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Pregabalin Versus Levetiracetam In Partial Seizures

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ClinicalTrials.gov Identifier: NCT00537238
Recruitment Status : Completed
First Posted : October 1, 2007
Results First Posted : July 11, 2013
Last Update Posted : July 11, 2013
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Partial Seizures
Interventions Drug: pregabalin
Drug: levetiracetam
Enrollment 509
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description Pregabalin 75 milligram (mg) capsule orally twice daily (BID) for 1 Week followed by pregabalin 150 mg orally BID up to Week 4 in the titration phase (TP). If seizure control was inadequate (adequate: at least [>=] 50% reduction in seizures), pregabalin dose was escalated to 225 mg orally BID for Week 2 through Week 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 maintenance phase(MP). Participants who had inadequate seizure control, received pregabalin 300 mg orally BID during MP. Participants also received placebo matched to levetiracetam capsule orally BID along with pregabalin during TP and MP. After MP, participants were allowed to progress into optional (opt) blinded continuation phase, and remained on dose from MP for a maximum of 2 years or until last participant either completed or discontinued from MP. Participants underwent an end-of-study medication taper over a 1-week period. 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.
Period Title: Overall Study
Started 254 255
Completed Titration Phase 226 236
Completed Maintenance Phase 208 [1] 210 [1]
Entered Opt Blinded Continuation Phase 185 [2] 195 [2]
Completed 80 [3] 82 [3]
Not Completed 174 173
Reason Not Completed
Death             1             2
Adverse Event             31             22
Lack of Efficacy             20             21
Lost to Follow-up             12             8
Withdrawal by Subject             51             47
Protocol Violation             15             19
Does not meet entrance criteria             0             2
Other             44             52
[1]
Primary analysis drawn from the population in the maintenance phase.
[2]
Participants who had clinical benefit were eligible to progress into opt blinded continuation phase.
[3]
Completed designates participants who completed the opt blinded continuation phase.
Arm/Group Title Pregabalin Levetiracetam Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 254 255 509
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 254 participants 255 participants 509 participants
32.7  (11.2) 36.3  (12.2) 34.5  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 254 participants 255 participants 509 participants
Female
134
  52.8%
130
  51.0%
264
  51.9%
Male
120
  47.2%
125
  49.0%
245
  48.1%
1.Primary Outcome
Title Proportion of Participants With Response to Treatment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 164 177
Measure Type: Number
Unit of Measure: proportion of participants
0.59 0.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the difference in proportion (Pregabalin - Levetiracetam) was greater than -0.12.
Method of Estimation Estimation Parameter Difference in Proportion
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-0.08 to 0.09
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in 28 Day Seizure Frequency at Week 16
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 254
Median (Full Range)
Unit of Measure: percent change
-53.93
(-100.0 to 533.1)
-57.28
(-100.0 to 276.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3571
Comments [Not Specified]
Method Ranked ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median difference
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
-2.6 to 10.9
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 107 111
Mean (Standard Deviation)
Unit of Measure: percentage of all partial seizure/28days
Baseline (n=107, 111) 39.41  (38.141) 38.94  (35.870)
Change at Week 16 (n=102, 101) 3.93  (30.158) 6.33  (32.071)
4.Secondary Outcome
Title Percentage of Participants Without Seizures
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 210
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
All Partial Seizure
19.9
(14.4 to 25.4)
27.6
(21.6 to 33.7)
Simple Partial Seizure
65.7
(59.1 to 72.2)
66.2
(59.8 to 72.6)
Complex Partial Seizure
49.3
(42.3 to 56.2)
59.0
(52.4 to 65.7)
SGTC Seizure
80.6
(75.1 to 86.1)
79.0
