Seizures
Conditions
Keywords
Partial Seizures, Complex Partial Seizures, Epilepsy, Potassium Channels, Anticonvulsant
Brief summary
This Phase 3 study is being conducted to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs).
Detailed description
This Phase 3 study is being conducted in Europe, Israel, Australia, and South Africa to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs). The primary objective is to demonstrate a superior change in total partial seizure frequency for four weeks from baseline to the double-blind period. The proportion of responders (greater than or equal to 50% reduction in seizure frequency for four weeks from baseline to the double-blind period) will also be evaluated.
Interventions
DRUGRetigabine
Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 3, patients will enter a 12 week maintenance phase.
DRUGPlacebo
Oral tablet.
Sponsors
Bausch Health Americas, Inc.
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of refractory epilepsy with simple or complex partial onset seizures with or without secondary generalization * 28-day partial seizure frequency rate of four or more partial seizures over the 8-week baseline phase * Currently treated with up to three established AEDs * Vagal Nerve Stimulator may be included
Exclusion criteria
* Existing medical or psychiatric condition which could affect patient's health or compromise ability to participate in the study * Clinically significant abnormalities on physical exam, vital signs, ECG, or liver function tests * Impaired renal function (creatinine clearance less than 50 mL/minute) * Evidence of progressive central nervous disease, lesion, or encephalopathy * History of primary generalized seizures * History of clustering or flurries or status epilepticus within 12 months of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases) | Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16) | 28-day total PS (PSs \[also called focal seizures\] are seizures limited to a specific area of the brain) frequency in the BL period = (Number \[No.\] of total PSs reported in the BL period divided by the No. of days of available total PS data in the BL period) x 28 days. 28-day total PS frequency in the DB period = (No. of total PSs reported in the DB period divided by the No. of days of available total PS data in the DB period) x 28 days. Percent change = (\[value in the DB period minus value at BL\] divided by the BL value) x 100%. Negative valu es indicate a reduction in seizure frequency. |
| Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Week 5 through Week 16 | Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the Maintenance Phase as compared to the Baseline period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | Baseline (Week -7 through Week 0), Week 1 through Week 16 | Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a reduction of 75-100%, 50-\<75%, 25-\<50%, or \<25%, in addition to having no reduction. This quartile cutting was specified in the study protocol. Participants without any post-baseline data are included in the No reduction category. |
| Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Baseline (Week -7 through Week 0), Week 1 through Week 16 | Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized in decile cutting, i.e., reduction categories of 90-100%, 80-\<90%, 70-\<80%, 60-\<70%, 50-\<60%, 40-\<50%, 30-\<40%, 20-\<30%, 10-\<20%, \>0-\<10%, and increase categories of 0-10%, \>10-20%, \>20-30%, \>30% (FDA endpoint). Participants without any post-baseline data were included in the category 0-10% increase category. |
| Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | Baseline (Week -7 through Week 0), Week 5 through Week 16 | Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a \>75%, a 50-75%, or a \<50% reduction, in addition to having no reduction (EMEA endpoint). |
| Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | Baseline (Week -7 through Week 0), Week 5 through Week 16 | Participants who experienced an exacerbation from Baseline in the 28-day total partial seizure frequency were categorized as having a 0-25% or a \>25% increase (EMEA endpoint). The number of participants experiencing a \>0% reduction from Baseline in the 28-day total partial seizure frequency are also presented. |
| Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Baseline (Week -7 through Week 0), Week 1 through Week 16 | New seizure types included those seizures which were not reported by any participant at Baseline. |
| Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Week 1 through Week 16 | Participants were considered to be seizure-free if they had not reported any seizures during the DB treatment period (Weeks 1-18). For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18. |
