Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00537940
• Collaborator: (none)
• Enrollment: 482
• Locations: 8
• Arms: 2
• Duration (Months): 65
• Patients Per Site: 60.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

To compare the efficacy of pregabalin and gabapentin, as adjunctive therapy in subjects with partial seizures.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy; Partial Seizure Disorder; Epilepsies, Partial; Complex Partial Seizure Disorder	Drug: Pregabalin; Drug: Gabapentin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 482 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Parallel-group Multi-center Comparative Flexible-dose Trial Of Pregabalin Versus Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures.
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A	Drug: Pregabalin; 150, 300, 450 mg/day administered orally TID, until seizure control/improvement or intolerable side effects
Active Comparator: B	Drug: Gabapentin; 300, 600, 1200, 2000 mg/day administered orally TID, until seizure control/improvement or intolerable side effects

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in 28-day Seizure Frequency at Week 21. [6 weeks Baseline, 21 weeks through End of MP for 27 weeks]

   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. Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + secondary generalized tonic clonic seizure [SGTC]).

Secondary Outcome Measures

1. Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. [6 weeks Baseline, 21 weeks through End of MP for 27 weeks]

   Participants who had at least 50% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 50% responders. If percent change from baseline <= -50 then responder rate = 1 (yes) otherwise responder rate = 0 (no).

2. Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. [6 weeks Baseline, 21 weeks through End of MP for 27 weeks]

   Participants who had at least 75% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 75% responders. If percent change from baseline <= -75 then 75% responder rate = 1 (yes) otherwise responder rate = 0 (no). Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + SGTC).

3. Percentage of Participants Without Seizures. [6 weeks Baseline, 21 weeks through End of MP for 27 weeks]

   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 MP. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure.

4. Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21. [6 weeks Baseline, 21 weeks through End of MP for 27 weeks]

   Change in SGTC = (Proportion of SGTC/All Partial Seizure rate during at the double-blind phase) - (Proportion of SGTC/All Partial Seizure rate at Baseline). Negative values indicate reduction from baseline.

5. Reduction in Proportion of the 28-day SGTC Seizure Rate Over the Total Partial Seizure Rate at Week 21. [6 weeks Baseline, 21 weeks through End of MP for 27 weeks]

   SGTC Responder is defined as a participant who shows reduction from Baseline to double-blind phase in proportion of 28-Day SGTC Seizure Rate to 28-Day All Partial Seizure Rate.

6. Hospital Anxiety and Depression Scale (HADS) Score. [Baseline, Week 21]

   HADS: participant rated questionnaire with 2 subscales. Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (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.

7. Medical Outcomes Study Sleep Scale (MOS-SS) Score. [Baseline, Week 21]

   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.

8. Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score. [Baseline, Week 21]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects (male or female) must be > 18 years or ≤ 80 years of age, with a diagnosis of epilepsy with partial seizures, as defined in the International League Against Epilepsy (ILAE) classification of seizures; partial seizures may be simple or complex, with or without secondary tonic-clonic generalization.

• Subjects must be have been diagnosed with epilepsy for at least 2 years, and must have been unresponsive to treatment with at least two but no more than five prior antiepileptic drugs (AEDs), and at the time of study enrollment are on stable dosages of 1 or 2 standard AEDs.

• They must have had a 12 lead electrocardiogram (ECG) without clinically significant abnormal findings prior to randomization.

• Subjects must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy.

• Women of childbearing potential must be established on an effective method of contraception during the study. Women should also have a negative pregnancy test prior to study entry.

• During the 6-week baseline period, subjects must have had a minimum of four partial seizures, with no 28 day period free of partial seizures with or without secondary generalization. A caregiver or witness must be with the subject for a sufficient duration to accurately chronicle the occurrence of seizures. These seizures must have been documented in the subject's diary.

• Subjects with electroencephalograph (EEG) testing done within 2 years of randomization. EEG abnormalities should be consistent with a diagnosis of focal-onset epilepsy.

• Signed and dated informed consent will be obtained from each subject (only include those able to consent) in accordance with the local regulatory and legal requirements.

• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Subjects who are willing, but need assistance for self administered questionnaires may be considered acceptable, but must first be discussed on a case-by-case basis with the Pfizer monitor prior to any to any screening tests or procedures for the study.

Exclusion Criteria:

• Females who are pregnant, breastfeeding, or intending to become pregnant during the course of the trial.

• Subjects with other neurologic illness that could impair endpoint assessment, or patients with Lennox-Gastaut syndrome, absence seizures, status epilepticus within the 12 months prior to study entry, or with seizures due to an underlying medical illness or metabolic syndrome.

• Subjects with clinically significant liver disease or with a calculated creatinine clearance of <60mL/min.

• Subjects with a history of lack of response, hypersensitivity or poor tolerability to gabapentin or pregabalin.

• Previous use of gabapentin or pregabalin within 2 weeks prior to screening or likelihood of engaging in these treatments during the study period.

• Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol.

• Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study.

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.

• Subjects who are not suitable to be treated with pregabalin or gabapentin according to the respective local labeling.

• Subjects with a history of retinal abnormalities or treatment with retinotoxic agents.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clinica Biblica	San Jose		Costa Rica
2	Instituto de Neurociencias	San Salvador		El Salvador	01503
3	Clinica de Especialidades Neurologicas	San Salvador		El Salvador
4	Private Office	Guatemala Ciudad		Guatemala	01014
5	Private Office	Guatemala		Guatemala
6	Clinica Anglo Americana	Lima		Peru	27
7	Torre de Consultorios Clinica Anglo Americana	Lima		Peru	L-27
8	Hospital Nacional Guillermo Almenara Irigoyen - Essalud	Lima		Peru	L13

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00537940
• Other Study ID Numbers: A0081143; 2007-003161-40; 207103
• First Posted: Oct 2, 2007
• Last Update Posted: Jan 22, 2021
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Epilepsy; Seizures; Epilepsies, Partial; Epilepsy, Complex Partial; Disease; Pregabalin; Gabapentin

Study Results

Participant Flow

Recruitment Details	Overall, 561 participants were screened and 482 participants participated in the study; 242 participants were randomized but one participant from the pregabalin group and one participant from the gabapentin group were not treated. Hence 241 participants were treated in each treatment group. Participants were randomized at 56 centers.
Pre-assignment Detail	One participant from the pregabalin group and one participant from the gabapentin group were randomized but not treated.

Arm/Group Title	Pregabalin	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Period Title: Overall Study
STARTED	241	241
Completed Titration Phase	213	210
Completed Maintenance Phase	187	172
Entered Opt Blinded Continuation Phase	140	139
COMPLETED	58	62
NOT COMPLETED	183	179

Baseline Characteristics

Arm/Group Title	Pregabalin	Gabapentin	Total
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.	Total of all reporting groups
Overall Participants	241	241	482
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.9 (13.0)	35.3 (12.9)	35.1 (13.0)
Sex: Female, Male (Count of Participants)
Female	114 47.3%	111 46.1%	225 46.7%
Male	127 52.7%	130 53.9%	257 53.3%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in 28-day Seizure Frequency at Week 21.
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. Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + secondary generalized tonic clonic seizure [SGTC]).
Time Frame	6 weeks Baseline, 21 weeks through End of MP for 27 weeks

Outcome Measure Data

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	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	238	240
Median (Full Range) [percent change]	-58.65	-57.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8708
	Comments
	Method	Ranked ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -6.0 to 7.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21.
Description	Participants who had at least 50% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 50% responders. If percent change from baseline <= -50 then responder rate = 1 (yes) otherwise responder rate = 0 (no).
Time Frame	6 weeks Baseline, 21 weeks through End of MP for 27 weeks

Outcome Measure Data

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=is the number of subjects that can be analyzed for each treatment group.