(73.5 to 84.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments All partial seizure: p-value was calculated from the 2-sided Fisher’s exact test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0822
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments Simple partial seizure: p-value was calculated from the 2-sided Fisher’s exact test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9175
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments Complex partial seizure: p-value was calculated from the 2-sided Fisher’s exact test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0483
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments SGTC seizure: p-value was calculated from the 2-sided Fisher’s exact test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7139
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 254
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Baseline: Total BPRS-A Score (n=253, 254) 27.26  (0.55) 26.09  (0.56)
Baseline: Core BPRS-A Score (n=253, 254) 5.18  (0.13) 5.01  (0.13)
Change at Week 7: Total BPRS-A Score (n=217, 225) -2.16  (0.36) -1.70  (0.36)
Change at Week 7: Core BPRS-A Score (n=216, 225) -0.34  (0.08) -0.22  (0.08)
Change at Week 10: Total BPRS-A Score (n=217, 219) -2.64  (0.37) -2.42  (0.38)
Change at Week 10: Core BPRS-A Score (n=217, 219) -0.40  (0.08) -0.34  (0.08)
Change at Week 13: Total BPRS-A Score (n=209, 214) -2.99  (0.39) -2.68  (0.39)
Change at Week 13: Core BPRS-A Score (n=209, 214) -0.51  (0.07) -0.38  (0.07)
Change at Week 16: Total BPRS-A Score (n=235, 241) -2.70  (0.40) -1.92  (0.40)
Change at Week 16: Core BPRS-A Score (n=235, 241) -0.40  (0.08) -0.26  (0.08)
Change at Follow-up: Total BPRS-A Score(n=178,189) -2.77  (0.44) -1.42  (0.43)
Change at Follow-up: Core BPRS-A Score(n=178,189) -0.37  (0.10) -0.11  (0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1334
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
-0.36 to 2.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3551
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.19 to 0.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3638
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-1.45 to 0.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.50
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2457
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.34 to 0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6640
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-1.26 to 0.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5950
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.30 to 0.17
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5701
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-1.38 to 0.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2452
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.33 to 0.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1697
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-1.88 to 0.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.56
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2283
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.36 to 0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0262
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -1.35
Confidence Interval (2-Sided) 95%
-2.54 to -0.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0495
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.52 to 0.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.13
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Hospital Anxiety and Depression Scale (HADS) Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 253
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Baseline: HADS-A (n=253, 253) 7.25  (0.26) 7.34  (0.27)
Baseline: HADS-D (n=253, 253) 6.22  (0.25) 6.00  (0.25)
Week 16: HADS-A (n=228, 241) 6.32  (0.22) 6.06  (0.22)
Week 16: HADS-D (n=228, 241) 5.41  (0.22) 5.42  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8084
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.82 to 0.64
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5263
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-0.47 to 0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4008
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.34 to 0.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9749
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.61 to 0.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Medical Outcomes Study Sleep Scale (MOS-SS) Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 254
