Study Of The Safety And Efficacy Of Lyrica In The Treatment Of Newly Diagnosed Partial Epilepsy

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00280059
• Collaborator: (none)
• Enrollment: 660
• Locations: 102
• Arms: 2
• Duration (Months): 44
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether Lyrica is a safe and effective treatment for partial epilepsy in comparison with an established treatment, Lamictal.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy, Partial	Drug: Pregabalin; Drug: Lamotrigine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 660 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Comparative, Double-Blind, Parallel-Group, Multicenter, Monotherapy, Study Of Pregabalin (Lyrica) And Lamotrigine (Lamictal) In Patients With Newly Diagnosed Partial Seizures
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Pregabalin; dose 150-600 mg/day given BID
Active Comparator: 2	Drug: Lamotrigine; dose 100-500 mg/day given BID

Outcome Measures

Primary Outcome Measures

1. Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase [Week 5 up to Week 56]

   Responders = participants who achieved any 6 consecutive months (>182 days) of seizure-freedom (absence of partial seizures, generalized seizures and unclassified epileptic seizures) during the 52 week efficacy assessment phase.

Secondary Outcome Measures

1. Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures [Week 4 up to Week 56]

   Time in days, from first day of study medication to the first 6 months of seizure freedom after Day 28. Participants who did not achieve 6 months seizure freedom after Day 28 were censored from analysis.

2. Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase) [Week 0 to Week 56]

   Number of participants who exited the study due to adverse events during the double-blind treatment period. Time in days, from first day of study treatment to day of exit from the study due to an adverse event (ie, last day on study medication) during the double blind treatment period (including dose escalation phase) was inestimable. Observations with other reasons for exiting or participants who did not exit the study were right censored as of the last day on study medication.

3. Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase) [Week 0 to Week 56]

   Number of participants who exited the study for any reason during the double blind treatment phase. Time in days, from first day of study treatment to day of exit from the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit the study were right censored as of the last day on study medication.

4. Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase [Week 4 up to Week 56]

   Number of participants who exited the study due to lack of efficacy after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit due to lack of efficacy after Day 28 of the escalation phase (ie, last day on study medication) was inestimable. Participants who did not exit or exited for a different reason were right censored as of the last day on study medication.

5. Exit Due to Any Reason After 4-week Dose Escalation Phase [Week 4 up to Week 56]

   Number of participants who exited the study due to any reason after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit after Day 28 of the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit or did not reach this phase were right censored as of the last day on study medication.

6. Time to First Seizure After the 4-Week Dose Escalation Phase [Week 4 up to Week 56]

   Time in days, from first day of study treatment to the day of first seizure after Day 28 of the escalation phase (ie, last day on study medication). Participants who did not reach this phase or who did not have a seizure after Day 28 were right censored from the analysis as of the last day on study medication.

7. Median Monthy Seizure Frequency: All Partial Seizures [Baseline up to Week 60]

   All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).

8. Mean Monthy Seizure Frequency: All Partial Seizures [Baseline up to Week 60]

   All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).

9. Median Monthy Seizure Frequency: All Seizures [Baseline up to Week 60]

   Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).

10. Mean Monthy Seizure Frequency: All Seizures [Baseline up to Week 60]

    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).

11. Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures [Month 1 through Month 9 (after 6 months seizure freedom achieved)]

    All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

12. Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures [Month 1 through Month 9 (after 6 months seizure freedom achieved)]

    All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

13. Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures [Month 1 through Month 9 (after 6 months seizure freedom achieved)]

    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

14. Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures [Month 1 through Month 9 (after 6 months seizure freedom achieved)]

    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

15. Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group [Week 5 up to Week 56]

    Responder = participant who achieved at least 6-months of seizure freedom (all seizures) after Week 4, and up to Week 56. Dose Level defined as last total-daily-dose received after Week 4, and up to Week 56.

16. Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) [Baseline to Week 56]

    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; 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 symptoms. Scores relative to start of randomized treatment.

17. Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale [Week 8, Week 32, and Week 56]

    MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Optimal Sleep subscale is derived from sleep quantity average hours of sleep each night during the past week. Number of subjects with response Optimal if sleep quantity was 7 or 8 hours of sleep per night, and Non-optimal if average sleep was less than or greater than 7 to 8 hours per night. Analysis assesses the MOS-Sleep scale relative to the start of randomized treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be diagnosed with partial epilepsy and have experienced at least 2 partial seizures (simple partial, complex partial or partial seizure with secondary generalization) in the past year with one in the past 6 months.

Exclusion Criteria:

• Treatable causes of seizures, for example identified etiologies including metabolic, neoplastic or active infectious origin.

