Study in Pediatric Subjects With Epilepsy

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01494584
• Collaborator: Bausch Health Americas, Inc. (Industry)
• Enrollment: 5
• Locations: 4
• Arm: 1
• Actual Duration (Months): 9.1
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label study to evaluate the pharmacokinetics, safety and tolerability of ezogabine/retigabine in subjects aged 12 years to less than 18 years with uncontrolled partial onset seizures or Lennos-Gastaut syndrome.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: ezogabine/retigabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Multiple Dose Study to Evaluate the Parmacokinetics, Safety and Tolerability of Ezogabine/Retigabine as Adjunctive Treatment in Subjects Aged From 12 Years to Less Than 18 Years With Partial Onset Seizures or Lennox-Gastaut Syndrome
• Actual Study Start Date: Jul 25, 2012
• Actual Primary Completion Date: Apr 29, 2013
• Actual Study Completion Date: Apr 29, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ezogabine/retigabine ezogabine dose escalation	Drug: ezogabine/retigabine; ezogabine dose escalation

Outcome Measures

Primary Outcome Measures

1. The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

   The steady state pharmacokinetic profile following oral administration of ezogabine/retigabine included determining the area under the curve over the dosing interval (AUC[0-tau]). The area under the plasma concentration-time curve over the dosing interval (AUC[0-tau]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate AUC(0-tau).

2. Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

   Clearance (CL/F) is defined as dose/AUC(0-tau). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate CL/F.

3. Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

   Cmax is defined as the first occurrence of the maximum observed plasma concentration. Ctau refers to the pre-dose (trough) concentration after the dosing interval which is equal to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate Cmax and Ctau.

4. Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

   The volume of distribution (Vd/F) is defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate the apparent volume of distribution.

Secondary Outcome Measures

1. Number of Participants With Any Adverse Event (AE) [From the start of the first titration until follow-up (assessed up to 46 days)]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

2. Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

3. Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

4. Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

5. Change From Baseline in Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (BUN) at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

6. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC [Total Absolute Neutrophil Count]), Platelet Count, and White Blood Cell Count at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

7. Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

8. Change From Baseline in Hematocrit at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. The International System of Units (SI) "Fraction of one unit (1)" is reported here.

9. Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

   Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

10. Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

    Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

11. Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration [Baseline (Screening), Day 7, Day 21, and Day 35]

    Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.

12. Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up [Screening, Day 1 (D1), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), Day 35 (D35), and at the Follow-up Visit (up to Day 46)]

    Urinalysis parameters analyzed included: urine occult blood (UOB), urine glucose (UG), urine ketones (UK), and urine protein (UP). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test provides results in a semi-quantitative manner, and results can be read as negative (Neg), Trace, and 80, indicating proportional concentrations in the urine sample. Urinalysis parameters were assessed at Titration 1 (T1; 300 mg/day), Titration 2 (T2; 450 mg/day), Titration 3 (T3; 600 mg/day), Titration 4 (T4; 750 mg/day), and Titration 5 (T5; 900 mg/day).

13. Percent Change From Baseline in 28-day Seizure Frequency Rate [Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)]

    Participants or their caregivers recorded the number of seizures experienced by the participant, by seizure type (e.g., simple partial seizure [seizure that affects only a small region of the brain; consciousness is unaffected], complex partial seizure [seizure associated with unilateral cerebral hemisphere involvement and causing impairment of awareness or responsiveness], etc.), as well as by duration of episodes of innumerable seizure activity, in their daily diaries during all phases of this study. Percent change from baseline is defined as 100 * (rate in a given period minus the baseline rate) / (baseline rate). baseline seizures are defined as those seizures that occurred after Screening and before the start of the treatment. Post-baseline seizures are defined as those seizures that occurred from the start of the treatment until the start of Follow-up. Seizure frequency rate was computed as: 28 * (number of seizures during given period / number of days in given period).

14. Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t]) for the N-acetyl Metabolite of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

    The area under the curve was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the plasma n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.

15. Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) for the N-acetyl Metabolite of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

    Ctau refers to the pre-dose (trough) concentration at the end of the dosing interval which is equivalent to the minimum observed concetration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the Ctau for n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.

16. Time to Maximum Concentration (Tmax) Following Oral Administration of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

    Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma Tmax.

17. Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine [Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35]

    Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma t1/2. Steady-state t1/2 is derived as (Vd/F) / (CL/F), where Vd/F is defined as the apparent volume of distribution after extravascular (e.g., oral) administration, and CL/F is defined as the apparent clearance following oral dosing.

18. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Baseline (Screening) and Day 7 post up-titration, up to Day 35]

    An ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate (QTc intervals) was used. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). ECG parameters were assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose, and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. The number of participants with abnormal (Abn) clinically significant (CS) and not clinically significant (NCS) ECG findings was recorded. The investigator determined if an ECG finding was CS or NCS.

19. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points [Baseline (Screening) and Day 7 post up-titration, up to Day 35]

    Vital sign assessment included the measurement of systolic and diastolic blood pressure at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), Day 7 pre-dose, and 3 h post dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): Day 21 pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): Day 35 pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value.

20. Change From Baseline in Heart Rate (HR) [Baseline (Screening) and Day 7 post up-titration, up to Day 35]

    Vital sign assessment included heart rate measurement and was assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value.

21. Change From Baseline in Post Void Residual Ultrasound at Day 21 [Screening and Day 7 of Titration 3 (Day 21)]

    A post void residual (PVR) bladder ultrasound was carried out as a measure of bladder function. PVR was clinically indicated following the occurrence of adverse events relating to the lower urinary tract (e.g., micturition difficulties, including urinary hesitancy or urinary retention). These assessments were also repeated following drug withdrawal following such events. A prompt follow-up PVR was recommended if a high score was obtained from a participant on the Pediatric Lower Urinary Tract Symptom scale (the PLUTS scale is a clinician-rated scale used to assess lower urinary tract symptoms, including urinary retention) and if the clinician felt that the participant was at risk or had symptoms of urinary retention. PVR was measured at Day 7 of Titration 3 (600 mg/day). Baseline is defined as the Screening visit.

22. Number of Participants With the Indicated Neurological Abnormality [Screening and Day 7 of Titration 3 (Day 21)]

    Abnormal Central Nervous System (CNS) symptoms were assessed by a full and brief neurological examination. A full neurological examination included assessment of mental status, cranial nerves, gait, coordination, sensation, speech/language, muscle strength, muscle tone, and reflexes. A brief neurological examination included assessment of mental status, cranial nerves, gait, coordination, reflexes, and speech/language. Neurological parameters assessed were memory impairment, impaired intellect, decreased attention, psychomotor slowing, decreased muscle strength, hpertonia, somnolence, right and left bicpes, right and left brachioradialis, right and left knee, right and left ankle, and right and left planter response. Neurological examination was performed at Day 7 of Titration 3 (600 mg/day).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Between 12 and 18 years of age.

• Diagnosis of uncontrolled partial onset seizures (with or without secondarily generalized seizures) or Lennox-Gastaut syndrome.

• Taking between one and three antiepileptic drugs.

• Able to swallow tablets.

• Females must be of : (1) Non-childbearing potential or (2) Child-bearing potential and agrees to use acceptable contraception.

Exclusion Criteria:

• Epilepsy secondary to progressive cerebral disease, tumor or any progressive neurodegenerative disease.

• History of status epilepticus in the last six months.

• Currently treated with felbamate or has been treated with vigabatrin within the past 6 months.

• Following the ketogenic diet.

• Suicidal intent or history of suicide attempt in the last 2 years.

• Elevated liver enzymes or abnormal kidney function.

• Current disturbance of micturition or known urinary obstructions.

• History of vesicoureteric reflux.

• Abnormal post-void residual bladder ultrasound.

• Urinary retention and/or required urinary catheterization in the preceding 6 months.

• Abnormal urine sample at screening/.baseline.

• Abnormal blood sample at screening.

• Clinically significant arrhythmias.

• Abnormal ECG at screening.

• BMI lower than the 10th percentile for age and gender or subject weighs less than 30kg.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Los Angeles	California	United States	90027
2	GSK Investigational Site	Wellington	Florida	United States	33414
3	GSK Investigational Site	Memphis	Tennessee	United States	38105
4	GSK Investigational Site	Dallas	Texas	United States	75230-2507

Sponsors and Collaborators

• GlaxoSmithKline
• Bausch Health Americas, Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Tompson DJ, Buraglio M, Andrews SM, Wheless JW. Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability. J Pediatr Pharmacol Ther. 2016 Sep-Oct;21(5):404-412.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01494584
• Other Study ID Numbers: 113284
• First Posted: Dec 19, 2011
• Last Update Posted: Nov 30, 2020
• Last Verified: Nov 1, 2020

• Additional relevant MeSH terms: Epilepsy; Ezogabine

Study Results

Participant Flow

Recruitment Details	Enrolled participants (par.) were aged 12 years to less than 18 years with partial onset seizures or Lennox-Gastaut syndrome (LGS), and were required to be on at least 1 but not more than 3 anti-epileptic therapies without achieving complete control of their seizures.
Pre-assignment Detail	A total of 5 par. who met the eligibility criteria were assigned to Regimen A (>50 kilograms [kg]) or B (30 to <=50 kg) based on body weight and entered a 2-week Screening phase, followed by a dosing phase (up to 5 weeks). Upon completion of the dosing phase, par. either entered a follow-up phase or a separate extension study.

