Trial Outcomes & Findings for Pregabalin Versus Levetiracetam In Partial Seizures (NCT NCT00537238)

Last Updated: 2021-01-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

509 participants

Primary outcome timeframe

Baseline up to Week 16

Results posted on

2021-01-28

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin 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 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 Study STARTED	254	255
Overall Study Completed Titration Phase	226	236
Overall Study Completed Maintenance Phase	208	210
Overall Study Entered Opt Blinded Continuation Phase	185	195
Overall Study COMPLETED	80	82
Overall Study NOT COMPLETED	174	173

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin 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 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 Study Death	1	2
Overall Study Adverse Event	31	22
Overall Study Lack of Efficacy	20	21
Overall Study Lost to Follow-up	12	8
Overall Study Withdrawal by Subject	51	47
Overall Study Protocol Violation	15	19
Overall Study Does not meet entrance criteria	0	2
Overall Study Other	44	52

Baseline Characteristics

Pregabalin Versus Levetiracetam In Partial Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin n=254 Participants 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 n=255 Participants 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 n=509 Participants Total of all reporting groups
Age, Continuous	32.7 years STANDARD_DEVIATION 11.2 • n=5 Participants	36.3 years STANDARD_DEVIATION 12.2 • n=7 Participants	34.5 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	134 Participants n=5 Participants	130 Participants n=7 Participants	264 Participants n=5 Participants
Sex: Female, Male Male	120 Participants n=5 Participants	125 Participants n=7 Participants	245 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pregabalin n=164 Participants 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 n=177 Participants 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.
Proportion of Participants With Response to Treatment	0.59 proportion of participants	0.59 proportion of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=253 Participants 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 n=254 Participants 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.
Percent Change From Baseline in 28 Day Seizure Frequency at Week 16	-53.93 percent change Interval -100.0 to 533.1	-57.28 percent change Interval -100.0 to 276.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=107 Participants 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 n=111 Participants 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.
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	38.94 percentage of all partial seizure/28days Standard Deviation 35.870
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	6.33 percentage of all partial seizure/28days Standard Deviation 32.071

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=201 Participants 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 n=210 Participants 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.
Percentage of Participants Without Seizures All Partial Seizure	19.9 percentage of participants Interval 14.4 to 25.4	27.6 percentage of participants Interval 21.6 to 33.7
Percentage of Participants Without Seizures Simple Partial Seizure	65.7 percentage of participants Interval 59.1 to 72.2	66.2 percentage of participants Interval 59.8 to 72.6
Percentage of Participants Without Seizures Complex Partial Seizure	49.3 percentage of participants Interval 42.3 to 56.2	59.0 percentage of participants Interval 52.4 to 65.7
Percentage of Participants Without Seizures SGTC Seizure	80.6 percentage of participants Interval 75.1 to 86.1	79.0 percentage of participants Interval 73.5 to 84.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=253 Participants 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 n=254 Participants 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.
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	26.09 units on a scale Standard Error 0.56
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	5.01 units on a scale Standard Error 0.13
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	-1.70 units on a scale Standard Error 0.36
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	-0.22 units on a scale Standard Error 0.08
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	-2.42 units on a scale Standard Error 0.38
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	-0.34 units on a scale Standard Error 0.08
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	-2.68 units on a scale Standard Error 0.39
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	-0.38 units on a scale Standard Error 0.07
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 0.40	-1.92 units on a scale Standard Error 0.40
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	-0.26 units on a scale Standard Error 0.08
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	-1.42 units on a scale Standard Error 0.43
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 0.10	-0.11 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pregabalin n=253 Participants 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 n=253 Participants 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.
Hospital Anxiety and Depression Scale (HADS) Score Baseline: HADS-A (n=253, 253)	7.25 units on a scale Standard Error 0.26	7.34 units on a scale Standard Error 0.27
Hospital Anxiety and Depression Scale (HADS) Score Baseline: HADS-D (n=253, 253)	6.22 units on a scale Standard Error 0.25	6.00 units on a scale Standard Error 0.25
Hospital Anxiety and Depression Scale (HADS) Score Week 16: HADS-A (n=228, 241)	6.32 units on a scale Standard Error 0.22	6.06 units on a scale Standard Error 0.22
Hospital Anxiety and Depression Scale (HADS) Score Week 16: HADS-D (n=228, 241)	5.41 units on a scale Standard Error 0.22	5.42 units on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=253 Participants 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 n=254 Participants 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.
Medical Outcomes Study Sleep Scale (MOS-SS) Score Baseline: Sleep Disturbance (n=253, 253)	27.06 units on a scale Standard Error 1.45	28.10 units on a scale Standard Error 1.48
Medical Outcomes Study Sleep Scale (MOS-SS) Score Baseline: Snoring (n=253, 254)	30.72 units on a scale Standard Error 2.25	32.42 units on a scale Standard Error 2.29
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	17.26 units on a scale Standard Error 1.57
Medical Outcomes Study Sleep Scale (MOS-SS) Score Baseline: Quantity of Sleep (n=252, 252)	7.77 units on a scale Standard Error 0.10	7.82 units on a scale Standard Error 0.10
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	64.40 units on a scale Standard Error 1.83
Medical Outcomes Study Sleep Scale (MOS-SS) Score Baseline: Somnolence (n=253, 254)	34.85 units on a scale Standard Error 1.43	33.77 units on a scale Standard Error 1.45
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	29.49 units on a scale Standard Error 1.18
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	23.61 units on a scale Standard Error 1.17
Medical Outcomes Study Sleep Scale (MOS-SS) Score Week 16: Snoring (n=230, 240)	33.77 units on a scale Standard Error 1.72	23.75 units on a scale Standard Error 1.73
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	14.27 units on a scale Standard Error 1.48
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	7.75 units on a scale Standard Error 0.09
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	66.46 units on a scale Standard Error 1.73
Medical Outcomes Study Sleep Scale (MOS-SS) Score Week 16: Somnolence (n=230, 241)	31.56 units on a scale Standard Error 1.33	32.29 units on a scale Standard Error 1.34
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	26.00 units on a scale Standard Error 0.96

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pregabalin n=252 Participants 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 n=252 Participants 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.
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	55.6 percentage of participants
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	50.2 percentage of participants

Adverse Events

Pregabalin

Serious events: 24 serious events

Other events: 148 other events

Deaths: 0 deaths

Levetiracetam

Serious events: 24 serious events

Other events: 127 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Pregabalin n=254 participants at risk 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 n=255 participants at risk 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.
Gastrointestinal disorders Nausea	2.0% 5/254 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.	5.9% 15/255 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.
Infections and infestations Nasopharyngitis	9.4% 24/254 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.	7.5% 19/255 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.
Investigations Weight increased	10.2% 26/254 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.	3.1% 8/255 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.
Nervous system disorders Dizziness	23.2% 59/254 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.	16.5% 42/255 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.
Nervous system disorders Headache	14.6% 37/254 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.	11.8% 30/255 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.
Nervous system disorders Somnolence	32.7% 83/254 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.	29.8% 76/255 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.
Psychiatric disorders Insomnia	2.0% 5/254 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.	5.9% 15/255 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.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
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Restriction type: OTHER