Partial Seizures
Conditions
Keywords
Epilepsies partial, Partial Seizure Disorder, Complex Partial Seizure Disorder, Epilepsy
Brief summary
This study will compare pregabalin and levetiracetam in patients with partial seizures. It will also evaluate the safety and tolerability of pregabalin and levetiracetam in these patients.
Interventions
DRUGpregabalin
300, 450, 600 mg/day administered orally, BID until seizure control/improvement or intolerable side effects
DRUGlevetiracetam
1000, 2000, 3000 mg/day administered orally, BID until seizure control/improvement or intolerable side effects
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects (male or female) must be \> 18 years of age, with a diagnosis of epilepsy with partial seizures, as defined in the International League Against Epilepsy (ILAE) classification of seizures. * Partial seizures may be simple or complex, with or without secondary tonic-clonic generalization. * Subjects must be have been diagnosed with epilepsy for at least 2 years, and must have been unresponsive to treatment with at least two but no more than five prior antiepileptic drugs (AEDs), and at the time of study enrollment are on stable dosages of 1 or 2 standard AEDs.
Exclusion criteria
* Females who are pregnant, breastfeeding, or intend to become pregnant during the course of the trial will be excluded * Subjects with other neurologic illness that could impair endpoint assessment, or subjects with Lennox-Gastaut syndrome, absence seizures, status epileptics within the 12 months prior to trial entry, or with seizures due to an underlying medical illness or metabolic syndrome, will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Response to Treatment | Baseline up to Week 16 | Participants who had at least 50% reduction in 28-day seizure rate from baseline to the end of the maintenance phase were considered as responders. The 28-day seizure rate was calculated as number of partial seizures in the period divided by difference of number of days in the period and number of missing diary day entries in the period, multiplied by 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16 | Baseline, Week 16 | Change was calculated as (proportion of SGTC seizure rate divided by all partial seizure rates during double blind phase) minus (proportion of SGTC seizure rate divided by all partial seizure rates at baseline). Negative values indicated reductions in seizures. |
| Percentage of Participants Without Seizures | Baseline up to Week 16 | Seizure free for 28 days was defined as participants who have not experienced any seizure (simple partial, complex partial and SGTC) for at least 28 consecutive days from their last seizure until the end of the maintenance phase. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure. |
| Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Baseline, Week 7, 10, 13, 16 and Follow-up (Day 7 of taper phase) | BPRS-A:18-item clinician rated scale assesses somatic concern,anxiety, emotional withdrawal,conceptual disorganization,hallucinatory behavior(HB), guilt feelings,suspiciousness,disorientation,tension,mannerisms and posturing,grandiosity,depressive mood,hostility,motor retardation,uncooperativeness,unusual thought content,blunted affect,excitement. Items rated on 7-point scale 1 (not reported) to 7 (very severe). Total score=sum of items(range 18-126), core score=sum of conceptual disorganization, suspiciousness, HB, unusual thought content(range 4-28). Higher total/core score=more impairment. |
| Percent Change From Baseline in 28 Day Seizure Frequency at Week 16 | Baseline, Week 16 | The seizures were recorded by the participants, by a family member, by a caregiver, or by a legal guardian and documented in a daily seizure diary. Participant's 28-day seizure frequency of all partial seizure was assessed during double blind (TP + MP) phase compared with baseline. |
| Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline, Week 16 | Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales:sleep disturbance,snoring,awakened short of breath,sleep adequacy,somnolence (range:0-100);sleep quantity (range:0-24),optimal sleep(yes/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem. Except adequacy,optimal sleep and quantity, higher scores=more impairment. Scores transformed (actual raw score\[RS\] minus lowest possible score divided by possible RS range\*100);total score range:0-100;higher score=more intensity of attribute. |
| Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score | Baseline, Week 16 | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Percentage of participants with optimal sleep are reported. |
| Hospital Anxiety and Depression Scale (HADS) Score | Baseline, Week 16 | HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. |
