Epilepsy
Conditions
Keywords
Pregabalin for partial seizures
Brief summary
The objective of study is to assess the clinical improvement (change in seizure frequency), safety, and tolerability of subjects with partial seizures following adjunctive therapy of pregabalin BID (150 to 600 mg/day titration) in addition to existing standards AEDs.
Interventions
DRUGPregabalin
Pregabalin treatment, given as 2 divided doses, is initiated at a dose of 150 mg/day (75 mg BID). Based on individual subject response and tolerability, the dosage may be increased to 300 mg/day after 1 week (150 mg BID given as two 75-mg capsules BID). Based on subjects individual response and tolerability, dosage can be incrementally increased further after an additional week to 600 mg/day (300 mg BID given as four 75-mg capsules BID).
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients equal to or greater than 18 years of age with diagnosis of epilepsy with partial seizures having minimum of two partial seizures during a two month period before the baseline visit * Having a clinical history of epilepsy and AED treatment at least 1 year prior to inclusion
Exclusion criteria
* AED or Seizures/Epilepsy Related Exclusions:having a treatable cause of seizures * Having absences seizures * Having had status epileptics within the year prior to inclusion * Having a progressive neurological or systematic disorder * Having known significant renal or hepatic dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period | 8 week baseline period & 12 week treatment observation period | Percentage change from baseline=\[(12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate)/ 8 week baseline period seizure frequency rate\] x 100. Seizure frequencies per 28-day period: = (total # of partial seizures in period x 28 / (total # of days in period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | 8 week baseline period and 21 week treatment period | Percentage change from baseline = \[(4 week seizure frequency minus 8 week baseline) / (8 week baseline seizure frequency)\] x 100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency. |
| Number of Subjects Seizure-free | last 4 weeks & whole 12 week treatment observation period | Count of subjects seizure free during the period. |
| Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. | 8 week baseline observation period & last 4 weeks of observation period | Number of subjects with at least a 50% or 75% reduction in partial seizure frequency between baseline and treatment period. |
| Subjects Achieving Seizure Freedom During Observation Period | Day 147 from the first dose of study drug | Number of subjects achieving seizure freedom (no seizures) during last 4 weeks or duration of 12 week observation period. |
| Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency | 8 week baseline observation period & 12 week treatment observation period | Percentage change from baseline = ((12 weeks - 8 weeks)/8 weeks)\*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency. |
| Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period. | 8 week baseline period and 21 week treatment period | Percentage change from baseline = ((21 weeks-8 weeks)/8 weeks)\*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency. |
| Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | End of 21-week treatment | The CGIC is a clinician's judgment of the overall change in the patient's condition over a defined period on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
| Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Baseline, end of 21-week treatment | Subjects recall sleep related activities over the previous 4 weeks. Low scores reflect greater impairment (except sleep adequacy, optimal sleep, &quantity). Range = 0 - 100 for Sleep Disturbance, Snoring, Awaken Short of Breath, Sleep Adequacy, Somnolence, & Sleep Problems Index. Quantity of Sleep Range = 0 - 24. Optimal Sleep Range 0 - 1. |
| Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. | Baseline, End of 21-week treatment | Change in total HADS score between Baseline and Week 21. Each of the 14 items is scored 0, 1, 2 or 3 where a score of 3 corresponds to the most anxious/depressed. 7-item depression and 7-item anxiety subscales are summed; each resulting in a total score of 0-21. |
| Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline | Baseline, End of 21-week treatment | Count of subjects with a weight gain of at least 7 percent relative to baseline. |
| Subjects Assessment of Optimal Sleep | Baseline, End of 21-week treatment | Number of subjects that responded optimal or non-optimal sleep in Optimal Sleep subscale of Medical Outcomes Study (MOS) Sleep scale. |
| Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | End of 21-week treatment | The PGIC is a patient-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
Countries
Greece
Participant flow
Recruitment details
Planned to enroll approximately 100 subjects with partial seizures at up to 10 study centers in Greece.