Arm/Group Title	Pregabalin	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	238	240
All Partial Seizure (n=238, 240)	56.3 23.4%	58.3 24.2%
Simple Partial (n=87, 88)	55.2 22.9%	53.4 22.2%
Complex Partial (n=161, 158)	56.5 23.4%	55.1 22.9%
SGTC (n=112, 114)	50.9 21.1%	60.5 25.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	The odds ratio and its 95% CI are calculated by exponentiating the log odds ratio and 95% CI that correspond to the treatment contrast in the logistic regression model with treatment as fixed effect and Baseline term and country as covariate. All statistical tests for secondary efficacy parameters were two sided and performed at significance level of α = 0.05. The above statistical analysis applies to All Partial Seizures - FAS Population.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.662
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.920
	Confidence Interval	(2-Sided) 95%; 0.635 to 1.335
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21.
Description	Participants who had at least 75% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 75% responders. If percent change from baseline <= -75 then 75% responder rate = 1 (yes) otherwise responder rate = 0 (no). Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + SGTC).
Time Frame	6 weeks Baseline, 21 weeks through End of MP for 27 weeks

Outcome Measure Data

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=is the number of participants that can be analyzed for each treatment group.

Arm/Group Title	Pregabalin	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	238	240
All Partial Seizure (n=238, 240)	33.6 13.9%	34.2 14.2%
Simple Partial (n=87, 88)	36.8 15.3%	33.0 13.7%
Complex Partial (n=161, 158)	37.3 15.5%	36.1 15%
SGTC (n=112, 114)	38.4 15.9%	43.9 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9232
	Comments	All partial seizure: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6361
	Comments	Simple Partial: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9075
	Comments	Complex partial: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4203
	Comments	SGTC seizure: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Percentage of Participants Without Seizures.
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 MP. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure.
Time Frame	6 weeks Baseline, 21 weeks through End of MP for 27 weeks

Outcome Measure Data

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	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	189	182
All Partial Seizure (n=189, 182)	30.7 12.7%	34.1 14.1%
Simple Partial (n=74, 66)	29.7 12.3%	36.4 15.1%
Complex Partial (n=126, 123)	37.3 15.5%	40.7 16.9%
SGTC (n=95, 91)	46.3 19.2%	42.9 17.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5069
	Comments	All partial seizure: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4721
	Comments	Simple partial seizure: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6054
	Comments	Complex partial seizure: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6603
	Comments	SGTC seizure: p-value was calculated from the 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21.
Description	Change in SGTC = (Proportion of SGTC/All Partial Seizure rate during at the double-blind phase) - (Proportion of SGTC/All Partial Seizure rate at Baseline). Negative values indicate reduction from baseline.
Time Frame	6 weeks Baseline, 21 weeks through End of MP for 27 weeks

Outcome Measure Data

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	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	114	114
Baseline (n=114, 114)	56.53 (40.856)	59.60 (40.571)
Change from Baseline at Double Blind (n=104, 98)	1.59 (28.164)	-2.17 (26.024)

6. Secondary Outcome

Title	Reduction in Proportion of the 28-day SGTC Seizure Rate Over the Total Partial Seizure Rate at Week 21.
Description	SGTC Responder is defined as a participant who shows reduction from Baseline to double-blind phase in proportion of 28-Day SGTC Seizure Rate to 28-Day All Partial Seizure Rate.
Time Frame	6 weeks Baseline, 21 weeks through End of MP for 27 weeks

Outcome Measure Data

Analysis Population Description

SGTC population included all participants who had at least 1 SGTC seizure during either Baseline or double-blind phase. n is the number of participants analyzed for SGTC. Twenty-six participants were not included in the n because they did not have a post Baseline all partial seizure, but they were included in the analysis by seizure type.

