) Standard Deviation 0.3039
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 8 (Month 20); n=11	-0.037 Giga unit per liter (GI/L) Standard Deviation 0.3250
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 9 (Month 24); n=10	0.052 Giga unit per liter (GI/L) Standard Deviation 0.4157
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 10 (Month 28); n=10	0.108 Giga unit per liter (GI/L) Standard Deviation 0.2986
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 11 (Month 32); n=9	0.022 Giga unit per liter (GI/L) Standard Deviation 0.4280
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Visit 12 (Month 36); n=4	-0.268 Giga unit per liter (GI/L) Standard Deviation 0.3096
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Study Conclusion/Withdrawal; n=28	-0.068 Giga unit per liter (GI/L) Standard Deviation 0.5778
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Lymphocytes; Follow-Up Visit; n=5	-0.070 Giga unit per liter (GI/L) Standard Deviation 0.3466
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 1-Day 1; n= 29	-0.018 Giga unit per liter (GI/L) Standard Deviation 0.1204
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 2 - Month 1; n=28	-0.028 Giga unit per liter (GI/L) Standard Deviation 0.1357
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 3 - Month 3; n=26	-0.044 Giga unit per liter (GI/L) Standard Deviation 0.1350
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 4 - Month 6; n=16	0.033 Giga unit per liter (GI/L) Standard Deviation 0.1445
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 5 - Month 9; n=16	-0.042 Giga unit per liter (GI/L) Standard Deviation 0.1348
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 6 - Month 12; n= 13	0.076 Giga unit per liter (GI/L) Standard Deviation 0.1711
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 7 (Month 16); n=12	-0.021 Giga unit per liter (GI/L) Standard Deviation 0.1717
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 8 (Month 20); n=11	0.129 Giga unit per liter (GI/L) Standard Deviation 0.1936
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 9 (Month 24); n=10	-0.021 Giga unit per liter (GI/L) Standard Deviation 0.1358
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 10 (Month 28); n=10	-0.022 Giga unit per liter (GI/L) Standard Deviation 0.1781
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 11 (Month 32); n=9	0.088 Giga unit per liter (GI/L) Standard Deviation 0.1384
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Visit 12 (Month 36); n=4	0.035 Giga unit per liter (GI/L) Standard Deviation 0.0823
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Study Conclusion/Withdrawal; n=28	0.014 Giga unit per liter (GI/L) Standard Deviation 0.1809
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Monocytes; Follow-Up Visit; n=5	0.054 Giga unit per liter (GI/L) Standard Deviation 0.1011
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 1-Day 1; n=28	8.3 Giga unit per liter (GI/L) Standard Deviation 25.26
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 2 - Month 1; n=28	6.3 Giga unit per liter (GI/L) Standard Deviation 24.01
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 3 - Month 3; n=25	14.5 Giga unit per liter (GI/L) Standard Deviation 26.01
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 4 - Month 6; n=18	5.8 Giga unit per liter (GI/L) Standard Deviation 37.84
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 5 - Month 9; n=17	6.0 Giga unit per liter (GI/L) Standard Deviation 29.90
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 6 - Month 12; n=15	10.2 Giga unit per liter (GI/L) Standard Deviation 35.51
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 7 (Month 16); n=14	18.5 Giga unit per liter (GI/L) Standard Deviation 23.65
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 8 (Month 20); n=11	16.6 Giga unit per liter (GI/L) Standard Deviation 39.64
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 9 (Month 24); n=11	15.5 Giga unit per liter (GI/L) Standard Deviation 22.98
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 10 (Month 28); n=10	20.3 Giga unit per liter (GI/L) Standard Deviation 40.66
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 11 (Month 32); n=9	17.1 Giga unit per liter (GI/L) Standard Deviation 50.38
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Visit 12 (Month 36); n=4	28.5 Giga unit per liter (GI/L) Standard Deviation 13.53
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Study Conclusion/Withdrawal; n=28	17.0 Giga unit per liter (GI/L) Standard Deviation 37.37
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Platelet count; Follow-Up Visit; n=5	-2.0 Giga unit per liter (GI/L) Standard Deviation 26.93
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 1-Day 1; n=30	-0.099 Giga unit per liter (GI/L) Standard Deviation 1.3450
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 2 - Month 1; n=28	-0.028 Giga unit per liter (GI/L) Standard Deviation 1.1045
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 3 - Month 3; n=26	0.369 Giga unit per liter (GI/L) Standard Deviation 1.7061
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 4 - Month 6; n=16	-0.318 Giga unit per liter (GI/L) Standard Deviation 1.4286
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 5 - Month 9; n=16	-0.158 Giga unit per liter (GI/L) Standard Deviation 1.6801
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 6 - Month 12; n=13	0.182 Giga unit per liter (GI/L) Standard Deviation 0.9911
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 7 (Month 16); n=12	0.252 Giga unit per liter (GI/L) Standard Deviation 0.9079
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 8 (Month 20); n=11	0.325 Giga unit per liter (GI/L) Standard Deviation 1.0561
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 9 (Month 24); n=10	0.656 Giga unit per liter (GI/L) Standard Deviation 1.0269
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) Total Neutrophils; Visit 10 (Month 28); n=10	0.238 Giga unit per liter (GI/L) Standard Deviation 0.8603
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 4 - Month 6; n=18	-0.42 Giga unit per liter (GI/L) Standard Deviation 1.545
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 5 - Month 9; n=17	-0.12 Giga unit per liter (GI/L) Standard Deviation 1.630
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 6 - Month 12; n=15	0.34 Giga unit per liter (GI/L) Standard Deviation 1.330
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC ; Visit 7 (Month 16); n=14	0.20 Giga unit per liter (GI/L) Standard Deviation 0.927
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC ; Visit 8 (Month 20); n=12	0.53 Giga unit per liter (GI/L) Standard Deviation 1.127
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC ; Visit 9 (Month 24); n=11	0.64 Giga unit per liter (GI/L) Standard Deviation 0.837
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 10 (Month 28); n=10	0.33 Giga unit per liter (GI/L) Standard Deviation 1.003
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 12 (Month 36); n=4	0.08 Giga unit per liter (GI/L) Standard Deviation 0.991
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Visit 11 (Month 32); n=9	1.43 Giga unit per liter (GI/L) Standard Deviation 2.155
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Study Conclusion/Withdrawal;n=28	0.01 Giga unit per liter (GI/L) Standard Deviation 1.212
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC) WBC; Follow-Up Visit; n=5	-0.28 Giga unit per liter (GI/L) Standard Deviation 1.395

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Hematocrit Visit 1-Day 1; n=30	-0.0035 Proportion of red blood cells in blood Standard Deviation 0.02749
Change From Baseline in Hematocrit Visit 2 - Month 1; n=28	-0.0048 Proportion of red blood cells in blood Standard Deviation 0.02512
Change From Baseline in Hematocrit Visit 3 - Month 3; n=26	-0.0033 Proportion of red blood cells in blood Standard Deviation 0.02175
Change From Baseline in Hematocrit Visit 4 - Month 6; n=18	-0.0022 Proportion of red blood cells in blood Standard Deviation 0.01659
Change From Baseline in Hematocrit Visit 5 - Month 9; n=17	-0.0004 Proportion of red blood cells in blood Standard Deviation 0.01790
Change From Baseline in Hematocrit Visit 6 - Month 12; n=15	-0.0014 Proportion of red blood cells in blood Standard Deviation 0.01883
Change From Baseline in Hematocrit Visit 7 (Month 16); n=14	0.0027 Proportion of red blood cells in blood Standard Deviation 0.01887
Change From Baseline in Hematocrit Visit 8 (Month 20); n=12	0.0105 Proportion of red blood cells in blood Standard Deviation 0.01857
Change From Baseline in Hematocrit Visit 9 (Month 24); n=11	0.0174 Proportion of red blood cells in blood Standard Deviation 0.02331
Change From Baseline in Hematocrit Visit 10 (Month 28); n=10	0.0189 Proportion of red blood cells in blood Standard Deviation 0.01987
Change From Baseline in Hematocrit Visit 11 (Month 32); n=9	0.0344 Proportion of red blood cells in blood Standard Deviation 0.02959
Change From Baseline in Hematocrit Visit 12 (Month 36); n=4	0.0408 Proportion of red blood cells in blood Standard Deviation 0.02608
Change From Baseline in Hematocrit Study Conclusion/Withdrawal;n=28	0.0055 Proportion of red blood cells in blood Standard Deviation 0.02345
Change From Baseline in Hematocrit Follow-Up Visit; n=5	0.0048 Proportion of red blood cells in blood Standard Deviation 0.02100