Countries
Belgium, Bulgaria, Colombia, Costa Rica, Czechia, France, Germany, Greece, India, Italy, Lithuania, Mexico, Panama, Peru, Philippines, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Venezuela
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Pregabalin 75 mg capsule orally BID for 1 Week followed by pregabalin 150 mg orally BID up to Week 4 in the TP. If seizure control was inadequate (adequate: \>=50% reduction in seizures), the pregabalin dose was escalated to 225 mg orally BID for Week 2 through 4. Participants who had adequate seizure control with pregabalin 150 mg or 225 mg orally BID dose in TP, continued same dose during the 12-week MP. Participants who had inadequate seizure control, received pregabalin 300 mg orally BID during the MP. Participants also received placebo matched to levetiracetam capsule orally BID along with pregabalin during the TP and the MP. After the MP, participants were allowed to progress into the opt blinded continuation phase, and remained on dose from the MP for a maximum of 2 years or until the last participant either completed or discontinued from MP. Participants underwent an end-of-study medication taper over a 1-week period. | 254 |
| Levetiracetam Levetiracetam 500 mg capsule orally BID for 2 Weeks in the TP. If seizure control was inadequate (adequate: \>= 50% reduction in seizures), the levetiracetam dose was escalated to 1000 mg orally BID for Week 2 through Week 4. Participants who had adequate seizure control with levetiracetam 500 or 1000 mg orally BID dose in the TP, continued same dose in the 12-week MP. Participants who had inadequate seizure control, received levetiracetam 1500 mg orally BID during the MP. Participants also received placebo matched to pregabalin capsule orally BID along with levetiracetam during TP and MP. After the MP, participants were allowed to progress into the opt blinded continuation phase, and remained on the dose from the MP for a maximum of 2 years or until the last participant either completed or discontinued from the MP. Participants underwent an end-of-study medication taper over a 1-week period. | 255 |
| Total | 509 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 31 | 22 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Does not meet entrance criteria | 0 | 2 |
| Overall Study | Lack of Efficacy | 20 | 21 |
| Overall Study | Lost to Follow-up | 12 | 8 |
| Overall Study | Other | 44 | 52 |
| Overall Study | Protocol Violation | 15 | 19 |
| Overall Study | Withdrawal by Subject | 51 | 47 |
Baseline characteristics
| Characteristic | Pregabalin | Levetiracetam | Total |
|---|---|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 11.2 | 36.3 years STANDARD_DEVIATION 12.2 | 34.5 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 134 Participants | 130 Participants | 264 Participants |
| Sex: Female, Male Male | 120 Participants | 125 Participants | 245 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 148 / 254 | 127 / 255 |
| serious Total, serious adverse events | 24 / 254 | 24 / 255 |
Outcome results
Primary
Proportion of Participants With Response to Treatment
Participants who had at least 50% reduction in 28-day seizure rate from baseline to the end of the maintenance phase were considered as responders. The 28-day seizure rate was calculated as number of partial seizures in the period divided by difference of number of days in the period and number of missing diary day entries in the period, multiplied by 28.
Time frame: Baseline up to Week 16
Population: Per protocol population included all randomized participants who had at least 28 days of study drug during the maintenance phase and a minimum of 28 days of utilizable seizure diary data during baseline and maintenance phases of the study and had no major protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Proportion of Participants With Response to Treatment | 0.59 proportion of participants |
| Levetiracetam | Proportion of Participants With Response to Treatment | 0.59 proportion of participants |
90% CI: [-0.08, 0.09]
Secondary
Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up
BPRS-A:18-item clinician rated scale assesses somatic concern,anxiety, emotional withdrawal,conceptual disorganization,hallucinatory behavior(HB), guilt feelings,suspiciousness,disorientation,tension,mannerisms and posturing,grandiosity,depressive mood,hostility,motor retardation,uncooperativeness,unusual thought content,blunted affect,excitement. Items rated on 7-point scale 1 (not reported) to 7 (very severe). Total score=sum of items(range 18-126), core score=sum of conceptual disorganization, suspiciousness, HB, unusual thought content(range 4-28). Higher total/core score=more impairment.