Arm/Group Title	Ezogabine/Retigabine
Arm/Group Description	Participants recieved an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ezogabine/Retigabine
Arm/Group Description	Participants received an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Overall Participants	5
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	14.6 (1.34)
Sex: Female, Male (Count of Participants)
Female	1 20%
Male	4 80%
Race/Ethnicity, Customized (Number) [Number]
White-White/Caucasian/European Heritage	5 100%

Outcome Measures

1. Primary Outcome

Title	The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine
Description	The steady state pharmacokinetic profile following oral administration of ezogabine/retigabine included determining the area under the curve over the dosing interval (AUC[0-tau]). The area under the plasma concentration-time curve over the dosing interval (AUC[0-tau]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate AUC(0-tau).
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population: all participants in the All Subjects Population (defined as all participants who received at least one dose of study medication) for whom a pharmacokinetic sample was obtained and analyzed

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants (par.) with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Geometric Mean (95% Confidence Interval) [Hour*Nanograms/Milliliter (h.ng/mL)]	1680.0	2558.8	3783.8

2. Primary Outcome

Title	Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine
Description	Clearance (CL/F) is defined as dose/AUC(0-tau). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate CL/F.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Geometric Mean (95% Confidence Interval) [Liters/Hour]	178.6	234.5	237.9

3. Primary Outcome

Title	Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine
Description	Cmax is defined as the first occurrence of the maximum observed plasma concentration. Ctau refers to the pre-dose (trough) concentration after the dosing interval which is equal to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate Cmax and Ctau.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Cmax	370.0	535.9	750.9
Ctau	105.32	199.77	287.48

4. Primary Outcome

Title	Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine
Description	The volume of distribution (Vd/F) is defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate the apparent volume of distribution.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	3	3	1
Geometric Mean (95% Confidence Interval) [Liters]	1130.9	2118.0	1934.3

5. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE)
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Time Frame	From the start of the first titration until follow-up (assessed up to 46 days)

Outcome Measure Data

Analysis Population Description

All Subjects Population: all participants who received at least one dose of study medication

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300 mg	Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an uptitrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	5	4	4	3
Number [Participants]	1 20%	1 NaN	1 NaN	0 NaN	0 NaN

6. Secondary Outcome

Title	Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Albumin, n=4, 4, 3	-3.8 (0.96)	-3.0 (3.46)	-0.7 (3.06)
Total protein, n=4, 4, 3	-4.0 (2.94)	-3.5 (3.79)	-0.7 (5.03)

7. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Alkaline phosphatse, n=4, 4, 3	-5.8 (16.17)	10.3 (35.93)	5.0 (6.93)
Alanine amino transferase, n=4, 4, 3	-2.0 (2.16)	35.0 (74.02)	-1.0 (2.00)
Aspartate amino transferase, n=4, 4, 3	-0.8 (2.50)	10.8 (17.75)	1.7 (3.21)
Gamma glutamyl transferase, n=3, 3, 2	-1.3 (0.58)	111.0 (181.06)	50.5 (47.38)

8. Secondary Outcome

Title	Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Direct bilirubin, n=1, 2, 1	2.7360 (NA)	2.7360 (3.86929)	-0.8550 (NA)
Total bilirubin, n=4, 4, 3	0.855 (2.2076)	2.138 (2.5650)	4.560 (0.9873)
Creatinine, n=4, 4, 3	1.3260 (1.14124)	-4.1990 (5.02015)	0.5893 (3.34677)
Uric acid, n=4, 3, 1	16.3570 (19.04289)	15.8613 (36.34288)	23.7920 (NA)