| Number of Participants Who Were Seizure-free During the Maintenance Phase | Week 5 through Week 16 | Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase. |
| Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases) | Week 1 through Week 16 | A seizure-free day was a day without any seizures. For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18. The percentage of seizure-free days was calculated as the total number of days without seizures in the DB period divided by the number of days in DB period x 100%. |
| Number of Participants Who Were Responders and Non-responders During the DB Phase | Week 1 through Week 16 | Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the DB Phase as compared to the Baseline period. Participants without any post-baseline data were considered non-responders. |
| Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase | Week 16/end of treatment phase | Clinical Global Impression of Improvement (CGI-I) is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the treatment. Scores on the scale are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. |
| Patient Global Impression (PGI) Score at the End of the Maintenance Phase | Week 16/end of treatment phase | PGI is a participant-rated scale of improvement that was administered at the end of the Maintenance Phase in order to assess the participant's impression of his or her own improvement. PGI assessments were scored using a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. |
| Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | End of Baseline (Week 0), Weeks 4, 8, and 16 | The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, overall QOL. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are first converted to 0-100 point scores; higher converted scores always reflect better QOL. The overall score is derived by weighting and then summing the 7 domain scores. |
| Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Week 1 through Week 16 | Clinically important changes in laboratory values were to be reported as an adverse event if they met one of the following criteria: (1) intervention required; (2) change in dose of study drug required; (3) other treatment/therapy required; (4) association with other diagnoses. |
| Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Week 1 through Week 16 | A summary of the adverse events classified as renal or urinary disorders and in which at least 2% (rounded to an integer) of participants in any treatment arm reported during the study is presented. |
| Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Baseline (Week -7 through 0), Weeks 8 and 16 | Post-void residual (PVR) urine refers to the amount of urine remaining in the bladder after normal urination. To investigate the possible effects of retigabine on bladder function, all participants underwent post-void residual bladder ultrasound at Baseline and during the Maintenance Phase. The PVR bladder ultrasound was performed by a urologist, a qualified ultrasound technician, or a qualified study nurse who was certified to do PVR bladder ultrasound. Change from Baseline in PVR residual volume was calculated as the values at Week 10 and Week 16 minus the value at Baseline. |
| Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase | The number of participants with recorded weight gain of \>=7% over their baseline weight was measured. |
| Percentage of Seizure-free Days During the Maintenance Phase | Week 5 through Week 16 | A seizure-free day was a day without any seizures. The percentage of seizure-free days was calculated as the total number of days without seizures in the Maintenance Phase divided by the number of days in the Maintenance Phase x 100%. |
| Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | Baseline (Week -7 through Week 0), Week 5 through Week 16 | 28-day total partial seizure frequency in the BL period = (No. of total partial seizures reported in the BL period divided by the No. of days of available total partial seizure data in the BL period) x 28 days. 28-day total partial seizure frequency in the Maintenance Phase = (No. of total partial seizures reported in the Maintenance Phase divided by the No. of days of available total partial seizure data in the same phase) x 28 days. Percent change = (value in the Maintenance Phase minus value at BL divided by the BL value) x 100%. Negative values indicate a reduction in seizure frequency. |
Countries
Australia, Belgium, France, Germany, Hungary, Israel, Poland, Russia, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Participants who completed the Double-blind Phase (Titration plus Maintenance Phases) who elected to continue in the Open-Label Extension Study (OLE-S) entered the Transition Phase, for titration, if on placebo, or to maintain the blind if on retigabine. Participants who did not enter the Titration Phase entered a Taper Phase.
