Trial Outcomes & Findings for Study in Pediatric Subjects With Epilepsy (NCT NCT01494584)

NCT ID: NCT01494584

Last Updated: 2020-11-30

Results Overview

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).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 5 participants
• Primary outcome timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
• Results posted on: 2020-11-30

Participant Flow

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.

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.

Participant milestones

Measure	Ezogabine/Retigabine 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.
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Ezogabine/Retigabine 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.

Overall Study Study Closed/Terminated

1

Baseline Characteristics

Study in Pediatric Subjects With Epilepsy

Baseline characteristics by cohort

Measure	Ezogabine/Retigabine n=5 Participants 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.
Age, Continuous	14.6 Years STANDARD_DEVIATION 1.34 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Population: 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

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).

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine	1680.0 Hour*Nanograms/Milliliter (h.ng/mL) Interval 1162.4 to 2428.2	2558.8 Hour*Nanograms/Milliliter (h.ng/mL) Interval 1873.4 to 3494.8	3783.8 Hour*Nanograms/Milliliter (h.ng/mL) Interval 1059.6 to 13512.0	—	—

PRIMARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Population: Pharmacokinetic Population

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine	178.6 Liters/Hour Interval 123.5 to 258.1	234.5 Liters/Hour Interval 171.7 to 320.3	237.9 Liters/Hour Interval 66.6 to 849.4	—	—

PRIMARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Population: Pharmacokinetic Population

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine Cmax	370.0 Nanograms/Milliliter (ng/mL) Interval 260.9 to 524.7	535.9 Nanograms/Milliliter (ng/mL) Interval 344.4 to 833.8	750.9 Nanograms/Milliliter (ng/mL) Interval 289.8 to 1945.3	—	—
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine Ctau	105.32 Nanograms/Milliliter (ng/mL) Interval 58.7 to 188.98	199.77 Nanograms/Milliliter (ng/mL) Interval 140.67 to 283.72	287.48 Nanograms/Milliliter (ng/mL) Interval 44.38 to 1862.12	—	—

PRIMARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=3 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=3 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=1 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine	1130.9 Liters Interval 511.1 to 2502.1	2118.0 Liters Interval 539.4 to 8315.8	1934.3 Liters Although 3 subjects were on this dose level during the study, only 1 provided data to calculate Volume of Distribution therefore the 95% CI is not available because of small sample size (n=1).	—	—

SECONDARY outcome

Timeframe: From the start of the first titration until follow-up (assessed up to 46 days)