Time frame: Baseline, Week 7, 10, 13, 16 and Follow-up (Day 7 of taper phase)
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Baseline: Total BPRS-A Score (n=253, 254) | 27.26 units on a scale | Standard Error 0.55 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Baseline: Core BPRS-A Score (n=253, 254) | 5.18 units on a scale | Standard Error 0.13 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 7: Total BPRS-A Score (n=217, 225) | -2.16 units on a scale | Standard Error 0.36 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 7: Core BPRS-A Score (n=216, 225) | -0.34 units on a scale | Standard Error 0.08 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 10: Total BPRS-A Score (n=217, 219) | -2.64 units on a scale | Standard Error 0.37 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 10: Core BPRS-A Score (n=217, 219) | -0.40 units on a scale | Standard Error 0.08 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 13: Total BPRS-A Score (n=209, 214) | -2.99 units on a scale | Standard Error 0.39 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 13: Core BPRS-A Score (n=209, 214) | -0.51 units on a scale | Standard Error 0.07 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 16: Total BPRS-A Score (n=235, 241) | -2.70 units on a scale | Standard Error 0.4 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 16: Core BPRS-A Score (n=235, 241) | -0.40 units on a scale | Standard Error 0.08 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Follow-up: Total BPRS-A Score(n=178,189) | -2.77 units on a scale | Standard Error 0.44 |
| Pregabalin | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Follow-up: Core BPRS-A Score(n=178,189) | -0.37 units on a scale | Standard Error 0.1 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Follow-up: Total BPRS-A Score(n=178,189) | -1.42 units on a scale | Standard Error 0.43 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Baseline: Total BPRS-A Score (n=253, 254) | 26.09 units on a scale | Standard Error 0.56 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 13: Total BPRS-A Score (n=209, 214) | -2.68 units on a scale | Standard Error 0.39 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Baseline: Core BPRS-A Score (n=253, 254) | 5.01 units on a scale | Standard Error 0.13 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 16: Core BPRS-A Score (n=235, 241) | -0.26 units on a scale | Standard Error 0.08 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 7: Total BPRS-A Score (n=217, 225) | -1.70 units on a scale | Standard Error 0.36 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 13: Core BPRS-A Score (n=209, 214) | -0.38 units on a scale | Standard Error 0.07 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 7: Core BPRS-A Score (n=216, 225) | -0.22 units on a scale | Standard Error 0.08 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Follow-up: Core BPRS-A Score(n=178,189) | -0.11 units on a scale | Standard Error 0.1 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 10: Total BPRS-A Score (n=217, 219) | -2.42 units on a scale | Standard Error 0.38 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 16: Total BPRS-A Score (n=235, 241) | -1.92 units on a scale | Standard Error 0.4 |
| Levetiracetam | Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up | Change at Week 10: Core BPRS-A Score (n=217, 219) | -0.34 units on a scale | Standard Error 0.08 |
Comparison: Baseline, total BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.133495% CI: [-0.36, 2.69]ANCOVA
Comparison: Baseline, core BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.355195% CI: [-0.19, 0.52]ANCOVA
Comparison: Change at Week 7, total BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.363895% CI: [-1.45, 0.53]ANCOVA
Comparison: Change at Week 7, core BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.245795% CI: [-0.34, 0.09]ANCOVA
Comparison: Change at Week 10, total BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.66495% CI: [-1.26, 0.81]ANCOVA
Comparison: Change at Week 10, core BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.59595% CI: [-0.3, 0.17]ANCOVA
Comparison: Change at Week 13, total BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.570195% CI: [-1.38, 0.76]ANCOVA
Comparison: Change at Week 13, core BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.245295% CI: [-0.33, 0.08]ANCOVA
Comparison: Change at Week 16, total BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.169795% CI: [-1.88, 0.33]ANCOVA
Comparison: Change at Week 16, core BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.228395% CI: [-0.36, 0.09]ANCOVA
Comparison: Change at Follow-up, total BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.026295% CI: [-2.54, -0.16]ANCOVA
Comparison: Change at Follow-up, core BPRS score: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.049595% CI: [-0.52, 0]ANCOVA
Secondary
Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16
Change was calculated as (proportion of SGTC seizure rate divided by all partial seizure rates during double blind phase) minus (proportion of SGTC seizure rate divided by all partial seizure rates at baseline). Negative values indicated reductions in seizures.