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Matching placebo tablets of dummy strengths of 50 milligrams (mg) and 100 mg were administered orally thrice a day (TID) during the 4-week Titration Phase and the 12-week Maintenance Phase | 179 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID | 181 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID | 178 |
| Total | 538 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 12-Week Maintenance Phase | Abnormal Electrocardiogram Test Result | 1 | 0 | 0 |
| 12-Week Maintenance Phase | Adverse Event | 8 | 12 | 26 |
| 12-Week Maintenance Phase | Lack of Efficacy | 5 | 0 | 0 |
| 12-Week Maintenance Phase | Lost to Follow-up | 2 | 3 | 0 |
| 12-Week Maintenance Phase | Protocol Violation | 0 | 4 | 2 |
| 12-Week Maintenance Phase | Withdrawal by Subject | 0 | 8 | 3 |
| 4-Week Titration Phase | Adverse Event | 6 | 14 | 20 |
| 4-Week Titration Phase | Lost to Follow-up | 0 | 1 | 1 |
| 4-Week Titration Phase | Participant Did Not Receive Study Drug | 0 | 0 | 1 |
| 4-Week Titration Phase | Prolonged QT Interval at Visit 3 | 1 | 0 | 0 |
| 4-Week Titration Phase | Protocol Violation | 2 | 2 | 1 |
| 4-Week Titration Phase | Randomization Occurred in Error | 1 | 0 | 0 |
| 4-Week Titration Phase | Withdrawal by Subject | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Total |
|---|---|---|---|---|
| Age, Continuous | 37.5 Years STANDARD_DEVIATION 12.02 | 37.7 Years STANDARD_DEVIATION 12.77 | 37.7 Years STANDARD_DEVIATION 11.75 | 37.6 Years STANDARD_DEVIATION 12.16 |
| Race/Ethnicity, Customized African-American (black) | 2 participants | 1 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Caucasian | 173 participants | 170 participants | 169 participants | 512 participants |
| Race/Ethnicity, Customized Mixed Race | 6 participants | 5 participants | 5 participants | 16 participants |
| Sex: Female, Male Female | 105 Participants | 85 Participants | 90 Participants | 280 Participants |
| Sex: Female, Male Male | 76 Participants | 93 Participants | 89 Participants | 258 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 56 / 179 | 38 / 147 | 92 / 181 | 18 / 132 | 117 / 178 | 29 / 114 |
| serious Total, serious adverse events | 7 / 179 | 2 / 147 | 14 / 181 | 3 / 132 | 15 / 178 | 3 / 114 |
Outcome results
Primary
Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the Maintenance Phase as compared to the Baseline period.
Time frame: Week 5 through Week 16
Population: ITT European Medicines Evaluation Agency (EMEA) Population: all randomized participants who had received at least 1 dose of study drug in the Maintenance Phase and had at least 1 seizure measurement (whether or not they had a seizure) recorded in the Maintenance Phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Responders | 31 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Non-responders | 133 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Responders | 70 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Non-responders | 79 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Responders | 61 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Classified as Responders and Non-responders During the Maintenance Phase | Non-responders | 97 participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Primary
Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases)
28-day total PS (PSs \[also called focal seizures\] are seizures limited to a specific area of the brain) frequency in the BL period = (Number \[No.\] of total PSs reported in the BL period divided by the No. of days of available total PS data in the BL period) x 28 days. 28-day total PS frequency in the DB period = (No. of total PSs reported in the DB period divided by the No. of days of available total PS data in the DB period) x 28 days. Percent change = (\[value in the DB period minus value at BL\] divided by the BL value) x 100%. Negative valu es indicate a reduction in seizure frequency.
Time frame: Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
Population: Intent-to-Treat Food and Drug Administration (ITT FDA) Population: all randomized participants (P) who received at least 1 dose of study drug. Only participants with post-BL seizure data are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases) | -15.9 percent change in seizure frequency |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases) | -39.9 percent change in seizure frequency |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases) | -27.9 percent change in seizure frequency |
p-value: <0.001Non-parametric rank ANCOVA
p-value: 0.007Non-parametric rank ANCOVA
Secondary
Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase
Post-void residual (PVR) urine refers to the amount of urine remaining in the bladder after normal urination. To investigate the possible effects of retigabine on bladder function, all participants underwent post-void residual bladder ultrasound at Baseline and during the Maintenance Phase. The PVR bladder ultrasound was performed by a urologist, a qualified ultrasound technician, or a qualified study nurse who was certified to do PVR bladder ultrasound. Change from Baseline in PVR residual volume was calculated as the values at Week 10 and Week 16 minus the value at Baseline.
