Trial Outcomes & Findings for An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures (NCT NCT01607346)
NCT ID: NCT01607346
Last Updated: 2020-12-04
Results Overview
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.
TERMINATED
PHASE4
10 participants
Baseline (Day -1) and on Day 49 (Visit 5)
2020-12-04
Participant Flow
This was a multicenter, open label study to examine the effect of ezogabine/retigabine added to existing anti-epileptic drugs on the voiding function of adult participants with drug-resistant partial onset seizures (POS). The study was conducted in two countries: United States and France.
The study was conducted in 5 phases:Screening (Day-30 to Day-2), Baseline (Day-1), treatment (Day1-49), taper-down titration (Day 50-70). A total of 10 participants were enrolled into the study and received at least one dose of the study medication.
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
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10
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Overall Study
COMPLETED
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7
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Overall Study
NOT COMPLETED
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3
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Reasons for withdrawal
| Measure |
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.
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Overall Study
Adverse Event
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3
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Baseline Characteristics
An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures
Baseline characteristics by cohort
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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|---|---|
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Age, Continuous
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40.8 Years
STANDARD_DEVIATION 9.62 • n=5 Participants
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Sex: Female, Male
Female
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4 Participants
n=5 Participants
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Sex: Female, Male
Male
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6 Participants
n=5 Participants
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Race/Ethnicity, Customized
Hispanic or Latino
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0 Participants
n=5 Participants
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Race/Ethnicity, Customized
Not Hispanic or Latino
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10 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline (Day -1) and on Day 49 (Visit 5)Population: Safety Population
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.
Outcome measures
| Measure |
Ezogabine/Retigabine
n=7 Participants
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.
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|---|---|
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Change From Baseline in Maximum Flow Rate (Qmax) at Visit 5.
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-1.49 Milliliter (mL) per second
Standard Deviation 4.797
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in Maximum Flow Rate (Qmax) at Visits 3, 4 and 6
Visit 3, n=9
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-5.32 mL per second
Standard Deviation 5.669
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Change From Baseline in Maximum Flow Rate (Qmax) at Visits 3, 4 and 6
Visit 4, n=8
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-3.83 mL per second
Standard Deviation 9.796
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Change From Baseline in Maximum Flow Rate (Qmax) at Visits 3, 4 and 6
Visit 6, n=10
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-2.22 mL per second
Standard Deviation 6.742
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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)
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Percent Change From Baseline in Qmax at Visits 3, 4, 5 and 6
Visit 3, n=9
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-23.45 Percent change
Standard Deviation 22.444
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Percent Change From Baseline in Qmax at Visits 3, 4, 5 and 6
Visit 4, n=8
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-6.53 Percent change
Standard Deviation 38.253
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Percent Change From Baseline in Qmax at Visits 3, 4, 5 and 6
Visit 5, n=7
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-1.44 Percent change
Standard Deviation 18.800
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Percent Change From Baseline in Qmax at Visits 3, 4, 5 and 6
Visit 6, n=10
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-7.14 Percent change
Standard Deviation 27.743
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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)
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in Percentage Residual Urinary Volume (RUV) at Visits 3, 4, 5 and 6
Visit 5, n=7
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-0.18 Percentage of residual urinary volume
Standard Deviation 19.716
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Change From Baseline in Percentage Residual Urinary Volume (RUV) at Visits 3, 4, 5 and 6
Visit 6, n=10
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7.56 Percentage of residual urinary volume
Standard Deviation 18.253
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Change From Baseline in Percentage Residual Urinary Volume (RUV) at Visits 3, 4, 5 and 6
Visit 3, n=9
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1.09 Percentage of residual urinary volume
Standard Deviation 17.450
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Change From Baseline in Percentage Residual Urinary Volume (RUV) at Visits 3, 4, 5 and 6
Visit 4, n=8
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3.77 Percentage of residual urinary volume
Standard Deviation 15.167
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in Voided Volume (VV) at Visits 3, 4, 5 and 6
Visit 3, n=9
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-81.3 mL
Standard Deviation 208.21
