An Open Label Study to Evaluate the Effects of Ezogabine/... | NCT01607346

NCT01607346

ID	Type	Description	Link
2012-002260-26	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Brief Summary

This is a multicentre, open label study to examine the effect of ezogabine/retigabine on the voiding function of adult subjects with drug-resistant partial onset seizures (POS). Subjects fulfilling the study entry criteria at Screening and at Baseline including a comprehensive eye examination by an ophthalmologist or retina specialist and a skin assessment by the investigator will receive ezogabine/retigabine.

The starting dose of ezogabine/retigabine will be 300 mg/day. Subjects will be up titrated by 150 mg/day weekly up to the maximum ezogabine/retigabine daily dose of 1200 mg (or the highest tolerated dose). During the 49 days of the treatment phase, subjects will undergo three repeat non-invasive assessments of voiding function. In addition, subjects who meet pre-determined criteria for voiding dysfunction will undergo multichannel cystometry in order to characterise bladder hypocontractility, bladder outlet obstruction or a combination of events which clinically is manifest with difficulty emptying the bladder or acute urinary retention.

At the end of the Treatment Phase, all subjects will enter the Taper Phase, a 3-week down titration period. Subjects who have new findings of abnormal pigmentation of the retina, unexplained vision loss, pigmentation of non-retinal ocular tissue or discoloration of skin, lip, nail, or mucosa since baseline will be asked to enter the Safety Follow-Up / Continuation Phase. All subjects will undergo 6-monthly comprehensive eye examinations during the Safety Follow-Up / Continuation Phase. Subjects who have not developed abnormal discoloration of the skin, lips, nails or mucosa will continue to undergo skin assessments by the investigator. Any subject who has developed abnormal discoloration of the skin, lips, nails or mucosa since baseline will be referred to a dermatologist for evaluation and 6-monthly follow up assessments. All subjects will continue to be followed until the pigmentation and/or discoloration has resolved or stabilised, as defined by no change over 2 consecutive 6-monthly assessments conducted over at least 12 months after discontinuation of ezogabine/retigabine.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
ezogabine/retigabine	Experimental	Open-label	Drug: ezogabine/retigabine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ezogabine/retigabine	Drug	Starting dose of 300mg/day, titrate up to a targeted maximum dose of 1200 mg/day. Dose can be reduced to a minimum of 600 mg/day if unable to tolerate higher doses

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Maximum Flow Rate (Qmax) at Visit 5.	Maximum urine flow rate was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3, 4 and 5 (Days 21, 35 and 49 respectively). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value at Visit 5. Safety Population was defined as all participants who received more than or equal to one dose of study medication.	Baseline (Day -1) and on Day 49 (Visit 5)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Maximum Flow Rate (Qmax) at Visits 3, 4 and 6	Maximum urine flow rate was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is ≥18 years of age (male or female).
Has a confident diagnosis of epilepsy with partial onset seizures with or without secondary generalization (classified according to International League Against Epilepsy (ILAE) Guidelines, 1981) ≥ 2 years.
Is currently being treated with a stable regimen of one to three AEDs during the 4 weeks prior to the Screening Visit.
Following Amendment 03: must be considered drug resistant, consistent with the definition proposed by Kwan, et al 2010 [Kwan].
Note: Vagus Nerve Stimulator (VNS), VNS will not be counted as a concurrent AED. Subjects with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met:
The VNS has been in place for at least 24 weeks prior to the Screening Visit
The settings must remain the same for at least 4 weeks prior to the Screening Visit and throughout the study
The battery is expected to last for the duration of the study
Subject who are considering implantation of a VNS are excluded from participating in this study
Note: The chronic use of benzodiazepines as a concurrent AED is permitted as long as the dose is kept constant for at least 4 weeks before the Screen Visit and throughout the study.
Is able and willing to maintain an accurate and complete a two (2) day Voiding Diary at protocol specified time points.
Is able and willing to maintain an accurate and complete daily written Seizure Calendar at specified time points or has a caregiver who is able and willing to maintain an accurate and complete daily written Seizure Calendar for the entire duration of the study.
Has given written informed consent, prior to the performance of any study assessments.
A female subject is eligible to enter and participate in the study if she is not pregnant or lactating or planning to become pregnant during the study and is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal).
Pre-menopausal females with a documented (medical report verification) hysterectomy with or without oophorectomy or bi-lateral oophorectomy when reproductive status has been confirmed by hormone level assessment
Post-menopausal females defined as being amenorrhoeic for greater than one year with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by oestradiol and follicle stimulating hormone (FSH) levels consistent with menopause (according to local laboratory ranges).
Women who have not been confirmed as post-menopausal should be advised to use contraception as outlined in Appendix 2.
Child-bearing potential, has a negative pregnancy test at screening and baseline, and agrees to satisfy one of the requirements in as listed in Appendix 2.
Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2 x upper limit of normal (ULN); alkaline phosphatase and bilirubin less than or equal to 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Has a normal creatinine clearance (age corrected) as calculated with the Cockcroft-Gault formula.