• Primary generalized seizures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Brugge		Belgium	8000
2	Pfizer Investigational Site	Bruxelles		Belgium	1070
3	Pfizer Investigational Site	Leuven		Belgium	3000
4	Pfizer Investigational Site	Plovdiv		Bulgaria	4000
5	Pfizer Investigational Site	Sofia		Bulgaria	1113
6	Pfizer Investigational Site	Sofia		Bulgaria	1309
7	Pfizer Investigational Site	Sofia		Bulgaria	1524
8	Pfizer Investigational Site	Varna		Bulgaria	9010
9	Pfizer Investigational Site	Xi'an	Shanxi	China	710032
10	Pfizer Investigational Site	Cheng Du Si Chaun		China	610041
11	Pfizer Investigational Site	Chongqing		China	400016
12	Pfizer Investigational Site	Tian Jin		China	300052
13	Pfizer Investigational Site	Bogota	Cundinamarca	Colombia	0
14	Pfizer Investigational Site	Cali	Valle Del Cauca	Colombia
15	Pfizer Investigational Site	Brno 2		Czechia	602 00
16	Pfizer Investigational Site	Hradec Kralove		Czechia	500 05
17	Pfizer Investigational Site	Ostrava		Czechia	708 58
18	Pfizer Investigational Site	Pelhrimov		Czechia	393 01
19	Pfizer Investigational Site	Praha 4		Czechia	140 59
20	Pfizer Investigational Site	Rychnov nad Kneznou		Czechia	516 01
21	Pfizer Investigational Site	Zlin		Czechia	760 01
22	Pfizer Investigational Site	Tallinn		Estonia	10138
23	Pfizer Investigational Site	Tartu		Estonia	51014
24	Pfizer Investigational Site	Kuopio		Finland	70210
25	Pfizer Investigational Site	Tampere		Finland	33520
26	Pfizer Investigational Site	Bordeaux Cedex		France	33076
27	Pfizer Investigational Site	Nancy Cedex		France	54035
28	Pfizer Investigational Site	Strasbourg Cedex		France	67091
29	Pfizer Investigational Site	Berlin		Germany	10365
30	Pfizer Investigational Site	Bonn		Germany	53105
31	Pfizer Investigational Site	Essen		Germany	45147
32	Pfizer Investigational Site	Frankfurt		Germany	60528
33	Pfizer Investigational Site	Ulm		Germany	89075
34	Pfizer Investigational Site	Ulm		Germany	89081
35	Pfizer Investigational Site	Hong Kong		Hong Kong
36	Pfizer Investigational Site	Kowloon		Hong Kong
37	Pfizer Investigational Site	Shatin		Hong Kong
38	Pfizer Investigational Site	Budapest		Hungary	1145
39	Pfizer Investigational Site	Gyor		Hungary	9023
40	Pfizer Investigational Site	Nyiregyhaza		Hungary	4400
41	Pfizer Investigational Site	Bangalore	Karnataka	India	560 054
42	Pfizer Investigational Site	Indore	Madhya Pradesh	India	452001
43	Pfizer Investigational Site	Chennai	Tamil Nadu	India	600 006
44	Pfizer Investigational Site	Bangalore		India	560 034
45	Pfizer Investigational Site	Lucknow		India	226 014
46	Pfizer Investigational Site	New Delhi		India	110 002
47	Pfizer Investigational Site	Tallaght	Dublin	Ireland	24
48	Pfizer Investigational Site	Bologna		Italy	40139
49	Pfizer Investigational Site	Firenze		Italy	50125
50	Pfizer Investigational Site	Foggia		Italy	71100
51	Pfizer Investigational Site	Pisa		Italy	56126
52	Pfizer Investigational Site	Daejeon		Korea, Republic of	301-721
53	Pfizer Investigational Site	Gwangju		Korea, Republic of	501-757
54	Pfizer Investigational Site	Incheon		Korea, Republic of	405-760
55	Pfizer Investigational Site	Seoul		Korea, Republic of	110-744
56	Pfizer Investigational Site	Seoul		Korea, Republic of	120-752
57	Pfizer Investigational Site	Seoul		Korea, Republic of	134-701
58	Pfizer Investigational Site	Seoul		Korea, Republic of	135-710
59	Pfizer Investigational Site	Seoul		Korea, Republic of	137-701
60	Pfizer Investigational Site	Seoul		Korea, Republic of	138-736
61	Pfizer Investigational Site	Riga		Latvia	LV 1002
62	Pfizer Investigational Site	Riga		Latvia	LV 1038
63	Pfizer Investigational Site	Kaunas		Lithuania	50009
64	Pfizer Investigational Site	Vilnius		Lithuania	03215
65	Pfizer Investigational Site	Vilnius		Lithuania	08661
66	Pfizer Investigational Site	Mexico	DF	Mexico	14000
67	Pfizer Investigational Site	San Luis Potosi		Mexico	78223
68	Pfizer Investigational Site	Den Haag	ZH	Netherlands	2512 VA
69	Pfizer Investigational Site	Lillehammer		Norway	2629
70	Pfizer Investigational Site	Trondheim		Norway	7006
71	Pfizer Investigational Site	Amadora		Portugal	2700-276
72	Pfizer Investigational Site	Coimbra		Portugal	3000-548
73	Pfizer Investigational Site	Coimbra		Portugal	3040-853 Coimbra
74	Pfizer Investigational Site	Porto		Portugal	4099-001
75	Pfizer Investigational Site	Porto		Portugal	4200-319
76	Pfizer Investigational Site	Cluj-Napoca	Jud. Cluj	Romania	400012
77	Pfizer Investigational Site	Bucuresti		Romania	050098
78	Pfizer Investigational Site	Bucuresti		Romania	11461
79	Pfizer Investigational Site	Singapore		Singapore	169608
80	Pfizer Investigational Site	Bratislava		Slovakia	813 69
81	Pfizer Investigational Site	Bratislava		Slovakia	82606
82	Pfizer Investigational Site	Bratislava		Slovakia	833 05
83	Pfizer Investigational Site	Kosice		Slovakia	04015
84	Pfizer Investigational Site	Zilina		Slovakia	012 07
85	Pfizer Investigational Site	Badalona	Barcelona	Spain	08916
86	Pfizer Investigational Site	Girona		Spain	17007
87	Pfizer Investigational Site	Madrid		Spain	28040
88	Pfizer Investigational Site	Valencia		Spain	46009
89	Pfizer Investigational Site	Valencia		Spain	46014
90	Pfizer Investigational Site	Goteborg		Sweden	413 45
91	Pfizer Investigational Site	Linkoping		Sweden	581 85
92	Pfizer Investigational Site	Uppsala		Sweden	75185
93	Pfizer Investigational Site	Tainan		Taiwan
94	Pfizer Investigational Site	Taipei		Taiwan	112
95	Pfizer Investigational Site	Taipei		Taiwan
96	Pfizer Investigational Site	Rajthevee	Bangkok	Thailand	10400
97	Pfizer Investigational Site	Muang	Khon Kaen	Thailand	40002
98	Pfizer Investigational Site	Bangkok		Thailand	10400
99	Pfizer Investigational Site	Stoke-on-Trent	Staffordshire	United Kingdom	ST4 7LN
100	Pfizer Investigational Site	Glasgow		United Kingdom	G11 6NT
101	Pfizer Investigational Site	Liverpool		United Kingdom	L9 7LJ
102	Pfizer Investigational Site	Treliske, Truro, Cornwall		United Kingdom	TR1 3LJ