Pre-assignment details
Single arm open label study without randomization. The study included the following 3 main phases with a total study treatment duration of up to 21 weeks: Treatment dose-optimization phase = 9 weeks. Treatment observation phase = 12 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period). | 98 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Pregabalin |
|---|---|
| Age, Customized 18 to 44 years | 69 Participants |
| Age, Customized 45 to 64 years | 25 Participants |
| Age, Customized >=65 years | 4 Participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / — |
| serious Total, serious adverse events | 3 / — |
Outcome results
Primary
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period
Percentage change from baseline=\[(12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate)/ 8 week baseline period seizure frequency rate\] x 100. Seizure frequencies per 28-day period: = (total # of partial seizures in period x 28 / (total # of days in period).
Time frame: 8 week baseline period & 12 week treatment observation period
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period | -33.33 percentage change in events |
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-34.16, -11.28]
Secondary
Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21.
Change in total HADS score between Baseline and Week 21. Each of the 14 items is scored 0, 1, 2 or 3 where a score of 3 corresponds to the most anxious/depressed. 7-item depression and 7-item anxiety subscales are summed; each resulting in a total score of 0-21.
Time frame: Baseline, End of 21-week treatment
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). n is the number of subjects contributing to the mean at the specified time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pregabalin | Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. | HADS Depression Subscale (n=76) | -0.59 score on scale |
| Pregabalin | Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. | HADS Anxiety Subscale (n=76) | -1.68 score on scale |
Secondary
Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency
Percentage change from baseline = ((12 weeks - 8 weeks)/8 weeks)\*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.
Time frame: 8 week baseline observation period & 12 week treatment observation period
Population: Full analysis set (FAS)/intent-to-treat (ITT) (all subjects who received at least 1 dose of study treatment \& minimum 2 partial seizures during baseline pd). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pregabalin | Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency | Baseline seizure frequency ≤3 per 28 days (n=43) | -33.33 percentage change in events |
| Pregabalin | Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency | Baseline seizure frequency >3 per 28 days (n=49) | -21.99 percentage change in events |
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-43.66, -6.2]
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-35.24, -6.33]
Secondary
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores
Subjects recall sleep related activities over the previous 4 weeks. Low scores reflect greater impairment (except sleep adequacy, optimal sleep, &quantity). Range = 0 - 100 for Sleep Disturbance, Snoring, Awaken Short of Breath, Sleep Adequacy, Somnolence, & Sleep Problems Index. Quantity of Sleep Range = 0 - 24. Optimal Sleep Range 0 - 1.
Time frame: Baseline, end of 21-week treatment
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). n is the number of subjects contributing to the mean at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Sleep Disturbance (n=72) | -3.95 score on scale | 95% Confidence Interval 20.787 |
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Snoring (n=76) | 7.89 score on scale | — |
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Awaken Short of Breath (n=77) | -1.82 score on scale | — |
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Quantity of Sleep (n=66) | 0.05 score on scale | — |
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Sleep Adequacy (n=77) | 4.29 score on scale | — |
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Somnolence (n=77) | 0.52 score on scale | — |
| Pregabalin | Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Sleep Problems Index (n=72) | -2.81 score on scale | — |
Secondary
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC)
The PGIC is a patient-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: End of 21-week treatment
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment and had a minimum of 2 partial seizures during the baseline period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Much Improved | 36 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Very Much Improved | 14 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Minimally Improved | 17 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | No Change | 9 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Minimally Worse | 3 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Much Worse | 1 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Very Much Worse | 0 participants |
| Pregabalin | Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | Missing / Not Done | 13 participants |
Secondary
Number of Subjects Seizure-free
Count of subjects seizure free during the period.
Time frame: last 4 weeks & whole 12 week treatment observation period
Population: Full analysis set(FAS)/intent-to-treat(ITT) all subjects who received \>= 1 dose of study Tx \& \>= 2 partial seizures during baseline pd. LOCF if subjects withdrew then last 4 wks prior to last dose (but after visit 3). 12 wk subjects who withdrew were regarded as missing. n= # subjects evaluable for seizure freedom during defined observation pd.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Subjects Seizure-free | During 12 week Observation period (n=84) | 18 participants |
| Pregabalin | Number of Subjects Seizure-free | During the last 4 weeks of Obs. period (n=86) | 30 participants |
Secondary
Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline
Count of subjects with a weight gain of at least 7 percent relative to baseline.
Time frame: Baseline, End of 21-week treatment
Population: Safety population (all subjects who had taken at least~1 dose of study drug).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline | Weight gain ≥7% to <10% | 8 participants |
| Pregabalin | Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline | Weight gain ≥10% to <15% | 2 participants |
| Pregabalin | Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline | Weight gain ≥15% to <20% | 2 participants |
| Pregabalin | Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline | Weight gain ≥20% | 1 participants |
Secondary
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period.