Time frame: Baseline, Week 16
Population: SGTC population included all participants who had at least 1 SGTC seizure during either baseline or double-blind phase. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16 | Baseline (n=107, 111) | 39.41 percentage of all partial seizure/28days | Standard Deviation 38.141 |
| Pregabalin | Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16 | Change at Week 16 (n=102, 101) | 3.93 percentage of all partial seizure/28days | Standard Deviation 30.158 |
| Levetiracetam | Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16 | Baseline (n=107, 111) | 38.94 percentage of all partial seizure/28days | Standard Deviation 35.87 |
| Levetiracetam | Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16 | Change at Week 16 (n=102, 101) | 6.33 percentage of all partial seizure/28days | Standard Deviation 32.071 |
Secondary
Hospital Anxiety and Depression Scale (HADS) Score
HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.
Time frame: Baseline, Week 16
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. N (number of participants analyzed)=participants who were evaluable for this measure. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score | Baseline: HADS-A (n=253, 253) | 7.25 units on a scale | Standard Error 0.26 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score | Baseline: HADS-D (n=253, 253) | 6.22 units on a scale | Standard Error 0.25 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score | Week 16: HADS-A (n=228, 241) | 6.32 units on a scale | Standard Error 0.22 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score | Week 16: HADS-D (n=228, 241) | 5.41 units on a scale | Standard Error 0.22 |
| Levetiracetam | Hospital Anxiety and Depression Scale (HADS) Score | Week 16: HADS-D (n=228, 241) | 5.42 units on a scale | Standard Error 0.22 |
| Levetiracetam | Hospital Anxiety and Depression Scale (HADS) Score | Baseline: HADS-A (n=253, 253) | 7.34 units on a scale | Standard Error 0.27 |
| Levetiracetam | Hospital Anxiety and Depression Scale (HADS) Score | Week 16: HADS-A (n=228, 241) | 6.06 units on a scale | Standard Error 0.22 |
| Levetiracetam | Hospital Anxiety and Depression Scale (HADS) Score | Baseline: HADS-D (n=253, 253) | 6.00 units on a scale | Standard Error 0.25 |
Comparison: Baseline, HADS-A: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.808495% CI: [-0.82, 0.64]ANCOVA
Comparison: Baseline, HADS-D: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.526395% CI: [-0.47, 0.91]ANCOVA
Comparison: Week 16, HADS-A: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.400895% CI: [-0.34, 0.85]ANCOVA
Comparison: Week 16, HADS-D: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.974995% CI: [-0.61, 0.59]ANCOVA
Secondary
Medical Outcomes Study Sleep Scale (MOS-SS) Score
Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales:sleep disturbance,snoring,awakened short of breath,sleep adequacy,somnolence (range:0-100);sleep quantity (range:0-24),optimal sleep(yes/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem. Except adequacy,optimal sleep and quantity, higher scores=more impairment. Scores transformed (actual raw score\[RS\] minus lowest possible score divided by possible RS range\*100);total score range:0-100;higher score=more intensity of attribute.