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: NCT00280059
• Other Study ID Numbers: A0081046
• First Posted: Jan 20, 2006
• Last Update Posted: Jan 28, 2021
• Last Verified: Mar 1, 2015

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Epilepsy; partial seizures; pregabalin monotherapy; lamotrigine comparator; double-blind and randomized trial
• Additional relevant MeSH terms: Epilepsy; Epilepsies, Partial; Pregabalin; Lamotrigine

Study Results

Participant Flow

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Period Title: Efficacy Assessment Phase
STARTED	330	330
COMPLETED	236	250
NOT COMPLETED	94	80
Period Title: Efficacy Assessment Phase
STARTED	194	215
COMPLETED	145	177
NOT COMPLETED	49	38

Baseline Characteristics

Arm/Group Title	Pregabalin	Lamotrigine	Total
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Total of all reporting groups
Overall Participants	330	330	660
Age, Customized (participants) [Number]
< 18 years	9 2.7%	9 2.7%	18 2.7%
Between 18 and 44 years	228 69.1%	228 69.1%	456 69.1%
Between 45 and 64 years	79 23.9%	74 22.4%	153 23.2%
>= 65 years	14 4.2%	19 5.8%	33 5%
Sex: Female, Male (Count of Participants)
Female	165 50%	146 44.2%	311 47.1%
Male	165 50%	184 55.8%	349 52.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase
Description	Responders = participants who achieved any 6 consecutive months (>182 days) of seizure-freedom (absence of partial seizures, generalized seizures and unclassified epileptic seizures) during the 52 week efficacy assessment phase.
Time Frame	Week 5 up to Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) (intent to treat population): randomized participants who took at least 1 dose of study medication. N = number of participants who had at least 1 dose of study treatment and seizure efficacy data. Analysis excludes participants who did not enter maintenance phase of study.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	314	308
Number [percentage of participants]	51.6 15.6%	67.9 20.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Analysis of the binary response variable for 6 consecutive months seizure freedom analyzed by comparing the proportions of favorable responders between the two treatment groups after stratifying by clusters and correcting for skewness (Gart and Nam, 1990). Percentage can be obtained by multiplying proportion by 100.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Non-inferiority margin for the proportion of seizure free participants set at 10%; non-inferiority declared if the lower bound of the 95% confidence interval (CI) of the difference in seizure-free proportion between pregabalin and lamotrigine was no more than 10% in favor of lamotrigine, but 0 was contained within the lower bound of the CI. Interpretation of superiority required lower bound of CI did not contain 0 in favor of pregabalin.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.24 to -0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% confidence interval for the true difference in proportions, as well as a one-sided test at α=0.025; confidence interval adjusted for centers clustered within a geographical region, with upper and lower confidence limits.