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Change From Baseline in Voided Volume (VV) at Visits 3, 4, 5 and 6
Visit 4, n=8
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-96.8 mL
Standard Deviation 205.80
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Change From Baseline in Voided Volume (VV) at Visits 3, 4, 5 and 6
Visit 5, n=7
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37.6 mL
Standard Deviation 225.33
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Change From Baseline in Voided Volume (VV) at Visits 3, 4, 5 and 6
Visit 6, n=10
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-68.9 mL
Standard Deviation 164.20
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in Time to Maximum Flow at Visits 3, 4, 5 and 6
Visit 3, n=9
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2.80 Seconds
Standard Deviation 6.588
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Change From Baseline in Time to Maximum Flow at Visits 3, 4, 5 and 6
Visit 4, n=8
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3.63 Seconds
Standard Deviation 12.683
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Change From Baseline in Time to Maximum Flow at Visits 3, 4, 5 and 6
Visit 5, n=7
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6.51 Seconds
Standard Deviation 11.476
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Change From Baseline in Time to Maximum Flow at Visits 3, 4, 5 and 6
Visit 6, n=10
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-1.78 Seconds
Standard Deviation 6.296
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in Flow Time at Visits 3, 4, 5 and 6
Visit 3, n=9
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0.22 Seconds
Standard Deviation 10.269
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Change From Baseline in Flow Time at Visits 3, 4, 5 and 6
Visit 4, n=8
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-1.13 Seconds
Standard Deviation 6.873
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Change From Baseline in Flow Time at Visits 3, 4, 5 and 6
Visit 5, n=7
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9.07 Seconds
Standard Deviation 14.007
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Change From Baseline in Flow Time at Visits 3, 4, 5 and 6
Visit 6, n=10
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-1.63 Seconds
Standard Deviation 12.278
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in Average Flow Rate (Qmean) at Visits 3, 4, 5 and 6
Visit 3, n=9
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-1.97 mL per second
Standard Deviation 5.406
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Change From Baseline in Average Flow Rate (Qmean) at Visits 3, 4, 5 and 6
Visit 4, n=8
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-2.80 mL per second
Standard Deviation 7.085
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Change From Baseline in Average Flow Rate (Qmean) at Visits 3, 4, 5 and 6
Visit 5, n=7
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-1.04 mL per second
Standard Deviation 4.295
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Change From Baseline in Average Flow Rate (Qmean) at Visits 3, 4, 5 and 6
Visit 6, n=10
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-2.62 mL per second
Standard Deviation 5.765
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Frequency of Micturition as Recorded on the Voiding Diary for 2 Days Prior to Each Visit
Visit 3, n=8
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8.1 Micturition voided
Standard Deviation 3.60
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Frequency of Micturition as Recorded on the Voiding Diary for 2 Days Prior to Each Visit
Visit 4, n=8
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9.4 Micturition voided
Standard Deviation 5.32
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Frequency of Micturition as Recorded on the Voiding Diary for 2 Days Prior to Each Visit
Visit 5, n=6
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9.7 Micturition voided
Standard Deviation 4.72
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Frequency of Micturition as Recorded on the Voiding Diary for 2 Days Prior to Each Visit
Visit 6, n=9
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9.7 Micturition voided
Standard Deviation 5.27
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Volume Voided as Recorded on the Voiding Diary for 2 Days Prior to Each Post-baseline Visit
Visit 3, n=8
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2850.1 mL
Standard Deviation 1238.42
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Volume Voided as Recorded on the Voiding Diary for 2 Days Prior to Each Post-baseline Visit
Visit 4, n=8
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3558.1 mL
Standard Deviation 1713.81
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Volume Voided as Recorded on the Voiding Diary for 2 Days Prior to Each Post-baseline Visit
Visit 5, n=6
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3470.8 mL
Standard Deviation 1463.08
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Volume Voided as Recorded on the Voiding Diary for 2 Days Prior to Each Post-baseline Visit
Visit 6, n=9
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2736.1 mL
Standard Deviation 1466.70
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SECONDARY outcome
Timeframe: Baseline (Day -1) and up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in American Urological Association Symptom Index (AUA SI) at Visits 3, 4, 5 and 6
Visit 6, n=10
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0.4 Scores on a scale
Standard Deviation 1.51
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Change From Baseline in American Urological Association Symptom Index (AUA SI) at Visits 3, 4, 5 and 6
Visit 3, n=10
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1.6 Scores on a scale
Standard Deviation 3.10
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Change From Baseline in American Urological Association Symptom Index (AUA SI) at Visits 3, 4, 5 and 6
Visit 5, n=7
|
0.7 Scores on a scale
Standard Deviation 1.25
|
SECONDARY outcome
Timeframe: Up to Day 80 (Visit 6)Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Day 80 (Visit 6)Population: Safety Population
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).