9. Secondary Outcome

Title	Change From Baseline in Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (BUN) at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Calcium, n=4, 4, 3	0.00624 (0.062375)	-0.04366 (0.117689)	0.02495 (0.194866)
Chloride, n=4, 4, 3	1.8 (0.96)	3.0 (0.82)	3.0 (1.73)
Carbon dioxide content/bicarbonate, n=4, 4, 3	0.8 (3.50)	-1.5 (1.73)	-2.7 (2.08)
Glucose, n=4, 4, 3	0.69388 (1.184069)	0.15265 (0.821317)	0.29605 (0.279394)
Potassium, n=4, 4, 3	0.08 (0.206)	0.17 (0.574)	0.20 (0.624)
Sodium, n=4, 4, 3	1.8 (0.50)	2.0 (1.83)	2.3 (3.06)
Inorganic phosphorus, n=4, 3, 1	-0.39555 (0.727481)	-0.04305 (0.189202)	0.09687 (NA)
Urea/BUN, n=4, 4, 3	-0.3570 (1.23668)	0.7140 (0.71400)	1.3090 (0.74315)

10. Secondary Outcome

Title	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC [Total Absolute Neutrophil Count]), Platelet Count, and White Blood Cell Count at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Basophils, n=3, 3, 2	0.03 (0.062)	0.04 (0.053)	0.00 (0.006)
Eosinophils, n=3, 3, 2	0.07 (0.059)	0.09 (0.200)	0.10 (0.005)
Lymphocytes, n=3, 3, 2	14.77 (26.358)	-0.45 (0.654)	-0.65 (0.918)
Monocytes, n=3, 3, 2	-0.04 (0.347)	0.09 (0.101)	0.05 (0.065)
Total neutrophils, n=3, 3, 2	14.90 (24.176)	-0.11 (0.370)	0.61 (0.263)
Platelet count, n=4, 4, 3	-17.0 (40.12)	-15.8 (34.32)	-1.3 (17.16)
White blood cell count, n=4, 4, 3	0.393 (1.2125)	-0.600 (0.6272)	-0.583 (1.3345)

11. Secondary Outcome

Title	Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Hemoglobin, n=4, 4, 3	-3.0 (4.90)	-10.3 (6.85)	-2.0 (4.36)
Mean corpuscle hemoglobin concentration, n=4, 4, 3	-2.5 (2.38)	0.3 (10.59)	-6.7 (4.93)

12. Secondary Outcome

Title	Change From Baseline in Hematocrit at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. The International System of Units (SI) "Fraction of one unit (1)" is reported here.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	4	4	3
Mean (Standard Deviation) [Fraction of one unit (1)]	-0.0057 (0.01452)	-0.0303 (0.02198)	0.0017 (0.1201)

13. Secondary Outcome

Title	Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	4	4	3
Mean (Standard Deviation) [Picograms (PG) per cell (PG/cell)]	-0.07 (0.126)	0.15 (0.569)	-0.23 (0.153)

14. Secondary Outcome

Title	Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	4	4	3
Mean (Standard Deviation) [Femtoliters (FL)]	0.52 (1.056)	0.45 (1.034)	1.00 (1.000)

15. Secondary Outcome

Title	Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration
Description	Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Time Frame	Baseline (Screening), Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	4	4	3
Mean (Standard Deviation) [10^12 cells/L (TI/L)]	-0.090 (0.1463)	-0.357 (0.2304)	-0.030 (0.1136)

16. Secondary Outcome

Title	Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up
Description	Urinalysis parameters analyzed included: urine occult blood (UOB), urine glucose (UG), urine ketones (UK), and urine protein (UP). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test provides results in a semi-quantitative manner, and results can be read as negative (Neg), Trace, and 80, indicating proportional concentrations in the urine sample. Urinalysis parameters were assessed at Titration 1 (T1; 300 mg/day), Titration 2 (T2; 450 mg/day), Titration 3 (T3; 600 mg/day), Titration 4 (T4; 750 mg/day), and Titration 5 (T5; 900 mg/day).
Time Frame	Screening, Day 1 (D1), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), Day 35 (D35), and at the Follow-up Visit (up to Day 46)

Outcome Measure Data

Analysis Population Description

All Subjects Population (ASP). Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X in the category titles). Different participants may have been analyzed at different time points and for different parameters, so the overall number of participants analyzed reflects everyone in the ASP.

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300 mg	Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an up-titrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of>50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	5	4	4	3
UOB, T1, D1, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T1, D1, Negative, n=5, 0, 0, 0, 0	4 80%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T1, D1, Trace, n=5, 0, 0, 0, 0	1 20%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T1, D7, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T1, D7, Negative, n=5, 0, 0, 0, 0	4 80%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T1, D7, Trace, n=5, 0, 0, 0, 0	1 20%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T2, D7, 80, n=0, 5, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T2, D7, Negative, n=0, 5, 0, 0, 0	0 0%	5 NaN	0 NaN	0 NaN	0 NaN
UOB, T2, D7, Trace, n=0, 5, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T3, D7, 80, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T3, D7, Negative, n=0, 0, 4, 0, 0	0 0%	0 NaN	3 NaN	0 NaN	0 NaN
UOB, T3, D7, Trace, n=0, 0, 4, 0, 0	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
UOB, T3, D14, 80, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T3,D14, Negative, n=0, 0, 1, 0, 0	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
UOB, T3, D14, Trace, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
Urine Occult Blood, T4, D7, 80, n=0,0,0,3,0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T4, D7, Negative, n=0, 0, 0, 3, 0	0 0%	0 NaN	3 NaN	0 NaN	0 NaN
Urine Occult Blood, T4, D7, Trace, n=0,0,0,3,0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T5, D7, 80, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UOB, T5, D7, Negative, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	2 NaN
UOB, T5, D7, Trace, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	1 NaN
UG, T1, D1, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T1, D1, Negative, n=5, 0, 0, 0, 0	5 100%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T1, D1, Trace, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T1, D7, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T1, D7, Negative, n=5, 0, 0, 0, 0	5 100%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T1, D7, Trace, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T2, D7, 80, n=0, 5, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T2, D7, Negative, n=0, 5, 0, 0, 0	0 0%	5 NaN	0 NaN	0 NaN	0 NaN
UG, T2, D7, Trace, n=0, 5, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T3, D7, 80, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T3, D7, Negative, n=0, 0, 4, 0, 0	0 0%	0 NaN	4 NaN	0 NaN	0 NaN
UG, T3, D7, Trace, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T3, D14, 80, n=0, 0,1,0,0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T3, D14, Negative, n=0, 0, 1, 0, 0	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
UG, T3, D14, Trace, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T4, D7, 80, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T4, D7, Negative, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	4 NaN	0 NaN
UG, T4, D7, Trace, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T5, D7, 80, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UG, T5, D7, Negative, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	3 NaN
UG, T5, D7, Trace, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T1, D1, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T1, D1, Negative, n=5, 0, 0, 0, 0	5 100%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T1, D1, Trace, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T1, D7, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T1, D7, Negative, n=5, 0, 0, 0, 0	5 100%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T1, D7, Trace, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T2, D7, 80, n=0, 5, 0, 0, 0	0 0%	1 NaN	0 NaN	0 NaN	0 NaN
UK, T2, D7, Negative, n=0, 5, 0, 0, 0	0 0%	3 NaN	0 NaN	0 NaN	0 NaN
UK, T2, D7, Trace, n=0, 5, 0, 0, 0	0 0%	1 NaN	0 NaN	0 NaN	0 NaN
UK, T3, D7, 80, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T3, D7, Negative, n=0, 0, 4, 0, 0	0 0%	0 NaN	4 NaN	0 NaN	0 NaN
UK, T3, D7, Trace, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T3, D14, 80, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T3, D14, Negative, n=0, 0, 1, 0, 0	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
UK, T3, D14, Trace, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T4, D7, 80, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T4, D7, Negative, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	4 NaN	0 NaN
UK, T4, D7, Trace, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T5, D7, 80, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UK, T5, D7, Negative, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	3 NaN
UK, T5, D7, Trace, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T1, D1, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T1, D1, Negative, n=5, 0, 0, 0, 0	4 80%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T1, D1, Trace, n=5, 0, 0, 0, 0	1 20%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T1, D7, 80, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T1, D7, Negative, n=5, 0, 0, 0, 0	5 100%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T1, D7, Trace, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T2, D7, 80, n=0, 5, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T2, D7, Negative, n=0, 5, 0, 0, 0	0 0%	4 NaN	0 NaN	0 NaN	0 NaN
UP, T2, D7, Trace, n=0, 5, 0, 0, 0	0 0%	1 NaN	0 NaN	0 NaN	0 NaN
UP, T3, D7, 80, n=0, 0, 4, 0,0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T3, D7, Negative, n=0, 0, 4, 0, 0	0 0%	0 NaN	3 NaN	0 NaN	0 NaN
UP, T3, D7, Trace, n=0, 0, 4, 0, 0	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
UP, T3, D14, 80, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T3, D14, Negative, n=0, 0, 1, 0, 0	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
UP, T3, D14, Trace, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T4, D7, 80, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T4, D7, Negative, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	4 NaN	0 NaN
UP, T4, D7, Trace, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T5, D7, 80, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
UP, T5, D7, Negative, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	3 NaN
UP, T5, D7, Trace, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN

17. Secondary Outcome

Title	Percent Change From Baseline in 28-day Seizure Frequency Rate
Description	Participants or their caregivers recorded the number of seizures experienced by the participant, by seizure type (e.g., simple partial seizure [seizure that affects only a small region of the brain; consciousness is unaffected], complex partial seizure [seizure associated with unilateral cerebral hemisphere involvement and causing impairment of awareness or responsiveness], etc.), as well as by duration of episodes of innumerable seizure activity, in their daily diaries during all phases of this study. Percent change from baseline is defined as 100 * (rate in a given period minus the baseline rate) / (baseline rate). baseline seizures are defined as those seizures that occurred after Screening and before the start of the treatment. Post-baseline seizures are defined as those seizures that occurred from the start of the treatment until the start of Follow-up. Seizure frequency rate was computed as: 28 * (number of seizures during given period / number of days in given period).
Time Frame	Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only participants with baseline and post-baseline seizure measurements were included in the analysis.

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants recieved an initial dose of ezogabine/retigabine 300 mg/day administered as 100 mg IR tablets TID orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5
Mean (Standard Deviation) [Percent change]	-41.5 (29.95)

18. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t]) for the N-acetyl Metabolite of Ezogabine/Retigabine
Description	The area under the curve was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the plasma n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Geometric Mean (95% Confidence Interval) [h*ng/mL]	2222.1	3479.2	5000.6

19. Secondary Outcome

Title	Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) for the N-acetyl Metabolite of Ezogabine/Retigabine
Description	Ctau refers to the pre-dose (trough) concentration at the end of the dosing interval which is equivalent to the minimum observed concetration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the Ctau for n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly upitration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Geometric Mean (95% Confidence Interval) [ng/mL]	170.51 (86.32)	307.85	415.66

20. Secondary Outcome

Title	Time to Maximum Concentration (Tmax) Following Oral Administration of Ezogabine/Retigabine
Description	Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma Tmax.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R)300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	4	3
Median (Full Range) [Hours]	1.000	1.550	2.000

21. Secondary Outcome

Title	Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine
Description	Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma t1/2. Steady-state t1/2 is derived as (Vd/F) / (CL/F), where Vd/F is defined as the apparent volume of distribution after extravascular (e.g., oral) administration, and CL/F is defined as the apparent clearance following oral dosing.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Regimen A: Ezogabine/Retigabine (E/R) 300 mg	Regimen A: E/R 300/450 mg Then 600 mg	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine adminstered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	3	3	1
Geometric Mean (95% Confidence Interval) [Hours]	4.168	5.897	3.473

22. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	An ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate (QTc intervals) was used. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). ECG parameters were assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose, and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. The number of participants with abnormal (Abn) clinically significant (CS) and not clinically significant (NCS) ECG findings was recorded. The investigator determined if an ECG finding was CS or NCS.
Time Frame	Baseline (Screening) and Day 7 post up-titration, up to Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300 mg	Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an up-titrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	5	4	4	3
T1, Day 1 pre-dose, Abn NCS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, Day 1 pre-dose, Abn CS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, Day 1, 3 h, Abn NCS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, Day 1, 3 h, Abn CS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, pre-dose, Abn NCS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, pre-dose, Abn CS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, 3 h, Abn NCS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T1, 3 h, Abn CS, n=5, 0, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T2, Day 7, Abn NCS, n=0, 5, 0, 0, 0	0 0%	1 NaN	0 NaN	0 NaN	1 NaN
T2, Day 7, Abn CS, n=0, 5, 0, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T3, pre-dose, Abn NCS, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T3, pre-dose, Abn CS, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T3, 3 h, Abn NCS, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T3, 3 h, Abn CS, n=0, 0, 4, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T3DH, pre-dose, Abn NCS, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T3DH, pre-dose, Abn CS, n=0, 0, 1, 0, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T4, Day 7, Abn NCS, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T4, Day 7, Abn CS, n=0, 0, 0, 4, 0	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T5, pre-dose, Abn NCS, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	1 NaN
T5, pre-dose, Abn CS, n=0, 0, 0, 0, 3	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T5, 3 h, Abn NCS, n=0, 0, 0, 0, 2	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
T5, 3 h, Abn CS, n=0, 0, 0, 0, 2	0 0%	0 NaN	0 NaN	0 NaN	0 NaN

23. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
Description	Vital sign assessment included the measurement of systolic and diastolic blood pressure at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), Day 7 pre-dose, and 3 h post dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): Day 21 pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): Day 35 pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value.
Time Frame	Baseline (Screening) and Day 7 post up-titration, up to Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those par. available at the specified time points were analyzed(represented by n=X, X, X, X, X in the category titles). Different par. may have been analyzed at different time points and for different parameters, so the overall number of par. analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300 mg	Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an up-titrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	5	4	4	3
SBP, T1, Day 1 3h, n=5, 0, 0, 0, 0	2.8 (6.02)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
SBP, T1, Day 7 Pre-dose, n=5, 0, 0, 0, 0	2.6 (5.18)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
SBP, T1, Day 7 3h, n=5, 0, 0, 0, 0	-1.2 (8.81)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
SBP, T2, Day 7, n=0, 5, 0, 0, 0	NA (NA)	5.4 (4.39)	NA (NA)	NA (NA)	NA (NA)
SBP, T3, Day 21 Pre-dose, n=0, 0, 4, 0, 0	NA (NA)	NA (NA)	11.3 (11.62)	NA (NA)	NA (NA)
SBP, T3, Day 21 3h, n=0, 0, 4, 0, 0	NA (NA)	NA (NA)	3.0 (10.68)	NA (NA)	NA (NA)
SBP, T3DH, Pre-dose, n=0, 0, 1, 0, 0	NA (NA)	NA (NA)	13.0 (NA)	NA (NA)	NA (NA)
SBP, T4, Day 28, n=0, 0, 0, 4, 0	NA (NA)	NA (NA)	NA (NA)	3.0 (3.27)	NA (NA)
SBP, T5, Day 35 Pre-dose, n=0, 0, 0, 0, 3	NA (NA)	NA (NA)	NA (NA)	NA (NA)	8.7 (13.32)
SBP, T5, Day 35 3h, n=0, 0, 0, 0, 3	NA (NA)	NA (NA)	NA (NA)	NA (NA)	5.3 (10.97)
DBP, T1, Day 1 3h, n=5, 0, 0, 0, 0	1.4 (7.92)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
DBP, T1, Pre-dose, n=5, 0, 0, 0, 0	0.2 (4.60)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
DBP, T1, 3h, n=5, 0, 0, 0, 0	4.4 (5.81)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
DBP, T2, Day 7, n=0, 5, 0, 0, 0	NA (NA)	-0.2 (15.55)	NA (NA)	NA (NA)	NA (NA)
DBP, T3, Pre-dose, n=0, 0, 4, 0, 0	NA (NA)	NA (NA)	1.8 (4.65)	NA (NA)	NA (NA)
DBP, T3, 3h, n=0, 0, 4, 0, 0	NA (NA)	NA (NA)	3.8 (12.89)	NA (NA)	NA (NA)
DBP, T3DH, Pre-dose, n=0, 0, 1, 0, 0	NA (NA)	NA (NA)	23.0 (NA)	NA (NA)	NA (NA)
DBP, T4, Day 7, n=0, 0, 0, 4, 0	NA (NA)	NA (NA)	NA (NA)	-0.3 (2.99)	NA (NA)
DBP, T5, Pre-dose, n=0, 0, 0, 0, 3	NA (NA)	NA (NA)	NA (NA)	NA (NA)	7.3 (12.70)
DBP, T5, 3h, n=0, 0, 0, 0, 3	NA (NA)	NA (NA)	NA (NA)	NA (NA)	3.7 (16.77)

24. Secondary Outcome

Title	Change From Baseline in Heart Rate (HR)
Description	Vital sign assessment included heart rate measurement and was assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value.
Time Frame	Baseline (Screening) and Day 7 post up-titration, up to Day 35

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those par. available at the specified time points were analyzed(represented by n=X, X, X, X, X in the category titles). Different par. may have been analyzed at different time points and for different parameters, so the overall number of par. analyzed reflects everyone in the All Subjects Population.