2. Secondary Outcome

Title	Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures
Description	Time in days, from first day of study medication to the first 6 months of seizure freedom after Day 28. Participants who did not achieve 6 months seizure freedom after Day 28 were censored from analysis.
Time Frame	Week 4 up to Week 56

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	314	308
Median (95% Confidence Interval) [days]	254	183

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio > 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments	Nominal value for 2-sided test calculated using Cox proportional hazards model, adjusted for geographic regions.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.60 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase)
Description	Number of participants who exited the study due to adverse events during the double-blind treatment period. Time in days, from first day of study treatment to day of exit from the study due to an adverse event (ie, last day on study medication) during the double blind treatment period (including dose escalation phase) was inestimable. Observations with other reasons for exiting or participants who did not exit the study were right censored as of the last day on study medication.
Time Frame	Week 0 to Week 56

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit due to adverse events was inestimable as survival estimate at end of maintenance phase was below 0.500.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	330	330
Number [participants]	33 10%	31 9.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8047
	Comments	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase)
Description	Number of participants who exited the study for any reason during the double blind treatment phase. Time in days, from first day of study treatment to day of exit from the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit the study were right censored as of the last day on study medication.
Time Frame	Week 0 to Week 56

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants who had at least 1 dose of study treatment and seizure efficacy data Time to exit for any reason during the double-blind treatment phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	330	330
Number [participants]	94 28.5%	80 24.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2537
	Comments	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase
Description	Number of participants who exited the study due to lack of efficacy after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit due to lack of efficacy after Day 28 of the escalation phase (ie, last day on study medication) was inestimable. Participants who did not exit or exited for a different reason were right censored as of the last day on study medication.
Time Frame	Week 4 up to Week 56

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit due to lack of efficacy after 4-week dose escalation phase was inestimable as survival estimate at end of maintenance phase was below 0.500.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	330
Number [participants]	78 23.6%	58 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	6.52
	Confidence Interval	(2-Sided) 95%; 1.93 to 22.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Exit Due to Any Reason After 4-week Dose Escalation Phase
Description	Number of participants who exited the study due to any reason after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit after Day 28 of the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit or did not reach this phase were right censored as of the last day on study medication.
Time Frame	Week 4 up to Week 56

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit for any reason after the 4-week dose escalation phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	300
Number [participants]	78 23.6%	58 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0744
	Comments	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Time to First Seizure After the 4-Week Dose Escalation Phase
Description	Time in days, from first day of study treatment to the day of first seizure after Day 28 of the escalation phase (ie, last day on study medication). Participants who did not reach this phase or who did not have a seizure after Day 28 were right censored from the analysis as of the last day on study medication.
Time Frame	Week 4 up to Week 56

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	300
Median (95% Confidence Interval) [days]	85	211

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95%; 1.19 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Median Monthy Seizure Frequency: All Partial Seizures
Description	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).
Time Frame	Baseline up to Week 60

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	330
Dose-escalation phase (Weeks 1 - 4) (n=329, 330)	0.0 (9.348)	0.0 (27.118)
Month 1 (n=314, 308)	0.0 (6.139)	0.0 (31.453)
Month 2 (n=300, 295)	0.0 (3.382)	0.0 (28.839)
Month 3 (n=287, 288)	0.0 (2.568)	0.0 (32.783)
Month 4 (n=279, 278)	0.0 (2.313)	0.0 (16.046)
Month 5 (n=274, 276)	0.0 (2.270)	0.0 (15.254)
Month 6 (n=266, 272)	0.0 (2.702)	0.0 (15.126)
Month 7 (n=260, 270)	0.0 (2.839)	0.0 (16.855)
Month 8 (n=256, 266)	0.0 (3.247)	0.0 (19.111)
Month 9 (n=253, 262)	0.0 (2.538)	0.0 (17.204)
Month 10 (n=250, 257)	0.0 (4.935)	0.0 (16.905)
Month 11 (n=242, 254)	0.0 (3.082)	0.0 (19.268)
Month 12 (n=238, 252)	0.0 (7.018)	0.0 (19.590)
Month 13 (n=210, 227)	0.0 (3.247)	0.0 (19.462)
Taper (Week 57 to Week 60) (n=71, 45)	0.0 (6.418)	0.0 (97.196)

9. Secondary Outcome

Title	Mean Monthy Seizure Frequency: All Partial Seizures
Description	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).
Time Frame	Baseline up to Week 60

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	330
Dose escalation phase (n=329, 330)	2.56 (9.348)	5.08 (27.118)
Month 1 (n=314, 308)	2.23 (6.139)	4.21 (31.453)
Month 2 (n=300, 295)	1.18 (3.382)	3.21 (28.839)
Month 3 (n=287, 288)	0.94 (2.568)	3.54 (32.783)
Month 4 (n=279, 278)	0.89 (2.313)	1.67 (16.046)
Month 5 (n=274, 276)	0.78 (2.270)	1.58 (15.254)
Month 6 (n=266, 272)	0.82 (2.702)	1.41 (15.126)
Month 7 (n=260, 270)	0.78 (2.839)	1.50 (16.855)
Month 8 (n=256, 266)	0.77 (3.247)	1.36 (19.111)
Month 9 (n=253, 262)	0.71 (2.538)	1.38 (17.204)
Month 10 (n=250, 257)	1.05 (4.935)	1.33 (16.905)
Month 11 (n=242, 254)	0.79 (3.082)	1.41 (19.268)
Month 12 (n=238, 252)	0.94 (7.018)	1.67 (19.590)
Month 13 (n=210, 227)	0.65 (3.247)	2.11 (19.462)
Taper (n=71, 45)	2.13 (6.418)	19.97 (97.196)