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=5 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg n=3 Participants 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.
Number of Participants With Any Adverse Event (AE)	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration Albumin, n=4, 4, 3	-3.8 Grams per Liter (G/L) Standard Deviation 0.96	-3.0 Grams per Liter (G/L) Standard Deviation 3.46	-0.7 Grams per Liter (G/L) Standard Deviation 3.06	—	—
Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration Total protein, n=4, 4, 3	-4.0 Grams per Liter (G/L) Standard Deviation 2.94	-3.5 Grams per Liter (G/L) Standard Deviation 3.79	-0.7 Grams per Liter (G/L) Standard Deviation 5.03	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration Alkaline phosphatse, n=4, 4, 3	-5.8 International Units per Liter (IU/L) Standard Deviation 16.17	10.3 International Units per Liter (IU/L) Standard Deviation 35.93	5.0 International Units per Liter (IU/L) Standard Deviation 6.93	—	—
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration Alanine amino transferase, n=4, 4, 3	-2.0 International Units per Liter (IU/L) Standard Deviation 2.16	35.0 International Units per Liter (IU/L) Standard Deviation 74.02	-1.0 International Units per Liter (IU/L) Standard Deviation 2.00	—	—
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration Aspartate amino transferase, n=4, 4, 3	-0.8 International Units per Liter (IU/L) Standard Deviation 2.50	10.8 International Units per Liter (IU/L) Standard Deviation 17.75	1.7 International Units per Liter (IU/L) Standard Deviation 3.21	—	—
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration Gamma glutamyl transferase, n=3, 3, 2	-1.3 International Units per Liter (IU/L) Standard Deviation 0.58	111.0 International Units per Liter (IU/L) Standard Deviation 181.06	50.5 International Units per Liter (IU/L) Standard Deviation 47.38	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration Direct bilirubin, n=1, 2, 1	2.7360 Micromoles per liter (UMOL/L) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	2.7360 Micromoles per liter (UMOL/L) Standard Deviation 3.86929	-0.8550 Micromoles per liter (UMOL/L) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	—	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration Total bilirubin, n=4, 4, 3	0.855 Micromoles per liter (UMOL/L) Standard Deviation 2.2076	2.138 Micromoles per liter (UMOL/L) Standard Deviation 2.5650	4.560 Micromoles per liter (UMOL/L) Standard Deviation 0.9873	—	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration Creatinine, n=4, 4, 3	1.3260 Micromoles per liter (UMOL/L) Standard Deviation 1.14124	-4.1990 Micromoles per liter (UMOL/L) Standard Deviation 5.02015	0.5893 Micromoles per liter (UMOL/L) Standard Deviation 3.34677	—	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration Uric acid, n=4, 3, 1	16.3570 Micromoles per liter (UMOL/L) Standard Deviation 19.04289	15.8613 Micromoles per liter (UMOL/L) Standard Deviation 36.34288	23.7920 Micromoles per liter (UMOL/L) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
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 Calcium, n=4, 4, 3	0.00624 Millimoles per liter (MMOL/L) Standard Deviation 0.062375	-0.04366 Millimoles per liter (MMOL/L) Standard Deviation 0.117689	0.02495 Millimoles per liter (MMOL/L) Standard Deviation 0.194866	—	—
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 Chloride, n=4, 4, 3	1.8 Millimoles per liter (MMOL/L) Standard Deviation 0.96	3.0 Millimoles per liter (MMOL/L) Standard Deviation 0.82	3.0 Millimoles per liter (MMOL/L) Standard Deviation 1.73	—	—
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 Carbon dioxide content/bicarbonate, n=4, 4, 3	0.8 Millimoles per liter (MMOL/L) Standard Deviation 3.50	-1.5 Millimoles per liter (MMOL/L) Standard Deviation 1.73	-2.7 Millimoles per liter (MMOL/L) Standard Deviation 2.08	—	—
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 Glucose, n=4, 4, 3	0.69388 Millimoles per liter (MMOL/L) Standard Deviation 1.184069	0.15265 Millimoles per liter (MMOL/L) Standard Deviation 0.821317	0.29605 Millimoles per liter (MMOL/L) Standard Deviation 0.279394	—	—
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 Potassium, n=4, 4, 3	0.08 Millimoles per liter (MMOL/L) Standard Deviation 0.206	0.17 Millimoles per liter (MMOL/L) Standard Deviation 0.574	0.20 Millimoles per liter (MMOL/L) Standard Deviation 0.624	—	—