Percentage change from baseline = ((21 weeks-8 weeks)/8 weeks)\*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.
Time frame: 8 week baseline period and 21 week treatment period
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period. | -29.39 percentage change in events |
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-27.36, -7.15]
Secondary
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.
Percentage change from baseline = \[(4 week seizure frequency minus 8 week baseline) / (8 week baseline seizure frequency)\] x 100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.
Time frame: 8 week baseline period and 21 week treatment period
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure date from patients who discontinued during any of these 4 week intervals will not be included in the summary for that interval.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | 1-28 Days | -28.12 percentage change of events |
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | 29-56 Days | -22.50 percentage change of events |
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | 57-84 Days | -25.00 percentage change of events |
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | 85-112 Days | -40.00 percentage change of events |
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | 113-140 Days | -58.72 percentage change of events |
| Pregabalin | Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | >140 Days | -85.42 percentage change of events |
Comparison: Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts.Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.95% CI: [-34.16, -10.71]
Comparison: Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power,true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-34.74, -10.91]
Comparison: Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-39.9, -14.46]
Comparison: Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.95% CI: [-43.44, -18.06]
Comparison: Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.95% CI: [-51.79, -25.7]
Comparison: Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power,true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.95% CI: [-58.47, -30.01]
Secondary
Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period.
Number of subjects with at least a 50% or 75% reduction in partial seizure frequency between baseline and treatment period.
Time frame: 8 week baseline observation period & last 4 weeks of observation period
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Patients who discontinued less than 4 weeks into the observation period (after Visit 3/week 9) will be regarded as missing. No data prior to week 9 will be used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. | >= 50% reduction | 42 participants |
| Pregabalin | Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. | >= 75% reduction | 33 participants |
Secondary
Subjects Achieving Seizure Freedom During Observation Period
Number of subjects achieving seizure freedom (no seizures) during last 4 weeks or duration of 12 week observation period.
Time frame: Day 147 from the first dose of study drug
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Subjects Achieving Seizure Freedom During Observation Period | seizure-free during last 4 weeks | 30 participants |
| Pregabalin | Subjects Achieving Seizure Freedom During Observation Period | seizure-free during 12 weeks | 18 participants |
Secondary
Subjects Assessment of Optimal Sleep
Number of subjects that responded optimal or non-optimal sleep in Optimal Sleep subscale of Medical Outcomes Study (MOS) Sleep scale.
Time frame: Baseline, End of 21-week treatment
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Subjects Assessment of Optimal Sleep | Optimal Sleep Baseline, Optimal Sleep Wk21 | 21 participants |
| Pregabalin | Subjects Assessment of Optimal Sleep | Optimal Sleep Baseline, Non-Optimal Sleep Wk21 | 8 participants |
| Pregabalin | Subjects Assessment of Optimal Sleep | Non-Optimal Sleep Baseline, Optimal Sleep Wk21 | 12 participants |
| Pregabalin | Subjects Assessment of Optimal Sleep | Non-Optimal Sleep Baseline, Non-Optimal Sleep Wk21 | 25 participants |
Secondary
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC)
The CGIC is a clinician's judgment of the overall change in the patient's condition over a defined period on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: End of 21-week treatment
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment and had a minimum of 2 partial seizures during the baseline period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Very Much Improved | 15 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Much Improved | 35 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Minimally Improved | 24 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | No Change | 11 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Minimally Worse | 4 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Much Worse | 2 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Very Much Worse | 0 partcipants |
| Pregabalin | Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | Missing / Not Done | 2 partcipants |
Post Hoc
Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period.
Change from baseline = 12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate.
Time frame: 8 week baseline period & 12 week treatment observation period
Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pregabalin | Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. | Simple Partial Seizures (n=47) | 0.00 change in median partial seizures |
| Pregabalin | Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. | Complex Partial Seizures (n=76) | 0.00 change in median partial seizures |
| Pregabalin | Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. | Evolve to Secondary Generalized (n=30) | 0.00 change in median partial seizures |
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-17.6, 31.98]
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-37.8, -6.69]
Comparison: Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.95% CI: [-55.33, 7.64]