Exclusion Criteria:

Has generalized epilepsy (e.g., Lennox-Gastaut, Juvenile Myoclonic epilepsy, Absence, etc).
Has had status epilepticus (other than simple partial status epilepticus) within the 12 months prior to Screening or during the Baseline Phase.
Has a history of innumerable seizures within the 12 months prior to Screening where the individual seizures cannot be counted.
Has a history of pseudo seizures, non-epilepsy events or any other type of psychogenic seizures that could be confused with seizures.
Acute Urinary Retention (treated or untreated) within 6 months of screening or an episode of Acute Urinary Retention (treated) within the last two years with symptoms within the last 6 months.
Screening AUA SI Score >7 (>11 for subject over 55 years old).
Flowmetry Peak Flow < 15mL/sec out of a urine volume void of 150mL (<11 mL/sec for subject over 55 years old) at Screening.
PVR >125mL or >40% functional residual volume at Screening.
Prior history of administration of Botox® within genitourinary system.
Prior history or any type of medical or surgical therapy for urinary incontinence.
Prior history of treated or untreated, bladder, prostate, uterine or cervical cancer.
Use of sildenafil, tadalafil, vardenafil or other PDE-5 inhibitors within 2 weeks of study start.
Use of α-adrenoreceptor antagonists within 2 weeks of study start.
Has had previous exposure to ezogabine/retigabine.
Is currently or has been abusing substance(s) or any medications in the 12 months prior to Screening.
Has taken an investigational drug, or used an investigational device, within the previous 4 weeks prior to Screening or plans to take another investigational drug anytime during the study.
Is currently following or planning to follow the ketogenic diet.
Has been treated with felbamate or vigabatrin within the past 6 months prior to Screening; if a subject has been previously treated with vigabatrin, a visual perimetry test prior to screening (or within the past 6 months) must show normal visual fields or no worsening of recognized visual field abnormalities as compared with prior to vigabatrin treatment.
Use of CNS-active medication (other than concomitant AED therapy), unless subjects had been stabilized on such medication for more than 4 weeks prior to Screening.
Use of herbal treatments with CNS activity within 4 weeks prior to Screening.
Current use of any prohibited concomitant medication as indicated in Section 5.7.2.
Is planning surgery to control seizures during the study.
Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that, in the investigator's judgment, are likely to interfere with the objectives of the study.
Has any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.
Has an average QTc ≥ 450 msec or ≥ 480 msec for subjects with Bundle Branch Block at the time of Screening.

Note: If the initial electrocardiogram (ECG) at Screening indicates a corrected QT (QTc) interval outside these limits, two further ECGs should be performed and the average QTc value of these triplicate ECGs calculated. If the average value exceeds the stated limits, the subject is not eligible.

Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than one lifetime suicide attempt.
Has positive test results for hepatitis B surface antigen, positive hepatitis C virus, or human immunodeficiency virus (HIV)-1 or -2 at Screening.

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Bethesda	Maryland	20817	United States
GSK Investigational Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

ezogabine/retigabine

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Units	Counts
Participants	BG00010

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00040.8± 9.62

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004
Male	BG0006

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0000

Not Hispanic or Latino

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Maximum Flow Rate (Qmax) at Visit 5.

Maximum urine flow rate was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3, 4 and 5 (Days 21, 35 and 49 respectively). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value at Visit 5. Safety Population was defined as all participants who received more than or equal to one dose of study medication.

Safety Population

Posted

Mean

Standard Deviation

Milliliter (mL) per second

Baseline (Day -1) and on Day 49 (Visit 5)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Units	Counts
Participants	OG0007

Title

Denominators

Categories

Title	Measurements
	OG000-1.49± 4.797

Secondary

Change From Baseline in Maximum Flow Rate (Qmax) at Visits 3, 4 and 6

Maximum urine flow rate was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

mL per second

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Percent Change From Baseline in Qmax at Visits 3, 4, 5 and 6

Maximum urine flow rate was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. The percentage change from Baseline was calculated as post-baseline value minus Baseline value divided by Baseline value multiplied by 100. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)

Safety Population

Posted

Mean

Standard Deviation

Percent change

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in Percentage Residual Urinary Volume (RUV) at Visits 3, 4, 5 and 6

Percentage residual urinary volume is a standardized measure of post-residual volume and is defined as residual devided by residual plus voided multiplied by 100 where 'residual' is the post-void residual (PVR) volume collected on the bladder ultrasound and 'voided' is the voided volume collected on the uroflowmetry. Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated as post-baseline minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)

Safety Population

Posted

Mean

Standard Deviation

Percentage of residual urinary volume

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in Voided Volume (VV) at Visits 3, 4, 5 and 6

The volume of urine voided was measured by uroflowmetry test. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in Time to Maximum Flow at Visits 3, 4, 5 and 6

Time to maximum flow was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visits 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Seconds

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in Flow Time at Visits 3, 4, 5 and 6

Flow time was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visit 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Seconds