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 Sodium, n=4, 4, 3	1.8 Millimoles per liter (MMOL/L) Standard Deviation 0.50	2.0 Millimoles per liter (MMOL/L) Standard Deviation 1.83	2.3 Millimoles per liter (MMOL/L) Standard Deviation 3.06	—	—
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 Inorganic phosphorus, n=4, 3, 1	-0.39555 Millimoles per liter (MMOL/L) Standard Deviation 0.727481	-0.04305 Millimoles per liter (MMOL/L) Standard Deviation 0.189202	0.09687 Millimoles per liter (MMOL/L) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	—	—
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 Urea/BUN, n=4, 4, 3	-0.3570 Millimoles per liter (MMOL/L) Standard Deviation 1.23668	0.7140 Millimoles per liter (MMOL/L) Standard Deviation 0.71400	1.3090 Millimoles per liter (MMOL/L) Standard Deviation 0.74315	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
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 Eosinophils, n=3, 3, 2	0.07 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.059	0.09 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.200	0.10 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.005	—	—
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 Basophils, n=3, 3, 2	0.03 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.062	0.04 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.053	0.00 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.006	—	—
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 Lymphocytes, n=3, 3, 2	14.77 Giga (10^9) cells per liter (GI/L) Standard Deviation 26.358	-0.45 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.654	-0.65 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.918	—	—
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 Monocytes, n=3, 3, 2	-0.04 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.347	0.09 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.101	0.05 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.065	—	—
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 Total neutrophils, n=3, 3, 2	14.90 Giga (10^9) cells per liter (GI/L) Standard Deviation 24.176	-0.11 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.370	0.61 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.263	—	—
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 Platelet count, n=4, 4, 3	-17.0 Giga (10^9) cells per liter (GI/L) Standard Deviation 40.12	-15.8 Giga (10^9) cells per liter (GI/L) Standard Deviation 34.32	-1.3 Giga (10^9) cells per liter (GI/L) Standard Deviation 17.16	—	—
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 White blood cell count, n=4, 4, 3	0.393 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.2125	-0.600 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.6272	-0.583 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.3345	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration Hemoglobin, n=4, 4, 3	-3.0 Grams per liter (G/L) Standard Deviation 4.90	-10.3 Grams per liter (G/L) Standard Deviation 6.85	-2.0 Grams per liter (G/L) Standard Deviation 4.36	—	—
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration Mean corpuscle hemoglobin concentration, n=4, 4, 3	-2.5 Grams per liter (G/L) Standard Deviation 2.38	0.3 Grams per liter (G/L) Standard Deviation 10.59	-6.7 Grams per liter (G/L) Standard Deviation 4.93	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=4 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Hematocrit at Day 7 Post Each Up-titration	-0.0057 Fraction of one unit (1) Standard Deviation 0.01452	-0.0303 Fraction of one unit (1) Standard Deviation 0.02198	0.0017 Fraction of one unit (1) Standard Deviation 0.1201	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=4 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration	-0.07 Picograms (PG) per cell (PG/cell) Standard Deviation 0.126	0.15 Picograms (PG) per cell (PG/cell) Standard Deviation 0.569	-0.23 Picograms (PG) per cell (PG/cell) Standard Deviation 0.153	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=4 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration	0.52 Femtoliters (FL) Standard Deviation 1.056	0.45 Femtoliters (FL) Standard Deviation 1.034	1.00 Femtoliters (FL) Standard Deviation 1.000	—	—