Outcome measures
| Measure |
Ezogabine/Retigabine
n=10 Participants
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.
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Change From Baseline in PVR Volume by Bladder Ultrasound at Visits 3, 4, 5 and 6
Visit 3, n=10
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-17.2 mL
Standard Deviation 88.05
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Change From Baseline in PVR Volume by Bladder Ultrasound at Visits 3, 4, 5 and 6
Visit 4, n=8
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-6.3 mL
Standard Deviation 88.00
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Change From Baseline in PVR Volume by Bladder Ultrasound at Visits 3, 4, 5 and 6
Visit 5, n=7
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-13.9 mL
Standard Deviation 105.67
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Change From Baseline in PVR Volume by Bladder Ultrasound at Visits 3, 4, 5 and 6
Visit 6, n=10
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3.5 mL
Standard Deviation 64.09
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Adverse Events
Ezogabine/Retigabine
Serious adverse events
| Measure |
Ezogabine/Retigabine
n=10 participants at risk
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.
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Nervous system disorders
Ataxia
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Toxic encephalopathy
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Other adverse events
| Measure |
Ezogabine/Retigabine
n=10 participants at risk
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.
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|---|---|
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Cardiac disorders
Palpitations
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Eye disorders
Diplopia
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20.0%
2/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Eye disorders
Vision blurred
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30.0%
3/10 • Number of events 4 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Gastrointestinal disorders
Abdominal pain lower
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Gastrointestinal disorders
Abdominal pain upper
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Gastrointestinal disorders
Constipation
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Gastrointestinal disorders
Rectal haemorrhage
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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General disorders
Discomfort
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20.0%
2/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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General disorders
Fatigue
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20.0%
2/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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General disorders
Oedema
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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General disorders
Thirst
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Hepatobiliary disorders
Gallbladder polyp
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Infections and infestations
Vaginal infection
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Musculoskeletal and connective tissue disorders
Back pain
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Musculoskeletal and connective tissue disorders
Limb discomfort
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Aphasia
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Balance disorder
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20.0%
2/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Disturbance in attention
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Dizziness
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30.0%
3/10 • Number of events 6 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Dysarthria
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10.0%
1/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Paraesthesia
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20.0%
2/10 • Number of events 3 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Seizure
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Somnolence
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Nervous system disorders
Tremor
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Psychiatric disorders
Confusional state
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20.0%
2/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Psychiatric disorders
Libido decreased
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Renal and urinary disorders
Dysuria
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20.0%
2/10 • Number of events 2 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Renal and urinary disorders
Haematuria
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Skin and subcutaneous tissue disorders
Dry skin
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10.0%
1/10 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment until the follow-up visit within 14 days after the end-of-treatment eye examination (approximately up to 80 days).
On treatment SAEs and non-serious AEs were reported for the Safety Population which included all participants who received more than or equal to one dose of study medication.
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Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- 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