Time frame: Baseline, Week 16
Population: FAS included all randomized participants who had received at least 1 blinded dose of study medication and had at least 1 baseline and post baseline primary efficacy evaluation. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Quantity of Sleep (n=252, 252) | 7.77 units on a scale | Standard Error 0.1 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Sleep Disturbance (n=230, 241) | 21.97 units on a scale | Standard Error 1.16 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Sleep Disturbance (n=253, 253) | 27.06 units on a scale | Standard Error 1.45 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Snoring (n=230, 240) | 33.77 units on a scale | Standard Error 1.72 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Awaken Short of Breath (n=230, 241) | 15.15 units on a scale | Standard Error 1.48 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Adequacy of Sleep (n=253, 254) | 62.96 units on a scale | Standard Error 1.79 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Quantity of Sleep (n=230, 241) | 7.89 units on a scale | Standard Error 0.09 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Awaken Short of Breath (n=253, 254) | 15.72 units on a scale | Standard Error 1.54 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Adequacy of Sleep (n=230, 241) | 63.46 units on a scale | Standard Error 1.72 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Somnolence (n=253, 254) | 34.85 units on a scale | Standard Error 1.43 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Somnolence (n=230, 241) | 31.56 units on a scale | Standard Error 1.33 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Snoring (n=253, 254) | 30.72 units on a scale | Standard Error 2.25 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Sleep Problem Index (9) (n=230, 241) | 26.64 units on a scale | Standard Error 0.95 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Sleep Problem Index (9) (n=253, 253) | 29.62 units on a scale | Standard Error 1.16 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Sleep Problem Index (9) (n=230, 241) | 26.00 units on a scale | Standard Error 0.96 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Sleep Disturbance (n=253, 253) | 28.10 units on a scale | Standard Error 1.48 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Snoring (n=253, 254) | 32.42 units on a scale | Standard Error 2.29 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Awaken Short of Breath (n=253, 254) | 17.26 units on a scale | Standard Error 1.57 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Quantity of Sleep (n=252, 252) | 7.82 units on a scale | Standard Error 0.1 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Adequacy of Sleep (n=253, 254) | 64.40 units on a scale | Standard Error 1.83 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Somnolence (n=253, 254) | 33.77 units on a scale | Standard Error 1.45 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Baseline: Sleep Problem Index (9) (n=253, 253) | 29.49 units on a scale | Standard Error 1.18 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Sleep Disturbance (n=230, 241) | 23.61 units on a scale | Standard Error 1.17 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Awaken Short of Breath (n=230, 241) | 14.27 units on a scale | Standard Error 1.48 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Quantity of Sleep (n=230, 241) | 7.75 units on a scale | Standard Error 0.09 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Adequacy of Sleep (n=230, 241) | 66.46 units on a scale | Standard Error 1.73 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Somnolence (n=230, 241) | 32.29 units on a scale | Standard Error 1.34 |
| Levetiracetam | Medical Outcomes Study Sleep Scale (MOS-SS) Score | Week 16: Snoring (n=230, 240) | 23.75 units on a scale | Standard Error 1.73 |
Comparison: Baseline sleep disturbance: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.616195% CI: [-5.08, 3.01]ANCOVA
Comparison: Week 16 sleep disturbance: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.315495% CI: [-4.83, 1.56]ANCOVA
Comparison: Baseline snoring: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.59395% CI: [-7.94, 4.54]ANCOVA
Comparison: Week 16 snoring: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: <0.000195% CI: [5.27, 14.76]ANCOVA
Comparison: Baseline awaken short of breath: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.480795% CI: [-5.83, 2.75]ANCOVA
Comparison: Week 16 awaken short of breath: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.670895% CI: [-3.18, 4.94]ANCOVA
Comparison: Baseline quantity of sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.757495% CI: [-0.32, 0.24]ANCOVA
Comparison: Week 16 quantity of sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.261595% CI: [-0.1, 0.38]ANCOVA
Comparison: Baseline adequacy of sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.570395% CI: [-6.42, 3.54]ANCOVA
Comparison: Week 16 adequacy of sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.21695% CI: [-7.74, 1.75]ANCOVA
Comparison: Baseline somnolence: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.595295% CI: [-2.89, 5.03]ANCOVA
Comparison: Week 16 somnolence: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.698495% CI: [-4.4, 2.95]ANCOVA
Comparison: Baseline sleep problem index (9): ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.938995% CI: [-3.09, 3.34]ANCOVA
Comparison: Week 16 sleep problem index (9): ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, for post-baseline assessments baseline was included as a covariate.p-value: 0.634495% CI: [-2, 3.27]ANCOVA
Secondary
Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score
MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Percentage of participants with optimal sleep are reported.
Time frame: Baseline, Week 16
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. N (number of participants analyzed)=participants who were evaluable for this measure. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score | Week 16 (n=230, 241) | 58.3 percentage of participants |
| Pregabalin | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score | Baseline (n=252, 252) | 56.0 percentage of participants |
| Levetiracetam | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score | Baseline (n=252, 252) | 55.6 percentage of participants |
| Levetiracetam | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score | Week 16 (n=230, 241) | 50.2 percentage of participants |
Comparison: Baseline: Logistic regression model was used to estimate odds ratio and corresponding 95% CI of treatment difference, with treatment as fixed effect and for post-baseline assessments baseline was included as a covariate.p-value: 0.928595% CI: [0.715, 1.444]Regression, Logistic
Comparison: Week 16: Logistic regression model was used to estimate odds ratio and corresponding 95% CI of treatment difference, with treatment as fixed effect and for post-baseline assessments baseline was included as a covariate.p-value: 0.069695% CI: [0.972, 2.11]Regression, Logistic
Secondary
Percentage of Participants Without Seizures
Seizure free for 28 days was defined as participants who have not experienced any seizure (simple partial, complex partial and SGTC) for at least 28 consecutive days from their last seizure until the end of the maintenance phase. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure.
Time frame: Baseline up to Week 16
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. N (number of participants analyzed)=participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Percentage of Participants Without Seizures | All Partial Seizure | 19.9 percentage of participants |
| Pregabalin | Percentage of Participants Without Seizures | Simple Partial Seizure | 65.7 percentage of participants |
| Pregabalin | Percentage of Participants Without Seizures | Complex Partial Seizure | 49.3 percentage of participants |
| Pregabalin | Percentage of Participants Without Seizures | SGTC Seizure | 80.6 percentage of participants |
| Levetiracetam | Percentage of Participants Without Seizures | SGTC Seizure | 79.0 percentage of participants |
| Levetiracetam | Percentage of Participants Without Seizures | All Partial Seizure | 27.6 percentage of participants |
| Levetiracetam | Percentage of Participants Without Seizures | Complex Partial Seizure | 59.0 percentage of participants |
| Levetiracetam | Percentage of Participants Without Seizures | Simple Partial Seizure | 66.2 percentage of participants |
Comparison: All partial seizure: p-value was calculated from the 2-sided Fisher's exact test.p-value: 0.0822Fisher Exact
Comparison: Simple partial seizure: p-value was calculated from the 2-sided Fisher's exact test.p-value: 0.9175Fisher Exact
Comparison: Complex partial seizure: p-value was calculated from the 2-sided Fisher's exact test.p-value: 0.0483Fisher Exact
Comparison: SGTC seizure: p-value was calculated from the 2-sided Fisher's exact test.p-value: 0.7139Fisher Exact
Secondary
Percent Change From Baseline in 28 Day Seizure Frequency at Week 16
The seizures were recorded by the participants, by a family member, by a caregiver, or by a legal guardian and documented in a daily seizure diary. Participant's 28-day seizure frequency of all partial seizure was assessed during double blind (TP + MP) phase compared with baseline.
Time frame: Baseline, Week 16
Population: Full analysis set (FAS) included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Percent Change From Baseline in 28 Day Seizure Frequency at Week 16 | -53.93 percent change |
| Levetiracetam | Percent Change From Baseline in 28 Day Seizure Frequency at Week 16 | -57.28 percent change |
Comparison: Rank analysis of covariance (ANCOVA) model was used to derive p-value with treatment as main effect and cluster as cofactor, percent change in 28-day seizure counts between baseline and treatment periods as dependent variable. Median differences and 95% confidence interval (CI) were based on Hodges-Lehmann estimation.p-value: 0.357195% CI: [-2.6, 10.9]Ranked ANCOVA