10. Secondary Outcome

Title	Median Monthy Seizure Frequency: All Seizures
Description	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).
Time Frame	Baseline up to Week 60

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	330
Dose-escalation phase (Weeks 1 - 4)(n=329, 330)	0.0 (9.819)	0.0 (27.128)
Month 1 (n=314, 308)	0.0 (6.164)	0.0 (31.452)
Month 2 (n=300, 295)	0.0 (5.498)	0.0 (28.838)
Month 3 (n=287, 288)	0.0 (2.702)	0.0 (32.782)
Month 4 (n=279, 278)	0.0 (3.223)	0.0 (16.046)
Month 5 (n=274, 276)	0.0 (2.458)	0.0 (15.254)
Month 6 (n=266, 272)	0.0 (2.853)	0.0 (15.126)
Month 7 (n=260, 270)	0.0 (2.898)	0.0 (16.855)
Month 8 (n=256, 266)	0.0 (3.304)	0.0 (19.110)
Month 9 (n=253, 262)	0.0 (2.636)	0.0 (17.204)
Month 10 (n=250, 257)	0.0 (4.934)	0.0 (16.905)
Month 11 (n=242, 254)	0.0 (3.224)	0.0 (19.268)
Month 12 (n=238, 252)	0.0 (7.019)	0.0 (19.590)
Month 13 (n=210, 227)	0.0 (3.247)	0.0 (19.462)
Taper (Week 57 to Week 60) (n=71, 45)	0.0 (6.418)	0.0 (97.196)

11. Secondary Outcome

Title	Mean Monthy Seizure Frequency: All Seizures
Description	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).
Time Frame	Baseline up to Week 60

Outcome Measure Data

Analysis Population Description

FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	329	330
Dose-escalation phase (n=329, 330)	2.74 (9.819)	5.10 (27.128)
Month 1 (n=314, 308)	2.31 (6.164)	4.24 (31.452)
Month 2 (n=300, 295)	1.53 (5.498)	3.22 (28.838)
Month 3 (n=287, 288)	1.02 (2.702)	3.57 (32.782)
Month 4 (n=279, 278)	1.06 (3.223)	1.68 (16.046)
Month 5 (n=274, 276)	0.87 (2.458)	1.59 (15.254)
Month 6 (n=266, 272)	0.89 (2.853)	1.41 (15.126)
Month 7 (n=260, 270)	0.83 (2.898)	1.50 (16.855)
Month 8 (n=256, 266)	0.82 (3.304)	1.37 (19.110)
Month 9 (n=253, 262)	0.78 (2.636)	1.38 (17.204)
Month 10 (n=250, 257)	1.06 (4.934)	1.33 (16.905)
Month 11 (n=242, 254)	0.81 (3.224)	1.41 (19.268)
Month 12 (n=238, 252)	0.96 (7.019)	1.67 (19.590)
Month 13 (n=210, 227)	0.65 (3.247)	2.12 (19.462)
Taper (n=71, 45)	2.13 (6.418)	19.97 (97.196)

12. Secondary Outcome

Title	Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures
Description	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.
Time Frame	Month 1 through Month 9 (after 6 months seizure freedom achieved)

Outcome Measure Data

Analysis Population Description

FAS. N = number of responders; n = number of responders with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	162	208
Month 1 (n=162, 208)	0.0 (1.000)	0.0 (0.226)
Month 2 (n=155, 194)	0.0 (1.783)	0.0 (0.226)
Month 3 (n=147, 184)	0.0 (0.384)	0.0 (0.439)
Month 4 (n=139, 173)	0.0 (0.329)	0.0 (0.211)
Month 5 (n=127, 158)	0.0 (0.926)	0.0 (0.823)
Month 6 (n=122, 152)	0.0 (0.156)	0.0 (0.213)
Month 7 (n=105, 136)	0.0 (0.000)	0.0 (2.843)
Month 8 (n=1, 5)	0.0 (NA)	0.0 (0.000)
Month 9 (n=0, 1)	NA (NA)	6.0 (NA)

13. Secondary Outcome

Title	Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures
Description	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.
Time Frame	Month 1 through Month 9 (after 6 months seizure freedom achieved)