Arm/Group Title	Pregabalin	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	104	98
Number (95% Confidence Interval) [percentage of responders]	30.8	39.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1881
	Comments	p-value is calculated using Fisher Exact Test.
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Hospital Anxiety and Depression Scale (HADS) Score.
Description	HADS: participant rated questionnaire with 2 subscales. Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (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 21

Outcome Measure Data

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	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	238	240
Baseline HADS-A (n=238, 240)	7.82 (0.31)	7.60 (0.31)
HADS- A Change at Week 21/ET (n=212, 210)	-0.92 (0.26)	-0.83 (0.27)
Baseline HADS-D (n=238, 240)	5.94 (0.29)	5.65 (0.29)
HADS-D Change at Week 21/ET (n=212, 210)	-0.59 (0.24)	-0.42 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Baseline, HADS-A: ANCOVA model was used to calculate least square (LS) mean estimates of the treatment difference along with 95% CI, with main effects of treatment and and country as covariates.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5643
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.38
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Change at Week 21 / ET , 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 country as covariates.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7712
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.73 to 0.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4236
	Comments
	Method	Ranked ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Change at Week 21/ET, HADS-D: ANCOVA model was used to calculate LS mean estimates of the treatment1difference 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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5492
	Comments
	Method	Ranked ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.75 to 0.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.29
	Estimation Comments

8. Secondary Outcome

Title	Medical Outcomes Study Sleep Scale (MOS-SS) Score.
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 21

Outcome Measure Data

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	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	238	240
Baseline: Sleep Disturbance (n=238, 240)	29.68 (1.70)	26.43 (1.70)
Baseline: Snoring (n=238, 240)	29.28 (2.31)	28.09 (2.31)
Baseline: Awaken Short of Breath (n=238, 240)	23.64 (2.07)	19.61 (2.07)
Baseline: Quantity of Sleep (n=238, 240)	7.56 (0.11)	7.59 (0.11)
Baseline: Adequacy of Sleep (n=238, 240)	61.30 (2.01)	63.67 (2.01)
Baseline: Somnolence (n=238, 240)	32.29 (1.56)	29.31 (1.56)
Baseline: Sleep Problem Index (9) (n=238, 240)	31.60 (1.32)	28.15 (1.32)
Week 21: Sleep Disturbance (n=212, 210)	24.99 (1.37)	25.31 (1.39)
Week 21: Snoring (n=212, 210)	28.07 (1.89)	26.12 (1.90)
Week 21: Awaken Short of Breath (n=212, 210)	16.26 (1.73)	18.20 (1.74)
Week 21: Quantity of Sleep (n=212, 210)	8.79 (0.17)	8.77 (0.17)
Week 21: Adequacy of Sleep (n=212, 210)	63.87 (1.68)	64.53 (1.69)
Week 21: Somnolence (n=212, 210)	32.04 (1.36)	29.98 (1.37)
Week 21: Sleep Problem Index (9) (n=212, 210)	27.88 (1.04)	27.54 (1.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Baseline Sleep disturbance: ANCOVA model was used to calculate least square (LS) mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1160
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	3.25
	Confidence Interval	(2-Sided) 95%; -0.81 to 7.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.07
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8490
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -3.62 to 2.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.68
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6728
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; -4.34 to 6.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.82
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 snoring: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3954
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	1.96
	Confidence Interval	(2-Sided) 95%; -2.56 to 6.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.30
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1106
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	4.03
	Confidence Interval	(2-Sided) 95%; -0.92 to 8.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.52
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3603
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-1.93
	Confidence Interval	(2-Sided) 95%; -6.09 to 2.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.11
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8312
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9101
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.20
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3346
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-2.37
	Confidence Interval	(2-Sided) 95%; -7.19 to 2.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.45
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7491
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -4.69 to 3.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.05
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1162
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	2.98
	Confidence Interval	(2-Sided) 95%; -0.74 to 6.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.90
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 Somnolence: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2163
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95%; -1.21 to 5.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.66
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0321
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	3.45
	Confidence Interval	(2-Sided) 95%; 0.30 to 6.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.61
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21 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 country; for post-baseline, baseline was included as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7889
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -2.17 to 2.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.28
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score.
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 21

Outcome Measure Data

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 specifictime points for each arm group, respectively.