Time frame: Baseline (Week -7 through 0), Weeks 8 and 16
Population: Safety Population. Only participants who remained in the study at the indicated week and who also had a PVR assessment were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Week 8, n=143, 134, 121 | 0 milliliters |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Week 16, n=141, 131, 115 | 0 milliliters |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Week 8, n=143, 134, 121 | 0 milliliters |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Week 16, n=141, 131, 115 | 0 milliliters |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Week 8, n=143, 134, 121 | 0 milliliters |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase | Week 16, n=141, 131, 115 | 0 milliliters |
Secondary
Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
Clinical Global Impression of Improvement (CGI-I) is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the treatment. Scores on the scale are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time frame: Week 16/end of treatment phase
Population: ITT EMEA Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase | 3.2 scores on a scale | Standard Deviation 0.99 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase | 2.9 scores on a scale | Standard Deviation 1.05 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase | 2.9 scores on a scale | Standard Deviation 1.21 |
Secondary
Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline
New seizure types included those seizures which were not reported by any participant at Baseline.
Time frame: Baseline (Week -7 through Week 0), Week 1 through Week 16
Population: ITT FDA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Tonic seizures | 3 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial seizures with motor signs | 5 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial evolving to secondarily generalized | 6 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial seizures without motor signs | 9 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Tonic-clonic seizures | 0 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Unclassified seizures | 0 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Complex partial seizures | 1 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Flurries | 3 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Unclassified seizures | 1 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Tonic seizures | 0 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Complex partial seizures | 4 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial evolving to secondarily generalized | 5 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Flurries | 2 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial seizures with motor signs | 6 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Tonic-clonic seizures | 0 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial seizures without motor signs | 8 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Unclassified seizures | 0 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial seizures without motor signs | 12 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial evolving to secondarily generalized | 9 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Partial seizures with motor signs | 3 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Tonic-clonic seizures | 3 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Tonic seizures | 1 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Complex partial seizures | 4 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline | Flurries | 1 participants |
Secondary
Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase
Participants who experienced an exacerbation from Baseline in the 28-day total partial seizure frequency were categorized as having a 0-25% or a \>25% increase (EMEA endpoint). The number of participants experiencing a \>0% reduction from Baseline in the 28-day total partial seizure frequency are also presented.
Time frame: Baseline (Week -7 through Week 0), Week 5 through Week 16
Population: ITT EMEA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | >=25% increase | 22 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | 0% to 25% increase | 28 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | >0% reduction | 114 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | >=25% increase | 23 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | 0% to 25% increase | 14 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | >0% reduction | 121 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | 0% to 25% increase | 11 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | >0% reduction | 119 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase | >=25% increase | 19 participants |
Secondary
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
A summary of the adverse events classified as renal or urinary disorders and in which at least 2% (rounded to an integer) of participants in any treatment arm reported during the study is presented.
Time frame: Week 1 through Week 16
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Haematuria | 2 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Polyuria | 4 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Dysuria | 0 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary hesitation | 3 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary retention | 0 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Dysuria | 3 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Haematuria | 5 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary retention | 1 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary hesitation | 6 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Polyuria | 1 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Dysuria | 4 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Polyuria | 2 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary hesitation | 1 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Haematuria | 2 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary retention | 4 participants |
| Placebo - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Haematuria | 1 participants |
| Placebo - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Dysuria | 0 participants |
| Placebo - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary retention | 0 participants |
| Placebo - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Polyuria | 0 participants |
| Placebo - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary hesitation | 3 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Polyuria | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Haematuria | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Dysuria | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary retention | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary hesitation | 1 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary hesitation | 0 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Haematuria | 1 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Polyuria | 0 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Dysuria | 0 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm) | Urinary retention | 0 participants |
Secondary
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Clinically important changes in laboratory values were to be reported as an adverse event if they met one of the following criteria: (1) intervention required; (2) change in dose of study drug required; (3) other treatment/therapy required; (4) association with other diagnoses.