SECONDARY outcome

Timeframe: Baseline (Screening), Day 7, Day 21, and Day 35

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=4 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration	-0.090 10^12 cells/L (TI/L) Standard Deviation 0.1463	-0.357 10^12 cells/L (TI/L) Standard Deviation 0.2304	-0.030 10^12 cells/L (TI/L) Standard Deviation 0.1136	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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).

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=5 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg n=3 Participants 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.
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T1, D1, Trace, n=5, 0, 0, 0, 0	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T1, D7, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T3, D7, Negative, n=0, 0, 4, 0, 0	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T3, D7, Trace, n=0, 0, 4, 0, 0	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T3, D14, 80, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T3,D14, Negative, n=0, 0, 1, 0, 0	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T3, D14, Trace, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up Urine Occult Blood, T4, D7, 80, n=0,0,0,3,0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T4, D7, Negative, n=0, 0, 0, 3, 0	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up Urine Occult Blood, T4, D7, Trace, n=0,0,0,3,0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T5, D7, 80, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T5, D7, Negative, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T5, D7, Trace, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T1, D1, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T1, D1, Negative, n=5, 0, 0, 0, 0	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T1, D1, Trace, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T1, D7, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T1, D7, Negative, n=5, 0, 0, 0, 0	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T1, D7, Trace, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T2, D7, 80, n=0, 5, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T2, D7, Negative, n=0, 5, 0, 0, 0	0 Participants	5 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T2, D7, Trace, n=0, 5, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T3, D7, 80, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T3, D7, Negative, n=0, 0, 4, 0, 0	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T3, D7, Trace, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T3, D14, 80, n=0, 0,1,0,0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T1, D1, Trace, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T3, D14, Negative, n=0, 0, 1, 0, 0	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T3, D14, Trace, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T4, D7, 80, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T4, D7, Negative, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T4, D7, Trace, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T5, D7, 80, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T5, D7, Negative, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UG, T5, D7, Trace, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T1, D1, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T1, D1, Negative, n=5, 0, 0, 0, 0	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T1, D7, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T1, D7, Negative, n=5, 0, 0, 0, 0	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T1, D7, Trace, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T2, D7, 80, n=0, 5, 0, 0, 0	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T2, D7, Negative, n=0, 5, 0, 0, 0	0 Participants	3 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T2, D7, Trace, n=0, 5, 0, 0, 0	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T3, D7, 80, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T3, D7, Negative, n=0, 0, 4, 0, 0	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T3, D7, Trace, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T3, D14, 80, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T3, D14, Negative, n=0, 0, 1, 0, 0	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T3, D14, Trace, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T4, D7, 80, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T4, D7, Negative, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T4, D7, Trace, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T5, D7, 80, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T5, D7, Negative, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UK, T5, D7, Trace, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T1, D1, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T1, D1, Negative, n=5, 0, 0, 0, 0	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T1, D7, Negative, n=5, 0, 0, 0, 0	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T1, D7, Trace, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T2, D7, 80, n=0, 5, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T2, D7, Negative, n=0, 5, 0, 0, 0	0 Participants	4 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T2, D7, Trace, n=0, 5, 0, 0, 0	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T3, D7, 80, n=0, 0, 4, 0,0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T3, D7, Negative, n=0, 0, 4, 0, 0	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T3, D7, Trace, n=0, 0, 4, 0, 0	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T3, D14, 80, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T3, D14, Negative, n=0, 0, 1, 0, 0	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T3, D14, Trace, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T4, D7, 80, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T4, D7, Negative, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T4, D7, Trace, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T5, D7, 80, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T5, D7, Negative, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UP, T5, D7, Trace, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T1, D1, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T1, D1, Negative, n=5, 0, 0, 0, 0	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T1, D1, Trace, n=5, 0, 0, 0, 0	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T1, D7, 80, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T1, D7, Negative, n=5, 0, 0, 0, 0	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T1, D7, Trace, n=5, 0, 0, 0, 0	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T2, D7, 80, n=0, 5, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T2, D7, Negative, n=0, 5, 0, 0, 0	0 Participants	5 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T2, D7, Trace, n=0, 5, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up UOB, T3, D7, 80, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)

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

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).

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Percent Change From Baseline in 28-day Seizure Frequency Rate	-41.5 Percent change Standard Deviation 29.95	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Population: PK Population

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
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	2222.1 h*ng/mL Interval 1531.4 to 3224.4	3479.2 h*ng/mL Interval 2374.0 to 5099.0	5000.6 h*ng/mL Interval 1528.9 to 16355.7	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Population: PK Population

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) for the N-acetyl Metabolite of Ezogabine/Retigabine	170.51 ng/mL 95% Confidence Interval 86.32 • Interval 86.32 to 336.82	307.85 ng/mL Interval 190.25 to 498.14	415.66 ng/mL Interval 120.74 to 1430.93	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Population: PK Population

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=4 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=3 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Time to Maximum Concentration (Tmax) Following Oral Administration of Ezogabine/Retigabine	1.000 Hours Interval 0.5 to 1.08	1.550 Hours Interval 0.5 to 8.0	2.000 Hours Interval 0.5 to 6.0	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

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

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=3 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=3 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=1 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine	4.168 Hours Interval 2.363 to 7.35	5.897 Hours Interval 0.962 to 36.16	3.473 Hours The 95% CI cannot be calculated because only one participant has been analyzed in this treatment arm at this time point	—	—