Outcome Measure Data

Analysis Population Description

FAS. N = number of responders; n = number of responders with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	162	208
Month 1 (n=162, 208)	0.19 (1.000)	0.04 (0.226)
Month 2 (n=155, 194)	0.28 (1.783)	0.03 (0.226)
Month 3 (n=147, 184)	0.05 (0.384)	0.07 (0.439)
Month 4 (n=139, 173)	0.09 (0.329)	0.05 (0.211)
Month 5 (n=127, 158)	0.15 (0.926)	0.10 (0.823)
Month 6 (n=122, 152)	0.02 (0.156)	0.03 (0.213)
Month 7 (n=105, 136)	0.00 (0.000)	0.28 (2.843)
Month 8 (n=1, 5)	0.00 (NA)	0.00 (0.000)
Month 9 (n=0, 1)	NA (NA)	6.00 (NA)

14. Secondary Outcome

Title	Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures
Description	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.
Time Frame	Month 1 through Month 9 (after 6 months seizure freedom achieved)

Outcome Measure Data

Analysis Population Description

FAS. N = number of responders; n = number of responders with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	162	208
Month 1 (n=162, 208)	0.0 (1.000)	0.0 (0.236)
Month 2 (n=155, 194)	0.0 (1.783)	0.0 (0.226)
Month 3 (n=147, 184)	0.0 (0.400)	0.0 (0.439)
Month 4 (n=139, 173)	0.0 (0.359)	0.0 (0.211)
Month 5 (n=127, 158)	0.0 (0.971)	0.0 (0.823)
Month 6 (n=122, 152)	0.0 (0.156)	0.0 (0.213)
Month 7 (n=105, 136)	0.0 (0.000)	0.0 (2.844)
Month 8 (n=1, 5)	0.0 (NA)	0.0 (0.000)
Month 9 (n=0, 1)	NA (NA)	6.0 (NA)

15. Secondary Outcome

Title	Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures
Description	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.
Time Frame	Month 1 through Month 9 (after 6 months seizure freedom achieved)

Outcome Measure Data

Analysis Population Description

FAS. N = number of responders; n = number of responders with analyzable data at observation.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	162	208
Month 1 (n=162, 208)	0.19 (1.000)	0.05 (0.236)
Month 2 (n=155, 194)	0.28 (1.783)	0.03 (0.226)
Month 3 (n=147, 184)	0.07 (0.400)	0.07 (0.439)
Month 4 (n=139, 173)	0.09 (0.359)	0.05 (0.211)
Month 5 (n=127, 158)	0.18 (0.971)	0.10 (0.823)
Month 6 (n=122, 152)	0.02 (0.156)	0.03 (0.213)
Month 7 (n=105, 136)	0.00 (0.000)	0.29 (2.844)
Month 8 (n=1, 5)	0.00 (NA)	0.00 (0.000)
Month 9 (n=0, 1)	NA (NA)	6.00 (NA)

16. Secondary Outcome

Title	Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group
Description	Responder = participant who achieved at least 6-months of seizure freedom (all seizures) after Week 4, and up to Week 56. Dose Level defined as last total-daily-dose received after Week 4, and up to Week 56.
Time Frame	Week 5 up to Week 56

Outcome Measure Data

Analysis Population Description

FAS; N = number of participants with analyzable data.

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 300 mg/Day	Pregabalin 450 mg/Day	Pregabalin 600 mg/Day	Lamotrigine 100 mg/Day	Lamotrigine 200 mg/Day	Lamotrigine 400 mg/Day	Lamotrigine 500 mg/Day
Arm/Group Description	Pregabalin 150 mg/day administered twice daily (BID)	Pregabalin 300 mg/day administered BID	Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/day administered BID
Measure Participants	149	67	49	46	164	84	34	18
Number [percentage of participants]	70.5 21.4%	59.7 18.1%	20.4 3.1%	13.0 NaN	80.5 NaN	67.9 NaN	38.2 NaN	16.7 NaN

17. Secondary Outcome

Title	Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS)
Description	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; 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 symptoms. Scores relative to start of randomized treatment.
Time Frame	Baseline to Week 56

Outcome Measure Data

Analysis Population Description

FAS; N = number of participants with a HADS measurement at baseline and Week 56.

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	237	238
Anxiety	-0.3 (0.25)	-1.1 (0.25)
Depression	-0.1 (0.23)	-0.7 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Anxiety; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.3 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Depression; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0186
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.1 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale
Description	MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Optimal Sleep subscale is derived from sleep quantity average hours of sleep each night during the past week. Number of subjects with response Optimal if sleep quantity was 7 or 8 hours of sleep per night, and Non-optimal if average sleep was less than or greater than 7 to 8 hours per night. Analysis assesses the MOS-Sleep scale relative to the start of randomized treatment.
Time Frame	Week 8, Week 32, and Week 56