Time frame: Week 1 through Week 16
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Protenuria | 3 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hyperlipidemia | 3 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hypercholesterolemia | 2 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hematuria | 2 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hypercholesterolemia | 4 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hyperlipidemia | 0 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Protenuria | 2 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hematuria | 5 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hematuria | 2 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hypercholesterolemia | 1 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hyperlipidemia | 0 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Protenuria | 0 participants |
| Placebo - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Protenuria | 0 participants |
| Placebo - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hematuria | 1 participants |
| Placebo - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hyperlipidemia | 0 participants |
| Placebo - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hypercholesterolemia | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hypercholesterolemia | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hematuria | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hyperlipidemia | 0 participants |
| Retigabine 200 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Protenuria | 1 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hyperlipidemia | 0 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hypercholesterolemia | 1 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Hematuria | 1 participants |
| Retigabine 300 mg TID - Transition Phase | Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm) | Protenuria | 0 participants |
Secondary
Number of Participants Who Were Responders and Non-responders During the DB Phase
Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the DB Phase as compared to the Baseline period. Participants without any post-baseline data were considered non-responders.
Time frame: Week 1 through Week 16
Population: ITT FDA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Were Responders and Non-responders During the DB Phase | Responders | 31 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Were Responders and Non-responders During the DB Phase | Non-responders | 148 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Responders and Non-responders During the DB Phase | Responders | 57 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Responders and Non-responders During the DB Phase | Non-responders | 124 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Responders and Non-responders During the DB Phase | Responders | 70 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Responders and Non-responders During the DB Phase | Non-responders | 108 participants |
Secondary
Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Participants were considered to be seizure-free if they had not reported any seizures during the DB treatment period (Weeks 1-18). For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18.
Time frame: Week 1 through Week 16
Population: ITT FDA Population. Only participants with post-baseline seizure data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Seizure-free | 2 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Not seizure-free | 174 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Seizure-free | 0 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Not seizure-free | 179 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Seizure-free | 7 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases) | Not seizure-free | 168 participants |
Secondary
Number of Participants Who Were Seizure-free During the Maintenance Phase
Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.
Time frame: Week 5 through Week 16
Population: ITT EMEA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the Maintenance Phase | Seizure-free | 2 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the Maintenance Phase | Not seizure-free | 162 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the Maintenance Phase | Seizure-free | 5 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the Maintenance Phase | Not seizure-free | 153 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the Maintenance Phase | Seizure-free | 7 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants Who Were Seizure-free During the Maintenance Phase | Not seizure-free | 142 participants |
Secondary
Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase
The number of participants with recorded weight gain of \>=7% over their baseline weight was measured.
Time frame: Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase
Population: Safety Population. Only participants who remained in the study at the indicated week and who also had a body weight assessment were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 16, n=153, 139, 132 | 4 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 2, n=174, 180, 175 | 0 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 6, n=169, 165, 152 | 1 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 12, n=159, 151, 144 | 6 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 4, n=169, 172, 167 | 0 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 8, n=161, 160, 149 | 1 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 6, n=169, 165, 152 | 8 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 8, n=161, 160, 149 | 9 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 12, n=159, 151, 144 | 15 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 16, n=153, 139, 132 | 13 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 2, n=174, 180, 175 | 3 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 4, n=169, 172, 167 | 7 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 16, n=153, 139, 132 | 12 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 4, n=169, 172, 167 | 8 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 2, n=174, 180, 175 | 3 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 12, n=159, 151, 144 | 13 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 6, n=169, 165, 152 | 7 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase | Week 8, n=161, 160, 149 | 7 participants |
Secondary
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized in decile cutting, i.e., reduction categories of 90-100%, 80-\<90%, 70-\<80%, 60-\<70%, 50-\<60%, 40-\<50%, 30-\<40%, 20-\<30%, 10-\<20%, \>0-\<10%, and increase categories of 0-10%, \>10-20%, \>20-30%, \>30% (FDA endpoint). Participants without any post-baseline data were included in the category 0-10% increase category.
Time frame: Baseline (Week -7 through Week 0), Week 1 through Week 16
Population: ITT FDA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >10% to 20% | 13 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 50% to <60% | 9 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: 0% to 10% | 20 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >30% | 25 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 40% to <50% | 9 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 90% to 100% | 3 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 80% to <90% | 4 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 30% to <40% | 15 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >20% to 30% | 8 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: >0% to <10% | 16 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 20% to <30% | 24 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 60% to <70% | 7 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 10% to <20% | 18 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 70% to <80% | 8 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 10% to <20% | 18 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: >0% to <10% | 13 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: 0% to 10% | 11 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 70% to <80% | 11 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >10% to 20% | 9 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >20% to 30% | 3 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 60% to <70% | 14 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 90% to 100% | 5 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 50% to <60% | 19 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 40% to <50% | 13 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 30% to <40% | 16 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 80% to <90% | 8 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 20% to <30% | 16 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >30% | 25 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >30% | 24 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 90% to 100% | 11 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 80% to <90% | 14 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 70% to <80% | 7 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 60% to <70% | 21 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 50% to <60% | 17 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 40% to <50% | 17 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 30% to <40% | 21 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 10% to <20% | 10 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: >0% to <10% | 8 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: 0% to 10% | 11 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >10% to 20% | 7 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Increase: >20% to 30% | 1 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories | Reduction: 20% to <30% | 9 participants |
Secondary
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories
Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a reduction of 75-100%, 50-\<75%, 25-\<50%, or \<25%, in addition to having no reduction. This quartile cutting was specified in the study protocol. Participants without any post-baseline data are included in the No reduction category.
Time frame: Baseline (Week -7 through Week 0), Week 1 through Week 16
Population: ITT FDA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | >0 to <25% reduction | 43 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 25% to <50% reduction | 39 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | No reduction | 66 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 75% to 100% reduction | 12 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 50% to <75% reduction | 19 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 50% to <75% reduction | 41 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 75% to 100% reduction | 16 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 25% to <50% reduction | 38 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | No reduction | 48 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | >0 to <25% reduction | 38 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | No reduction | 43 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 25% to <50% reduction | 41 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 75% to 100% reduction | 27 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | >0 to <25% reduction | 24 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories | 50% to <75% reduction | 43 participants |
Secondary
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a \>75%, a 50-75%, or a \<50% reduction, in addition to having no reduction (EMEA endpoint).
Time frame: Baseline (Week -7 through Week 0), Week 5 through Week 16
Population: ITT EMEA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | >75% reduction | 11 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | >0 to <50% reduction | 83 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | 50% to 75% reduction | 20 participants |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | No reduction | 50 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | No reduction | 37 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | >75% reduction | 27 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | 50% to 75% reduction | 34 participants |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | >0 to <50% reduction | 60 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | No reduction | 30 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | >75% reduction | 30 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | >0 to <50% reduction | 49 participants |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | 50% to 75% reduction | 40 participants |
Secondary
Patient Global Impression (PGI) Score at the End of the Maintenance Phase
PGI is a participant-rated scale of improvement that was administered at the end of the Maintenance Phase in order to assess the participant's impression of his or her own improvement. PGI assessments were scored using a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time frame: Week 16/end of treatment phase
Population: ITT EMEA Population. Only participants with post-baseline PGI scores were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Patient Global Impression (PGI) Score at the End of the Maintenance Phase | 3.3 scores on a scale | Standard Deviation 1 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Patient Global Impression (PGI) Score at the End of the Maintenance Phase | 2.9 scores on a scale | Standard Deviation 1.11 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Patient Global Impression (PGI) Score at the End of the Maintenance Phase | 3.0 scores on a scale | Standard Deviation 1.43 |
Secondary
Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
A seizure-free day was a day without any seizures. For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18. The percentage of seizure-free days was calculated as the total number of days without seizures in the DB period divided by the number of days in DB period x 100%.
Time frame: Week 1 through Week 16
Population: ITT FDA Population. Only participants who had post-baseline seizure data were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases) | 77.8 percentage of days |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases) | 79.5 percentage of days |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases) | 82.1 percentage of days |
Secondary
Percentage of Seizure-free Days During the Maintenance Phase
A seizure-free day was a day without any seizures. The percentage of seizure-free days was calculated as the total number of days without seizures in the Maintenance Phase divided by the number of days in the Maintenance Phase x 100%.
Time frame: Week 5 through Week 16
Population: ITT EMEA Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Percentage of Seizure-free Days During the Maintenance Phase | 78.1 percentage of days |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Percentage of Seizure-free Days During the Maintenance Phase | 81.6 percentage of days |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Percentage of Seizure-free Days During the Maintenance Phase | 84.5 percentage of days |
Secondary
Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
28-day total partial seizure frequency in the BL period = (No. of total partial seizures reported in the BL period divided by the No. of days of available total partial seizure data in the BL period) x 28 days. 28-day total partial seizure frequency in the Maintenance Phase = (No. of total partial seizures reported in the Maintenance Phase divided by the No. of days of available total partial seizure data in the same phase) x 28 days. Percent change = (value in the Maintenance Phase minus value at BL divided by the BL value) x 100%. Negative values indicate a reduction in seizure frequency.
Time frame: Baseline (Week -7 through Week 0), Week 5 through Week 16
Population: ITT EMEA Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | -17.4 Percent change in seizure frequency |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | -35.3 Percent change in seizure frequency |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase | -44.3 Percent change in seizure frequency |
Secondary
Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16
The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, overall QOL. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are first converted to 0-100 point scores; higher converted scores always reflect better QOL. The overall score is derived by weighting and then summing the 7 domain scores.
Time frame: End of Baseline (Week 0), Weeks 4, 8, and 16
Population: Safety Population: all randomized participants who received at least 1 dose of retigabine or placebo. Only participants with QOLIE-31-P data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Baseline, n=165, 173, 166 | 53.3 scores on a scale | Standard Deviation 16.62 |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 4 (Titration Phase), n=155, 155, 149) | 55.4 scores on a scale | Standard Deviation 16.41 |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 8 (Maintenance Phase), n=141, 146, 127 | 55.3 scores on a scale | Standard Deviation 17.05 |
| Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 16 (Maintenance Phase), n=143, 133, 123 | 54.7 scores on a scale | Standard Deviation 16.82 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 16 (Maintenance Phase), n=143, 133, 123 | 59.1 scores on a scale | Standard Deviation 16.57 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Baseline, n=165, 173, 166 | 56.0 scores on a scale | Standard Deviation 17.45 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 8 (Maintenance Phase), n=141, 146, 127 | 59.6 scores on a scale | Standard Deviation 17.32 |
| Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 4 (Titration Phase), n=155, 155, 149) | 57.3 scores on a scale | Standard Deviation 18.12 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 16 (Maintenance Phase), n=143, 133, 123 | 53.2 scores on a scale | Standard Deviation 16.38 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 4 (Titration Phase), n=155, 155, 149) | 52.7 scores on a scale | Standard Deviation 16.94 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Week 8 (Maintenance Phase), n=141, 146, 127 | 52.7 scores on a scale | Standard Deviation 16.47 |
| Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) | Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16 | Baseline, n=165, 173, 166 | 52.1 scores on a scale | Standard Deviation 15.93 |