Arm/Group Title	Pregabalin	Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.	Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
Measure Participants	238	240
Baseline (n=238, 240)	49.2 20.4%	58.8 24.4%
Week 21 (n=212, 210)	51.4 21.3%	58.6 24.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0252
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.653
	Confidence Interval	(2-Sided) 95%; 0.449 to 0.948
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Gabapentin
	Comments	Week 21: 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 (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3459
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.811
	Confidence Interval	(2-Sided) 95%; 0.524 to 1.254
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Pregabalin		Gabapentin
Arm/Group Description	Pregabalin was initiated at 150 mg/day [50 mg capsules orally three times a day (TID)] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: >=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP.		Gabapentin was initiated at 300 mg/day [100 mg capsules orally three times a day (TID)] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP.
All Cause Mortality
	Pregabalin		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/241 (5.4%)		14/241 (5.8%)
Cardiac disorders
Atrial fibrillation	1/241 (0.4%)		0/241 (0%)
Pericardial effusion	1/241 (0.4%)		0/241 (0%)
Ear and labyrinth disorders
Vertigo	0/241 (0%)		1/241 (0.4%)
Eye disorders
Diplopia	0/241 (0%)		1/241 (0.4%)
Gastrointestinal disorders
Rectal haemorrhage	1/241 (0.4%)		0/241 (0%)
Hepatobiliary disorders
Hepatitis	1/241 (0.4%)		0/241 (0%)
Infections and infestations
Bronchopneumonia	1/241 (0.4%)		0/241 (0%)
Encephalitis viral	0/241 (0%)		1/241 (0.4%)
Influenza	1/241 (0.4%)		0/241 (0%)
Pneumonia	2/241 (0.8%)		0/241 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/241 (0%)		1/241 (0.4%)
Contusion	1/241 (0.4%)		0/241 (0%)
Face injury	1/241 (0.4%)		0/241 (0%)
Fall	1/241 (0.4%)		0/241 (0%)
Hand fracture	0/241 (0%)		1/241 (0.4%)
Head injury	1/241 (0.4%)		0/241 (0%)
Overdose	0/241 (0%)		1/241 (0.4%)
Patella fracture	0/241 (0%)		1/241 (0.4%)
Skull fracture	0/241 (0%)		1/241 (0.4%)
Subdural haematoma	0/241 (0%)		1/241 (0.4%)
Metabolism and nutrition disorders
Hypoglycaemia	1/241 (0.4%)		0/241 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma	0/241 (0%)		1/241 (0.4%)
Nervous system disorders
Cerebral disorder	0/241 (0%)		1/241 (0.4%)
Convulsion	3/241 (1.2%)		0/241 (0%)
Dysarthria	0/241 (0%)		1/241 (0.4%)
Epilepsy	0/241 (0%)		2/241 (0.8%)
Grand mal convulsion	1/241 (0.4%)		0/241 (0%)
Hemiparesis	1/241 (0.4%)		0/241 (0%)
Loss of consciousness	1/241 (0.4%)		0/241 (0%)
Status epilepticus	0/241 (0%)		2/241 (0.8%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/241 (0.4%)		0/241 (0%)
Psychiatric disorders
Psychotic disorder	0/241 (0%)		1/241 (0.4%)
Suicidal ideation	2/241 (0.8%)		0/241 (0%)
Suicide attempt	0/241 (0%)		1/241 (0.4%)
Withdrawal syndrome	1/241 (0.4%)		0/241 (0%)
Renal and urinary disorders
Urogenital fistula	0/241 (0%)		1/241 (0.4%)
Reproductive system and breast disorders
Ovarian cyst	0/241 (0%)		1/241 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/241 (0.4%)		0/241 (0%)
Skin and subcutaneous tissue disorders
Skin necrosis	1/241 (0.4%)		0/241 (0%)
Vascular disorders
Hypertension	1/241 (0.4%)		0/241 (0%)
Other (Not Including Serious) Adverse Events
	Pregabalin		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/241 (32%)		77/241 (32%)
Gastrointestinal disorders
Dry mouth	12/241 (5%)		8/241 (3.3%)
Investigations
Weight increased	23/241 (9.5%)		15/241 (6.2%)
Nervous system disorders
Dizziness	22/241 (9.1%)		21/241 (8.7%)
Headache	21/241 (8.7%)		25/241 (10.4%)
Somnolence	35/241 (14.5%)		34/241 (14.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.