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Pregabalin	Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Measure Participants	330	330
Week 8: Optimal sleep	195 59.1%	173 52.4%
Week 8: Non-optimal sleep	103 31.2%	126 38.2%
Week 32: Optimal sleep	167 50.6%	155 47%
Week 32: Non-optimal sleep	97 29.4%	103 31.2%
Week 56: Optimal sleep	152 46.1%	145 43.9%
Week 56: Non-optimal sleep	82 24.8%	90 27.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Week 8: dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0683
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Week 32: dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5096
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Lamotrigine
	Comments	Week 56 (termination): dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6804
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Pregabalin		Lamotrigine
Arm/Group Description	Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.		Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
All Cause Mortality
	Pregabalin		Lamotrigine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin		Lamotrigine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/330 (13.3%)		32/330 (9.7%)
Blood and lymphatic system disorders
Pancytopenia	1/330 (0.3%)		0/330 (0%)
Splenomegaly	0/330 (0%)		1/330 (0.3%)
Cardiac disorders
Myocardial ischaemia	1/330 (0.3%)		0/330 (0%)
Congenital, familial and genetic disorders
Multiple endocrine adenomatosis Type II	1/330 (0.3%)		0/330 (0%)
Endocrine disorders
Parathyroid gland enlargement	1/330 (0.3%)		0/330 (0%)
Eye disorders
Entropion	0/330 (0%)		1/330 (0.3%)
Trichiasis	0/330 (0%)		1/330 (0.3%)
Gastrointestinal disorders
Dyspepsia	1/330 (0.3%)		0/330 (0%)
Gastritis	0/330 (0%)		1/330 (0.3%)
Vomiting	2/330 (0.6%)		0/330 (0%)
General disorders
Chest pain	0/330 (0%)		1/330 (0.3%)
Drowning	1/330 (0.3%)		0/330 (0%)
General physical health deterioration	0/330 (0%)		1/330 (0.3%)
Pyrexia	1/330 (0.3%)		0/330 (0%)
Sudden unexplained death in epilepsy	1/330 (0.3%)		0/330 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/330 (0.3%)		0/330 (0%)
Hepatic function abnormal	1/330 (0.3%)		0/330 (0%)
Infections and infestations
Diverticulitis	0/330 (0%)		1/330 (0.3%)
Hepatitis B	1/330 (0.3%)		0/330 (0%)
Pneumonia	1/330 (0.3%)		0/330 (0%)
Sinusitis	1/330 (0.3%)		0/330 (0%)
Tuberculosis	0/330 (0%)		1/330 (0.3%)
Upper respiratory tract infection	1/330 (0.3%)		0/330 (0%)
Vulvovaginitis	0/330 (0%)		1/330 (0.3%)
Injury, poisoning and procedural complications
Cartilage injury	1/330 (0.3%)		0/330 (0%)
Concussion	1/330 (0.3%)		0/330 (0%)
Excoriation	1/330 (0.3%)		0/330 (0%)
Fall	0/330 (0%)		4/330 (1.2%)
Foot fracture	0/330 (0%)		3/330 (0.9%)
Hand fracture	0/330 (0%)		1/330 (0.3%)
Head injury	0/330 (0%)		2/330 (0.6%)
Joint dislocation	0/330 (0%)		1/330 (0.3%)
Joint sprain	1/330 (0.3%)		0/330 (0%)
Ligament rupture	1/330 (0.3%)		0/330 (0%)
Limb injury	1/330 (0.3%)		0/330 (0%)
Meniscus lesion	0/330 (0%)		1/330 (0.3%)
Pelvic fracture	0/330 (0%)		1/330 (0.3%)
Road traffic accident	2/330 (0.6%)		0/330 (0%)
Thermal burn	1/330 (0.3%)		0/330 (0%)
Musculoskeletal and connective tissue disorders
Arthropathy	1/330 (0.3%)		0/330 (0%)
Back pain	1/330 (0.3%)		0/330 (0%)
Muscle haemorrhage	0/330 (0%)		1/330 (0.3%)
Musculoskeletal pain	0/330 (0%)		1/330 (0.3%)
Trigger finger	1/330 (0.3%)		0/330 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal neoplasm	0/330 (0%)		1/330 (0.3%)
Brain neoplasm	0/330 (0%)		1/330 (0.3%)
Metastases to lymph nodes	1/330 (0.3%)		0/330 (0%)
T-cell lymphoma	0/330 (0%)		1/330 (0.3%)
Thyroid cancer	1/330 (0.3%)		1/330 (0.3%)
Uterine leiomyoma	1/330 (0.3%)		1/330 (0.3%)
Waldenstrom's macroglobulinaemia	0/330 (0%)		1/330 (0.3%)
Nervous system disorders
Brain oedema	1/330 (0.3%)		0/330 (0%)
Cerebrovascular accident	0/330 (0%)		1/330 (0.3%)
Convulsion	10/330 (3%)		1/330 (0.3%)