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300 mg	Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an up-titrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	5	5	4	4	3
HR, T1, Day 1 3h, n=5, 0, 0, 0, 0	3.6 (11.26)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
HR, T1, Pre-dose, n=5, 0, 0, 0, 0	-0.8 (7.22)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
HR, T1, 3h, n=5, 0, 0, 0, 0	2.8 (5.89)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
HR, T2, Day 7, n=0, 5, 0, 0, 0	NA (NA)	8.2 (11.67)	NA (NA)	NA (NA)	NA (NA)
HR, T3, Pre-dose, n=0, 0, 4, 0, 0	NA (NA)	NA (NA)	0.5 (7.51)	NA (NA)	NA (NA)
HR, T3, 3h, n=0, 0, 4, 0, 0	NA (NA)	NA (NA)	6.0 (5.48)	NA (NA)	NA (NA)
HR, T3DH, Pre-dose, n=0, 0, 1, 0, 0	NA (NA)	NA (NA)	8.0 (NA)	NA (NA)	NA (NA)
HR, T4, Day 7, n=0, 0, 0, 4, 0	NA (NA)	NA (NA)	NA (NA)	1.8 (6.18)	NA (NA)
HR, T5, Pre-dose, n=0, 0, 0, 0, 3	NA (NA)	NA (NA)	NA (NA)	NA (NA)	1.7 (4.16)
HR, T5, 3h, n=0, 0, 0, 0, 3	NA (NA)	NA (NA)	NA (NA)	NA (NA)	2.3 (4.16)

25. Secondary Outcome

Title	Change From Baseline in Post Void Residual Ultrasound at Day 21
Description	A post void residual (PVR) bladder ultrasound was carried out as a measure of bladder function. PVR was clinically indicated following the occurrence of adverse events relating to the lower urinary tract (e.g., micturition difficulties, including urinary hesitancy or urinary retention). These assessments were also repeated following drug withdrawal following such events. A prompt follow-up PVR was recommended if a high score was obtained from a participant on the Pediatric Lower Urinary Tract Symptom scale (the PLUTS scale is a clinician-rated scale used to assess lower urinary tract symptoms, including urinary retention) and if the clinician felt that the participant was at risk or had symptoms of urinary retention. PVR was measured at Day 7 of Titration 3 (600 mg/day). Baseline is defined as the Screening visit.
Time Frame	Screening and Day 7 of Titration 3 (Day 21)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	4
Mean (Standard Deviation) [ML]	14.4 (21.00)

26. Secondary Outcome

Title	Number of Participants With the Indicated Neurological Abnormality
Description	Abnormal Central Nervous System (CNS) symptoms were assessed by a full and brief neurological examination. A full neurological examination included assessment of mental status, cranial nerves, gait, coordination, sensation, speech/language, muscle strength, muscle tone, and reflexes. A brief neurological examination included assessment of mental status, cranial nerves, gait, coordination, reflexes, and speech/language. Neurological parameters assessed were memory impairment, impaired intellect, decreased attention, psychomotor slowing, decreased muscle strength, hpertonia, somnolence, right and left bicpes, right and left brachioradialis, right and left knee, right and left ankle, and right and left planter response. Neurological examination was performed at Day 7 of Titration 3 (600 mg/day).
Time Frame	Screening and Day 7 of Titration 3 (Day 21)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
Measure Participants	4
Memory impairment	0 0%
Impaired intellect	0 0%
Decreased attention	0 0%
Psychomotor slowing	0 0%
Decreased muscle strength	0 0%
Hypertonia	0 0%
Somnolence	1 20%
Bicep right	NA NaN
Bicep left	NA NaN
Brachioradialis right	NA NaN
Brachioradialis left	NA NaN
Knee right	NA NaN
Knee left	NA NaN
Ankle right	NA NaN
Ankle left	NA NaN
Planter response right	NA NaN
Planter response left	NA NaN

Adverse Events

Time Frame	Adverse event data, volunteered by the participant, discovered by the investigator, or detected by other means, were collected from the start of study treatment until the Follow-up contact (maximum of 46 days).
Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprsised of all participants who received at least one dose of study medication.
Arm/Group Title	Regimen A: Ezogabine/Retigabine 300 mg		Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg		Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg		Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg		Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
Arm/Group Description	Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.		Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an up-titrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.		Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.		Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.		Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
All Cause Mortality
	Regimen A: Ezogabine/Retigabine 300 mg		Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg		Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg		Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg		Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Regimen A: Ezogabine/Retigabine 300 mg		Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg		Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg		Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg		Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Regimen A: Ezogabine/Retigabine 300 mg		Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg		Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg		Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg		Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/5 (20%)		1/4 (25%)		0/4 (0%)		0/3 (0%)
Gastrointestinal disorders
Diarrhoea	1/5 (20%)		0/5 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)
Nervous system disorders
Somnolence	0/5 (0%)		0/5 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)
Renal and urinary disorders
Urinary hesitation	0/5 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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