Efficacy And Safety Study Of Pregabalin (Lyrica) As Monotherapy In Patients With Partial Seizures

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00524030
• Collaborator: (none)
• Enrollment: 161
• Locations: 73
• Arms: 2
• Duration (Months): 45
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will determine the safety and efficacy of pregabalin (Lyrica) when administered by itself (without any other anti-epileptic medication) to epilepsy subjects for the treatment of partial seizures. The duration of the trial is about 6 months.

Condition or Disease	Intervention/Treatment	Phase
Epilepsies, Partial	Drug: pregabalin 600 mg/day; Drug: pregabalin 150 mg/day	Phase 3

Detailed Description

After review of the interim analysis results, the independent Data Monitoring Committee (DMC) recommended to stop the study based on positive efficacy findings for the primary efficacy endpoint according to pre-specified stopping rules. Pfizer accepted the DMC recommendation and made the decision to stop the study on September 7, 2011.

Study Design

• Study Type: Interventional
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Multicenter Efficacy And Safety Study Of Pregabalin (Lyrica) As Monotherapy In Patients With Partial Seizures
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: pregabalin 600 mg/day; pregabalin 600 mg/day (300mg BID), duration is 20 weeks.
Experimental: 2	Drug: pregabalin 150 mg/day; pregabalin 150 mg/day (75mg BID), duration is 20 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants in the Pregabalin 600 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria [Week 2 up to Week 18]

   Participants who discontinued due to: episode of status epilepticus (SE); secondarily generalized tonic-clonic (SGTC) seizure if none within 2 years of study entry; 28-day study seizure rate during double-blind phase (DBP) greater than (>)2 times maximum (Max) 28-day study seizure rate during baseline phase (BLP); 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate:(1-Kaplan-Meier [KM] product limit estimate for survival function) * 100%

Secondary Outcome Measures

1. Percentage of Participants in the Pregabalin 150 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria [Week 2 up to Week 18]

   Participants who discontinued due to: episode of SE; SGTC seizure if none within 2 years of study entry; 28-day study seizure rate during DBP >2 times Max 28-day study seizure rate during BLP; 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate, defined as (1-KM product limit estimate for survival function) * 100%

2. Percentage of Participants Completing 20 Weeks of Double-Blind Treatment [Randomization up to Week 20]

3. Percentage of Participants Who Met Protocol-Specified Exit Events [Week 2 up to Week 18]

   Percentage of participants experiencing any of the following (could have had more than 1): 1) episode of SE; 2) SGTC seizure if none had been experienced within 2 years of study entry; 3) 28-day study seizure rate during DBP >2 times the Max 28-day study seizure rate during BLP; 4) 2-day study seizure rate during the DBP >2 times the Max 2-day study seizure rate during BLP; or 5) unacceptable clinically significant increase in frequency/intensity of seizure activity

4. Mean Time on Pregabalin Monotherapy [Week 2 to Week 20]

5. Percentage of Seizure-Free Participants by Study Phase [Day 1 up to Day 140]

   Percentage of participants who were seizure-free during the last 28 days on double-blind study medication (monotherapy phase, Days 112-140), during the monotherapy portion of the double-blind treatment phase (Days 56-140), and during all of the double-blind treatment phase (Days 1-140)

6. Pregabalin Population Pharmacokinetics (PK) [Baseline up to 20 weeks]

   Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

7. Pregabalin Exposure-Response Analysis [Day 126]

   Percentage of participants predicted to exit the study due to any seizure exit criteria at Day 126. The exit rate at Day 126 was predicted using the final model (log normal distribution with respect to treatment group) and the parameter estimates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of epilepsy with partial seizures.

• Males or females, age 18 years or older.

• Documented history of at least 4 partial seizures in the 8 weeks prior to the screening visit.

• Stable treatment with 1 to 2 anti-epileptic drugs in the 8 weeks prior to the screening visit.

Exclusion Criteria:

• Current diagnosis of febrile seizures or seizures related to an ongoing acute medical event.

• Seizures occurring only in cluster patterns, or seizures of a metabolic, toxic or infectious origin.