Dementia	1/330 (0.3%)		0/330 (0%)
Dizziness	1/330 (0.3%)		0/330 (0%)
Drug withdrawal convulsions	1/330 (0.3%)		0/330 (0%)
Epilepsy	5/330 (1.5%)		4/330 (1.2%)
Grand mal convulsion	2/330 (0.6%)		0/330 (0%)
Headache	1/330 (0.3%)		0/330 (0%)
Hemiparesis	0/330 (0%)		1/330 (0.3%)
Partial seizures	2/330 (0.6%)		0/330 (0%)
Partial seizures with secondary generalisation	2/330 (0.6%)		0/330 (0%)
Postictal headache	0/330 (0%)		1/330 (0.3%)
Spinal cord disorder	1/330 (0.3%)		0/330 (0%)
Status epilepticus	4/330 (1.2%)		1/330 (0.3%)
Transient ischaemic attack	1/330 (0.3%)		0/330 (0%)
Wernicke's encephalopathy	0/330 (0%)		1/330 (0.3%)
Psychiatric disorders
Anxiety	1/330 (0.3%)		0/330 (0%)
Conversion disorder	1/330 (0.3%)		1/330 (0.3%)
Delirium tremens	0/330 (0%)		1/330 (0.3%)
Depression	0/330 (0%)		1/330 (0.3%)
Psychotic disorder	0/330 (0%)		1/330 (0.3%)
Renal and urinary disorders
Calculus ureteric	0/330 (0%)		1/330 (0.3%)
Urinary retention	1/330 (0.3%)		0/330 (0%)
Reproductive system and breast disorders
Vulval oedema	0/330 (0%)		1/330 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/330 (0%)		1/330 (0.3%)
Dyspnoea	1/330 (0.3%)		1/330 (0.3%)
Vocal cord cyst	0/330 (0%)		1/330 (0.3%)
Skin and subcutaneous tissue disorders
Rash	1/330 (0.3%)		0/330 (0%)
Stevens-Johnson syndrome	1/330 (0.3%)		0/330 (0%)
Toxic epidermal necrolysis	0/330 (0%)		1/330 (0.3%)
Surgical and medical procedures
Carpal tunnel decompression	1/330 (0.3%)		0/330 (0%)
Hip arthroplasty	1/330 (0.3%)		0/330 (0%)
Ostectomy	1/330 (0.3%)		0/330 (0%)
Splenectomy	0/330 (0%)		1/330 (0.3%)
Vascular disorders
Haematoma	0/330 (0%)		1/330 (0.3%)
Vasculitis	0/330 (0%)		1/330 (0.3%)
Other (Not Including Serious) Adverse Events
	Pregabalin		Lamotrigine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	186/330 (56.4%)		171/330 (51.8%)
Eye disorders
Vision blurred	7/330 (2.1%)		2/330 (0.6%)
Gastrointestinal disorders
Abdominal pain	4/330 (1.2%)		9/330 (2.7%)
Abdominal pain upper	12/330 (3.6%)		17/330 (5.2%)
Constipation	9/330 (2.7%)		5/330 (1.5%)
Diarrhoea	12/330 (3.6%)		13/330 (3.9%)
Dyspepsia	8/330 (2.4%)		12/330 (3.6%)
Nausea	14/330 (4.2%)		11/330 (3.3%)
Toothache	9/330 (2.7%)		4/330 (1.2%)
Vomiting	7/330 (2.1%)		8/330 (2.4%)
General disorders
Fatigue	30/330 (9.1%)		19/330 (5.8%)
Pyrexia	6/330 (1.8%)		14/330 (4.2%)
Infections and infestations
Influenza	14/330 (4.2%)		12/330 (3.6%)
Nasopharyngitis	15/330 (4.5%)		21/330 (6.4%)
Pharyngitis	7/330 (2.1%)		4/330 (1.2%)
Upper respiratory tract infection	20/330 (6.1%)		23/330 (7%)
Investigations
Weight increased	22/330 (6.7%)		7/330 (2.1%)
Metabolism and nutrition disorders
Decreased appetite	2/330 (0.6%)		7/330 (2.1%)
Musculoskeletal and connective tissue disorders
Back pain	9/330 (2.7%)		10/330 (3%)
Myalgia	7/330 (2.1%)		6/330 (1.8%)
Nervous system disorders
Disturbance in attention	7/330 (2.1%)		6/330 (1.8%)
Dizziness	57/330 (17.3%)		47/330 (14.2%)
Headache	75/330 (22.7%)		73/330 (22.1%)
Memory impairment	8/330 (2.4%)		13/330 (3.9%)
Somnolence	29/330 (8.8%)		16/330 (4.8%)
Psychiatric disorders
Anxiety	5/330 (1.5%)		10/330 (3%)
Depression	10/330 (3%)		14/330 (4.2%)
Insomnia	15/330 (4.5%)		19/330 (5.8%)
Sleep disorder	2/330 (0.6%)		7/330 (2.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/330 (0.6%)		9/330 (2.7%)
Oropharyngeal pain	2/330 (0.6%)		10/330 (3%)
Skin and subcutaneous tissue disorders
Pruritus	4/330 (1.2%)		8/330 (2.4%)
Rash	12/330 (3.6%)		18/330 (5.5%)
Vascular disorders
Hypertension	4/330 (1.2%)		7/330 (2.1%)

Limitations/Caveats

Cox proportional hazards model for time to event (TTE) analyses; three summary statistics were not generated as median TTE will not exist if survival function (Kaplan-Meier product limit estimates) does not fall below 0.5 (post-hoc analysis).

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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.