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in Average Flow Rate (Qmean) at Visits 3, 4, 5 and 6

Average flow rate was measured by uroflowmetry test. It is a non-invasive diagnostic test that measures the speed of urinary flow. Uroflowmetry was assessed at Baseline visit 2 (Day -1) and on visit 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

mL per second

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Frequency of Micturition as Recorded on the Voiding Diary for 2 Days Prior to Each Visit

The participants were asked to complete a voiding diary for two days preceding each visit. Frequency of micturition for 2 days prior to dach visit was defined as total number of entries recorded within 2 days prior to each post-baseline visit. Voiding diary was assessed at Baseline visit 2 (Day -1) and on visit 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Micturition voided

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Volume Voided as Recorded on the Voiding Diary for 2 Days Prior to Each Post-baseline Visit

The participants were asked to complete a voiding diary for two days preceding each visit. Volume voided for 2 days prior to each visit was defined as sum of urine recorded within 2 days prior to each post-baseline visit. Voiding diary was assessed at Baseline visit 2 (Day -1) and on visit 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in American Urological Association Symptom Index (AUA SI) at Visits 3, 4, 5 and 6

The America Urological Association Symptom Index is a 7-item Likert-scored scale describing urinary bladder function. It is the sum of the responses to the 7 AUA symptom questions. Score ranges from 0 to 5 (0=not at all and 5=almost always for questions 1 to 6; 0=None and 5=five times or more for question 7). The total score ranges from 0-35 where higher scores indicate more severe symptoms. It was completed by the investigator at Baseline visit 2 (Day -1) and on visit 3 (Day 21), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Measurement at visit 2 (Day -1) was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Scores on a scale

Baseline (Day -1) and up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Cystometry Assessment at Visits 3, 4, 5 and 6

Cystometry is a test of bladder function in which pressure and volume of fluid in the bladder is measured during filling, storage, and voiding. Cystometry was assessed at Baseline visit 2 (Day -1) and on visit 3 (Day 21), visit 4 (Day 35), visit 5 (Day 49) and visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). The requirement for cystometry was discovered by the study monitor and discussed with the GSK medical monitor after the participants had completed the study.

Data were not collected, although 3 participants met at least 1 of the criteria for multichannel cystometry during the study, the assessment was not performed.

Posted

Up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Secondary

Change From Baseline in PVR Volume by Bladder Ultrasound at Visits 3, 4, 5 and 6

PVR is the the amount of urine left in the bladder after urination. Bladder ultrasound was performed to assess PVR at Baseline/Visit 2 (Day -1), Visit 3 (Day 21), Visit 4 (Day 35), Visit 5 (Day 49) and Visit 6 (follow-up visit within 14 days after the end-of-treatment eye examination). Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Safety Population

Posted

Mean

Standard Deviation

Up to Day 80 (Visit 6)

ID	Title	Description
OG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ezogabine/Retigabine	Participants received ezogabine/retigabine tablets orally in three equally divided doses each day with or without food. The starting dose of ezogabine/retigabine was 300 milligrams (mg)/day. Participants were to be up titrated by 150 mg/day weekly up to a minimum ezogabine/retigabine daily dose of 600 mg/day and a maximum ezogabine/retigabine daily dose of 1200 mg/day. If participants missed one dose or more, it was recommended that they took a single dose as soon as they remember. After taking a missed dose, at least 3 hours were to elapse before the next dose and then the normal dosing schedule was to be resumed. After Day 22 of treatment, if a participant was unable to tolerate doses of ezogabine/retigabine greater than 600 mg/day, the investigator was able to decrease the dose as appropriate.	0	10	2	10	9	10

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Ataxia	Nervous system disorders	MedDRA 19.1	Systematic Assessment		EG0001 events1 affected10 at risk
Toxic encephalopathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment		EG0001 events1 affected10 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Diplopia	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected10 at risk
Vision blurred	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected10 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Discomfort	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected10 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected10 at risk
Oedema	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Thirst	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Gallbladder polyp	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Vaginal infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Aphasia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Balance disorder	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected10 at risk
Disturbance in attention	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0006 events3 affected10 at risk
Dysarthria	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected10 at risk
Paraesthesia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected10 at risk
Seizure	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Somnolence	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Tremor	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Confusional state	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected10 at risk
Libido decreased	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Dysuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected10 at risk
Haematuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected10 at risk

The study was terminated after 10 of 100 subjects had been enrolled. Statistical analyses were not performed as the sample size enrolled was too small to allow for these analyses to be meaningful. The data are presented as summary statistics only.

Certain Agreements

ID	Term
D004827	Epilepsy
D016055	Urinary Retention

Ancestor Terms

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D014555	Urination Disorders
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases

ID	Term
C101866	ezogabine

Units	Counts
Participants	OG00010

Units	Counts
Participants	OG00010

Units	Counts
Participants	OG00010

Units	Counts
Participants	OG00010

Units	Counts
Participants	OG0000