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Baseline: Sleep Disturbance (n=253, 253) 27.06  (1.45) 28.10  (1.48)
Baseline: Snoring (n=253, 254) 30.72  (2.25) 32.42  (2.29)
Baseline: Awaken Short of Breath (n=253, 254) 15.72  (1.54) 17.26  (1.57)
Baseline: Quantity of Sleep (n=252, 252) 7.77  (0.10) 7.82  (0.10)
Baseline: Adequacy of Sleep (n=253, 254) 62.96  (1.79) 64.40  (1.83)
Baseline: Somnolence (n=253, 254) 34.85  (1.43) 33.77  (1.45)
Baseline: Sleep Problem Index (9) (n=253, 253) 29.62  (1.16) 29.49  (1.18)
Week 16: Sleep Disturbance (n=230, 241) 21.97  (1.16) 23.61  (1.17)
Week 16: Snoring (n=230, 240) 33.77  (1.72) 23.75  (1.73)
Week 16: Awaken Short of Breath (n=230, 241) 15.15  (1.48) 14.27  (1.48)
Week 16: Quantity of Sleep (n=230, 241) 7.89  (0.09) 7.75  (0.09)
Week 16: Adequacy of Sleep (n=230, 241) 63.46  (1.72) 66.46  (1.73)
Week 16: Somnolence (n=230, 241) 31.56  (1.33) 32.29  (1.34)
Week 16: Sleep Problem Index (9) (n=230, 241) 26.64  (0.95) 26.00  (0.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6161
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-5.08 to 3.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.06
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3154
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -1.63
Confidence Interval (2-Sided) 95%
-4.83 to 1.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.62
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5930
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -1.70
Confidence Interval (2-Sided) 95%
-7.94 to 4.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.18
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 10.02
Confidence Interval (2-Sided) 95%
5.27 to 14.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.42
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4807
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -1.54
Confidence Interval (2-Sided) 95%
-5.83 to 2.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.18
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6708
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
-3.18 to 4.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.07
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7574
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.32 to 0.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2615
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.10 to 0.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5703
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-6.42 to 3.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.53
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2160
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -2.99
Confidence Interval (2-Sided) 95%
-7.74 to 1.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.41
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5952
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
-2.89 to 5.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.02
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6984
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-4.40 to 2.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.87
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9389
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-3.09 to 3.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.64
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6344
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differences
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
-2.00 to 3.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.34
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 252 252
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=252, 252) 56.0 55.6
Week 16 (n=230, 241) 58.3 50.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9285
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.016
Confidence Interval (2-Sided) 95%
0.715 to 1.444
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin, Levetiracetam
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0696
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.432
Confidence Interval (2-Sided) 95%
0.972 to 2.110
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Pregabalin Levetiracetam
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Pregabalin Levetiracetam
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pregabalin Levetiracetam
Affected / at Risk (%) Affected / at Risk (%)