• Primary generalized epilepsy or status epilepticus within the previous year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Northport	Alabama	United States	35476
2	Pfizer Investigational Site	Phoenix	Arizona	United States	85003
3	Pfizer Investigational Site	Phoenix	Arizona	United States	85013
4	Pfizer Investigational Site	Sun City	Arizona	United States	85351
5	Pfizer Investigational Site	Fayetteville	Arkansas	United States	72703
6	Pfizer Investigational Site	Fullerton	California	United States	92835
7	Pfizer Investigational Site	Long Beach	California	United States	90806
8	Pfizer Investigational Site	Modesto	California	United States	95355
9	Pfizer Investigational Site	Murrieta	California	United States	92562
10	Pfizer Investigational Site	Newport Beach	California	United States	92660
11	Pfizer Investigational Site	Temecula	California	United States	92591
12	Pfizer Investigational Site	Denver	Colorado	United States	80204
13	Pfizer Investigational Site	Jacksonville	Florida	United States	32209
14	Pfizer Investigational Site	Melbourne	Florida	United States	32901
15	Pfizer Investigational Site	Miami	Florida	United States	33126
16	Pfizer Investigational Site	Miami	Florida	United States	33136
17	Pfizer Investigational Site	Sarasota	Florida	United States	34232
18	Pfizer Investigational Site	Sarasota	Florida	United States	34233
19	Pfizer Investigational Site	Atlanta	Georgia	United States	30309
20	Pfizer Investigational Site	Atlanta	Georgia	United States	30342
21	Pfizer Investigational Site	Decatur	Georgia	United States	30033
22	Pfizer Investigational Site	Lawrenceville	Georgia	United States	30045
23	Pfizer Investigational Site	Suwanee	Georgia	United States	30024
24	Pfizer Investigational Site	Anderson	Indiana	United States	46016
25	Pfizer Investigational Site	Danville	Indiana	United States	46122
26	Pfizer Investigational Site	Fort Wayne	Indiana	United States	46805
27	Pfizer Investigational Site	Kansas City	Kansas	United States	66160
28	Pfizer Investigational Site	Bowling Green	Kentucky	United States	42101
29	Pfizer Investigational Site	Lexington	Kentucky	United States	40536-0284
30	Pfizer Investigational Site	Lexington	Kentucky	United States	40536
31	Pfizer Investigational Site	Houma	Louisiana	United States	70363
32	Pfizer Investigational Site	Shreveport	Louisiana	United States	71105-5634
33	Pfizer Investigational Site	Pikesville	Maryland	United States	21208
34	Pfizer Investigational Site	Worcester	Massachusetts	United States	01605
35	Pfizer Investigational Site	Worcester	Massachusetts	United States	01608
36	Pfizer Investigational Site	Detroit	Michigan	United States	48202
37	Pfizer Investigational Site	Minneapolis	Minnesota	United States	55422
38	Pfizer Investigational Site	Flowood	Mississippi	United States	39232
39	Pfizer Investigational Site	Hattiesburg	Mississippi	United States	39401-7246
40	Pfizer Investigational Site	Great Falls	Montana	United States	59405
41	Pfizer Investigational Site	Cedarhurst	New York	United States	11516
42	Pfizer Investigational Site	Charlotte	North Carolina	United States	28207
43	Pfizer Investigational Site	Charlotte	North Carolina	United States	28209
44	Pfizer Investigational Site	Rocky Mount	North Carolina	United States	27804
45	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
46	Pfizer Investigational Site	Columbus	Ohio	United States	43210-1250
47	Pfizer Investigational Site	Columbus	Ohio	United States	43210
48	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73112
49	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73120
50	Pfizer Investigational Site	Altoona	Pennsylvania	United States	16602
51	Pfizer Investigational Site	Indiana	Pennsylvania	United States	15701
52	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19140
53	Pfizer Investigational Site	Memphis	Tennessee	United States	38120
54	Pfizer Investigational Site	Memphis	Tennessee	United States	38163
55	Pfizer Investigational Site	Nashville	Tennessee	United States	37232
56	Pfizer Investigational Site	Dallas	Texas	United States	75230
57	Pfizer Investigational Site	Houston	Texas	United States	77074-2906
58	Pfizer Investigational Site	San Antonio	Texas	United States	78258
59	Pfizer Investigational Site	Temple	Texas	United States	76508
60	Pfizer Investigational Site	Murray	Utah	United States	84107
61	Pfizer Investigational Site	Salt Lake City	Utah	United States	84107
62	Pfizer Investigational Site	West Jordan	Utah	United States	84088
63	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53226
64	Pfizer Investigational Site	Beroun		Czechia	266 01
65	Pfizer Investigational Site	Brno 2		Czechia	602 00
66	Pfizer Investigational Site	Litomysl		Czechia	570 14
67	Pfizer Investigational Site	New Territories		Hong Kong
68	Pfizer Investigational Site	Dnipropetrovsk		Ukraine	49027
69	Pfizer Investigational Site	Dnipropetrovsk		Ukraine	49115
70	Pfizer Investigational Site	Kharkiv		Ukraine	61018
71	Pfizer Investigational Site	Kharkiv		Ukraine	61068
72	Pfizer Investigational Site	Lugansk		Ukraine	91045
73	Pfizer Investigational Site	Odessa		Ukraine	65025

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: NCT00524030
• Other Study ID Numbers: A0081047
• First Posted: Sep 3, 2007
• Last Update Posted: Jan 20, 2021
• Last Verified: Dec 1, 2018

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

Study Results

Participant Flow

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Period Title: Overall Study
STARTED	32	129
Completed Double-Blind Treatment Phase	15	70
Completed Taper/Titration Phase	15	70
COMPLETED	15	70
NOT COMPLETED	17	59

Baseline Characteristics

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day	Total
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.	Total of all reporting groups
Overall Participants	32	129	161
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.2 (12.4)	39.9 (13.2)	39.0 (13.2)
Sex: Female, Male (Count of Participants)
Female	18 56.3%	71 55%	89 55.3%
Male	14 43.8%	58 45%	72 44.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants in the Pregabalin 600 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria
Description	Participants who discontinued due to: episode of status epilepticus (SE); secondarily generalized tonic-clonic (SGTC) seizure if none within 2 years of study entry; 28-day study seizure rate during double-blind phase (DBP) greater than (>)2 times maximum (Max) 28-day study seizure rate during baseline phase (BLP); 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate:(1-Kaplan-Meier [KM] product limit estimate for survival function) * 100%
Time Frame	Week 2 up to Week 18

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat (MITT) Efficacy Set: The first 125 participants randomized who received at least 1 dose of pregabalin in DB treatment phase, had BL seizure assessment, and participated in DB efficacy assessment after Week 2. Number of participants analyzed (N)= number of MITT participants with discontinuation/completion data.

Arm/Group Title	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	102
Number (95% Confidence Interval) [Percentage of Participants]	31.9 99.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 600 mg/Day
	Comments	Null hypothesis (H0): Exit rate greater than or equal to (≥)74%
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wald Test
	Comments	2-sided 95% adjusted confidence interval constructed using KM product limit estimation and Greenwood's formula for variance with continuity correction

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 600 mg/Day
	Comments	H0: Exite rate ≥68%
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wald Test
	Comments	2-sided 95% adjusted confidence interval constructed using KM product limit estimation and Greenwood's formula for variance with continuity correction

2. Secondary Outcome

Title	Percentage of Participants in the Pregabalin 150 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria
Description	Participants who discontinued due to: episode of SE; SGTC seizure if none within 2 years of study entry; 28-day study seizure rate during DBP >2 times Max 28-day study seizure rate during BLP; 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate, defined as (1-KM product limit estimate for survival function) * 100%
Time Frame	Week 2 up to Week 18

Outcome Measure Data

Analysis Population Description

MITT Full Study Set: all randomized participants who met the MITT definition (received at least 1 dose of pregabalin in DB treatment phase, had BL seizure assessment, and participated in DB efficacy assessment after Week 2)

Arm/Group Title	Pregabalin 150 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
Measure Participants	28
Number (95% Confidence Interval) [Percentage of Participants]	37.7 117.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 600 mg/Day
	Comments	H0: Exit rate ≥74%
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wald test
	Comments	2-sided 95% adjusted confidence interval constructed using KM product limit estimation and Greenwood's formula for variance with continuity correction

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 600 mg/Day
	Comments	H0: Exit rate ≥68%
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wald test
	Comments	2-sided 95% adjusted confidence interval constructed using KM product limit estimation and Greenwood's formula for variance with continuity correction

3. Secondary Outcome

Title	Percentage of Participants Completing 20 Weeks of Double-Blind Treatment
Time Frame	Randomization up to Week 20

Outcome Measure Data

Analysis Population Description

MITT Full Study Set

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	28	120
Number [Percentage of Participants]	53.6 167.5%	58.3 45.2%

4. Secondary Outcome

Title	Percentage of Participants Who Met Protocol-Specified Exit Events
Description	Percentage of participants experiencing any of the following (could have had more than 1): 1) episode of SE; 2) SGTC seizure if none had been experienced within 2 years of study entry; 3) 28-day study seizure rate during DBP >2 times the Max 28-day study seizure rate during BLP; 4) 2-day study seizure rate during the DBP >2 times the Max 2-day study seizure rate during BLP; or 5) unacceptable clinically significant increase in frequency/intensity of seizure activity
Time Frame	Week 2 up to Week 18

Outcome Measure Data

Analysis Population Description

MITT Efficacy Set

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	23	102
Status Epilepticus	0 0%	1.0 0.8%
SGTC Seizure (not experienced in previous 2 years)	0 0%	2.9 2.2%
28-Day Seizure Rate >2 times Max Baseline Rate	13.0 40.6%	10.8 8.4%
2-Day Seizure Rate >2 times Max Baseline Rate	13.0 40.6%	7.8 6%
Increased Frequency/Intensity of Seizure Activity	17.4 54.4%	14.7 11.4%
Total	39.1 122.2%	28.4 22%

5. Secondary Outcome

Title	Mean Time on Pregabalin Monotherapy
Time Frame	Week 2 to Week 20

Outcome Measure Data

Analysis Population Description

MITT Full Study Set; N=number of participants entering Monotherapy Period

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	22	97
Mean (Standard Deviation) [Days]	73.8 (30.15)	78.0 (28.24)

6. Secondary Outcome

Title	Percentage of Seizure-Free Participants by Study Phase
Description	Percentage of participants who were seizure-free during the last 28 days on double-blind study medication (monotherapy phase, Days 112-140), during the monotherapy portion of the double-blind treatment phase (Days 56-140), and during all of the double-blind treatment phase (Days 1-140)
Time Frame	Day 1 up to Day 140

Outcome Measure Data

Analysis Population Description

MITT Full Study Set

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	28	120
Last 28 Days of Monotherapy (Days 112-140)	17.9 55.9%	12.5 9.7%
Monotherapy (Days 56-140)	7.1 22.2%	6.7 5.2%
Entire Double-Blind Treatment (Days 1-140)	0 0%	1.7 1.3%

7. Secondary Outcome

Title	Pregabalin Population Pharmacokinetics (PK)
Description	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame	Baseline up to 20 weeks

Outcome Measure Data

Analysis Population Description

Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	0	0

8. Secondary Outcome

Title	Pregabalin Exposure-Response Analysis
Description	Percentage of participants predicted to exit the study due to any seizure exit criteria at Day 126. The exit rate at Day 126 was predicted using the final model (log normal distribution with respect to treatment group) and the parameter estimates.
Time Frame	Day 126

Outcome Measure Data

Analysis Population Description

MITT Full Study Set

Arm/Group Title	Pregabalin 150 mg/Day	Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
Measure Participants	28	120
Number [Percentage of Participants]	37.2 116.3%	26.3 20.4%

Adverse Events

Time Frame	Baseline to Week 21
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 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 150 mg/Day		Pregabalin 600 mg/Day
Arm/Group Description	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.		Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
All Cause Mortality
	Pregabalin 150 mg/Day		Pregabalin 600 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin 150 mg/Day		Pregabalin 600 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)		17/129 (13.2%)
Cardiac disorders
Angina pectoris	0/32 (0%)		1/129 (0.8%)
Cardio-respiratory arrest	0/32 (0%)		1/129 (0.8%)
Gastrointestinal disorders
Abdominal pain	0/32 (0%)		1/129 (0.8%)
General disorders
Chest pain	0/32 (0%)		1/129 (0.8%)
Infections and infestations
Meningitis bacterial	0/32 (0%)		1/129 (0.8%)
Pneumonia	0/32 (0%)		2/129 (1.6%)
Nervous system disorders
Complex partial seizures	0/32 (0%)		1/129 (0.8%)
Convulsion	0/32 (0%)		5/129 (3.9%)
Epilepsy	0/32 (0%)		1/129 (0.8%)
Grand mal convulsion	0/32 (0%)		2/129 (1.6%)
Lethargy	0/32 (0%)		1/129 (0.8%)
Status epilepticus	0/32 (0%)		1/129 (0.8%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/32 (3.1%)		0/129 (0%)
Psychiatric disorders
Homicidal ideation	0/32 (0%)		1/129 (0.8%)
Respiratory, thoracic and mediastinal disorders
Wheezing	0/32 (0%)		1/129 (0.8%)
Other (Not Including Serious) Adverse Events
	Pregabalin 150 mg/Day		Pregabalin 600 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/32 (46.9%)		75/129 (58.1%)
Eye disorders
Vision blurred	1/32 (3.1%)		8/129 (6.2%)
Gastrointestinal disorders
Dry mouth	2/32 (6.3%)		2/129 (1.6%)
Flatulence	0/32 (0%)		8/129 (6.2%)
General disorders
Fatigue	2/32 (6.3%)		20/129 (15.5%)
Oedema peripheral	1/32 (3.1%)		8/129 (6.2%)
Investigations
Alanine aminotransferase increased	2/32 (6.3%)		1/129 (0.8%)
Weight increased	2/32 (6.3%)		21/129 (16.3%)
Nervous system disorders
Balance disorder	0/32 (0%)		8/129 (6.2%)
Disturbance in attention	3/32 (9.4%)		4/129 (3.1%)
Dizziness	5/32 (15.6%)		25/129 (19.4%)
Dysarthria	2/32 (6.3%)		2/129 (1.6%)
Headache	0/32 (0%)		13/129 (10.1%)
Somnolence	5/32 (15.6%)		22/129 (17.1%)
Psychiatric disorders
Confusional state	0/32 (0%)		7/129 (5.4%)

Limitations/Caveats

External Data Monitoring Committee (DMC) determined study met criteria to stop early for positive efficacy. Exit rate was the basis for primary analysis and is what is reported here.

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.