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 4 - Month 6; n=18	-0.2 Gram per Liter (G/L) Standard Deviation 5.33
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 1-Day 1; n=30	-2.6 Gram per Liter (G/L) Standard Deviation 8.23
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 2 - Month 1; n=28	-2.8 Gram per Liter (G/L) Standard Deviation 7.75
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 3 - Month 3; n=26	-2.2 Gram per Liter (G/L) Standard Deviation 6.83
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 5 - Month 9; n=17	-0.8 Gram per Liter (G/L) Standard Deviation 5.96
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 6 - Month 12; n=15	-1.9 Gram per Liter (G/L) Standard Deviation 6.28
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 7 (Month 16); n=14	-1.5 Gram per Liter (G/L) Standard Deviation 6.00
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 8 (Month 20); n=12	2.3 Gram per Liter (G/L) Standard Deviation 5.10
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 9 (Month 24); n=11	2.6 Gram per Liter (G/L) Standard Deviation 6.55
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 10 (Month 28); n=10	1.9 Gram per Liter (G/L) Standard Deviation 6.12
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 11 (Month 32); n=9	9.1 Gram per Liter (G/L) Standard Deviation 9.84
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Visit 12 (Month 36); n=4	8.0 Gram per Liter (G/L) Standard Deviation 6.98
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Study Conclusion/Withdrawal;n=28	1.3 Gram per Liter (G/L) Standard Deviation 6.31
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin; Follow-Up Visit; n=5	1.8 Gram per Liter (G/L) Standard Deviation 7.92
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 1-Day 1; n=30	-3.1 Gram per Liter (G/L) Standard Deviation 8.45
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 2 - Month 1; n=28	-2.9 Gram per Liter (G/L) Standard Deviation 7.92
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 3 - Month 3; n=26	-2.4 Gram per Liter (G/L) Standard Deviation 9.27
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 4 - Month 6; n=18	1.2 Gram per Liter (G/L) Standard Deviation 7.31
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 5 - Month 9; n=17	-1.1 Gram per Liter (G/L) Standard Deviation 4.61
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 6 - Month 12; n=15	-2.6 Gram per Liter (G/L) Standard Deviation 7.21
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 7 (Month 16); n=14	-5.1 Gram per Liter (G/L) Standard Deviation 9.63
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 8 (Month 20); n=12	-2.3 Gram per Liter (G/L) Standard Deviation 7.80
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 9 (Month 24); n=11	-6.4 Gram per Liter (G/L) Standard Deviation 8.56
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 10 (Month 28); n=10	-9.9 Gram per Liter (G/L) Standard Deviation 8.24
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 11 (Month 32); n=9	-4.6 Gram per Liter (G/L) Standard Deviation 6.31
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Visit 12 (Month 36); n=4	-12.8 Gram per Liter (G/L) Standard Deviation 4.19
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; StudyConclusion/Withdrawal;n=28	-1.3 Gram per Liter (G/L) Standard Deviation 8.47
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC; Follow-Up Visit; n=5	0.8 Gram per Liter (G/L) Standard Deviation 10.43

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Follow-Up Visit; n=5	-0.64 Picogram (Pg) Standard Deviation 0.611
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 1-Day 1; n=30	-0.30 Picogram (Pg) Standard Deviation 0.539
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 2 - Month 1; n=28	-0.16 Picogram (Pg) Standard Deviation 0.807
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 3 - Month 3; n=26	-0.23 Picogram (Pg) Standard Deviation 0.759
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 4 - Month 6; n=18	-0.14 Picogram (Pg) Standard Deviation 0.731
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 5 - Month 9; n=17	-0.46 Picogram (Pg) Standard Deviation 0.600
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 6 - Month 12; n=15	-0.65 Picogram (Pg) Standard Deviation 0.588
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 7 (Month 16); n=14	-0.56 Picogram (Pg) Standard Deviation 0.717
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 8 (Month 20); n=12	-0.73 Picogram (Pg) Standard Deviation 0.574
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 9 (Month 24); n=11	-0.87 Picogram (Pg) Standard Deviation 0.461
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 10 (Month 28); n=10	-0.76 Picogram (Pg) Standard Deviation 0.435
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 11 (Month 32); n=9	-0.73 Picogram (Pg) Standard Deviation 0.391
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level Visit 12 (Month 36); n=4	-1.53 Picogram (Pg) Standard Deviation 0.506
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level StudyConclusion/Withdrawal; n=28	-0.52 Picogram (Pg) Standard Deviation 0.731

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 11- (Month 32); n=9	0.21 Femtoliter (fL) Standard Deviation 0.933
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 1-Day 1; n=30	0.1 Femtoliter (fL) Standard Deviation 2.15
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 2 - Month 1; n=28	0.4 Femtoliter (fL) Standard Deviation 2.35
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 3 - Month 3; n=26	0.1 Femtoliter (fL) Standard Deviation 2.42
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 4 - Month 6; n=18	-0.7 Femtoliter (fL) Standard Deviation 1.75
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 5 - Month 9; n=17	-1.1 Femtoliter (fL) Standard Deviation 1.52
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 6 - Month 12; n=15	-1.2 Femtoliter (fL) Standard Deviation 2.08
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 7-(Month 16); n=14	-0.1 Femtoliter (fL) Standard Deviation 2.06
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 8-(Month 20); n=12	-1.3 Femtoliter (fL) Standard Deviation 2.01
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 9-(Month 24); n=11	-0.7 Femtoliter (fL) Standard Deviation 1.85
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 10-(Month 28); n=10	0.8 Femtoliter (fL) Standard Deviation 2.44
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 1- (Month 32); n=9	-0.8 Femtoliter (fL) Standard Deviation 2.05
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Visit 12- (Month 36); n=4	-0.8 Femtoliter (fL) Standard Deviation 1.26
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; StudyConclusion/Withdrawal; n=28	-1.0 Femtoliter (fL) Standard Deviation 2.16
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MCV; Follow-Up Visit; n=5	-2.2 Femtoliter (fL) Standard Deviation 1.64
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 1- Day 1; n=28	-0.43 Femtoliter (fL) Standard Deviation 0.526
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 2 - Month 1; n=28	-0.41 Femtoliter (fL) Standard Deviation 0.610
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 3 - Month 3; n=25	-0.34 Femtoliter (fL) Standard Deviation 0.579
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 4 - Month 6; n=18	-0.07 Femtoliter (fL) Standard Deviation 0.642
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 5 - Month 9; n=17	-0.32 Femtoliter (fL) Standard Deviation 0.645
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 6 - Month 12; n=15	-0.19 Femtoliter (fL) Standard Deviation 0.678
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 7-(Month 16); n=14	-0.36 Femtoliter (fL) Standard Deviation 0.624
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 8-(Month 20); n=11	-0.15 Femtoliter (fL) Standard Deviation 0.658
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 9-(Month 24); n=11	0.07 Femtoliter (fL) Standard Deviation 0.629
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 10-(Month 28); n=10	-0.14 Femtoliter (fL) Standard Deviation 0.435
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Visit 12- (Month 36); n=4	-0.73 Femtoliter (fL) Standard Deviation 0.386
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; StudyConclusion/Withdrawal; n=28	-0.18 Femtoliter (fL) Standard Deviation 0.572
Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) MPV; Follow-Up Visit; n=5	0.28 Femtoliter (fL) Standard Deviation 0.349

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Red Blood Cell (RBC) Count Visit 1- Day 1; n=30	-0.03 Tetra unit per liter (TI/L) Standard Deviation 0.266
Change From Baseline in Red Blood Cell (RBC) Count Visit 2 - Month 1; n=28	-0.06 Tetra unit per liter (TI/L) Standard Deviation 0.256
Change From Baseline in Red Blood Cell (RBC) Count Visit 3 - Month 3; n=26	-0.03 Tetra unit per liter (TI/L) Standard Deviation 0.241
Change From Baseline in Red Blood Cell (RBC) Count Visit 4 - Month 6; n=18	0.01 Tetra unit per liter (TI/L) Standard Deviation 0.227
Change From Baseline in Red Blood Cell (RBC) Count Visit 5 - Month 9; n=17	0.05 Tetra unit per liter (TI/L) Standard Deviation 0.218
Change From Baseline in Red Blood Cell (RBC) Count Visit 6 - Month 12; n=15	0.04 Tetra unit per liter (TI/L) Standard Deviation 0.188
Change From Baseline in Red Blood Cell (RBC) Count Visit 7 - (Month 16); n=14	0.04 Tetra unit per liter (TI/L) Standard Deviation 0.198
Change From Baseline in Red Blood Cell (RBC) Count Visit 8 - (Month 20); n=12	0.19 Tetra unit per liter (TI/L) Standard Deviation 0.207
Change From Baseline in Red Blood Cell (RBC) Count Visit 9 - (Month 24); n=11	0.22 Tetra unit per liter (TI/L) Standard Deviation 0.214
Change From Baseline in Red Blood Cell (RBC) Count Visit 10 -(Month 28); n=10	0.17 Tetra unit per liter (TI/L) Standard Deviation 0.200
Change From Baseline in Red Blood Cell (RBC) Count Visit 11- (Month 32); n=9	0.41 Tetra unit per liter (TI/L) Standard Deviation 0.322
Change From Baseline in Red Blood Cell (RBC) Count Visit 12- (Month 36); n=4	0.45 Tetra unit per liter (TI/L) Standard Deviation 0.265
Change From Baseline in Red Blood Cell (RBC) Count StudyConclusion/Withdrawal; n=28	0.13 Tetra unit per liter (TI/L) Standard Deviation 0.229
Change From Baseline in Red Blood Cell (RBC) Count Follow-Up Visit; n=5	0.16 Tetra unit per liter (TI/L) Standard Deviation 0.241