Total   24/254 (9.45%)   24/255 (9.41%) 
Blood and lymphatic system disorders     
Neutropenia * 1  1/254 (0.39%)  0/255 (0.00%) 
Thrombocytopenia * 1  0/254 (0.00%)  1/255 (0.39%) 
Gastrointestinal disorders     
Gastroduodenitis * 1  1/254 (0.39%)  0/255 (0.00%) 
Haemorrhoids * 1  0/254 (0.00%)  1/255 (0.39%) 
General disorders     
Asthenia * 1  1/254 (0.39%)  0/255 (0.00%) 
Drowning * 1  1/254 (0.39%)  0/255 (0.00%) 
Polyp * 1  0/254 (0.00%)  1/255 (0.39%) 
Infections and infestations     
Abscess limb * 1  1/254 (0.39%)  0/255 (0.00%) 
Acute tonsillitis * 1  0/254 (0.00%)  1/255 (0.39%) 
Bronchitis * 1  1/254 (0.39%)  0/255 (0.00%) 
Bronchopneumonia * 1  1/254 (0.39%)  0/255 (0.00%) 
Pharyngotonsillitis * 1  0/254 (0.00%)  1/255 (0.39%) 
Pneumonia * 1  0/254 (0.00%)  1/255 (0.39%) 
Pulmonary tuberculosis * 1  0/254 (0.00%)  1/255 (0.39%) 
Septic shock * 1  1/254 (0.39%)  0/255 (0.00%) 
Urinary tract infection * 1  1/254 (0.39%)  0/255 (0.00%) 
Injury, poisoning and procedural complications     
Brain contusion * 1  0/254 (0.00%)  1/255 (0.39%) 
Burns third degree * 1  1/254 (0.39%)  0/255 (0.00%) 
Clavicle fracture * 1  0/254 (0.00%)  1/255 (0.39%) 
Craniocerebral injury * 1  1/254 (0.39%)  0/255 (0.00%) 
Fall * 1  1/254 (0.39%)  1/255 (0.39%) 
Hip fracture * 1  1/254 (0.39%)  0/255 (0.00%) 
Humerus fracture * 1  1/254 (0.39%)  0/255 (0.00%) 
Intentional overdose * 1  0/254 (0.00%)  1/255 (0.39%) 
Laceration * 1  1/254 (0.39%)  0/255 (0.00%) 
Spinal compression fracture * 1  0/254 (0.00%)  1/255 (0.39%) 
Subdural haematoma * 1  1/254 (0.39%)  0/255 (0.00%) 
Thermal burn * 1  1/254 (0.39%)  0/255 (0.00%) 
Wrist fracture * 1  1/254 (0.39%)  0/255 (0.00%) 
Investigations     
Weight increased * 1  2/254 (0.79%)  0/255 (0.00%) 
Metabolism and nutrition disorders     
Hyponatraemia * 1  0/254 (0.00%)  1/255 (0.39%) 
Musculoskeletal and connective tissue disorders     
Costochondritis * 1  1/254 (0.39%)  0/255 (0.00%) 
Rotator cuff syndrome * 1  1/254 (0.39%)  0/255 (0.00%) 
Spinal disorder * 1  0/254 (0.00%)  1/255 (0.39%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Retroperitoneal cancer * 1  0/254 (0.00%)  1/255 (0.39%) 
Nervous system disorders     
Complex partial seizures * 1  0/254 (0.00%)  1/255 (0.39%) 
Convulsion * 1  5/254 (1.97%)  1/255 (0.39%) 
Dizziness * 1  1/254 (0.39%)  0/255 (0.00%) 
Drug withdrawal convulsions * 1  0/254 (0.00%)  1/255 (0.39%) 
Epilepsy * 1  1/254 (0.39%)  2/255 (0.78%) 
Ischaemic stroke * 1  0/254 (0.00%)  1/255 (0.39%) 
Postictal state * 1  0/254 (0.00%)  1/255 (0.39%) 
Sedation * 1  0/254 (0.00%)  1/255 (0.39%) 
Status epilepticus * 1  1/254 (0.39%)  2/255 (0.78%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1  1/254 (0.39%)  0/255 (0.00%) 
Abortion threatened * 1  0/254 (0.00%)  1/255 (0.39%) 
Psychiatric disorders     
Aggression * 1  0/254 (0.00%)  2/255 (0.78%) 
Depressed mood * 1  0/254 (0.00%)  1/255 (0.39%) 
Personality change * 1  0/254 (0.00%)  1/255 (0.39%) 
Personality disorder * 1  1/254 (0.39%)  0/255 (0.00%) 
Somatoform disorder neurologic * 1  1/254 (0.39%)  0/255 (0.00%) 
Suicide attempt * 1  0/254 (0.00%)  2/255 (0.78%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  0/254 (0.00%)  1/255 (0.39%) 
Ovarian cyst * 1  1/254 (0.39%)  0/255 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  0/254 (0.00%)  1/255 (0.39%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pregabalin Levetiracetam
Affected / at Risk (%) Affected / at Risk (%)
Total   148/254 (58.27%)   127/255 (49.80%) 
Gastrointestinal disorders     
Nausea * 1  5/254 (1.97%)  15/255 (5.88%) 
Infections and infestations     
Nasopharyngitis * 1  24/254 (9.45%)  19/255 (7.45%) 
Investigations     
Weight increased * 1  26/254 (10.24%)  8/255 (3.14%) 
Nervous system disorders     
Dizziness * 1  59/254 (23.23%)  42/255 (16.47%) 
Headache * 1  37/254 (14.57%)  30/255 (11.76%) 
Somnolence * 1  83/254 (32.68%)  76/255 (29.80%) 
Psychiatric disorders     
Insomnia * 1  5/254 (1.97%)  15/255 (5.88%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v15.1
Results for BPRS were provided as change in scores at Week 16 compared to baseline instead of absolute scores as per planned analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00537238     History of Changes
Other Study ID Numbers: A0081157
First Submitted: September 27, 2007
First Posted: October 1, 2007
Results First Submitted: May 21, 2013
Results First Posted: July 11, 2013
Last Update Posted: July 11, 2013