SECONDARY outcome

Timeframe: Baseline (Screening) and Day 7 post up-titration, up to Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=5 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg n=3 Participants 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.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, Day 1 pre-dose, Abn NCS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, Day 1 pre-dose, Abn CS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, Day 1, 3 h, Abn NCS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, Day 1, 3 h, Abn CS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, pre-dose, Abn NCS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, pre-dose, Abn CS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, 3 h, Abn NCS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T1, 3 h, Abn CS, n=5, 0, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T2, Day 7, Abn NCS, n=0, 5, 0, 0, 0	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T2, Day 7, Abn CS, n=0, 5, 0, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T3, pre-dose, Abn NCS, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T3, pre-dose, Abn CS, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T3, 3 h, Abn NCS, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T3, 3 h, Abn CS, n=0, 0, 4, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T3DH, pre-dose, Abn NCS, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T3DH, pre-dose, Abn CS, n=0, 0, 1, 0, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T4, Day 7, Abn NCS, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T4, Day 7, Abn CS, n=0, 0, 0, 4, 0	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T5, pre-dose, Abn NCS, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T5, pre-dose, Abn CS, n=0, 0, 0, 0, 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T5, 3 h, Abn NCS, n=0, 0, 0, 0, 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings T5, 3 h, Abn CS, n=0, 0, 0, 0, 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Screening) and Day 7 post up-titration, up to Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=5 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg n=3 Participants 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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T1, Day 1 3h, n=5, 0, 0, 0, 0	2.8 Millimeters of Mercury (mmHg) Standard Deviation 6.02	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T1, Day 7 Pre-dose, n=5, 0, 0, 0, 0	2.6 Millimeters of Mercury (mmHg) Standard Deviation 5.18	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T1, Day 7 3h, n=5, 0, 0, 0, 0	-1.2 Millimeters of Mercury (mmHg) Standard Deviation 8.81	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T2, Day 7, n=0, 5, 0, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	5.4 Millimeters of Mercury (mmHg) Standard Deviation 4.39	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T3, Day 21 Pre-dose, n=0, 0, 4, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	11.3 Millimeters of Mercury (mmHg) Standard Deviation 11.62	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T3, Day 21 3h, n=0, 0, 4, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	3.0 Millimeters of Mercury (mmHg) Standard Deviation 10.68	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T3DH, Pre-dose, n=0, 0, 1, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	13.0 Millimeters of Mercury (mmHg) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T4, Day 28, n=0, 0, 0, 4, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	3.0 Millimeters of Mercury (mmHg) Standard Deviation 3.27	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T5, Day 35 Pre-dose, n=0, 0, 0, 0, 3	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	8.7 Millimeters of Mercury (mmHg) Standard Deviation 13.32
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, T5, Day 35 3h, n=0, 0, 0, 0, 3	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	5.3 Millimeters of Mercury (mmHg) Standard Deviation 10.97
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T1, Day 1 3h, n=5, 0, 0, 0, 0	1.4 Millimeters of Mercury (mmHg) Standard Deviation 7.92	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T1, Pre-dose, n=5, 0, 0, 0, 0	0.2 Millimeters of Mercury (mmHg) Standard Deviation 4.60	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T1, 3h, n=5, 0, 0, 0, 0	4.4 Millimeters of Mercury (mmHg) Standard Deviation 5.81	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T2, Day 7, n=0, 5, 0, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	-0.2 Millimeters of Mercury (mmHg) Standard Deviation 15.55	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T3, Pre-dose, n=0, 0, 4, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	1.8 Millimeters of Mercury (mmHg) Standard Deviation 4.65	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T3, 3h, n=0, 0, 4, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	3.8 Millimeters of Mercury (mmHg) Standard Deviation 12.89	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T3DH, Pre-dose, n=0, 0, 1, 0, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	23.0 Millimeters of Mercury (mmHg) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T4, Day 7, n=0, 0, 0, 4, 0	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	-0.3 Millimeters of Mercury (mmHg) Standard Deviation 2.99	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T5, Pre-dose, n=0, 0, 0, 0, 3	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	7.3 Millimeters of Mercury (mmHg) Standard Deviation 12.70
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, T5, 3h, n=0, 0, 0, 0, 3	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Millimeters of Mercury (mmHg) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	3.7 Millimeters of Mercury (mmHg) Standard Deviation 16.77

SECONDARY outcome

Timeframe: Baseline (Screening) and Day 7 post up-titration, up to Day 35

Population: 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.