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Red Cell Distribution Width (RDW) Visit 1- Day 1; n=30	0.31 Percentage of width Standard Deviation 0.887
Change From Baseline in Red Cell Distribution Width (RDW) Visit 2 - Month 1; n=28	0.43 Percentage of width Standard Deviation 0.716
Change From Baseline in Red Cell Distribution Width (RDW) Visit 3 - Month 3; n=26	0.18 Percentage of width Standard Deviation 1.016
Change From Baseline in Red Cell Distribution Width (RDW) Visit 4 - Month 6; n=18	-0.33 Percentage of width Standard Deviation 0.806
Change From Baseline in Red Cell Distribution Width (RDW) Visit 5 - Month 9; n=17	-0.03 Percentage of width Standard Deviation 1.025
Change From Baseline in Red Cell Distribution Width (RDW) Visit 6 - Month 12; n=15	0.01 Percentage of width Standard Deviation 0.684
Change From Baseline in Red Cell Distribution Width (RDW) Visit 7 - (Month 16); n=14	0.13 Percentage of width Standard Deviation 0.685
Change From Baseline in Red Cell Distribution Width (RDW) Visit 8 - (Month 20); n=12	-0.33 Percentage of width Standard Deviation 0.735
Change From Baseline in Red Cell Distribution Width (RDW) Visit 9 - (Month 24); n=11	-0.01 Percentage of width Standard Deviation 0.468
Change From Baseline in Red Cell Distribution Width (RDW) Visit 10 -(Month 28); n=10	0.35 Percentage of width Standard Deviation 0.665
Change From Baseline in Red Cell Distribution Width (RDW) Visit 11- (Month 32); n=9	-0.36 Percentage of width Standard Deviation 0.814
Change From Baseline in Red Cell Distribution Width (RDW) Visit 12- (Month 36); n=4	-0.33 Percentage of width Standard Deviation 0.690
Change From Baseline in Red Cell Distribution Width (RDW) Study Conclusion/Withdrawal; n=28	-0.01 Percentage of width Standard Deviation 1.009
Change From Baseline in Red Cell Distribution Width (RDW) Follow-Up Visit; n=5	-0.14 Percentage of width Standard Deviation 0.885

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
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) AST; Visit 3 - Month 3; n=24	0.0 International unit per liter (IU/L) Standard Deviation 4.57
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) CK; Visit 5 - Month 9; n=17	-10.9 International unit per liter (IU/L) Standard Deviation 63.16
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) LD; Visit 2 - Month 1; n=26	0.8 International unit per liter (IU/L) Standard Deviation 22.57
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) LD; Visit 3 - Month 3; n=24	1.7 International unit per liter (IU/L) Standard Deviation 17.96
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) LD; Visit 4 - Month 6; n=19	-8.5 International unit per liter (IU/L) Standard Deviation 19.35
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) LD; Visit 5 - Month 9; n=17	1.9 International unit per liter (IU/L) Standard Deviation 17.71
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) LD; Visit 6 - Month 12; n=15	-1.6 International unit per liter (IU/L) Standard Deviation 22.21
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) LD; Visit 7-(Month 16); n=14	1.3 International unit per liter (IU/L) Standard Deviation 21.21
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) LD; Visit 8 - (Month 20); n=12	-0.5 International unit per liter (IU/L) Standard Deviation 12.08
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) LD; Visit 9 - (Month 24); n=11	12.2 International unit per liter (IU/L) Standard Deviation 8.40
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) LD; Visit 10-(Month 28); n=9	8.3 International unit per liter (IU/L) Standard Deviation 16.65
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) LD; Visit 11-(Month 32); n=9	18.8 International unit per liter (IU/L) Standard Deviation 18.98
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) LD; Visit 12-(Month 36); n=4	8.5 International unit per liter (IU/L) Standard Deviation 7.90
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) LD; Study Conclusion/Withdrawal; n=27	2.6 International unit per liter (IU/L) Standard Deviation 23.41
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) LD; Follow-Up Visit; n=4	2.5 International unit per liter (IU/L) Standard Deviation 8.19
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) ALT; Visit 1-Day 1; n= 28	0.8 International unit per liter (IU/L) Standard Deviation 4.78
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) ALT; Visit 2 - Month 1; n=27	3.3 International unit per liter (IU/L) Standard Deviation 14.86
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) ALT; Visit 3 - Month 3; n=24	0.3 International unit per liter (IU/L) Standard Deviation 5.44
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) ALT; Visit 4 - Month 6; n=19	0.9 International unit per liter (IU/L) Standard Deviation 6.20
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) ALT; Visit 5 - Month 9; n=17	0.6 International unit per liter (IU/L) Standard Deviation 4.17
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) ALT; Visit 6 - Month 12; n=15	1.5 International unit per liter (IU/L) Standard Deviation 6.41
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) ALT; Visit 7 (Month 16); n=14	0.3 International unit per liter (IU/L) Standard Deviation 4.61
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) ALT; Visit 8 (Month 20); n=12	0.4 International unit per liter (IU/L) Standard Deviation 4.62
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) ALT; Visit 9 (Month 24); n=11	0.8 International unit per liter (IU/L) Standard Deviation 8.59
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) ALT; Visit 10 (Month 28); n=10	1.6 International unit per liter (IU/L) Standard Deviation 6.00
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) ALT; Visit 11 (Month 32); n=9	7.4 International unit per liter (IU/L) Standard Deviation 13.57
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) ALT; Visit 12 (Month 36); n=4	0.0 International unit per liter (IU/L) Standard Deviation 5.29
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) ALT; Study Conclusion/Withdrawal; n=27	1.1 International unit per liter (IU/L) Standard Deviation 6.05
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) ALT ; Follow-Up Visit; n=4	9.8 International unit per liter (IU/L) Standard Deviation 15.65
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) Alk. Phosph.; Visit 1-Day 1; n= 28	-1.5 International unit per liter (IU/L) Standard Deviation 13.64
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) Alk. Phosph; Visit 2 - Month 1; n=27	-2.2 International unit per liter (IU/L) Standard Deviation 12.43
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) Alk. Phosph; Visit 3 - Month 3; n=24	-2.5 International unit per liter (IU/L) Standard Deviation 17.09
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) Alk. Phosph; Visit 4 - Month 6; n=19	-5.1 International unit per liter (IU/L) Standard Deviation 13.82
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) Alk. Phosph; Visit 5 - Month 9; n=17	-4.7 International unit per liter (IU/L) Standard Deviation 14.50
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) Alk. Phosph; Visit 6 - Month 12; n=15	-2.5 International unit per liter (IU/L) Standard Deviation 18.28
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) Alk. Phosph; Visit 7 (Month 16); n=14	0.2 International unit per liter (IU/L) Standard Deviation 20.10
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) Alk. Phosph; Visit 8 (Month 20); n=12	0.5 International unit per liter (IU/L) Standard Deviation 19.15
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) Alk. Phosph; Visit 9 (Month 24); n=11	-3.5 International unit per liter (IU/L) Standard Deviation 16.42
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) Alk. Phosph; Visit 10 (Month 28); n=10	-5.3 International unit per liter (IU/L) Standard Deviation 12.68
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) Alk. Phosph; Visit 11 (Month 32); n=9	5.8 International unit per liter (IU/L) Standard Deviation 15.91
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) Alk. Phosph; Visit 12 (Month 36); n=4	7.8 International unit per liter (IU/L) Standard Deviation 18.03
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) Alk. Phosph; Study Conclusion/Withdrawal; n=27	-2.7 International unit per liter (IU/L) Standard Deviation 16.65
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) Alk. Phosph ; Follow-Up Visit; n=4	-21.3 International unit per liter (IU/L) Standard Deviation 19.69
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) AST; Visit 1-Day 1; n= 27	0.5 International unit per liter (IU/L) Standard Deviation 6.35
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) AST; Visit 2 - Month 1; n=26	2.0 International unit per liter (IU/L) Standard Deviation 10.61
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) AST; Visit 4 - Month 6; n=19	1.3 International unit per liter (IU/L) Standard Deviation 4.13
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) AST; Visit 5 - Month 9; n=17	2.6 International unit per liter (IU/L) Standard Deviation 6.02
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) AST; Visit 6 - Month 12; n=15	2.1 International unit per liter (IU/L) Standard Deviation 5.42
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) AST; Visit 7 (Month 16); n=14	1.8 International unit per liter (IU/L) Standard Deviation 3.17
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) AST; Visit 8 (Month 20); n=12	1.6 International unit per liter (IU/L) Standard Deviation 3.32
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) AST; Visit 9 (Month 24); n=11	2.5 International unit per liter (IU/L) Standard Deviation 4.30
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) AST; Visit 10 (Month 28); n=9	2.9 International unit per liter (IU/L) Standard Deviation 4.88
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) AST; Visit 11 (Month 32); n=9	4.7 International unit per liter (IU/L) Standard Deviation 4.58
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) AST; Visit 12 (Month 36); n=4	0.8 International unit per liter (IU/L) Standard Deviation 2.50
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) AST; Study Conclusion/Withdrawal; n=27	1.5 International unit per liter (IU/L) Standard Deviation 6.08
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) AST; Follow-Up Visit; n=4	7.5 International unit per liter (IU/L) Standard Deviation 10.34
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) CK; Visit 1-Day 1; n= 28	-103.3 International unit per liter (IU/L) Standard Deviation 483.91
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) CK; Visit 2 - Month 1; n=27	-72.5 International unit per liter (IU/L) Standard Deviation 414.16
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) CK; Visit 3 - Month 3; n=24	-88.8 International unit per liter (IU/L) Standard Deviation 461.41
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) CK; Visit 4 - Month 6; n=19	-10.3 International unit per liter (IU/L) Standard Deviation 56.38
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) CK; Visit 6 - Month 12; n=15	11.9 International unit per liter (IU/L) Standard Deviation 62.40
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) CK; Visit 7-(Month 16); n=14	9.2 International unit per liter (IU/L) Standard Deviation 23.66
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) CK; Visit 8 -(Month 20); n=12	1.3 International unit per liter (IU/L) Standard Deviation 21.83
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) CK; Visit 9 -(Month 24); n=11	4.8 International unit per liter (IU/L) Standard Deviation 35.02
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) CK; Visit 10-(Month 28); n=10	2.6 International unit per liter (IU/L) Standard Deviation 27.47
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) CK; Visit 11-(Month 32); n=9	93.7 International unit per liter (IU/L) Standard Deviation 185.31
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) CK; Visit 12-(Month 36); n=4	26.3 International unit per liter (IU/L) Standard Deviation 51.06
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) CK; Study Conclusion/Withdrawal; n=27	24.7 International unit per liter (IU/L) Standard Deviation 658.19
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) CK; Follow-Up Visit; n=4	261.0 International unit per liter (IU/L) Standard Deviation 553.52
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) GGT; Visit 1-Day 1; n= 28	4.6 International unit per liter (IU/L) Standard Deviation 21.15
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) GGT; Visit 2 - Month 1; n=27	4.2 International unit per liter (IU/L) Standard Deviation 37.01
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) GGT; Visit 3 - Month 3; n=24	-4.5 International unit per liter (IU/L) Standard Deviation 24.84
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) GGT; Visit 4 - Month 6; n=19	-2.7 International unit per liter (IU/L) Standard Deviation 18.93
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) GGT; Visit 5 - Month 9; n=17	-2.5 International unit per liter (IU/L) Standard Deviation 31.07
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) GGT; Visit 6 - Month 12; n=15	-4.7 International unit per liter (IU/L) Standard Deviation 21.26
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) GGT; Visit 7-(Month 16); n=14	-3.6 International unit per liter (IU/L) Standard Deviation 20.89
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) GGT; Visit 8 - (Month 20); n=12	-13.1 International unit per liter (IU/L) Standard Deviation 29.03
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) GGT; Visit 9 - (Month 24); n=11	-6.0 International unit per liter (IU/L) Standard Deviation 29.25
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) GGT; Visit 10-(Month 28); n=10	8.3 International unit per liter (IU/L) Standard Deviation 23.32
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) GGT; Visit 11-(Month 32); n=9	24.3 International unit per liter (IU/L) Standard Deviation 32.31
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) GGT; Visit 12-(Month 36); n=4	10.0 International unit per liter (IU/L) Standard Deviation 27.48
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) GGT; StudyConclusion/Withdrawal; n=27	2.1 International unit per liter (IU/L) Standard Deviation 33.39
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) GGT; Follow-Up Visit; n=4	-3.8 International unit per liter (IU/L) Standard Deviation 9.03
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) LD; Visit 1-Day 1; n=27	-1.4 International unit per liter (IU/L) Standard Deviation 20.13

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Albumin and Total Protein Albumin; Visit 1-Day 1; n=28	-0.9 G/L Standard Deviation 2.03
Change From Baseline in Albumin and Total Protein Albumin; Visit 2 - Month 1; n=27	-0.3 G/L Standard Deviation 2.22
Change From Baseline in Albumin and Total Protein Albumin; Visit 3 - Month 3; n=24	-0.3 G/L Standard Deviation 1.85
Change From Baseline in Albumin and Total Protein Albumin; Visit 4 - Month 6; n=19	0.1 G/L Standard Deviation 2.41
Change From Baseline in Albumin and Total Protein Albumin; Visit 5 - Month 9; n=17	-0.3 G/L Standard Deviation 2.34
Change From Baseline in Albumin and Total Protein Albumin; Visit 6 - Month 12; n=15	-1.1 G/L Standard Deviation 3.02
Change From Baseline in Albumin and Total Protein Albumin; Visit 7-(Month 16); n=14	-0.7 G/L Standard Deviation 2.97
Change From Baseline in Albumin and Total Protein Albumin; Visit 8 - (Month 20); n=12	-0.6 G/L Standard Deviation 2.02
Change From Baseline in Albumin and Total Protein Albumin; Visit 9 - (Month 24); n=11	-0.3 G/L Standard Deviation 2.33
Change From Baseline in Albumin and Total Protein Albumin; Visit 10-(Month 28); n=10	-0.2 G/L Standard Deviation 2.66
Change From Baseline in Albumin and Total Protein Albumin; Visit 11-(Month 32); n=9	1.2 G/L Standard Deviation 3.77
Change From Baseline in Albumin and Total Protein Albumin; Visit 12-(Month 36); n=4	-0.3 G/L Standard Deviation 0.96
Change From Baseline in Albumin and Total Protein Albumin; Study Conclusion/Withdrawal; n=27	-0.6 G/L Standard Deviation 2.48
Change From Baseline in Albumin and Total Protein Albumin; Follow-Up Visit; n=4	-0.3 G/L Standard Deviation 2.87
Change From Baseline in Albumin and Total Protein Total protein; Visit 1-Day 1; n=28	-0.7 G/L Standard Deviation 2.84
Change From Baseline in Albumin and Total Protein Total protein; Visit 2 - Month 1; n=27	-0.7 G/L Standard Deviation 4.08
Change From Baseline in Albumin and Total Protein Total protein; Visit 3 - Month 3; n=24	0.1 G/L Standard Deviation 3.35
Change From Baseline in Albumin and Total Protein Total protein; Visit 4 - Month 6; n=19	0.5 G/L Standard Deviation 3.66
Change From Baseline in Albumin and Total Protein Total protein; Visit 5 - Month 9; n=17	-0.4 G/L Standard Deviation 3.87
Change From Baseline in Albumin and Total Protein Total protein; Visit 6 - Month 12; n=15	-0.3 G/L Standard Deviation 5.23
Change From Baseline in Albumin and Total Protein Total protein; Visit 7-(Month 16); n=14	0.6 G/L Standard Deviation 5.36
Change From Baseline in Albumin and Total Protein Total protein; Visit 8 - (Month 20); n=12	1.3 G/L Standard Deviation 4.41
Change From Baseline in Albumin and Total Protein Total protein; Visit 9 - (Month 24); n=11	2.4 G/L Standard Deviation 4.37
Change From Baseline in Albumin and Total Protein Total protein; Visit 10-(Month 28); n=10	2.5 G/L Standard Deviation 4.86
Change From Baseline in Albumin and Total Protein Total protein; Visit 11-(Month 32); n=9	3.8 G/L Standard Deviation 6.63
Change From Baseline in Albumin and Total Protein Total protein; Visit 12-(Month 36); n=4	1.8 G/L Standard Deviation 2.22
Change From Baseline in Albumin and Total Protein Total protein; Study Conclusion/Withdrawal; n=27	0.7 G/L Standard Deviation 3.52
Change From Baseline in Albumin and Total Protein Total protein; Follow-Up Visit; n=4	0.5 G/L Standard Deviation 3.00

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 6 - Month 12; n=15	5.5 Ratio Standard Deviation 13.43
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 7-(Month 16); n=14	4.2 Ratio Standard Deviation 24.49
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 8 - (Month 20); n=12	12.8 Ratio Standard Deviation 21.46
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 1-Day 1; n=28	4.2 Ratio Standard Deviation 21.83
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 2 - Month 1; n=27	6.2 Ratio Standard Deviation 20.92
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 3 - Month 3; n=24	7.0 Ratio Standard Deviation 22.03
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 4 - Month 6; n=19	7.0 Ratio Standard Deviation 18.11
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 5 - Month 9; n=17	18.11 Ratio Standard Deviation 16.40
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 9 - (Month 24); n=11	7.0 Ratio Standard Deviation 16.25
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 10-(Month 28); n=10	1.9 Ratio Standard Deviation 21.97
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 11-(Month 32); n=9	13.8 Ratio Standard Deviation 25.29
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Visit 12-(Month 36); n=4	30.0 Ratio Standard Deviation 24.04
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Study Conclusion/Withdrawal; n=27	3.1 Ratio Standard Deviation 24.50
Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio Follow-Up Visit; n=4	1.0 Ratio Standard Deviation 29.39

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 1-Day 1; n=27	-0.015 Millimoles per liter (mmol/L) Standard Deviation 0.0759
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 2 - Month 1; n=26	-0.009 Millimoles per liter (mmol/L) Standard Deviation 0.0813
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 3 - Month 3; n=24	0.017 Millimoles per liter (mmol/L) Standard Deviation 0.0586
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 4 - Month 6; n=19	0.009 Millimoles per liter (mmol/L) Standard Deviation 0.0819
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 5 - Month 9; n=17	0.020 Millimoles per liter (mmol/L) Standard Deviation 0.0742
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 6 - Month 12; n=15	-0.013 Millimoles per liter (mmol/L) Standard Deviation 0.0786
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 7-(Month 16); n=14	0.009 Millimoles per liter (mmol/L) Standard Deviation 0.0809
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 8 - (Month 20); n=12	0.013 Millimoles per liter (mmol/L) Standard Deviation 0.0628
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 9 - (Month 24); n=11	0.006 Millimoles per liter (mmol/L) Standard Deviation 0.0543
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 10-(Month 28); n=9	0.012 Millimoles per liter (mmol/L) Standard Deviation 0.0602
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 11-(Month 32); n=9	0.026 Millimoles per liter (mmol/L) Standard Deviation 0.0915
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Visit 12-(Month 36); n=4	0.013 Millimoles per liter (mmol/L) Standard Deviation 0.0171
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; StudyConclusion/Withdrawal; n=27	0.015 Millimoles per liter (mmol/L) Standard Deviation 0.0820
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Calcium; Follow-Up Visit; n=4	0.068 Millimoles per liter (mmol/L) Standard Deviation 0.0634
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 1-Day 1; n=27	-0.3 Millimoles per liter (mmol/L) Standard Deviation 2.11
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 2 - Month 1; n=26	-0.3 Millimoles per liter (mmol/L) Standard Deviation 2.94
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 3 - Month 3; n=24	-0.3 Millimoles per liter (mmol/L) Standard Deviation 3.52
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 4 - Month 6; n=19	-0.6 Millimoles per liter (mmol/L) Standard Deviation 2.80
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 5 - Month 9; n=17	-0.5 Millimoles per liter (mmol/L) Standard Deviation 2.70
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 6 - Month 12; n=15	-0.9 Millimoles per liter (mmol/L) Standard Deviation 1.44
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 7-(Month 16); n=14	-0.1 Millimoles per liter (mmol/L) Standard Deviation 2.59
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 8 - (Month 20); n=12	-0.8 Millimoles per liter (mmol/L) Standard Deviation 1.96
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 9 - (Month 24); n=11	-1.5 Millimoles per liter (mmol/L) Standard Deviation 2.58
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 10-(Month 28); n=9	-1.8 Millimoles per liter (mmol/L) Standard Deviation 1.39
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 11-(Month 32); n=9	2.4 Millimoles per liter (mmol/L) Standard Deviation 1.94
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Visit 12-(Month 36); n=4	-1.5 Millimoles per liter (mmol/L) Standard Deviation 1.91
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2content/Bicarb;Study Conclusion/Withdrawal;n=27	-1.0 Millimoles per liter (mmol/L) Standard Deviation 2.72
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN CO2 content/Bicarb; Follow-Up Visit; n=4	0.8 Millimoles per liter (mmol/L) Standard Deviation 2.36
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 1-Day 1; n=28	-0.4 Millimoles per liter (mmol/L) Standard Deviation 2.97
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 2 - Month 1; n=27	-0.2 Millimoles per liter (mmol/L) Standard Deviation 3.32
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 3 - Month 3; n=24	-0.2 Millimoles per liter (mmol/L) Standard Deviation 2.91
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 4 - Month 6; n=19	-0.3 Millimoles per liter (mmol/L) Standard Deviation 2.89
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 5 - Month 9; n=17	0.1 Millimoles per liter (mmol/L) Standard Deviation 3.22
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 6 - Month 12; n=15	0.6 Millimoles per liter (mmol/L) Standard Deviation 3.54
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 7-(Month 16); n=14	0.7 Millimoles per liter (mmol/L) Standard Deviation 3.73
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 8 - (Month 20); n=12	1.3 Millimoles per liter (mmol/L) Standard Deviation 3.70
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 9 - (Month 24); n=11	1.0 Millimoles per liter (mmol/L) Standard Deviation 3.32
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 10-(Month 28); n=10	0.9 Millimoles per liter (mmol/L) Standard Deviation 3.87
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 11-(Month 32); n=9	1.3 Millimoles per liter (mmol/L) Standard Deviation 5.32
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Visit 12-(Month 36); n=4	-1.5 Millimoles per liter (mmol/L) Standard Deviation 3.87
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; StudyConclusion/Withdrawal;n=27	-0.4 Millimoles per liter (mmol/L) Standard Deviation 3.67
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Chloride; Follow-Up Visit; n=4	-0.8 Millimoles per liter (mmol/L) Standard Deviation 2.22
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 1-Day 1; n=28	-0.42 Millimoles per liter (mmol/L) Standard Deviation 1.458
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 2 - Month 1; n=27	0.13 Millimoles per liter (mmol/L) Standard Deviation 1.554
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 3 - Month 3; n=24	0.12 Millimoles per liter (mmol/L) Standard Deviation 1.426
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 4 - Month 6; n=19	0.55 Millimoles per liter (mmol/L) Standard Deviation 1.094
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 5 - Month 9; n=17	0.32 Millimoles per liter (mmol/L) Standard Deviation 1.709
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 6 - Month 12; n=15	0.05 Millimoles per liter (mmol/L) Standard Deviation 1.477
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 7-(Month 16); n=14	1.97 Millimoles per liter (mmol/L) Standard Deviation 6.817
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 8 - (Month 20); n=12	0.08 Millimoles per liter (mmol/L) Standard Deviation 1.298
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 9 - (Month 24); n=11	0.49 Millimoles per liter (mmol/L) Standard Deviation 1.713
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 10-(Month 28); n=10	1.14 Millimoles per liter (mmol/L) Standard Deviation 2.303
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 11-(Month 32); n=9	1.13 Millimoles per liter (mmol/L) Standard Deviation 0.892
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Visit 12-(Month 36); n=4	1.75 Millimoles per liter (mmol/L) Standard Deviation 2.533
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; StudyConclusion/Withdrawal;n=27	0.72 Millimoles per liter (mmol/L) Standard Deviation 2.312
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Glucose; Follow-Up Visit; n=4	-0.30 Millimoles per liter (mmol/L) Standard Deviation 1.152
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 1-Day 1; n=28	-0.004 Millimoles per liter (mmol/L) Standard Deviation 0.0522
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 2 - Month 1; n=27	-0.017 Millimoles per liter (mmol/L) Standard Deviation 0.0716
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 3 - Month 3; n=24	-0.019 Millimoles per liter (mmol/L) Standard Deviation 0.0733
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 4 - Month 6; n=19	-0.016 Millimoles per liter (mmol/L) Standard Deviation 0.0565
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 5 - Month 9; n=17	0.006 Millimoles per liter (mmol/L) Standard Deviation 0.0662
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 6 - Month 12; n=15	0.027 Millimoles per liter (mmol/L) Standard Deviation 0.0640
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 7-(Month 16); n=14	0.041 Millimoles per liter (mmol/L) Standard Deviation 0.0434
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 8 - (Month 20); n=12	0.040 Millimoles per liter (mmol/L) Standard Deviation 0.0628
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 9 - (Month 24); n=11	0.035 Millimoles per liter (mmol/L) Standard Deviation 0.0520
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 10-(Month 28); n=10	0.058 Millimoles per liter (mmol/L) Standard Deviation 0.0692
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 11-(Month 32); n=9	0.050 Millimoles per liter (mmol/L) Standard Deviation 0.0585
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Visit 12-(Month 36); n=4	0.020 Millimoles per liter (mmol/L) Standard Deviation 0.0606
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Study Conclusion/Withdrawal;n=27	0.016 Millimoles per liter (mmol/L) Standard Deviation 0.0582
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Magnesium; Follow-Up Visit; n=4	0.053 Millimoles per liter (mmol/L) Standard Deviation 0.1424
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 1-Day 1; n=27	0.01 Millimoles per liter (mmol/L) Standard Deviation 0.277
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 2 - Month 1; n=26	-0.05 Millimoles per liter (mmol/L) Standard Deviation 0.258
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 3 - Month 3; n=24	0.00 Millimoles per liter (mmol/L) Standard Deviation 0.227
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 4 - Month 6; n=19	0.07 Millimoles per liter (mmol/L) Standard Deviation 0.341
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 5 - Month 9; n=17	0.01 Millimoles per liter (mmol/L) Standard Deviation 0.398
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 6 - Month 12; n=15	0.10 Millimoles per liter (mmol/L) Standard Deviation 0.321
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 7-(Month 16); n=14	0.06 Millimoles per liter (mmol/L) Standard Deviation 0.247
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 8 - (Month 20); n=12	0.09 Millimoles per liter (mmol/L) Standard Deviation 0.215
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 9 - (Month 24); n=11	0.08 Millimoles per liter (mmol/L) Standard Deviation 0.264
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 10-(Month 28); n=9	0.21 Millimoles per liter (mmol/L) Standard Deviation 0.318
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 11-(Month 32); n=9	-0.02 Millimoles per liter (mmol/L) Standard Deviation 0.367
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Visit 12-(Month 36); n=4	0.18 Millimoles per liter (mmol/L) Standard Deviation 0.222
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Study Conclusion/Withdrawal;n=27	-0.02 Millimoles per liter (mmol/L) Standard Deviation 0.275
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Potassium; Follow-Up Visit; n=4	0.20 Millimoles per liter (mmol/L) Standard Deviation 0.163
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 1-Day 1; n=28	-0.9 Millimoles per liter (mmol/L) Standard Deviation 3.37
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 2 - Month 1; n=27	-0.3 Millimoles per liter (mmol/L) Standard Deviation 3.48
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 3 - Month 3; n=24	0.8 Millimoles per liter (mmol/L) Standard Deviation 3.00
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 4 - Month 6; n=19	-0.3 Millimoles per liter (mmol/L) Standard Deviation 2.79
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 5 - Month 9; n=17	0.7 Millimoles per liter (mmol/L) Standard Deviation 2.52
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 6 - Month 12; n=15	0.7 Millimoles per liter (mmol/L) Standard Deviation 3.58
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 7-(Month 16); n=14	0.2 Millimoles per liter (mmol/L) Standard Deviation 4.21
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 8 - (Month 20); n=12	0.8 Millimoles per liter (mmol/L) Standard Deviation 4.13
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 9 - (Month 24); n=11	1.1 Millimoles per liter (mmol/L) Standard Deviation 2.07
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 10-(Month 28); n=10	1.3 Millimoles per liter (mmol/L) Standard Deviation 3.53
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 11-(Month 32); n=9	1.2 Millimoles per liter (mmol/L) Standard Deviation 4.74
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Visit 12-(Month 36); n=4	-2.0 Millimoles per liter (mmol/L) Standard Deviation 4.76
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; StudyConclusion/Withdrawal;n=27	0.2 Millimoles per liter (mmol/L) Standard Deviation 3.14
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Sodium; Follow-Up Visit; n=4	0.5 Millimoles per liter (mmol/L) Standard Deviation 2.08
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 1-Day 1; n=28	0.14 Millimoles per liter (mmol/L) Standard Deviation 1.176
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 2 - Month 1; n=27	0.36 Millimoles per liter (mmol/L) Standard Deviation 1.239
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 3 - Month 3; n=24	0.46 Millimoles per liter (mmol/L) Standard Deviation 1.353
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 4 - Month 6; n=19	0.37 Millimoles per liter (mmol/L) Standard Deviation 1.180
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 5 - Month 9; n=17	0.62 Millimoles per liter (mmol/L) Standard Deviation 0.884
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 6 - Month 12; n=15	0.51 Millimoles per liter (mmol/L) Standard Deviation 0.877
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 7-(Month 16); n=14	0.25 Millimoles per liter (mmol/L) Standard Deviation 1.260
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 8 - (Month 20); n=12	0.91 Millimoles per liter (mmol/L) Standard Deviation 1.372
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 9 - (Month 24); n=11	0.46 Millimoles per liter (mmol/L) Standard Deviation 1.016
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 10-(Month 28); n=10	0.39 Millimoles per liter (mmol/L) Standard Deviation 1.325
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 11-(Month 32); n=9	0.77 Millimoles per liter (mmol/L) Standard Deviation 1.578
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Visit 12-(Month 36); n=4	1.90 Millimoles per liter (mmol/L) Standard Deviation 1.971
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Study Conclusion/Withdrawal;n=27	0.18 Millimoles per liter (mmol/L) Standard Deviation 1.409
Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN Urea/BUN; Follow-Up Visit; n=4	0.25 Millimoles per liter (mmol/L) Standard Deviation 1.287

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 1-Day 1; n=28	-2.18 Micromoles per liter (µmol/L) Standard Deviation 5.860
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 2 - Month 1; n=27	-0.79 Micromoles per liter (µmol/L) Standard Deviation 6.450
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 3 - Month 3; n=24	-0.35 Micromoles per liter (µmol/L) Standard Deviation 5.360
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 4 - Month 6; n=19	-1.39 Micromoles per liter (µmol/L) Standard Deviation 6.575
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 5 - Month 9; n=17	0.32 Micromoles per liter (µmol/L) Standard Deviation 4.770
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 6 - Month 12; n=15	0.61 Micromoles per liter (µmol/L) Standard Deviation 4.837
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 7-(Month 16); n=14	-0.94 Micromoles per liter (µmol/L) Standard Deviation 6.951
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 8 - (Month 20); n=12	-0.05 Micromoles per liter (µmol/L) Standard Deviation 5.970
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 9 - (Month 24); n=11	-0.15 Micromoles per liter (µmol/L) Standard Deviation 5.095
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 10-(Month 28); n=10	4.31 Micromoles per liter (µmol/L) Standard Deviation 8.665
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 11-(Month 32); n=9	-3.30 Micromoles per liter (µmol/L) Standard Deviation 4.268
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Visit 12-(Month 36); n=4	-2.73 Micromoles per liter (µmol/L) Standard Deviation 11.099
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Study Conclusion/Withdrawal;n=27	-0.08 Micromoles per liter (µmol/L) Standard Deviation 5.467
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Creatinine; Follow-Up Visit; n=4	4.30 Micromoles per liter (µmol/L) Standard Deviation 20.628
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 1-Day 1; n=28	-0.2 Micromoles per liter (µmol/L) Standard Deviation 0.67
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 2 - Month 1; n=27	0.0 Micromoles per liter (µmol/L) Standard Deviation 0.65
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 3 - Month 3; n=24	0.0 Micromoles per liter (µmol/L) Standard Deviation 0.46
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 4 - Month 6; n=19	0.0 Micromoles per liter (µmol/L) Standard Deviation 0.58
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 5 - Month 9; n=17	-0.2 Micromoles per liter (µmol/L) Standard Deviation 0.64
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 6 - Month 12; n=15	-0.1 Micromoles per liter (µmol/L) Standard Deviation 0.35
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 7-(Month 16); n=14	-0.1 Micromoles per liter (µmol/L) Standard Deviation 0.53
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 8 - (Month 20); n=12	-0.1 Micromoles per liter (µmol/L) Standard Deviation 0.51
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 9 - (Month 24); n=11	-0.2 Micromoles per liter (µmol/L) Standard Deviation 0.75
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 10-(Month 28); n=10	-0.1 Micromoles per liter (µmol/L) Standard Deviation 0.32
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 11-(Month 32); n=9	-0.2 Micromoles per liter (µmol/L) Standard Deviation 0.44
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Visit 12-(Month 36); n=4	0.0 Micromoles per liter (µmol/L) Standard Deviation 0.82
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Study Conclusion/Withdrawal;n=27	0.0 Micromoles per liter (µmol/L) Standard Deviation 0.59
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Direct Bilirubin; Follow-Up Visit; n=4	0.3 Micromoles per liter (µmol/L) Standard Deviation 1.26
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 1-Day 1; n=28	3.0 Micromoles per liter (µmol/L) Standard Deviation 2.57
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 2 - Month 1; n=27	3.7 Micromoles per liter (µmol/L) Standard Deviation 2.69
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 3 - Month 3; n=24	3.8 Micromoles per liter (µmol/L) Standard Deviation 2.14
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 4 - Month 6; n=19	3.7 Micromoles per liter (µmol/L) Standard Deviation 2.87
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 5 - Month 9; n=17	2.8 Micromoles per liter (µmol/L) Standard Deviation 1.85
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 6 - Month 12; n=15	3.1 Micromoles per liter (µmol/L) Standard Deviation 3.03
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 7-(Month 16); n=14	3.5 Micromoles per liter (µmol/L) Standard Deviation 1.65
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 8 - (Month 20); n=12	2.8 Micromoles per liter (µmol/L) Standard Deviation 1.90
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 9 - (Month 24); n=11	2.7 Micromoles per liter (µmol/L) Standard Deviation 1.95
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 10-(Month 28); n=10	3.0 Micromoles per liter (µmol/L) Standard Deviation 2.11
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 11-(Month 32); n=9	2.6 Micromoles per liter (µmol/L) Standard Deviation 1.51
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Visit 12-(Month 36); n=4	4.5 Micromoles per liter (µmol/L) Standard Deviation 2.65
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Study Conclusion/Withdrawal;n=27	2.9 Micromoles per liter (µmol/L) Standard Deviation 2.83
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Total Bilirubin; Follow-Up Visit; n=4	2.3 Micromoles per liter (µmol/L) Standard Deviation 4.99
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 1-Day 1; n=28	-0.6 Micromoles per liter (µmol/L) Standard Deviation 31.72
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 2 - Month 1; n=27	6.3 Micromoles per liter (µmol/L) Standard Deviation 33.86
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 3 - Month 3; n=24	-5.8 Micromoles per liter (µmol/L) Standard Deviation 31.63
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 4 - Month 6; n=19	0.3 Micromoles per liter (µmol/L) Standard Deviation 32.18
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 5 - Month 9; n=17	4.3 Micromoles per liter (µmol/L) Standard Deviation 25.30
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 6 - Month 12; n=15	-5.5 Micromoles per liter (µmol/L) Standard Deviation 38.81
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 7-(Month 16); n=14	-15.0 Micromoles per liter (µmol/L) Standard Deviation 51.93
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 8 - (Month 20); n=12	-10.5 Micromoles per liter (µmol/L) Standard Deviation 45.12
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 9 - (Month 24); n=11	8.6 Micromoles per liter (µmol/L) Standard Deviation 51.81
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 10-(Month 28); n=10	6.3 Micromoles per liter (µmol/L) Standard Deviation 64.91
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 11-(Month 32); n=9	-5.2 Micromoles per liter (µmol/L) Standard Deviation 66.94
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Visit 12-(Month 36); n=4	-30.3 Micromoles per liter (µmol/L) Standard Deviation 46.50
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Study Conclusion/Withdrawal;n=26	9.7 Micromoles per liter (µmol/L) Standard Deviation 46.87
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid Uric acid; Follow-Up Visit; n=4	15.8 Micromoles per liter (µmol/L) Standard Deviation 62.74

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 1-Day 1; n=22	-0.05 Ratio Standard Deviation 1.603
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 2 - Month 1; n=19	0.16 Ratio Standard Deviation 0.932
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 3 - Month 3; n=18	1.51 Ratio Standard Deviation 5.755
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 4 - Month 6; n=14	-0.32 Ratio Standard Deviation 1.342
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 5 - Month 9; n=12	-0.26 Ratio Standard Deviation 1.006
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 6 - Month 12; n=10	9.80 Ratio Standard Deviation 31.071
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 7-(Month 16); n=8	0.69 Ratio Standard Deviation 1.733
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 8 - (Month 20); n=7	-0.24 Ratio Standard Deviation 0.547
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 9 - (Month 24); n=7	-0.34 Ratio Standard Deviation 2.070
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 10-(Month 28); n=6	0.38 Ratio Standard Deviation 1.450
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 11-(Month 32); n=6	0.87 Ratio Standard Deviation 1.519
Change From Baseline in Urine Albumin/Creatinine Ratio Visit 12-(Month 36); n=1	0.80 Ratio Standard Deviation NA NA indicates data was not available as standard deviation could not be calculated for single participant.
Change From Baseline in Urine Albumin/Creatinine Ratio Study Conclusion/Withdrawal;n=17	0.51 Ratio Standard Deviation 1.715
Change From Baseline in Urine Albumin/Creatinine Ratio Follow-Up Visit; n=5	3.30 Ratio Standard Deviation 7.044

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

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).

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day1, Glucose, 4+or 2 or more g/dL,n=30	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 1-3,n=29	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 3-5, n=29	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 5-10, n=29	6 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 10-15, n=29	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 15-25, n=29	6 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 25-50, n=29	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, RBC, 50-100, n=29	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, WBC,1-3, n=29	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, WBC,3-5, n=29	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, WBC,5-10, n=29	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, Occult Blood,1+, n=30	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, Occult Blood,4+, n=30	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 1 Day 1, protein, 1+, n=30	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, Glucose,1+ or 1/4 g/dL, n=28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, Glucose,4+or 2 or more g/dL,n=28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, Ketone 1+, n=28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, RBC, 1-3, n=27	7 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, RBC, 3-5, n=27	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, RBC, 5-10, n=27	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, RBC, 10-15, n=27	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, RBC, 15-25, n=27	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, RBC, 50-100, n=27	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1,WBC,1-3, n=27	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, WBC,3-5, n=27	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, Occult Blood,1+, n=28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 2 Month 1, protein, 1+, n=28	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, Ketones,1+, n=26	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC, 1-3, n=26	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC, 3-5, n=26	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC, 5-10, n=26	6 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC, 10-15, n=26	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC, 15-25, n=26	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC, 25-50, n=26	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, RBC,innumerable, n=26	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, WBC,1-3, n=26	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, WBC,15-25, n=26	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, WBC,innumerable, n=26	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, Occult Blood,1+, n=26	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, Occult Blood,4+, n=26	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 3 Month 3, protein, 1+, n=26	6 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, Glucose,3+ or 1 g/dL, n=19	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, RBC, 1-3, n=19	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, RBC, 3-5, n=19	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, RBC, 5-10, n=19	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6 RBC, 10-15,n=19	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, RBC, 15-25, n=19	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, RBC, 25-50, n=19	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, RBC, 50-100, n=19	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, WBC,1-3, n=19	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, WBC,3-5, n=19	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, Occult Blood,1+, n=19	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 4 Month 6, protein, 1+,n=19	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, Glucose,2+ or 1/2 g/dL, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, Glucose,3+ or 1 g/dL, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, 1-3, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, 3-5, n=17	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, 5-10, n=17	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, 10-15, n=17	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, 15-25, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, 25-50, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, RBC, innumerable, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, WBC,1-3, n=17	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, WBC,15-25, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, WBC, innumerable, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9,Occult Blood,1+, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, Occult Blood,4+, n=17	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 5 Month 9, protein, 1+, n=17	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6 Month 12, RBC, 1-3, n= 15	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6 Month 12, RBC, 3-5, n= 15	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6 Month 12, RBC, 5-10, n= 15	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6 Month 12, RBC, 10-15, n= 15	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6 Month 12, RBC, 15-25, n= 15	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6, Month 12, WBC, 1-3, n= 15	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6, Month 12, WBC, 3-5, n= 15	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6, Month 12, Occult blood, 1+, n= 15	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6, Month 12, Protein, 1+, n= 15	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 6, Month 12, Protein, 2+, n= 15	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7,Month16,Glucose, 4+ or 2 or more g/dL,n=14	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, Ketone, 1+, n= 14	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, RBC, 1-3, n= 13	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, RBC, 3-5, n= 13	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, RBC, 5-10, n= 13	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, RBC, 10-15, n= 13	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, RBC, 25-50, n= 13	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, WBC, 1-3, n= 13	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, WBC, 3-5, n= 13	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, Occult blood, 1+, n= 14	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, Occult blood, 4+, n= 14	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 7, Month 16, Protein, 1+, n= 14	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, RBC, 1-3, n= 12	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, RBC, 3-5, n= 12	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, RBC, 10-15, n= 12	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, RBC, 15-25, n= 12	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, RBC, 25-50, n= 12	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, WBC, 1-3, n= 12	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, WBC, 3-5, n= 12	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 8, Month 20, Occult blood, 1+, n= 12	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9,Month24,Glucose,4+ or 2 or more g/dL,n=11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, RBC, 1-3, n= 11	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, RBC, 3-5, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, RBC, 5-10, n= 11	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, RBC, 10-15, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, RBC, 50-100, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, WBC, 3-5, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, WBC, Innumerable, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, Occult blood, 1+, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, Occult blood, 4+, n= 11	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, Protein, 1+, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 9, Month 24, Protein, 2+, n= 11	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10,Month28,Glucose,4+ or 2 or more g/dL,n=10	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, RBC, 1-3, n= 9	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, RBC, 3-5, n= 9	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, RBC, 5-10, n= 9	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, RBC, 25-50, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, WBC, 1-3, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, Occult blood, 1+, n= 10	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 10, Month 28, Protein, 1+, n= 10	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11,Month 32,Glucose,4+ or 2 or more g/dL,n=9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, RBC, 3-5, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, RBC, 5-10, n= 9	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, RBC, 10-15, n= 9	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, RBC, 25-50, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, RBC, 50-100, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, WBC, 1-3, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, WBC, 10-15, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, WBC, innumerable, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, Occult blood, 1+, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, Occult blood, 2+, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 11, Month 32, Occult blood, 4+, n= 9	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 12,Month 36,Glucose,4+ or 2 or more g/dL,n=4	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 12, Month 36, RBC, 3-5, n= 4	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 12, Month 36, RBC, 5-10, n= 4	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Visit 12, Month 36, Occult blood, 1+, n= 4	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal,Glucose,3+or1g/dL,n=28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal,Glucose,4+or2g/dL,n=28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, Ketones, trace, n= 28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, RBC, 1-3, n= 28	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, RBC, 3-5, n= 28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, RBC, 5-10, n= 28	7 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, RBC, 10-15, n= 28	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, RBC, 15-25, n= 28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, RBC, 25-50, n= 28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, WBC, 1-3, n= 28	4 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, WBC, 3-5, n= 28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, WBC, 5-10, n= 28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, WBC 10-15, n= 28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, WBC 15-25, n= 28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, Occult blood,1+ n= 28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, Occult blood,2+ n= 28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, Occult blood,4+ n= 28	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, Protein, trace, n= 28	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Study conclusion/Withdrawal, Protein, 1+, n= 28	5 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Follow up, Ketones, trace, n= 5	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Follow up, RBC, 1-3, n= 5	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Follow up, RBC, 5-10, n= 5	2 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Follow up, WBC, 1-3, n= 5	3 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Follow up, WBC, 10-15, n= 5	1 Participants
Number of Participants With Abnormal Urinalysis Values (Categorical Data) Follow up, Protein, 1+, n= 5	1 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

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).

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Specific Gravity of Urine at Indicated Time Points Visit 1-Day 1; n=30	1.0160 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00423
Specific Gravity of Urine at Indicated Time Points Visit 2 - Month 1; n=28	1.0157 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00522
Specific Gravity of Urine at Indicated Time Points Visit 3 - Month 3; n=26	1.0187 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00437
Specific Gravity of Urine at Indicated Time Points Visit 4 - Month 6; n=19	1.0161 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00542
Specific Gravity of Urine at Indicated Time Points Visit 5 - Month 9; n=17	1.0153 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00413
Specific Gravity of Urine at Indicated Time Points Visit 6 - Month 12; n=15	1.0157 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00458
Specific Gravity of Urine at Indicated Time Points Visit 7-(Month 16); n=14	1.0146 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00414
Specific Gravity of Urine at Indicated Time Points Visit 8 - (Month 20); n=12	1.0158 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00359
Specific Gravity of Urine at Indicated Time Points Visit 9 - (Month 24); n=11	1.0145 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00350
Specific Gravity of Urine at Indicated Time Points Visit 10-(Month 28); n=10	1.0140 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00459
Specific Gravity of Urine at Indicated Time Points Visit 11-(Month 32); n=9	1.0139 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00486
Specific Gravity of Urine at Indicated Time Points Visit 12-(Month 36); n=4	1.0150 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00408
Specific Gravity of Urine at Indicated Time Points Study Conclusion/Withdrawal;n=28	1.0166 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00409
Specific Gravity of Urine at Indicated Time Points Follow-Up Visit; n=5	1.0198 Kilograms per meter^3 (Kg/m^3) Standard Deviation 0.00476

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

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).

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Potential of Hydrogen (pH) of Urine at Indicated Time Points Follow-Up Visit; n=5	6.10 Scores on a scale Standard Deviation 0.548
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 1-Day 1; n=30	6.68 Scores on a scale Standard Deviation 0.771
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 2 - Month 1; n=28	6.48 Scores on a scale Standard Deviation 0.659
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 3 - Month 3; n=26	6.35 Scores on a scale Standard Deviation 0.784
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 4 - Month 6; n=19	6.39 Scores on a scale Standard Deviation 0.756
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 5 - Month 9; n=17	6.74 Scores on a scale Standard Deviation 0.640
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 6 - Month 12; n=15	6.40 Scores on a scale Standard Deviation 0.828
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 7-(Month 16); n=14	6.54 Scores on a scale Standard Deviation 0.746
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 8 - (Month 20); n=12	6.71 Scores on a scale Standard Deviation 0.620
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 9 - (Month 24); n=11	6.86 Scores on a scale Standard Deviation 1.051
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 10-(Month 28); n=10	6.80 Scores on a scale Standard Deviation 0.919
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 11-(Month 32); n=9	6.78 Scores on a scale Standard Deviation 0.667
Potential of Hydrogen (pH) of Urine at Indicated Time Points Visit 12-(Month 36); n=4	6.88 Scores on a scale Standard Deviation 0.250
Potential of Hydrogen (pH) of Urine at Indicated Time Points Study Conclusion/Withdrawal;n=28	6.52 Scores on a scale Standard Deviation 0.687

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Urine Creatinine Concentration Visit 1-Day 1; n=30	-1803.3 µmol/L Standard Deviation 6012.94
Change From Baseline in Urine Creatinine Concentration Visit 2 - Month 1; n=27	-1725.9 µmol/L Standard Deviation 6632.88
Change From Baseline in Urine Creatinine Concentration Visit 3 - Month 3; n=25	-508.0 µmol/L Standard Deviation 6155.28
Change From Baseline in Urine Creatinine Concentration Visit 4 - Month 6; n=19	-94.7 µmol/L Standard Deviation 7902.92
Change From Baseline in Urine Creatinine Concentration Visit 5 - Month 9; n=17	-58.8 µmol/L Standard Deviation 6676.18
Change From Baseline in Urine Creatinine Concentration Visit 6 - Month 12; n=15	-286.7 µmol/L Standard Deviation 3000.21
Change From Baseline in Urine Creatinine Concentration Visit 7-(Month 16); n=14	-235.7 µmol/L Standard Deviation 3996.27
Change From Baseline in Urine Creatinine Concentration Visit 8 - (Month 20); n=12	-341.7 µmol/L Standard Deviation 7648.46
Change From Baseline in Urine Creatinine Concentration Visit 9 - (Month 24); n=11	-81.8 µmol/L Standard Deviation 5230.07
Change From Baseline in Urine Creatinine Concentration Visit 10-(Month 28); n=10	4940.0 µmol/L Standard Deviation 9857.11
Change From Baseline in Urine Creatinine Concentration Visit 11-(Month 32); n=9	2944.4 µmol/L Standard Deviation 6495.98
Change From Baseline in Urine Creatinine Concentration Visit 12-(Month 36); n=3	1000.0 µmol/L Standard Deviation 11887.39
Change From Baseline in Urine Creatinine Concentration Study Conclusion/Withdrawal;n=27	-1781.5 µmol/L Standard Deviation 5805.11
Change From Baseline in Urine Creatinine Concentration Follow-Up Visit; n=5	7100.0 µmol/L Standard Deviation 4959.33

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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).

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 1-Day 1; n=29	-0.5 Scores on a scale Standard Deviation 2.68
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 2-Month 1; n=28	0.3 Scores on a scale Standard Deviation 2.37
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 3 - Month 3; n=25	-0.3 Scores on a scale Standard Deviation 2.41
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 6 - Month 12; n=15	-0.7 Scores on a scale Standard Deviation 1.58
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 7-(Month 16); n=1	-2.0 Scores on a scale Standard Deviation NA NA indicates data was not available as standard deviation could not be calculated for single participant.
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 9 - (Month 24); n=10	-0.1 Scores on a scale Standard Deviation 5.20
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 12-(Month 36); n=4	3.0 Scores on a scale Standard Deviation 5.48
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Visit 13 (Month 40); n=1	0.0 Scores on a scale Standard Deviation NA NA indicates data was not available as standard deviation could not be calculated for single participant.
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Study Conclusion/Withdrawal;n=29	1.1 Scores on a scale Standard Deviation 4.45
Change From Baseline in American Urological Association (AUA) Symptom Scale Scores Follow-Up Visit; n=5	1.2 Scores on a scale Standard Deviation 3.56

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 1-Day 1; n=29	-3.4 Milliliter (mL) Standard Deviation 36.38
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 2 - Month 1; n=28	9.2 Milliliter (mL) Standard Deviation 24.66
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 3 - Month 3; n=25	2.0 Milliliter (mL) Standard Deviation 39.72
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 6 - Month 12; n=15	1.7 Milliliter (mL) Standard Deviation 30.67
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 7-(Month 16); n=1	-8.0 Milliliter (mL) Standard Deviation NA NA indicates data was not available as standard deviation could not be calculated for single participant.
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 9 - (Month 24); n=10	-8.2 Milliliter (mL) Standard Deviation 36.79
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 12-(Month 36); n=4	-13.1 Milliliter (mL) Standard Deviation 31.50
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Visit 13 (Month 40); n=1	35.0 Milliliter (mL) Standard Deviation NA NA indicates data was not available as standard deviation could not be calculated for single participant.
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Study Conclusion/Withdrawal;n=29	-1.7 Milliliter (mL) Standard Deviation 31.01
Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes Follow-Up Visit; n=3	-22.0 Milliliter (mL) Standard Deviation 53.70

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

Number of participants with suicidal ideation or behavior during treatment were assessed using the C-SSRS score scale. It is a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. 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").

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal ideation	1 Participants
Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal behavior	0 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

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

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Number of Participants Who Discontinued From RTG Day 1007	1 Participants
Number of Participants Who Discontinued From RTG Day 1008	1 Participants
Number of Participants Who Discontinued From RTG Day 1098	0 Participants
Number of Participants Who Discontinued From RTG Day 0	0 Participants
Number of Participants Who Discontinued From RTG Day 3	1 Participants
Number of Participants Who Discontinued From RTG Day 17	1 Participants
Number of Participants Who Discontinued From RTG Day 62	1 Participants
Number of Participants Who Discontinued From RTG Day 66	1 Participants
Number of Participants Who Discontinued From RTG Day 98	1 Participants
Number of Participants Who Discontinued From RTG Day 111	1 Participants
Number of Participants Who Discontinued From RTG Day 126	1 Participants
Number of Participants Who Discontinued From RTG Day 163	1 Participants
Number of Participants Who Discontinued From RTG Day 168	2 Participants
Number of Participants Who Discontinued From RTG Day 169	1 Participants
Number of Participants Who Discontinued From RTG Day 229	1 Participants
Number of Participants Who Discontinued From RTG Day 240	1 Participants
Number of Participants Who Discontinued From RTG Day 287	1 Participants
Number of Participants Who Discontinued From RTG Day 339	1 Participants
Number of Participants Who Discontinued From RTG Day 413	1 Participants
Number of Participants Who Discontinued From RTG Day 498	1 Participants
Number of Participants Who Discontinued From RTG Day 559	1 Participants
Number of Participants Who Discontinued From RTG Day 650	1 Participants
Number of Participants Who Discontinued From RTG Day 781	1 Participants
Number of Participants Who Discontinued From RTG Day 852	1 Participants
Number of Participants Who Discontinued From RTG Day 927	1 Participants
Number of Participants Who Discontinued From RTG Day 930	0 Participants
Number of Participants Who Discontinued From RTG Day 943	0 Participants
Number of Participants Who Discontinued From RTG Day 1169	0 Participants
Number of Participants Who Discontinued From RTG Day 1233	0 Participants

PRIMARY outcome

Timeframe: Up to 4 years

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

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.

Outcome measures

Outcome measures
Measure	RTG IR n=22 Participants 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.
Percentage of Participants With Retinal Pigmentary Abnormalities	18 Percentage of participants

PRIMARY outcome

Timeframe: Up to 4 years

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

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.

Outcome measures

Outcome measures
Measure	RTG IR n=22 Participants 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.
Percentage of Participants With Pigmentation of Non-retinal Ocular Tissues	32 Percentage of participants

PRIMARY outcome

Timeframe: Up to 4 years

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

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

Outcome measures

Outcome measures
Measure	RTG IR n=25 Participants 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.
Percentage of Participants With Dermatologist-confirmed Abnormal Discoloration	0 Percentage of participants

PRIMARY outcome

Timeframe: Up to 4 years

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

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.

Outcome measures

Outcome measures
Measure	RTG IR n=19 Participants 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.
Percentage of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination	16 Percentage of participants

PRIMARY outcome

Timeframe: Up to 4 years

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

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

Outcome measures

Outcome measures
Measure	RTG IR n=19 Participants 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.
Percentage of Participants With Decrease in Confrontational Visual Field From Initial Examination	21 Percentage of participants

PRIMARY outcome

Timeframe: Up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Percentage of Responders to POS Frequency	23 Percentage of responders

PRIMARY outcome

Timeframe: Baseline and up to 4 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	RTG IR n=30 Participants 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.
Percent Change From Baseline in 28-day Total POS Frequency	-29.37 Percent change Standard Deviation 58.363

PRIMARY outcome

Timeframe: Up to 1.4 years

Population: All SFUCP Subjects

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.

Outcome measures

Outcome measures
Measure	RTG IR n=4 Participants 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.
Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of RTG Retinal pigmentary abnormality	0 Participants
Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of RTG Non-retinal ocular pigmentary abnormality	0 Participants

PRIMARY outcome

Timeframe: Up to 1.4 years

Population: All SFUCP Subjects

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.

Outcome measures

Outcome measures
Measure	RTG IR n=4 Participants 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.
Number of Participants With Resolution of Dermatologist-confirmed Abnormal Discoloration After Discontinuation of RTG	0 Participants

Adverse Events

RTG IR

Serious events: 5 serious events

Other events: 23 other events

Deaths: 0 deaths

RTG in SFUCP

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RTG IR n=30 participants at risk 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.	RTG in SFUCP n=4 participants at risk 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.
Eye disorders Diabetic retinopathy	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Eye disorders Vitreous haemorrhage	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Infections and infestations Endophthalmitis	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Metabolism and nutrition disorders Hypoglycaemia	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Postictal state	3.3% 1/30 • Number of events 2 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Cerebral haematoma	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Dizziness	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Headache	3.3% 1/30 • Number of events 1 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.

Other adverse events

Other adverse events
Measure	RTG IR n=30 participants at risk 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.	RTG in SFUCP n=4 participants at risk 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.
Eye disorders Retinal pigmentation	6.7% 2/30 • Number of events 2 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Eye disorders Vision blurred	6.7% 2/30 • Number of events 2 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
General disorders Fatigue	6.7% 2/30 • Number of events 2 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
General disorders Asthenia	10.0% 3/30 • Number of events 3 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Infections and infestations Upper respiratory tract infection	6.7% 2/30 • Number of events 2 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Infections and infestations Nasopharyngitis	10.0% 3/30 • Number of events 3 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Memory impairment	10.0% 3/30 • Number of events 3 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Headache	13.3% 4/30 • Number of events 4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Somnolence	30.0% 9/30 • Number of events 10 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Nervous system disorders Dizziness	36.7% 11/30 • Number of events 16 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.
Skin and subcutaneous tissue disorders Rash macular	6.7% 2/30 • Number of events 2 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.	0.00% 0/4 • 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. AEs and SAEs were collected in "Safety Population" for RTG IR arm and in "All SFUCP Subjects Population" for RTG in SFUCP arm.

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