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=5 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg n=5 Participants 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg n=4 Participants 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg n=3 Participants 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.
Change From Baseline in Heart Rate (HR) HR, T2, Day 7, n=0, 5, 0, 0, 0	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	8.2 Beats per Minute (BPM) Standard Deviation 11.67	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T1, 3h, n=5, 0, 0, 0, 0	2.8 Beats per Minute (BPM) Standard Deviation 5.89	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T3, Pre-dose, n=0, 0, 4, 0, 0	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	0.5 Beats per Minute (BPM) Standard Deviation 7.51	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T3, 3h, n=0, 0, 4, 0, 0	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	6.0 Beats per Minute (BPM) Standard Deviation 5.48	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T3DH, Pre-dose, n=0, 0, 1, 0, 0	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	8.0 Beats per Minute (BPM) Standard Deviation NA The standard deviation cannot be calculated because only one participant has been analyzed in this treatment arm at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T4, Day 7, n=0, 0, 0, 4, 0	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	1.8 Beats per Minute (BPM) Standard Deviation 6.18	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T5, Pre-dose, n=0, 0, 0, 0, 3	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	1.7 Beats per Minute (BPM) Standard Deviation 4.16
Change From Baseline in Heart Rate (HR) HR, T5, 3h, n=0, 0, 0, 0, 3	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	2.3 Beats per Minute (BPM) Standard Deviation 4.16
Change From Baseline in Heart Rate (HR) HR, T1, Day 1 3h, n=5, 0, 0, 0, 0	3.6 Beats per Minute (BPM) Standard Deviation 11.26	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.
Change From Baseline in Heart Rate (HR) HR, T1, Pre-dose, n=5, 0, 0, 0, 0	-0.8 Beats per Minute (BPM) Standard Deviation 7.22	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.	NA Beats per Minute (BPM) Standard Deviation NA No participants in this treatment arm were analyzed at this time point.

SECONDARY outcome

Timeframe: Screening and Day 7 of Titration 3 (Day 21)

Population: All Subjects Population

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.

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=4 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Change From Baseline in Post Void Residual Ultrasound at Day 21	14.4 ML Standard Deviation 21.00	—	—	—	—

SECONDARY outcome

Timeframe: Screening and Day 7 of Titration 3 (Day 21)

Population: All Subjects Population

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).

Outcome measures

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n=4 Participants 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.	Regimen A: E/R 300/450 mg Then 600 mg 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.	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg 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.
Number of Participants With the Indicated Neurological Abnormality Hypertonia	0 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Memory impairment	0 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Impaired intellect	0 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Decreased attention	0 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Psychomotor slowing	0 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Decreased muscle strength	0 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Somnolence	1 Participants	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Bicep right	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Bicep left	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Brachioradialis right	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Brachioradialis left	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Knee right	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Knee left	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Ankle right	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Ankle left	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Planter response right	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—
Number of Participants With the Indicated Neurological Abnormality Planter response left	NA Participants Only a brief neurological exam was conducted therefore this value was not measured	—	—	—	—

Adverse Events

Regimen A: Ezogabine/Retigabine 300 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Regimen A: Ezogabine/Retigabine 300 mg n=5 participants at risk 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.	Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg n=5 participants at risk 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.	Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg n=4 participants at risk 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.	Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg n=4 participants at risk 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.	Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg n=3 participants at risk 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.
Gastrointestinal disorders Diarrhoea	20.0% 1/5 • 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). 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.	0.00% 0/5 • 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). 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.	0.00% 0/4 • 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). 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.	0.00% 0/4 • 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). 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.	0.00% 0/3 • 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). 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.
Nervous system disorders Somnolence	0.00% 0/5 • 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). 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.	0.00% 0/5 • 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). 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.	25.0% 1/4 • 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). 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.	0.00% 0/4 • 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). 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.	0.00% 0/3 • 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). 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.
Renal and urinary disorders Urinary hesitation	0.00% 0/5 • 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). 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.	20.0% 1/5 • 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). 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.	0.00% 0/4 • 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). 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.	0.00% 0/4 • 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). 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.	0.00% 0/3 • 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). 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.

Additional Information

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• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER