Clinical trial NCT01463306
Conditions: Epilepsy, Partial Seizures Epilepsy, Primary Generalized Tonic-Clonic Seizures
Keywords: safety partial onset seizures primary generalized tonic-clonic seizures pregabalin pediatric adult open-label long term
Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Start date: 2012-02-21; Completion date: 2019-08-22
Enrollment: 605 participants; Allocation: NA; Intervention model: 

Brief summary:
Study A0081106 is a 12-month open-label study to evaluate the long term safety and tolerability of pregabalin as add-on therapy in pediatric subjects 1 month to 16 years of age with partial onset seizures and pediatric and adult subjects 5 to 65 years of age with primary generalized tonic-clonic seizures. Pregabalin will be administered in equally divided daily doses for 1 year, in either capsule or liquid oral formulation.

Detailed description:

Arms: arm 1: Pregabalin open label flexible dose
Interventions: intervention 1: Pregabalin
Intervention descriptions: intervention 1: Pregabalin administered as either capsule or liquid oral formulations. Subjects \<4 years of age at Visit 1 will receive study medication 3 times daily (TID) in equally divided doses. Subjects who are ≥4 years of age at Visit 1 will receive study medication twice daily (BID) in equally divided doses. Children less than 17 years of age will receive from 2.5 mg/kg/day to 10.0 mg/kg/day (maximum 600 mg/day. Adults 17 and older will receive from 150 mg/day to 600 mg/day.

Protocol documents:
Prot_000.pdf: 
Pregabalin
A0081106
Final Protocol Amendment 2, 07 May 2014
Page 1
CLINICAL PROTOCOL
A 12-MONTH OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND 
TOLERABILITY OF PREGABALIN AS ADJUNCTIVE THERAPY IN PEDIATRIC
SUBJECTS 1 MONTH TO 16 YEARS OF AGE WITH PARTIAL ONSET SEIZURES 
AND PEDIATRIC AND ADULT SUBJECTS 5 TO 65 YEARS OF AGE WITH 
PRIMARY GENERALIZED TONIC-CLONIC SEIZURES
Compound:
PD-144723
Compound Name (if applicable):
Pregabalin
US IND Number (if applicable):
49,393
European Clinical Trial Database
(EudraCT) Number:
2011-001412-65
Protocol Number:
A0081106
Phase:
3
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Document History
Document
Version Date
Summary of Changes
Amendment 2
07 May 2014

Updated to TID regimen for subjects <4 years old.

Added pediatric PK half-life that supports TID in 
subjects <4 years old.

Added information on the requirement to refer to a 
qualified mental health professional for subjects at-risk 
of suicide, and contact Pfizer study clinician.

On SOA, footnote “d”, added information on the Tanner 
assessment for children.

On SOA, footnote “j” added to clarify dispensation 
procedure of study medication.  Added also in 
Section 6.2.

Clarified in Section 4.1 the age limit for subjects 
completing A0081041 or A0081105.

Clarified the eligibility assessments for Direct enrolling 
subjects in Section 4.1 and 4.2.

Clarified the restriction associated with benzodiazepine 
use.

Clarified the restriction associated with non-AED. 

Revised the list of prohibited anti-epileptic drugs.

Revised subject compliance or non-compliance 
definition.

Added new section Sponsor Qualified Medical 
Personnel.

Revised the list of procedures in Section 6.2.

Corrected the Creatinine concentration conversion 
formula in Section 7.3, and clarified PK assessment to 
be made.

Clarified CBCL administration and scoring in 
Section 7.6.1.

Clarified Mini-Kid and CSSRS administration in 
Sections 7.6.2 and 7.6.3.

Updated the Adverse Event reporting section.

Updated the Subject Information and Consent section.

Updated section Communication of Results by Pfizer. 
Protocol Amendment 1
31 July 2012

On SOA, footnote “c”, added information on need for 
additional pregnancy tests based upon local regulations.

Added overall risk/benefit statement 1.2.

Clarified that direct enrolling subjects will come from 
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selected sites within the United States only 1.2, 3.

Clarified that subjects completing in A0081041 or 
A0081105 a minimum of 4 weeks, but <12, must 
consult with Study Clinician prior to consideration for 
A0081106 3.

Inclusion Criteria 4 modified to add a reference to 
Appendix 1 for seizure types allowed.

CT/MRI requirement for direct enrollers extended to 
60 months or if recent clinical change indicate necessity 
4.1.1.

Added “allergy to pregabalin or excipients…” in 
exclusion criteria 4.16.

Added statement that investigator should interview 
subjects about sexual and contraceptive history 4.3.1.

Use of anti-epileptic drugs clarified 5.4.1, 5.4.2.

Clarified that creatinine clearance will be calculated 
only for direct enrolling subjects 7.3.

Specified blood volumes in the Section 7.3.2 of the 
protocol.

Clarified that subjects who are 4-5 years old and have 
Greek and Cebuano speaking parents will be excluded 
due to lack of CBCL translations. Greek and Cebuano 
subjects age 6 years and older can be included 7.6.1.

Modified MINI-KID assessment such that Suicidality 
module not necessary if CSSRS is given unless the 
subject has endorsed significant depressive symptoms 
on the MINI-KID 7.6.2.

Clarified rater selection and training process 7.6.2.

Clarified written risk assessment requirement 7.6.4.

Clarified that mentally or physically handicapped 
subjects do not have to complete CogState if they are 
unable 7.7.1.

Adverse event section updated due to protocol template 
updates 8.1-8.14. 

Clarified description of posting of clinical trial results 
by Pfizer 15.1.

Added references for CBCL and MINI-KID.
Original protocol
06 July 2011
N/A
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Protocol Summary
Indication:
Adjunctive therapy for children with partial onset seizures with or without secondary 
generalization and adjunctive therapy for children and adults with primary generalized 
tonic-clonic (PGTC) seizures.
Background and Rationale:
Epilepsy is a common disorder in childhood affecting 4 to 5 of every 1000 children.  
Although epilepsy is often well controlled with existing antiepileptic drug (AED) therapy, 
more than 25% of pediatric patients have seizures that are uncontrolled by currently available 
agents, or have adverse effects related to AEDs that complicate management of their 
seizures.  In addition, children with epilepsy often suffer from impaired academic 
performance, with 55% functioning below their grade level and an additional 16% 
significantly behind in educational training.1  Children with epilepsy also have a higher 
likelihood of developing behavioral difficulties, which may persist into adulthood.2  Early 
age of onset and a higher number of total lifetime seizures are the strongest correlates of 
academic underachievement.  Therefore, the availability of a new AED that has been shown 
to improve seizure control, and that is generally well tolerated, is needed.
Pregabalin (Lyrica) is an alpha2-delta (2) agent approved for use the treatment of partial 
onset seizures in adults.  It is believed to exert its pharmacologic action by binding to the 
2site of voltage-gated calcium channels. The spectrum of activity of pregabalin in rodent 
models of epilepsy shows that it is potent to reduce or prevent both partial seizures from 
hippocampal stimulation and also primary generalized tonic-clonic (PGTC) seizures from 
either sound stimulation to genetically audiogenic mice or cranial electroshock in mice or
rats.12  The efficacy of pregabalin in patients with PGTC seizures has not been assessed to 
date in a placebo-controlled study.
Pregabalin is approved in more than 100 countries, with indications summarized below for 
the United States (US), European Union (EU), and Japan (JP).  In the US and EU, pregabalin 
is indicated for the adjunctive treatment of adult patients with partial onset seizures.  In 
addition, pregabalin is indicated for the treatment of central and peripheral neuropathic pain 
(EU), and for the management of neuropathic pain associated with postherpetic neuralgia and 
diabetic peripheral neuropathy and for fibromyalgia (US) and for the treatment of peripheral 
neuropathic pain (JP).  In the EU, pregabalin is also approved for the treatment of 
Generalized Anxiety Disorder in adults.  The approved dose range for the adjunctive 
treatment of partial onset seizures in adults is 150 to 600 mg/day, administered 2 times daily 
(BID) or 3 times daily (TID).  The most common adverse effects reported with pregabalin in 
placebo-controlled adjunctive trials in adults with partial onset seizures were dizziness and 
somnolence. Since initial market approval of Lyricain 2004, it is estimated that more than 
11,700,000 patient-years of exposure have accumulated worldwide.  More detailed 
information, including efficacy results in adults and the possible risks associated with 
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administration of pregabalin, are summarized in the Investigator’s Brochure which serves as 
the Single Reference Safety Document for this study.
Study A0081106 will assess the long term (12 month) safety and tolerability of pregabalin in 
pediatric subjects as adjunctive treatment for partial onset seizures and as adjunctive 
treatment in pediatric and adult subjects with primary generalized tonic-clonic seizures.  This 
study is one of several studies that will be conducted to assess the safety and efficacy of 
pregabalin in pediatric subjects with epilepsy and address post approval commitments to US 
and EU regulatory authorities.
Objectives:

To evaluate the long-term safety and tolerability of pregabalin in pediatric subjects 
1 month through 16 years of age with partial onset seizures and pediatric and adult 
subjects 5-65 years of age with PGTC seizures.
Study Design:
This is an open-label, flexible-dose study in pediatric subjects 1 month through 16 years of 
age with partial-onset seizures, who have participated in Study A0081041 (4-16 years of age) 
or Study A0081042 (1 month-3 years of age) or pediatric and adult subjects 5-65 years of age 
with PGTC seizures who have participated in Study A0081105.  Subjects who have 
completed the studies cited above will be eligible for screening for this study.  For subjects 
who have participated in, but did not complete Studies A0081041, A0081042, or A0081105, 
eligibility for Study A0081106 will be considered, after consultation with the Study 
Clinician, on a case by case basis.  A minimum of 4 weeks in the double-blind treatment 
phase of either Study A0081041 or Study A0081105 will be required for consideration of 
enrollment into Study A0081106.
Selected sites (within the United States only) that are not participating in studies A0081041 
or A0081042 may screen and enroll pediatric subjects (1 month to 16 years of age) with 
partial onset seizures directly into Study A0081106 provided they meet the study 
inclusion/exclusion criteria.  When subject enrollment for Studies A0081041 and A0081042 
is complete, sites that were enrolling subjects in Studies A0081041 or A0081042 may screen 
and enroll pediatric subjects (1 month to 16 years of age) with partial onset seizures directly 
into Study A0081106 until enrollment into Study A0081106 is closed by Pfizer. 
Endpoints:
The following safety and tolerability data will be collected at each clinic visit according to 
the schedule of activities:

Adverse event (AE) data (occurrence, nature, intensity, and relationship to study 
drug).

Physical and neurological examinations.
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
Vital signs.

Growth and development parameters (height and weight) including Tanner stage.

Clinical laboratory data (hematology, chemistry, urinalysis).

Electrocardiograms (ECGs).

28-day seizure rate (number of seizures per 28 day period).

Assessments of suicidal ideation and behavior.

Cognitive testing.
Study Treatments:
A0081106 study medication will be provided as pregabalin liquid oral solution or oral 
capsules.  Subjects <4 years of age at Visit 1 or who are enrolling from A0081042 will 
receive study medication 3 times daily (TID) in equally divided doses.  Subjects who are 
4 years of age at Visit 1 will receive study medication twice daily (BID) in equally divided 
doses.

All eligible pediatric subjects 1 month to 16 years and 11 months of age will take
pregabalin in Study A0081106 at a dosage according to their body weight:

Pediatric subjects weighing 30 kg will begin pregabalin dosing at 2.5 mg/kg/day 
(maximum 150 mg/day). Subjects will remain at the starting dose for 8 days until 
Visit 2. Thereafter, dosing will be flexible based on individual seizure response 
and tolerability. Pediatric subjects may have their dose adjusted up or down at 
clinic visits in increments of no more than 2.5 mg/kg/day (maximum 150 mg/day) 
to daily dose levels of 5.0 (maximum 300 mg/day), 7.5 (maximum 450 mg/day), 
or 10.0 mg/kg/day (maximum 600 mg/day). 

Pediatric subjects with body weight <30 kg will begin pregabalin dosing at 
3.5 mg/kg/day until Visit 2.  Thereafter, dosing will be flexible based on 
individual seizure response and tolerability.  Pediatric subjects may have their 
dose adjusted up or down at clinic visits in increments of no more than 
3.5 mg/kg/day to daily dose levels of 7.0, 10.5, or 14.0 mg/kg/day. This
40% higher dose per kg in pediatric subjects with body weight <30 kg is needed 
to achieve exposures similar to those of adults or pediatric subjects weighing 
30 kg.

All eligible adult subjects 17 to 65 years of age will begin dosing of pregabalin in 
Study A0081106 at the level of 150 mg/day. Subjects will remain at this dose for 
8 days until Visit 2.  Thereafter, dosing will be flexible based on individual seizure 
response and tolerability. Adult subjects may have their dose adjusted up or down at 
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clinic visits in increments of no more than 150 mg/day to dose levels of 300, 450, or 
600 mg/day.
The pregabalin liquid oral solution formulation (20 mg/ml) will be used for all subjects 
weighing less than 30 kg.  Pediatric and adult subjects weighing more than 30 kg may use 
either the liquid oral solution or solid capsule formulation.  Study medication formulation for 
administration will be as outlined below, with investigators (and subjects) determining the 
choice of solution or capsule for subjects 30 kg.  The choice will be based upon subject’s 
preference.  If capsules are preferred, the subject must demonstrate the ability to swallow the 
capsule without difficulty at the study visit using a placebo capsule for the demonstration.  
Pregabalin capsules and pregabalin liquid oral solution are bioequivalent.
Weight
Formulation
<30 kg
Liquid
Pediatric subjects 30 kg
Liquid or capsule
Adult subjects
Capsules or liquid
Statistical Methods:
Data will be summarized into 3 groups as defined by a combination of the subject’s 
randomized treatment group in studies A0081041, A0081042, or A0081105 (subjects 
previously on pregabalin will be combined across treatment groups) and the treatment 
received during this study.  All subjects in this study will receive pregabalin.  The 3 treatment 
summary groups will be described as:
1. Pregabalin-Pregabalin: any dose of pregabalin from the previous study and pregabalin 
in this study.
2. Placebo-Pregabalin: placebo in the previous study, and pregabalin in this study.
3. Direct Pregabalin: pregabalin only in this study.
Other than baseline, where relevant, information will be presented only for this study.  
Baseline values will be the last observation made prior to initiating double-blind dosing in 
Studies A0081041, A0081042, and A0081105. Subjects entering Study A0081106 directly 
will have baseline observations made at screening (Visit 1B).
Summaries will include data for all subjects who took at least one dose of study medication 
in this study (Safety population).  The safety data (including adverse events, clinical 
laboratory assessments, ECGs, vital signs, height/weight/Tanner stage, suicidality 
assessments, cognitive assessments, and physical/neurological examinations) will be 
summarized by treatment group and overall through standard data tabulations, descriptive 
statistics, and/or graphical presentations.  Twenty-eight day seizure rate will be calculated 
from the seizure diaries and will be reviewed as a means of determining seizure control.  
Seizure frequency for each seizure type will be summarized using descriptive statistics every 
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4 weeks thereafter until the end of the study by treatment group and overall.  No statistical 
inferences will be performed. 
Subgroup analysis will be done on the safety data and seizure rates for each age cohort and 
primary seizure type.
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SCHEDULE OF ACTIVITIES
The Schedule of Activities table provides an overview of the protocol visits and procedures. Refer to STUDY PROCEDURES
(Section 6) and ASSESSMENTS (Section 7) for detailed information on each procedure and assessment required for compliance with 
the protocol.
Study Period
Screening/
Baseline
12 Month Treatment Phase
End of Treatment & Taper Phase
Clinic Visit Number
Visit 
1A
Visit 
1B
Visit
2
Visit
3
Visit
4
TC*
Visit
5
TC*
Visit
6
TC*
TC*
Visit
7
TC*
TC*
Visit 
8
Visit
9
Study Month
Prior 
Study 
Subjec
ts
Direct 
Enroll
Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 Month 8 Month 9 Month 
10
Month 
11
Month 12/EOS/
Early Termg
Begin Taper
End Taper/
Follow up
Study Day
Day 
1Aa
Day
1Ba
8
(1)
30
(4)
60
(4)
90
(4)
120
(4)
150
(4)
180
(4)
210
(4)
240
(4)
270
(4)
300
(4)
330
(4)
365
(7)
7 days post
completioni
(3)
Informed 
Consent/Assent
X
X
Record Demographic 
Information
X
X
Record Medical 
History
Xb
X
Record Seizure 
History
Xb
X
Perform Physical and 
Neurological 
Examination
Xb
Xd
X
Xd
Review 
Inclusion/Exclusion 
Criteria
X
X
Record Antiepileptic 
Medication History
Xb
X
Record All Prior 
Medications 
Xb
X
Record all concurrent 
medications and 
non-drug 
treatment/procedures 
(include any ongoing 
AEDs)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Study Period
Screening/
Baseline
12 Month Treatment Phase
End of Treatment & Taper Phase
Clinic Visit Number
Visit 
1A
Visit 
1B
Visit
2
Visit
3
Visit
4
TC*
Visit
5
TC*
Visit
6
TC*
TC*
Visit
7
TC*
TC*
Visit 
8
Visit
9
Study Month
Prior 
Study 
Subjec
ts
Direct 
Enroll
Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 Month 8 Month 9 Month 
10
Month 
11
Month 12/EOS/
Early Termg
Begin Taper
End Taper/
Follow up
Study Day
Day 
1Aa
Day
1Ba
8
(1)
30
(4)
60
(4)
90
(4)
120
(4)
150
(4)
180
(4)
210
(4)
240
(4)
270
(4)
300
(4)
330
(4)
365
(7)
7 days post
completioni
(3)
Perform 12-Lead 
Electrocardiogram 
(ECG)
Xb
X
X
Collect and Record 
Vital Signs
Xb
X
X
X
X
X
Record Height & 
weight
Xb
X
X
X
Collect Urine Sample 
for Pregnancy Testc
Xb
X
X
X
X
X
Collect Blood and 
Urine Samples for 
Clinical Laboratory 
Assessments
Xb
X
X
X
Suicidality 
Assessments:  Child 
Behavior Checklist 
(CBCL)/MINI-KID, 
C-SSRS “Lifetime”f
Xb
X
Suicidality 
Assessments Child 
Behavior Checklist 
(CBCL)/CSSRS
“Since Last Visit”
Xb
X
X
X
X
X
X
X
X
Complete CogState 
Batteryh
Xb
X
X
IVRS assignment
X
X
Dispense Daily 
Seizure and Dosing 
Diary
X
X
X
X
X
X
X
X
X
Collect and Review
Seizure/Dosing Diary
X
X
X
X
X
X
X
X
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Study Period
Screening/
Baseline
12 Month Treatment Phase
End of Treatment & Taper Phase
Clinic Visit Number
Visit 
1A
Visit 
1B
Visit
2
Visit
3
Visit
4
TC*
Visit
5
TC*
Visit
6
TC*
TC*
Visit
7
TC*
TC*
Visit 
8
Visit
9
Study Month
Prior 
Study 
Subjec
ts
Direct 
Enroll
Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 Month 8 Month 9 Month 
10
Month 
11
Month 12/EOS/
Early Termg
Begin Taper
End Taper/
Follow up
Study Day
Day 
1Aa
Day
1Ba
8
(1)
30
(4)
60
(4)
90
(4)
120
(4)
150
(4)
180
(4)
210
(4)
240
(4)
270
(4)
300
(4)
330
(4)
365
(7)
7 days post
completioni
(3)
Dosing Compliance 
Training/Review and 
Demonstration
X
X
X
X
X
X
X
X
Evaluate Study 
Medication 
Compliance
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
* Telephone contact to 
assess dosing and 
diary compliance, 
concomitant 
medications and AE's
X
X
X
X
X
X
Dispense Study 
Medication
X
Xj
Xk
Xk
Xk
Xk
Xk
Xk
Xe
Assess and Record 
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a.
Visit 1A = Screening Visit for subjects from A0081041, A0081042, or A0081105:  This visit should be completed for subjects who previously 
participated in double-blind Studies A0081041, A0081042 or A0081105.  These subjects will enroll into Study A0081106 on the last day of the double-blind 
study with no interruption in their pregabalin treatment.  
Visit 1B = Direct-Enroll Screening Visit:  This visit should be completed for subjects who did NOT participate in Studies A0081041, A0081042, or 
A0081105.  These subjects will enroll directly into Study A0081106 to initiate treatment with open label pregabalin and must complete all of the screening 
assessment noted under Visit 1B. 
b.
If procedures were performed during participation in Studies A0081041, A0081042, or A0081105 the actual procedure will not need to be repeated for the 
Study A0081106 Screening Visit 1A (data from the subject’s previous study will be utilized). 
•
For at-risk subjects, a mental health risk assessment must be performed by a qualified mental health professional.
c.
Female subjects who are menarchal must have negative urine pregnancy test.  Pregnancy tests may be completed more frequently as per IRB’s/IEC’s or as 
required based upon local regulations.
d.
Include Tanner stage assessment at screening for direct enrolling pediatric/adolescent, and at last visit Month 12 for all pediatric/adolescent subjects only.  
This assessment is not applicable to subjects who participated in study A0081042.
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e.
This is a taper medication dispensation only for subjects who will cease treatment with pregabalin.  If the subject will continue to receive pregabalin 
treatment post-study, initiation of taper is at the discretion of the investigator.  Subjects who require early discontinuation and require taper, should begin the 
taper at the time the decision is made to discontinue.  These subjects should return approximately 1 week later for follow-up Visit 9.
f.
Assessment of suicidal ideation and behavior:
I.
MINI-KID only for children and adolescents 6 -<17 years of age at Visit 1B or if they did not have a MINI-KID performed during prior 
participation to studies referred in Visit 1A.
II.
C-SSRS “Lifetime” version performed at Visit 1 for all subjects aged 6-65 years who did not have a C-SSRS performed previously. C-SSRS 
“Since Last Visit” version for all subjects ages 6-65 years for each visit beginning at Visit 2 through Visit 9 or Early Termination.
III. Child Behavior Checklist (CBCL) performed for children 4-<6 years of age beginning at Visit 1 and at every subsequent visit until Visit 9 or 
Early Termination. 
g.
Month 12, Visit 8 is the End of Treatment/End of Study visit for subjects who will not initiate taper of pregabalin per the discretion of the investigator.  
Visit 8 will be the final study visit for these subjects.  For subjects who will taper their pregabalin treatment, Visit 8 is considered End of Treatment/End of 
Study Visit but they will initiate taper at this visit and return for a follow-up Visit 9 to end taper.  For early terminations, all Visit 8 procedures should be 
performed and if taper is initiated, subjects should return for follow-up Visit 9.
h.
Cogstate Battery will be completed only for pediatric partial onset seizure subjects (Protocol A0081041) 4-16 years of age.
i.
The follow-up visit is only required for subjects who received taper medication.
j.
All screening procedures must be completed prior to administration of first study medication. All eligibility criteria should be confirmed prior to, or on, 
Visit 2.
k.
Adjust the dose if needed based on seizure response and tolerability.
*
TC = Telephone Contact to assess dosing and diary compliance, concomitant medications, and AE’s. 
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................17
LIST OF FIGURES .................................................................................................................17
APPENDICES .........................................................................................................................17
1. INTRODUCTION ...............................................................................................................18
1.1. Indication.................................................................................................................18
1.2. Background and Rationale ......................................................................................18
1.3 Dose Rationale .........................................................................................................20
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................21
2.1. Objectives................................................................................................................21
2.2. Endpoints.................................................................................................................21
3. STUDY DESIGN.................................................................................................................22
3.1. Treatments and Visits..............................................................................................22
4. SUBJECT SELECTION......................................................................................................25
4.1. Inclusion Criteria for Subjects who have Participated in Studies A0081041, 
A0081042, or A0081105...........................................................................................25
4.1.1. Inclusion Criteria for Directly Enrolling Subjects (ie, partial onset 
seizure subjects who have not participated in either Studies A0081041 
or A0081042)...................................................................................................26
4.2. Exclusion Criteria....................................................................................................28
4.3. Life Style Guidelines...............................................................................................30
4.3.1. Contraceptive Guidelines............................................................................30
4.4. Sponsor Qualified Medical Personnel.....................................................................30
4.5. Rater Qualifications.................................................................................................31
5. STUDY TREATMENTS.....................................................................................................31
5.1. Allocation to Treatment ..........................................................................................31
5.2. Drug Supplies..........................................................................................................32
5.2.1. Formulation and Packaging........................................................................32
5.2.2. Preparation and Dispensing........................................................................32
5.2.3. Administration............................................................................................32
5.2.4. Compliance.................................................................................................33
5.3. Drug Storage and Drug Accountability...................................................................34
5.4. Concomitant Medication(s).....................................................................................35
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5.4.1. Permitted Medications................................................................................35
5.4.2. Prohibited Medications...............................................................................36
5.5. Benzodiazepine Use as Needed for Occasional Seizure Exacerbation...................36
6. STUDY PROCEDURES .....................................................................................................37
6.1. Clinic Visit 1A (Day 1A): Screening for Subjects who have participated in 
Studies A0081041, A0081042, or A0081105 ...........................................................37
6.2. Clinic Visit 1B (Day 1B): Screening for Subjects Directly Enrolling into 
Study A0081106 who have not Participated in Studies A0081041, A0081042, 
or A0081105..............................................................................................................38
6.3. Clinic Visit 2 (Week 1/Day 8 1 day).....................................................................40
6.4. Clinic Visit 3 (Month 1/Day 30 4 Days)...............................................................41
6.5. Clinic Visit 4 (Month 2/Day 60 4 Days)...............................................................41
6.6. Telephone Contact (Month 3/Day 90 4 Days)......................................................42
6.7. Clinic Visit 5 (Month 4/Day 120 4 Days).............................................................42
6.8. Telephone Contact (Month 5/Day 150 4 Days)....................................................42
6.9. Clinic Visit 6 (Month 6/Day 180 4 Days).............................................................43
6.10. Telephone Contact (Month 7/Day 210 4 Days)..................................................43
6.11. Telephone Contact (Month 8/Day 240 4 Days)..................................................44
6.12. Clinic Visit 7 (Month 9/Day 270 4 Days)..........................................................44
6.13. Telephone Contact (Month 10/Day 300 4 Days)................................................45
6.14. Telephone Contact (Month 11/Day 330 4 Days)................................................45
6.15. Clinic Visit 8 (Month 12/Early Termination Day 365 7 Days) ..........................45
6.16. Visit 9 (Follow-up/End of Taper Visit-7 days Post-Completion/ 
Discontinuation3 Days)...........................................................................................46
6.17. Subject Withdrawal...............................................................................................47
7. ASSESSMENTS..................................................................................................................49
7.1. Physical and Neurological Examination .................................................................49
7.2. Vital Signs, Height and Weight...............................................................................49
7.3. Clinical Laboratory Assessments............................................................................50
7.3.1. Pregnancy Test............................................................................................50
7.3.2. Hematology.................................................................................................51
7.3.3. Clinical Chemistry......................................................................................51
7.3.4. Urinalysis....................................................................................................51
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7.4. Electrocardiogram (ECG)........................................................................................51
7.5. Seizure Counts.........................................................................................................52
7.6. Assessment of Suicidal Ideation and Behavior (SIB) .............................................52
7.6.1. Child Behavior Checklist (CBCL); Subjects 4 to <6 Years of Age ...........52
7.6.2. Mini International Neuropsychiatric Interview (MINI-KID) –
Version 6.0 (Subjects 6-<17 Years of Age).....................................................53
7.6.3. Columbia-Suicide Severity Rating Scale (C-SSRS)- Subjects 6-65 
Years of Age ....................................................................................................53
7.6.4. Assessment of Suicidal Ideation and Behavior at Screening......................54
7.6.5. Assessment of Suicidal Ideation and Behavior During the Clinical 
Study ................................................................................................................54
7.7. Cognitive Testing....................................................................................................55
7.7.1. The CogState Battery..................................................................................55
8. ADVERSE EVENT REPORTING......................................................................................56
8.1. Adverse Events........................................................................................................56
8.2. Reporting Period .....................................................................................................57
8.3. Definition of an Adverse Event...............................................................................57
8.4. Medication Errors....................................................................................................58
8.5. Abnormal Test Findings..........................................................................................58
8.6. Serious Adverse Events...........................................................................................59
8.6.1. Protocol-Specified Serious Adverse Events...............................................59
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................59
8.7. Hospitalization ........................................................................................................60
8.8. Severity Assessment................................................................................................62
8.9. Causality Assessment..............................................................................................62
8.10. Exposure During Pregnancy..................................................................................62
8.11. Occupational Exposure .........................................................................................64
8.12. Withdrawal Due to Adverse Events (See also section on Subject 
Withdrawal)...............................................................................................................64
8.13. Eliciting Adverse Event Information ....................................................................64
8.14. Reporting Requirements........................................................................................64
8.14.1. Serious Adverse Event Reporting Requirements .....................................64
8.14.2. Non-Serious Adverse Event Reporting Requirements .............................65
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8.14.3. Sponsor Reporting Requirements to Regulatory Authorities ...................65
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................65
9.1. Sample Size Determination.....................................................................................66
9.2. Efficacy Analysis ....................................................................................................66
9.2.1. Analysis of Primary Endpoint ....................................................................66
9.2.2. Analysis of Secondary Endpoints...............................................................66
9.3. Analysis of Other Endpoints ...................................................................................66
9.4. Safety Analysis........................................................................................................66
9.5. Data Monitoring Committee ...................................................................................67
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................67
11. DATA HANDLING AND RECORD KEEPING .............................................................67
11.1. Case Report Forms/Electronic Data Record .........................................................67
11.2. Record Retention...................................................................................................68
12. ETHICS..............................................................................................................................68
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............68
12.2. Ethical Conduct of the Study ................................................................................68
12.3. Subject Information and Consent..........................................................................69
12.4. Subject Recruitment ..............................................................................................70
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................70
13. DEFINITION OF END OF TRIAL...................................................................................70
13.1. End of Trial in a Member State.............................................................................70
13.2. End of Trial in all Participating Countries ............................................................70
14. SPONSOR DISCONTINUATION CRITERIA ................................................................70
15. PUBLICATION OF STUDY RESULTS..........................................................................70
15.1. Communication of results by Pfizer......................................................................70
15.2. Publications by Investigators ................................................................................72
16. REFERENCES ..................................................................................................................73
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LIST OF TABLES
Table 1.
End-of-Treatment Taper Schedule for Pediatric Subjects >30 kg........................24
Table 2.
End-of-Treatment Taper Schedule for Pediatric Subjects <30 kg........................24
Table 3.
End-of-Treatment Taper Schedule for Adult Subjects .........................................25
Table 4.
Trials and Timing of each task in CogState- Cognitive Battery...........................56
LIST OF FIGURES
Figure 1.
Study Design Schematic.......................................................................................23
Figure 2.
Oral Dosing Syringes (1, 3, and 10 mL left to right)............................................80
Figure 3.
Dosing Example....................................................................................................81
APPENDICES
Appendix 1. International League Against Epilepsy 2010 and Revised 1981 
Classification ........................................................................................................75
Appendix 2. Clinical Dosing Instructions for Administration of the Liquid Oral 
Solution Formulation:...........................................................................................79
Appendix 3. List of Abbreviations: .........................................................................................82
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1. INTRODUCTION
Epilepsy is a common disorder in childhood affecting 4 to 5 of every 1000 children.  
Although epilepsy is often well controlled with existing antiepileptic drug (AED) therapy, 
more than 25% of pediatric patients have seizures that are uncontrolled by currently available 
agents, or have adverse effects related to AEDs that complicate their seizure control.  In 
addition, children with epilepsy often suffer from impaired academic performance, with 
55% functioning below their grade level and an additional 16% significantly behind in 
educational training.1  Children with epilepsy also have a higher likelihood of developing 
behavioral difficulties, which may persist into adulthood.2  Early age of onset and a higher 
number of total lifetime seizures are the strongest correlates of academic underachievement.  
Therefore, the availability of a new AED that has been shown to improve seizure control and 
that is generally well tolerated is needed.
1.1. Indication
Adjunctive therapy for pediatric subjects with partial onset seizures with or without 
secondary generalization and adjunctive therapy for pediatric and adult subjects with primary 
generalized tonic-clonic (PGTC) seizures.
1.2. Background and Rationale
Pregabalin [CI-1008, (S)-3-(aminomethyl)-5-methylhexanoic acid] binds with high affinity 
to the 2site (an auxiliary subunit of voltage gated calcium channels) in central nervous 
system tissues.  Results with genetically modified mice and with compounds structurally 
related to pregabalin indicate that binding to the 2subunit may be involved in pregabalin’s 
antiseizure effects in animal models.  In vitro, pregabalin reduces the calcium-dependent 
release of several neurotransmitters, possibly by modulation of calcium channel function.
Gabapentin (Neurontin) and pregabalin (Lyrica) are the only 2 alpha-2-delta (2-) agents 
that are approved for use as medications for the treatment of partial onset seizures.  Both are 
believed to exert their pharmacologic action by binding to the 2site of voltage-gated 
calcium channels.  Gabapentin is approved as adjunctive therapy in the treatment of partial 
seizures in adults and children (US-children aged 3 years of age and older: EU-children aged 
6 years of age and older).  Gabapentin is well-tolerated in both adult and pediatric patients.  
The most common treatment-emergent adverse events reported in a controlled trial of 
gabapentin for the adjunctive treatment of epilepsy in subjects 3 to 12 years of age were viral 
infection, fever, nausea and/or vomiting, and somnolence.  Gabapentin clearance, normalized 
for body weight, is higher in children younger than 5 years of age than in older children and 
adults. 
Pregabalin is approved in more than 100 countries, with indications summarized below for 
the United States (US), European Union (EU), and Japan.  In the US and EU, pregabalin is 
indicated for the adjunctive treatment of adult patients with partial onset seizures.  In 
addition, pregabalin is indicated for the treatment of central and peripheral neuropathic pain 
(EU), and for the management of neuropathic pain associated with postherpetic neuralgia and 
diabetic peripheral neuropathy and for the treatment of fibromyalgia (US) and for the 
treatment of peripheral neuropathic pain (JP).  In the EU, pregabalin is also approved for the 
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treatment of Generalized Anxiety Disorder (GAD) in adults. The efficacy of pregabalin in 
subjects with PGTC seizures has not been assessed to date in a placebo-controlled study.
The approved dose range for the adjunctive treatment of partial onset seizures in adults is 
150 to 600 mg/day, administered 2 times (BID) or 3 times (TID) a day.  The most common 
adverse effects reported with pregabalin in placebo-controlled adjunctive trials of pregabalin 
in adults with partial onset seizures were dizziness and somnolence. Since initial market 
approval of Lyricain 2004, it is estimated that more than 11,700,000 patient-years of 
exposure will have accumulated worldwide.  More detailed information, including efficacy 
results in adults and the possible risks associated with administration of pregabalin, are 
summarized in the Investigator’s Brochure which will serve as the Single Reference Safety 
Document for this study.
Pregabalin pharmacokinetic (PK) data from adult clinical pharmacology studies and one 
clinical pharmacology study in pediatric subjects with epilepsy (Study A0081074) show that
pregabalin pharmacokinetics are linear and predictable. Multiple-dose pharmacokinetics are
predictable from single-dose data.  Pregabalin is rapidly absorbed when administered in the 
fasted state, with oral bioavailability of 90% and peak plasma pregabalin concentrations
occurring 0.7 to 1.5 hours following both single- and multiple- dose administration.  
Pregabalin can be dosed either 2 or 3 times a day.  Pregabalin is essentially not metabolized 
and administration with food has no clinically relevant effect on the total amount of 
pregabalin absorbed.  Pregabalin is eliminated from the systemic circulation primarily by 
renal excretion as unchanged drug, with a mean plasma pregabalin half-life of 6.3 hr in 
adults.  Pregabalin terminal t½ averaged about 3 to 4 hours in pediatric subjects from 
1 month to 6 years of age, and 4 to 6 hours in those 7 years of age and older.  Pregabalin oral 
clearance normalized per body weight was 43% higher in the children with body weight less 
than 30 kg than in children whose body weight was 30 kg and higher.  Pregabalin clearance 
is proportional to creatinine clearance, and the major influence on its clearance is reduced or 
impaired renal function.
Pregabalin, at concentrations approximately 10 times those attained in clinical trials, does not 
inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 
enzyme systems.  In vitro drug interaction studies demonstrate that pregabalin does not 
induce CYP1A2 or CYP3A4 activity.  Population pharmacokinetic analyses of adult data 
have shown no interactions between pregabalin and either carbamazepine, lamotrigine, 
phenobarbital, phenytoin, topiramate, or valproic acid. Similar analyses show that tiagabine 
has no effect on the pharmacokinetics of pregabalin.
Study A0081074 was a placebo-controlled, parallel-group, multiple-dose, dose escalation 
study to characterize the safety, tolerability, and the single- and multiple-dose 
pharmacokinetics of pregabalin at several dose levels in pediatric subjects with partial onset 
seizures.  The adverse event profile observed in pediatric subjects aged 2-16 years of age in 
Study A0081074 is similar in nature to that seen in adult subjects with somnolence and 
dizziness being the most commonly reported adverse events.  Somnolence was observed at 
pregabalin doses of 2.5, 5.0, and 15.0 mg/kg/day. Dizziness was the next most common 
adverse event and was seen only at the pregabalin dose of 10.0 and 15.0 mg/kg/day. The 
data from Study A0081074 has been used to define the dose range to be investigated in this 
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study (Study A0081106) and additional Phase 3 efficacy and safety studies in the pediatric 
epilepsy population. 
Pregabalin has not yet been studied in large numbers of pediatric patients. This study will 
enroll those subjects who have participated in Studies A0081041, A0081042, and A0081105 
and in whom pregabalin shows acceptable safety and tolerability in those studies.  In addition 
to subjects who have participated in Studies A0081041, A0081042 and A0081105, pediatric 
subjects (1 month to 16 years of age) with partial onset seizures will also be considered for 
direct enrollment into Study A0081106 from selected sites (within the United States only) 
that are not participating in Studies A0081041, A0081042, or A0081105. 
Pregabalin has been shown to be effective in the treatment of epilepsy in adults and is 
currently approved for the adjunctive treatment of POS in adults over a dose range of 150 to 
600 mg/day (when taken 2 or 3 times a day).  Thus, pregabalin’s mechanism of action, being 
different from other anti-epileptic drugs, has the potential to expand treatment choices for 
children with epilepsy.  This study is considered to have a positive risk benefit ratio for 
enrolling patients based on extensive previous experience with pregabalin in adults with POS 
and with the comprehensive safety screening and monitoring plans included in the present 
study design.
This study is one of several studies that will be conducted to assess the safety and efficacy of 
pregabalin in pediatric subjects with epilepsy and to address post approval commitments to 
US and EU regulatory authorities.
Complete information for pregabalin may be found in the Single Reference Safety document 
which for this study is the Investigator Brochure.
The name, title, addresses, and telephone number(s) of the sponsor's medical expert for the 
study is documented in the study contact list.
1.3 Dose Rationale
The recommended dosing regimen in both the US and EU for adjunctive therapy with 
Lyricain adults with partial onset seizures ranges from 150 to 600 mg/day given BID or 
TID.  The recommended dose range in adults is approximated by the 2.5 mg/kg/day to 
10 mg/kg/day pregabalin dose range for pediatric subjects <60 kg in this study. This range of 
doses is anticipated to provide efficacy for the subjects enrolled and will characterize safety 
and tolerability of this dose range for pediatric subjects.
Doses in the range of 2.5 to 15 mg/kg/day were studied in pediatric subjects between 
1 month and 16 years of age in Study A0081074 and serial blood samples were collected to 
assess the pharmacokinetics of pregabalin in the pediatric population.  Data from Study 
A0081074 were compared with the adult data in a population pharmacokinetic analysis 
which showed that the relationship between creatinine clearance (CLcr) and pregabalin 
clearance (CL/F) was similar between both populations.  Therefore, knowing a subject’s 
CLcr value, the pregabalin oral clearance and thus pregabalin exposure can be estimated with 
a high degree of accuracy.  
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The noncompartmental and population pharmacokinetic analyses utilizing data from
pediatric subjects from Study A0081074 indicated that for subjects with body weight 30 kg 
exposure equivalent to that observed in adults would be achieved when the pediatric subjects 
were dosed on a mg/kg/day basis.  Due to higher clearance/kg in pediatric subjects with body 
weight <30 kg, a daily dose/kg 40% higher is needed to achieve exposure similar to that of 
adults or pediatric subjects weighing 30 kg.  Thus, pediatric subjects with body weight 
30 kg will initiate dosing at the daily dose of 2.5 mg/kg/day for a minimum of 1 week. 
Thereafter, dosing will be flexible, based on individual seizure response and tolerability. 
Doses may be adjusted up or down at clinic visits in increments no more than of
2.5 mg/kg/day.  For pediatric subjects with body weight <30 kg, the daily dose will be 
adjusted by 40% to an initial daily dose of 3.5 mg/kg/day for a minimum of 1 week.  
Thereafter, dosing will be flexible, based on individual seizure response and tolerability.  
Doses may be adjusted up or down at clinic visits in increments of no more than 
3.5 mg/kg/day.
Subjects <4 years of age at Visit 1 or participating from A0081042 will receive study 
medication TID in equally divided doses.  Subjects who are 4 years of age at Visit 1 will 
receive study medication BID in equally divided doses.  A TID dosing regimen accounts for 
a half life in youngest subjects shorter than in older pediatric and adult subjects.  Subjects 
will maintain a BID or TID dosing regimen throughout study participation based on age at 
Visit 1 or past participation in A0081042 in order to avoid potential dosing 
errors/noncompliance related to regimen switch.
Adult subjects (17 to 65 years of age) who enroll in this study following participation in 
Study A0081105 will initiate dosing at 150 mg/day. Thereafter, dosing will be flexible, 
based on individual seizure response and tolerability. Doses may be adjusted up or down at 
clinic visits in increments of 150 mg/day.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives

To evaluate the long-term safety and tolerability of pregabalin in pediatric subjects 
1 month through 16 years of age with partial onset seizures and pediatric and adult 
subjects 5 to 65 years of age with (PGTC) seizures.
2.2. Endpoints
Safety Endpoints:

Adverse event (AE) data (occurrence, nature, intensity, and relationship to study 
drug).

Physical and neurological examinations.

Vital signs.

Growth and development parameters (height, weight, Tanner stage).
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
Clinical laboratory data (hematology, chemistry, urinalysis).

Electrocardiograms (ECGs).

28-day seizure rate (number of seizures per 28 day period).

Assessment of suicidal ideation and behavior.

Cognitive assessment battery (POS pediatric subjects 4-16 years of age only).
3. STUDY DESIGN
Study A0081106 is a 12 month, open-label, flexible dose, multicenter study to evaluate the 
tolerability and safety of pregabalin (administered BID in subjects 4 years of age and TID 
in subjects <4 years of age) as adjunctive therapy in pediatric subjects 1 month to 16 years of 
age with partial onset seizures and pediatric and adult subjects 5 to 65 years of age with 
(PGTC) seizures. Subjects who have completed the studies A0081041, A0081042, or 
A0081105 will be eligible for screening for this study.  For subjects who have participated in, 
but did not complete Studies A0081041, A0081042, or A0081105, eligibility for Study 
A0081106 will be considered, after consultation with Study Clinician, on a case by case 
basis.  A minimum of 4 weeks in the double-blind treatment phase of either Study A0081041 
or Study A0081105 will be required for consideration of enrollment into Study A0081106.
Selected sites (within the United States only) that are not participating in studies A0081041 
or A0081042 may screen and enroll pediatric subjects (1 month to 16 years of age) with 
partial onset seizures directly into Study A0081106 provided they meet the study 
inclusion/exclusion criteria.  When subject enrollment for Studies A0081041 and A0081042 
is complete, sites that were enrolling subjects in Studies A0081041 or A0081042 may screen 
and enroll pediatric subjects (1 month to 16 years of age) with partial onset seizures directly 
into Study A0081106 until enrollment into Study A0081106 is closed by Pfizer.
3.1. Treatments and Visits
The day of the last visit (completion of taper phase) of Studies A0081041, A0081042, and 
A0081105 is designated as Day 1 (Visit 1A) of this study.  Baseline values for analysis of 
change in safety endpoints will be the assessments made prior to initiating double-blind 
dosing at Visit 1 of Studies A0081041, A0081042, or A0081105.  For subjects directly 
entering Study A0081106 without participation in one of the studies above, baseline values 
for analysis of change in safety endpoints will be the assessments made at the first visit 
(Screening Visit 1B) of this study.
For pediatric subjects, pregabalin dosing will initiate at the daily dose of 2.5 mg/kg/day
(subjects 30 kg) or 3.5 mg/kg/day (subjects <30 kg) at this visit.  Adult subjects who enroll 
in this study following participation in Study A0081105 will initiate dosing at 150 mg/day.  
All seizures experienced will be self-recorded by the subject or recorded by their 
parents/legally acceptable representative as appropriate, in a daily seizure diary beginning at 
Visit 1 and subsequently throughout the entire study.
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Subjects will return for the designated assessments of safety, tolerability, and drug 
accountability at Week 1 (Visit 2), Month 1 (Visit 3), Month 2 (Visit 4), Month 4 (Visit 5), 
Month 6 (Visit 6), Month 9 (Visit 7), Month 12/Early Termination (Visit 8), and Follow-up 
(Visit 9).  Investigator site staff will contact the subject and/or parent/caregiver by telephone 
at least monthly between visits, to address questions, assess safety and adverse events, and 
ensure compliance with study directives.
At Visit 2 and subsequent visits thereafter, the investigator or designee will review seizure 
diary data and tolerability with the subject and may adjust the dose at his/her discretion.  For 
pediatric subjects with body weight 30 kg (1 month to 16 years of age), doses may remain 
the same or be adjusted upward in increments of no more than 2.5 mg/kg/day to daily dose 
levels of 5.0, 7.5, or 10.0 mg/kg/day. For pediatric subjects with body weight <30 kg, doses 
may be adjusted in increments of no more than 3.5 mg/kg/day to daily dose levels of 7.0, 
10.5, or 14.0 mg/kg/day.  For adult subjects (17 to 65 years of age) doses may be adjusted in 
increments of 150 mg/day to daily dose levels of 300, 450, or 600 mg/day.
Figure 1.
Study Design Schematic
Subjects who discontinue early and those who complete the study and do not continue 
treatment with pregabalin are recommended to taper off of study medication (see below for 
recommended tapering schedule), and will return for Visit 9 when the taper is completed.
For pediatric subjects 30 kg who taper off of pregabalin, the following schedule is 
recommended:
Study 
A0081041
A0081042
A0081105
Study A0081106 
V2
Week
1
V3
Month
1
V4
Month
2
V6
Month     
6
V7
Month
9
        V8
    Month 12/
   Early Term
  End of study/
  Initiate Taper
V9
End 
Taper
    V1A
    Day 1
V5
Month     
4
V1B
Day 1
Directly 
Enrolling
Pediatric 
POS 
Subjects
Open Label Flexible Treatment Phase 2.5-10 mg/kg/day
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
Subjects receiving a dose of 10.0 mg/kg/day should receive 5.0 mg/kg/day for 4 days, 
then 2.5 mg/kg/day for 3 days, then discontinue study medication.

Subjects receiving a dose of 7.5 mg/kg/day should receive 5.0 mg/kg/day for 4 days, 
then 2.5 mg/kg/day for 3 days, then discontinue study medication.

Subjects receiving a dose of 5.0 mg/kg/day should receive 2.5 mg/kg/day for 7 days, 
and then discontinue study medication.

Subjects receiving a dose of 2.5 mg/kg/day may discontinue study medication without 
any taper.
Table 1.
End-of-Treatment Taper Schedule for Pediatric Subjects >30 kg
Day1 /
Total Daily Dose
Day
1
Day
2
Day
3
Day
4
Day
5
Day
6
Day 7/
Follow up
10.0 mg/kg/day
5.0
5.0
5.0
5.0
2.5
2.5
2.5
7.5 mg/kg/day
5.0
5.0
5.0
5.0
2.5
2.5
2.5
5.0 mg/kg/day
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5 mg/kg/day
0
0
0
0
0
0
0
1.  Days 1-7 post-Month 12/Early Termination visit.
For pediatric subjects <30 kg who taper off of pregabalin, the following schedule is 
recommended:

Subjects receiving a dose of 14.0 mg/kg/day should receive 7.0 mg/kg/day for 4 days, 
then 3.5 mg/kg/day for 3 days, then discontinue study medication.

Subjects receiving a dose of 10.5 mg/kg/day should receive 7.0 mg/kg/day for 4 days,
then 3.5 mg/kg/day for 3 days, then discontinue study medication.

Subjects receiving a dose of 7.0 mg/kg/day should receive 3.5 mg/kg/day for 7 days, 
and then discontinue study medication.

Subjects receiving a dose of 3.5 mg/kg/day may discontinue study medication without 
any taper.
Table 2.
End-of-Treatment Taper Schedule for Pediatric Subjects <30 kg
Day1 /
Total Daily Dose
Day
1
Day
2
Day
3
Day
4
Day
5
Day
6
Day 7/
Follow up
14.0 mg/kg/day
7.0
7.0
7.0
7.0
3.5
3.5
3.5
10.5 mg/kg/day
7.0
7.0
7.0
7.0
3.5
3.5
3.5
7.0 mg/kg/day
3.5
3.5
3.5
3.5
3.5
3.5
3.5
3.5 mg/kg/day
0
0
0
0
0
0
0
1.  Days 1-7 post-Month 12/Early Termination visit.
For adult subjects (17 to 65 years of age) who taper off of pregabalin, the following schedule 
is recommended:
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
Subjects receiving a dose of 600 mg/day should receive 300 mg/day for 4 days, then 
150 mg/day for 3 days, then discontinue study medication.

Subjects receiving a dose of 450 mg/day should receive 300 mg/day for 4 days, then 
150 mg/day for 3 days, then discontinue study medication.

Subjects receiving a dose of 300 mg/day should receive 150 mg/day for 7 days, and 
then discontinue study medication.

Subjects receiving a dose of 150 mg/day may discontinue study medication without 
any taper.
Table 3.
End-of-Treatment Taper Schedule for Adult Subjects
Day1 /
Total Daily Dose
Day
1
Day
2
Day
3
Day
4
Day
5
Day
6
Day 7/
Follow up
600 mg/day
300
300
300
300
150
150
150
450 mg/day
300
300
300
300
150
150
150
300 mg/day
150
150
150
150
150
150
150
150 mg/day
0
0
0
0
0
0
0
1.  Days 1-7 post-Month 12/Early Termination visit.
4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered 
appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject.
4.1. Inclusion Criteria for Subjects who have Participated in Studies A0081041, 
A0081042, or A0081105
Subject eligibility should be reviewed and documented by an appropriately qualified member 
of the investigator’s study team before subjects are included in the study.  Subjects must meet 
all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject (or a legally acceptable representative) has been informed of all pertinent 
aspects of Study A0081106.  When there are 2 parents or 2 legally acceptable 
representatives, consent should be obtained from both of the child’s parents/legal 
representatives if present at the meeting where the informed consent document is 
signed.  Subject to local regulations whenever the minor is able to give assent, the 
minor’s assent must be obtained.
2. Subjects and/or parents/legally acceptable representative who are willing and able to 
comply with scheduled visits, treatment plan, laboratory tests, and other study 
procedures.
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3. Male and female subjects who have participated in and completed, or participated in 
Studies A0081041, A0081042, or A0081105.  For subjects who have participated in, 
but did not complete Studies A0081041, A0081042, or A0081105, eligibility for 
Study A0081106 will be reviewed with a member of the Pfizer study team to 
determine further eligibility.  Subjects are required to have completed a minimum of 
4 weeks of double-blind treatment in Studies A0081041 or A0081105 to be 
considered potentially eligible for Study A0081106.
4. Male and female epilepsy subjects who have participated in either Study A0081041 
or Study A0081042, 1 month to 16 years of age inclusive on the date of the Screening 
Visit with diagnosis of epilepsy with seizures classified as simple partial, complex 
partial or partial becoming secondarily generalized, according to the International 
League Against Epilepsy (ILAE 20103) (See Appendix 1 for additional seizure types).  
The diagnosis must be established by:

Subject’s history (eg, description of seizures excluding confounding disorders 
such as pseudoseizures, syncope etc) family history and neurological exam.

Subjects must have had a contrast enhanced computed tomography (CT) or 
magnetic resonance imaging (MRI) scan of the brain and 
electroencephalogram (EEG) testing prior to Study A0081041 or Study 
A0081042.  Results must have been consistent with the diagnosis of 
focal-onset epilepsy and must have demonstrated that no abnormality was 
likely to be progressive.
5. Male and female subjects 5-65 years of age who have participated in Study 
A0081105 with a diagnosis of epilepsy (ILAE 20103) with PGTC seizures and who 
continue to satisfy seizure related inclusion criteria for that study (see Protocol 
A0081105). Subjects who have participated in study A0081105 and who reach the 
age limit of 66 years of age will still be allowed to enter this study.
6. Currently receiving a stable dose of 1 to 3 antiepileptic drugs at Visit 1.  
Benzodiazepine medication used on a regular basis will be considered 1 of the 
concurrent antiepileptic treatments.  The vagus nerve stimulator (VNS) is allowed and 
considered 1 of the 3 antiepileptic treatments.
7. A 12-lead ECG at (the last visit of Studies A0081041, A0081042, A0081105) without 
significant abnormal findings.
4.1.1. Inclusion Criteria for Directly Enrolling Subjects (ie, partial onset seizure 
subjects who have not participated in either Studies A0081041 or A0081042) 
In order for Direct Enrolling Subjects to be eligible, all of the following inclusion criteria 
must be met and confirmed prior to, or on, Visit 2:
1. Evidence of a personally signed and dated informed consent document indicating that 
the parent/legally acceptable representative has been informed of all pertinent aspects 
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of the study.  When there are 2 parents or 2 legally acceptable representatives, 
consent should be obtained from both of the child’s parents/legal representatives if 
present at the meeting where the informed consent document is signed.  Subject to 
local regulations whenever the minor is able to give assent, the minor’s assent must 
be obtained.
2. Subjects and/or parents/legally acceptable representative who are willing and able to 
comply with scheduled visits, treatment plan, laboratory tests, and other study 
procedures.
3. Subjects and/or parent/legally acceptable representative must be considered willing 
and able to complete daily seizure diaries and monitor seizure frequency.  
4. Male and female epilepsy subjects, 1 month (44 weeks gestational age) to 16 years of 
age inclusive on the date of the Screening Visit with diagnosis of epilepsy with 
seizures classified as simple partial, complex partial or partial becoming secondarily 
generalized, according to the International League Against Epilepsy (ILAE 20103) 
(See Appendix 1 for additional seizure types).  The diagnosis must be established by:

Subject’s history (eg, description of seizures excluding confounding disorders 
such as pseudoseizures, syncope etc.) family history and neurological exam.

Subjects must have had a contrast enhanced computed tomography (CT) or 
magnetic resonance imaging (MRI) scan of the brain within 60 months of the 
Screening Visit and an EEG within 24 months of the screening visit.  
However, if clinical symptoms have emerged or a change in a clinical status 
has occurred such that an imaging study would be required, then a CT with 
contrast or MRI of the head should be performed regardless of the amount of 
time that has elapsed since the previous CT/MRI scan.  Results must be 
available as soon as possible following screening and must be completed and 
reviewed prior to enrollment.  Imaging results must be consistent with the 
diagnosis of focal-onset epilepsy and must demonstrate that no abnormality is 
likely to be progressive.

Subjects must have had an average of at least 3 seizures per month in the 
3 months prior to screening.
5. Currently receiving a stable regimen of 1 to 3 antiepileptic treatments (stable within 
28 days prior to screening).  Benzodiazepine medication used on a regular basis at a 
stable dosage will be considered 1 of the concurrent antiepileptic treatments.  Any 
PRN benzodiazepine use in addition to AEDs must be discussed with the Pfizer 
clinician and allowance will be decided on a case-by-case basis. The vagus nerve 
stimulator (VNS) is allowed and considered 1 of the 3 antiepileptic treatments.
6. A 12-lead ECG at screening without clinically significant abnormal findings as 
determined by the investigator. 
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4.2. Exclusion Criteria
These exclusion criteria apply to subjects who have participated in Studies A0081041, 
A0081042, or A0081105, as well as those subjects who have not.  In order for Direct 
Enrolling Subjects to be eligible, all exclusion criteria should be confirmed prior to, or on, 
Visit 2.
Subjects presenting with any of the following will not be included in the study:
1. Lennox-Gastaut syndrome, Infantile Spasms, Absence seizures for Direct Enrolling 
subjects, BECT (Benign epilepsy with centrotemporal spikes) and Dravet syndrome.  
A current diagnosis of febrile seizures, any febrile seizures within 1 year of screening, 
or seizures related to an ongoing acute medical illness.  
Prior history (ie, more than 1 year prior to screening) of febrile seizures may be 
allowed on a case by case basis following consultation with study clinician. 
2. Status epilepticus within 1 year prior to Visit 1 of this study. 
3. Seizures related to drugs, alcohol, or acute medical illness.
4. Progressive structural central nervous system (CNS) lesion or a progressive 
encephalopathy.  Progressive inborn errors of metabolism.
5. Known or suspected chronic hematologic, hepatic or renal disease (aspartate 
aminotransferase –AST- and alanine aminotransferase –ALT- above 3 times the 
upper limit of normal; or bilirubin, BUN, or creatinine above 2 times the upper limit 
of normal within the previous 6 months for infants, children and adolescents aged 
6 months or more, or at any postnatal period for infants younger than 6 months).  
Estimated creatinine clearance (CLcr) <60 mL/min for subjects 17 yr and 
<80 mL/min/1.73m2 (using age appropriate equations) for subjects <17 years of age.  
For subjects who previously participated in A0081041, A0081042 or A0081105, it is 
assumed the subjects have already met entry criteria, therefore, the creatinine 
clearance exclusion is based upon results collected at the Screening Visit laboratory 
of A0081041, A0081042 or A0081105.  The laboratory exclusion criteria noted 
above will be based upon data collected at the Last visit (Visit 9, Early Termination, 
or Unscheduled Visit) of the A0081041, A0081042 or A0081105. 
6. Other severe acute or chronic medical (eg, genetic or chromosomal syndromes) or 
psychiatric condition or laboratory abnormality that may increase the risk associated 
with study participation or investigational product administration or may interfere 
with the interpretation of results and, in the judgment of the investigator or the 
sponsor, would make the subject inappropriate for entry into this study.
7. Pregnant or nursing females (females who are menarchal must have a negative urine 
pregnancy test); menarchal females of childbearing potential who are unwilling or 
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unable to use an acceptable method of contraception, as outlined in the protocol, until 
completion of follow-up procedures.
8. Taking any non-antiepileptic (non-AED) medication that could alter the effectiveness 
of the subject’s medication, response, seizure frequency or characteristics.  
Medications for Attention Deficit/Hyperactivity Disorder and other behavioral 
changes (eg, risperidone) will be permitted.  A ketogenic diet will also be allowed 
given that the diet is adhered to for the duration of the study. Note: changes in the 
dose, regimen and type of these medications during study participation may be 
allowed upon discussion with the study clinician. Continued participation of the 
subject will be evaluated and decided on a case-by-case basis.
9. Taking or have taken any other investigational drug (aside from participation in 
Studies A0081041, A0081042 or A0081105) within the last 30 days prior to 
screening. 
10. The concomitant use of gabapentin, felbamate and vigabatrin is prohibited.
11. Use of cocaine, phencyclidine (PCP), or other illegal or illicit drugs is prohibited.  
Use of marijuana, or its derivatives, including prescribed medical marijuana, is not 
allowed under any circumstances. Use of amphetamines, barbiturates, opiates, or 
benzodiazepines without a valid current prescription is prohibited.
12. Unwilling or unable to comply with the Life Style Guidelines.
13. Subjects not reasonably expected to complete the study.
14. Any subjects considered at risk of suicidal behavior based upon the Columbia 
Suicidality Rating Scale (C-SSRS) Lifetime (subjects 6 years of age) or Child 
Behavioral Check List (CBCL)(subjects <6 years of age) or responses obtained 
during the Modified International Neuropsychiatric Interview (MINI-KID). A subject 
should be excluded or a risk assessment should be done by a qualified mental health 
professional based on responses to assessment of suicidal ideation and behavior and if 
the subject has had suicidal ideation in the last 6 months prior to screening, suicidal 
behaviors or attempts in the past year, or current major psychiatric disorders that are 
not explicitly permitted in the inclusion/exclusion criteria.  A risk assessment should 
also be performed in any child <6 years of age who has ever exhibited any potentially 
self-injurious or high-risk behaviors such as hurting himself or herself, or unusual 
behaviors such as running into traffic or using items as weapons (eg, knife, bat). Any 
concerns regarding such behaviors should be discussed with the Pfizer clinician prior 
to study participation or continuation.
15. For subjects who have not participated in Studies A0081041, A0081042, or 
A0081105 and enrolling directly into Study A0081106, treatment with pregabalin for 
any reason within 60 days prior to screening, or prior participation in a pregabalin 
clinical study is prohibited.
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16. Known allergy or intolerance to pregabalin or its excipients, including lactose, or 
other 2ligands (eg, gabapentin).
17. Subjects, or subjects whose parents/legally acceptable representatives are 
investigational site staff members; and subjects, or subjects whose parents/legally 
acceptable representative are Pfizer employees directly involved in the conduct of the 
study.
4.3. Life Style Guidelines
Subjects should be advised that pregabalin may cause dizziness and somnolence.  
Accordingly, as age appropriate, subjects should be advised not to drive, consume alcohol or 
operate complex machinery until they have gained sufficient experience on study drug to 
assess its effects on performance.
4.3.1. Contraceptive Guidelines
The investigator should interview each subject to obtain his/her sexual and contraceptive 
history in order to give appropriate sexual counseling about conduct during the study.  All 
subjects (male and female) with reproductive potential must agree to practice simultaneously 
2 effective contraception methods or abstinence for at least 28 days prior to the first dose of 
study drug and for 28 days following the last dose of study drug.  These may include:

Barrier (condoms, diaphragm or cervical cap) with spermicide.

Oral or other acceptable contraceptives which may include but is not limited to: 
injectable, implanted or patch hormone therapy, IUD, or documented surgical 
sterilization.

Absolute sexual abstinence, without a second method.
A urine pregnancy test for female subjects who are menarchal will be collected at Visits 1, 6, 
7, and 8.  If the results of the urine pregnancy test are positive, the subject will not be eligible 
for study participation.  
4.4. Sponsor Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
trial is documented in the study contact list located in the team Sharepoint.
To facilitate access to appropriately qualified medical personnel on study related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational compound identifiers, patient study number, 
contact information for the investigational site and contact details for a help desk in the event 
that the investigational site staff cannot be reached to provide advice on a medical question 
or problem originating from another healthcare professional not involved in the subjects 
participation in the study. The help desk number can also be used by investigational staff if 
they are seeking advice on medical questions or problems, however it should only be used in 
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the event that the established communication pathways between the investigational site and 
the study team are not available. It is therefore intended to augment, but not replace the 
established communication pathways between the investigational site and study team for 
advice on medical questions or problems that may arise during the study. The help desk 
number is not intended for use by the subject directly and if a subject calls that number they 
will be directed back to the investigational site.
4.5. Rater Qualifications
The process of reviewing rater qualifications, approval of raters for training and the training 
of raters is administered by 
 as an agent of the Sponsor.  All 
designated raters must complete a Rater Qualification Survey available through the study 
web-based workspace
 in order to become qualified
as a rater.  All site personnel who require or request access to the workspace are granted 
access upon site activation.  All qualified raters must also successfully complete protocol 
required training prior to the administration of any assessment (ie, Mini-Kid; CBCL; C-SSRS 
– please see Section 7-ASSESSMENTS- for additional details). The assessment instruments 
have been designed for use by professionals who have been trained on their administration.  
Therefore, all raters must complete the required assessment training, either during attendance 
at an Investigator Meeting, or through the study web-based workspace. All training materials 
and instructions are located on the workspace.  The company 
 will issue a rater training 
completion certificate to qualified raters for training on each assessment instrument that has 
been completed.  Qualified raters must have a valid rater training completion certificate on 
file in order to perform the assessment.
5. STUDY TREATMENTS
5.1. Allocation to Treatment
Subjects who complete Visit 1 and meet the eligibility criteria will begin study treatment.
Subjects will be assigned sequentially a subject number at the time of screening (Visits 1A or 
1B) by a telerandomization system.  An IVRS drug supply management system will assign 
study medication by assigning appropriate container numbers.
Pediatric subjects with body weight ≥30 kg will initiate dosing of pregabalin at the daily dose 
of 2.5 mg/kg/day administered in 2 equally divided doses (BID) in subjects ≥4 years of age 
or in 3 equally divided doses (TID) in subjects <4 years of age for a minimum of 1 week. 
Thereafter, dosing will be flexible, based on individual seizure response and tolerability. 
Doses may be adjusted up or down at clinic visits in increments of no more than 
2.5 mg/kg/day to daily dose levels of 5.0, 7.5, or 10.0 mg/kg/day.  For pediatric subjects with 
body weight <30 kg, the daily dose will be adjusted by 40% to an initial daily dose of 
3.5 mg/kg/day administered in 2 equally divided doses (BID) in subjects ≥4 years of age or 
in 3 equally divided doses (TID) in subjects <4 years of age for a minimum of 1 week. 
Thereafter, dosing will be flexible, based on individual seizure response and tolerability. 
Doses may be adjusted in increments of no more than 3.5 mg/kg/day to daily dose levels of 
7.0, 10.5, or 14.0 mg/kg/day.  Subjects will maintain a BID or TID dosing regimen 
throughout study participation based on age at Visit 1 (especially for subjects rolling over
CCI
CCI
CCI
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from Study A0081042 who will remain on a TID regimen) to avoid potential dosing 
error/noncompliance related to regimen switch.
Adult subjects who enroll in this study following participation in Study A0081105 will 
initiate dosing of pregabalin at the level of 150 mg/day administered daily in 2 equally 
divided doses (BID) of 75 mg. Thereafter, dosing will be flexible and based on individual 
seizure response and tolerability. Doses may be adjusted in increments of no more than 
150 mg/day to daily dose levels of 300, 450, or 600 mg/day.
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular subject or affect the order in which subjects are enrolled.
5.2. Drug Supplies
5.2.1. Formulation and Packaging
Study medication will be supplied by Pfizer as capsules of pregabalin (50, 75, 100, 150, 200, 
225, and 300 mg), as well as 20 mg/mL solution. The pregabalin liquid oral solution
formulation (20 mg/mL) and the pregabalin oral capsules are bioequivalent. The pregabalin 
capsules are formulated into size #0 gray/gray capsules.  All study medication is to be 
packaged in bottles that are child-resistant.
Pregabalin capsules are composed of pregabalin, lactose monohydrate, cornstarch, and talc 
encapsulated in opaque hard gelatin capsule shells composed of gelatin and titanium dioxide.  
Pregabalin oral solution contains a sweetening agent (sucralose) and a flavor (artificial 
strawberry).
5.2.2. Preparation and Dispensing
The Investigator will receive shipments of clinical drug supplies and must verify and 
acknowledge the receipt of the clinical drug supplies and retain related documentation.
The Sponsor will provide study medication that will be dispensed through an interactive 
voice response system (IVRS). The supplies will be identified by the IVRS using a container 
number.  The IVRS will monitor the study medication inventory and re-supply as necessary. 
The study medication will be dispensed at Visit 1 through Visit 8. The 1-week taper 
medication will be dispensed at Visit 8, or for those subjects who discontinue before 
completing the study, between Visits 3 and 7.  
Additional bottles of placebo will be provided to each site for subjects to be able to test their 
ability to swallow the size #0 capsules.  These bottles will be clearly labeled for this purpose.
5.2.3. Administration
Pregabalin will be administered orally daily in 2 equally divided doses (BID; approximately 
q12 hr) in subjects 4 years of age or in 3 equally divided doses (TID; approximately q8 hr) 
in subjects <4 years of age, as specified in Section 5.1- Allocation to Treatment. Subjects 
weighing <30 kg will receive pregabalin as a liquid formulation.  Pediatric and adult subjects 
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with body weight 30 kg may choose either liquid or capsule formulation based on subject 
preference and ability to swallow the size # 0 capsules.  Study medication formulation for 
administration will be as outlined below, with investigators (and subjects) determining the 
choice of solution or capsule for children and adults >30 kg.
If a subject missed a dose, subject should skip the dose and wait until the next scheduled dose 
for administration.  No additional study medication administration (ie, double-dosing) is 
allowed at any time during the study.
Weight
Formulation
<30 kg
Liquid
Pediatric subjects 30 kg
Liquid or capsule
Adult subjects
Capsules or liquid
5.2.4. Compliance
Subjects will take the study medication according to the instructions provided, and should 
adhere to the dosing schedule as closely as possible, with study medication administered 
approximately every 12 hr (ie, q12 hours) in subjects 4 years of age or in 3 equally divided 
doses (ie, q8 hours) in subjects <4 years of age.  Compliance will be defined as the 
percentage of required doses that were ingested.  Subjects who are consistently not compliant 
with the dosing regimen should be evaluated by the Investigator and discussed with the 
Pfizer clinician for possible discontinuation from the study.
For subjects who begin taking capsules, but can no longer comply with swallowing after 
starting, parents/caregivers should break open the capsules and sprinkle the study drug into 
food for ingestion until the next study visit.  Sprinkling should only occur when the child is 
in danger of missing a dose due to inability to swallow the capsules and there is no liquid 
dose available at that time.  All of the food that the capsule has been sprinkled on must be 
ingested.  This should be noted in the Dosing Diaries and dosing log CRFs.  At the next study 
visit, the site should record the days that the study drug was sprinkled, and then switch the 
subject to the liquid oral solution form of the study drug for the remainder of the study. An 
unplanned visit may be scheduled to switch from capsules to liquid if necessary.  
If the subject regurgitates or spits out the study drug within 15 minutes after either liquid or 
capsule administration, the subject/parent/caregiver should re-administer the study drug.  If 
more than 15 minutes have elapsed since drug was taken, no additional study drug should be 
administered until the next scheduled dose.  This occurrence should be noted in the Dosing 
Diaries and dosing log CRFs.
Administration of the liquid oral solution through a nasogastric (NG) feeding tube will be 
permitted and should be documented accordingly. If a subject has an NG tube that was 
inserted prior to entry into the study, it should be documented in the subjects’ “Medical 
History”.  If a subject has an NG tube inserted during the course of the study, it should be 
documented in the subjects’ “Concomitant Treatments” as a non-drug treatment.  Specifying 
whether the NG tube was inserted or removed during the study is important to document.
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5.3. Drug Storage and Drug Accountability
It is the site’s responsibility to handle and store the clinical study supplies under secure and 
locked conditions.  Note that pregabalin, is a controlled substance (CV) in the US, and 
therefore in the US must be stored according to US/Federal Drug Enforcement Agency 
(DEA) regulations. The US sites will provide a copy of the DEA license, and proper 
state/local license if applicable, to the Sponsor.  For those countries where pregabalin is not a 
controlled substance, the sites are to comply with their local regulations.  
Study medication must be stored at 15-25C. Access to the stored study medication should 
be limited to the Investigator, the Study Coordinator, and the Pharmacist (when applicable).  
The Investigator, or an approved representative, eg, Pharmacist, will ensure that all study 
medications are stored in a secured area, under recommended storage conditions and in 
accordance with applicable regulatory requirements.  If the study medication is determined to 
have been stored or delivered outside the outlined temperature range, the information is to be 
brought to the appropriate study supply personnel for evaluation.  
Storage conditions stated in the investigator brochure may be superseded by the label storage.
Study medication will be dispensed under the supervision of investigator site personnel.  
Each subject will complete a dosing diary and will bring the diary and the medication 
bottle(s) back to the clinic at each visit.  For those subjects who are dispensed capsules, a pill 
count will be done by the site staff at each visit, and the subject/caregiver will be queried 
about any missed or extra doses taken.  For those subjects who are dispensed liquid oral 
solution, medication bottles will be weighed by the site staff when dispensed.  The bottles 
will again be weighed when returned at each visit, in order to determine the approximate 
volume of study medication consumed.  The subject/caregiver will be queried about any 
missed or extra doses taken or any volume discrepancies.
All dispensed study medication bottles will be locally kept available for checks by the study 
monitor.
The Investigator must maintain adequate records documenting the receipt, use, loss, or other 
disposition of the investigational product(s).  All medication bottles dispensed to study 
subjects must be returned to the Investigator. A Pfizer-approved drug accountability form 
must be used.  The form must identify the investigational product, including batch or code 
numbers, and account for its disposition on a subject-by-subject basis, including specific 
dates and quantities.  The forms must be signed by the individual who dispensed the drug, 
and copies must be provided to Pfizer.  
Unused study drug and unused or used study drug materials must be kept in a secure location 
for final accountability and reconciliation.  At the end of the clinical study all drug supplies 
unallocated or unused will be returned to a Pfizer vendor for destruction by completing the 
Destruction of Investigational Product Form.  The Investigator must provide an explanation 
for any destroyed or missing study drug and/or study drug materials.  Pfizer may authorize 
destruction at the study site, and the Investigator must ensure that the materials are destroyed 
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in compliance with applicable environmental regulations, institutional policy, and any special 
instructions provided by Pfizer.  Destruction must be adequately documented.  
5.4. Concomitant Medication(s)
Prior and concomitant medication information will be collected for all subjects for a period 
of 30 days prior to screening (for subjects enrolling directly into Study A0081106) and 
during the study.  Once enrolled, any medication a subject takes other than the study 
medication specified by the protocol is considered a concomitant medication.  This includes 
all antiepileptic medications.  All concomitant medication must be recorded in the subject’s 
medical record and on the appropriate Case Report Form (CRF) page.  Information collected 
must include medication, reason for use, start date and stop date.
5.4.1. Permitted Medications
The Investigator must be informed of all medications the subject receives prior to the 
subject's participation in the study. The following listing of medications/classes of 
medications is meant to provide guidance regarding permitted medications but should not be 
considered a comprehensive list.  A member of the Pfizer study team may be consulted for 
assistance in determining whether or not specific medications not contained on this list 
should be permitted or prohibited.  Initiation of new medications, including AEDs, during 
study participation is allowed if medically indicated. Initiation of certain drugs, however, 
such as CNS active compounds, like Risperidone, should be discussed with the study 
clinician. If there are any questions about the start of a new drug, the study clinician should 
be contacted.
Anti-epileptic drugs (including VNS) are permitted and the number and dosages are at the 
discretion of the investigator.  Changes in the dose, regimen and type of AED are allowed 
during the study participation upon the discretion of the investigator.
Non-prescription medications, including herbal and home remedies, are also considered 
concomitant medications and should be recorded, along with other medications on the 
Concomitant Medication Log of the Case Report Form (CRF).
Examples of medications or classes of medications for which Episodic Use is permitted:

Acetaminophen/paracetamol.

Aspirin (chronic use also permitted).

Bronchodilators (chronic use also permitted).

Inhaled steroids (chronic use also permitted).

Non-steriodal anti-inflammatory drugs (NSAIDs).

Over the counter medications (excluding medications such as Kava Kava or St. 
John’s Wort).
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Examples of medications or classes of medications for which Chronic Use is permitted:

Antihypertensive agents.

Lipid lowering agents.

Medications to treat ADHD [ie, stimulants (eg, methylphenidate; amphetamine); 
selective norepinephrine reuptake inhibitors (eg, atomoxetine); alpha agonists 
(eg, clonidine; guanifacine)].

Antiepileptic drugs.

Aspirin.

Bronchodilators.

Inhaled steroids.

Multivitamins.

NSAIDs.

Oral and depot contraceptives.
5.4.2. Prohibited Medications
Concurrent treatment with other investigational agents or devices is not allowed during the 
study.  Note: a previously implanted Vagus Nerve Stimulator (VNS) is allowed but will be 
considered as a concomitant AED.
The use of felbamate, gabapentin or vigabatrin is prohibited during the study.
Administration of CNS – active compounds, regardless of indication, is prohibited during the 
study, with the following exceptions:

Prescribed medications consistent with inclusion/exclusion criteria. 

Use of PRN benzodiazepines (See Section 5.5).
The washout period of all centrally- acting compounds (CNS-active) that have to be 
discontinued per protocol has to be at least 2 weeks prior to screening Visit 1.
5.5. Benzodiazepine Use as Needed for Occasional Seizure Exacerbation
Benzodiazepines may be used as needed (PRN) during this open-label study.  Use of PRN 
benzodiazepines will be permitted for the occasional seizure exacerbation. PRN 
benzodiazepine use should not exceed a total of 6 dosage administrations in any given 
3 month period. 
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If a benzodiazepine is prescribed for treatment on a regular basis (eg, weekly) then it is
considered one of the 3 allowed AEDs.  In such cases, additional benzodiazepines may also 
be used PRN as described above.  
6. STUDY PROCEDURES
The study schedule of events and the specific procedures performed at each visit are shown 
in the Schedule of Activities. A subject may be seen at any time for reasons of safety.
6.1. Clinic Visit 1A (Day 1A): Screening for Subjects who have participated in Studies 
A0081041, A0081042, or A0081105
The last day of Studies A0081041, A0081042, and A0081105 will be designated Day 1 of 
this study.  The subject may be screened, and if inclusion and exclusion criteria are met, 
enrolled into Study A0081106 after all procedures have been completed for Studies 
A0081041, A0081042, or A0081105.  For subjects who have participated in, but did not 
complete Studies A0081041, A0081042, or A0081105, eligibility for Study A0081106 will 
be reviewed with a member of the Pfizer study team to determine further eligibility.  Subjects 
are required to have completed a minimum of 4 weeks of double-blind treatment in Studies
A0081041 or A0081105 to be considered potentially eligible for Study A0081106.  The 
following activities will be performed at Visit 1:

Obtain written informed consent from both (if available) of the child’s legal 
representatives (parents or guardians) and obtain the child’s assent (if applicable). 
For adult subjects written informed consent will be obtained from the subject, or if 
necessary, a legally acceptable representative (parent or guardians).

Review eligibility per inclusion/exclusion criteria.

Record demographic data (eg, date of birth, sex [at birth], race, etc).

Record medical history including primary diagnosis.

Record seizure history including classify seizure type.

Record ongoing adverse events from Studies A0081041, A0081042, or A0081105 if 
appropriate.

Record all ongoing concomitant medications and non-drug treatments/procedures
from Studies A0081041, A0081042, or A0081105 if appropriate.

Evaluate study medication compliance from Studies A0081041, A0081105 and 
A0081042.

Assign subject number and dispense study medication via telerandomization system.

Dispense subject daily seizure and dosing diary.
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
The following assessments are not required to be completed at this visit as the results 
from Studies A0081041, A0081042, or A0081105 will be used: medical history 
including seizure related history and antiepileptic medication history; all prior 
medications; blood samples for hematology and chemistry; urine sample for 
urinalysis; full physical examination to include height, weight and vital signs and 
assessment of Tanner Stage for pediatric/adolescent subjects less than 16 years of 
age; full neurological examination; urine pregnancy test for female subjects who are 
menarchal, if the results of the urine pregnancy test are positive, the subject will not 
be eligible for study participation; 12-lead electrocardiogram; CogState battery 
(completed as part of the last visit of Study A0081041 only); assessment of suicidal 
ideation and behavior (C-SSRS Since Last Visit version or CBCL) using appropriate 
test for subject’s age.
Note: From Visit 1 onwards, weight of subjects will be recorded in the IVRS at every 
visit during the course of the study in order to adjust the volume and/or dose of study 
medication dispensed according to weight change to ensure appropriate study 
medication administration.
6.2. Clinic Visit 1B (Day 1B): Screening for Subjects Directly Enrolling into Study 
A0081106 who have not Participated in Studies A0081041, A0081042, or A0081105
Prior to study entry the following screening procedures will be performed at Visit 1:

Obtain written informed consent from both parents (if available), or the child’s 
legally acceptable representatives and obtain the child’s assent (if applicable).

Review eligibility per inclusion/exclusion criteria.

Review and record adverse events.

Record demographic data (eg, date of birth, sex [at birth], race, etc).

Record medical history including primary diagnosis. 

Record seizure history including classify seizure type.

Verify subjects have had an average of at least 3 seizures per month in the 3 months 
prior to screening. There must not be any seizure free months in the 3 months prior to 
screening.

Record complete medical history including seizure related history and antiepileptic 
medication history.

Perform complete full physical exam which includes vital signs, including blood 
pressure (BP) (sitting), pulse and assessment of Tanner Stage for pediatric/adolescent 
subjects <16 years of age.
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
Record height and weight.
Note: From Visit 1 onwards, weight of subjects will be recorded in the IVRS at every 
visit during the course of the study in order to adjust the volume and/or dose of study 
medication dispensed according to weight change to ensure appropriate study 
medication administration.

Perform full neurological examination. 

Perform electroencephalogram (EEG) (unless the procedure has been performed 
within 24 months prior to the Screening Visit).

Perform contrast-enhanced computed tomography (CT) or magnetic resonance 
imaging (MRI) scan of the brain if it has not been performed within 60 months prior 
to the Screening Visit or if it is clinically warranted.
Note: in the event that a CT or MRI scan is needed, it should be performed as soon as 
possible after Visit 1 if it cannot be performed on the day of this visit and must be 
completed and reviewed prior to Visit 2.

Record all concomitant medications and non-drug treatments/procedures currently 
and within 30 days of Visit 1.

Perform, review and transmit 12-lead ECG to central reader.

Administer CogState battery (POS subjects 4-16 years of age).

Perform urine pregnancy test for female subjects who are menarchal.  If the results of 
the urine pregnancy test are positive, the subject will not be eligible for study 
participation.

Collect blood and urine specimens for clinical laboratory assessments.  If it is not 
feasible to obtain a urine sample then no urine sample will be required.
Note: In the event that the subject has an exclusionary abnormal screening laboratory
value (see Exclusion Criteria 5) the laboratory test should be repeated.  If the repeated 
test is still abnormal, the subject should be withdrawn from the study at Visit 2. In 
the event that the subject has an abnormal laboratory value that the investigator 
determines is significant and exclusionary, the subject should be contacted to stop 
taking study medication and return to the clinic for an early termination visit.

Administer the MINI-KID and C-SSRS Lifetime or Child Behavioral Checklist 
(CBCL) as appropriate for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization.
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
Assign subject number and dispense study medication via tele-randomization system.

For direct-enrolling subjects that will receive liquid solution, train parents on dosing 
administration and demonstrate use of oral syringe/bottles. Have subject and/or 
child's parents/legally acceptable representative practice dosing in office to verify 
comprehension of dosing instructions.

Administer first dose of study medication in office.
Note: all screening procedures must be completed before subject is administered the 
first dose of study medication. All eligibility criteria should be confirmed prior to, or 
on Visit 2. If a subject is not deemed eligible, subject should be notified by phone to 
discontinue study medication, and should come back for an Early Termination visit as 
soon as possible.

Dispense subject daily seizure and dosing diary and train subject and/or child's 
parents/legally acceptable representative on its use and completion.
6.3. Clinic Visit 2 (Week 1/Day 8 1 day)
At this visit, the investigator will review dosing with the subject and/or child's parents/legally 
acceptable representative and may adjust the dose based on seizure response and tolerability.
The following activities will be performed at Visit 2:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate version or test for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization (please refer to Section 7 - ASSESSMENTS).

Collect and review daily seizure and dosing diary and record number and type of 
seizure.

Adjust the dose if needed based on seizure response and tolerability.

Evaluate and record study medication compliance.

Dispense study medication via tele-randomization system.

For direct-enrolling subjects assigned liquid solution, verify accurate dose 
administration via syringe/bottles.  Have subject and/or child's parents/legally 
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acceptable representative demonstrate dosing in office to verify continued 
comprehension of dosing instructions.

Dispense seizure and dosing diary and review instructions for completion.
6.4. Clinic Visit 3 (Month 1/Day 30 4 Days)
The following activities will be performed at Visit 3:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Collect and review seizure and dosing diary and record number and type of seizure.

Adjust the dose if needed based on seizure response and tolerability.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate versions or test for subject’s age.  If CBCL is administered, scores must 
be obtained as soon as possible.  If positive scores are obtained on the CBCL or 
CSSRS, a mental health risk assessment must be performed by a qualified mental 
health professional prior to randomization (please refer to Section 7 -
ASSESSMENTS).

Evaluate and record study medication compliance.

Dispense study medication via tele-randomization system.

Dispense subject daily seizure and dosing diary.
6.5. Clinic Visit 4 (Month 2/Day 60 4 Days)
The following activities will be performed at Visit 4:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Collect and review seizure and dosing diary and record number and type of seizure.

Adjust the dose if needed based on seizure response and tolerability.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate version or test for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization (please refer to Section 7 - ASSESSMENTS).
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
Collect and record vital signs.

Evaluate and record study medication compliance.

Dispense study medication via tele-randomization system.

Dispense subject daily seizure and dosing diary.
6.6. Telephone Contact (Month 3/Day 90 4 Days)
The Investigator (or designee) will contact the parent/subject by telephone to ensure 
medication compliance and provide guidance for accurate dosing as required. 

Review subject's compliance with dosing regimen.

Review compliance with completion of dosing and seizure diary.

Review concomitant medications and non-drug treatments/procedures.

Assess adverse events.
6.7. Clinic Visit 5 (Month 4/Day 120 4 Days)
The following activities will be performed at Visit 5:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Collect and review seizure and dosing diary and record number and type of seizure.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate version or test for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization (please refer to Section 7 - ASSESSMENTS).

Evaluate and record study medication compliance.

Dispense study medication via tele-randomization system.

Dispense subject daily seizure and dosing diary.
6.8. Telephone Contact (Month 5/Day 150 4 Days)
The Investigator (or designee) will contact the parent/subject by telephone to ensure 
medication compliance and provide guidance for accurate dosing as required. 
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
Review subject's compliance with dosing regimen.

Review compliance with completion of dosing and seizure diary.

Review concomitant medications and non-drug treatments/procedures.

Assess adverse events.
6.9. Clinic Visit 6 (Month 6/Day 180 4 Days)
The following activities will be performed at Visit 6:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Evaluate and record study medication compliance.

Collect and review seizure and dosing diary and record number and type of seizure.

Adjust the dose if needed based on seizure response and tolerability.

Complete brief physical and neurological exams to include height, weight, vital signs.

Collect blood samples for hematology, biochemistry.

Collect urine samples for urinalysis and a urine pregnancy test (for female subjects 
who are menarchal).

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate version or test for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization (please refer to Section 7 - ASSESSMENTS).

Dispense study medication via tele-randomization system.

Dispense subject daily seizure and dosing diary.
6.10. Telephone Contact (Month 7/Day 210 4 Days)
The Investigator (or designee) will contact the parent/subject by telephone to ensure 
medication compliance and provide guidance for accurate dosing as required. 

Review subject's compliance with dosing regimen.

Review completion of dosing and seizure diary.
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
Review concomitant medications and non-drug treatments/procedures.

Assess adverse events.
6.11. Telephone Contact (Month 8/Day 240 4 Days)
The Investigator (or designee) will contact the parent/subject by telephone to ensure 
medication compliance and provide guidance for accurate dosing as required. 

Review subject's compliance with dosing regimen.

Review completion of dosing and seizure diary.

Review concomitant medications and non-drug treatments/procedures.

Assess adverse events.
6.12. Clinic Visit 7 (Month 9/Day 270 4 Days)
The following activities will be performed at Visit 7:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Collect and review seizure and dosing diary and record number and type of seizure.

Adjust the dose if needed based on seizure response and tolerability.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate version or test for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization (please refer to Section 7 - ASSESSMENTS).

Evaluate and record study medication compliance.

Collect urine samples for a urine pregnancy test (for female subjects who are 
menarchal).

Collect and record vital signs.

Dispense study medication via tele-randomization system.

Dispense subject daily seizure and dosing diary.
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6.13. Telephone Contact (Month 10/Day 300 4 Days)
The Investigator (or designee) will contact the parent/subject by telephone to ensure 
medication compliance and provide guidance for accurate dosing as required: 

Review subject's compliance with dosing regimen.

Review completion of dosing and seizure diary.

Review concomitant medications and non-drug treatments/procedures.

Assess adverse events.
6.14. Telephone Contact (Month 11/Day 330 4 Days)
The Investigator (or designee) will contact the parent/subject by telephone to ensure 
medication compliance and provide guidance for accurate dosing as required: 

Review subject's compliance with dosing regimen.

Review completion of dosing and seizure diary.

Review concomitant medications and non-drug treatments/procedures.

Assess adverse events.
6.15. Clinic Visit 8 (Month 12/Early Termination Day 365 7 Days)
The 12 month treatment phase is completed.  Subjects who will not continue treatment with 
pregabalin, whether they complete, or require early termination prior to the completion of 
12 months of treatment, should begin the taper as described in Section 3 (Table 1) and follow 
the procedures for Visits 8 and 9. Subjects who continue on pregabalin following completion 
of the study will not require a taper.
The following activities will be performed at Visit 8:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Collect and review seizure and dosing diary and record number and type of seizure.

Perform 12-lead electrocardiogram (ECG).

Complete brief physical examination to include height, weight, vital signs and
assessment of Tanner stage (pediatric subjects only, but not applicable to subjects 
who participated to study A0081042).
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
Complete full neurological examination.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using
appropriate version or test for subject’s age.  If CBCL is administered, scores must be 
obtained as soon as possible.  If positive scores are obtained on the CBCL or CSSRS, 
a mental health risk assessment must be performed by a qualified mental health 
professional prior to randomization (please refer to Section 7 - ASSESSMENTS).

Administer CogState battery (POS pediatric subjects 4-16 years of age).

Collect blood samples for hematology, biochemistry.

Collect urine sample for urinalysis and a urine pregnancy test (for female subjects 
who are menarchal).

Evaluate and record study medication compliance.

Dispense taper medication if required via tele-randomization system.

Dispense subject daily seizure and dosing diary if subject will begin taper.
6.16. Visit 9 (Follow-up/End of Taper Visit-7 days Post-Completion/
Discontinuation3 Days) 
This visit is not required for subjects that do not enter the taper phase.
The following activities will be performed at Visit 9:

Review and record adverse events.

Review and record all concomitant medications and non-drug treatments/procedures.

Collect and review seizure and dosing diary and record number and type of seizure.

Collect urine sample for a urine pregnancy test (for female subjects who are 
menarchal).

Evaluate and record study medication compliance.

Complete assessment of suicidal ideation and behavior (C-SSRS or CBCL) using 
appropriate versions or test for subject’s age.  If CBCL is administered, scores must 
be obtained as soon as possible.  If positive scores are obtained on the CBCL or 
CSSRS, a mental health risk assessment must be performed by a qualified mental 
health professional prior to randomization (please refer to Section 7 -
ASSESSMENTS).
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6.17. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
or administrative reasons.  Events to consider could include but are not limited to:

Adverse events.

Intercurrent illness.

Loss to follow-up.
Note: All reasonable efforts must be made to locate subjects to determine and report 
their ongoing status.  This includes follow-up with persons authorized by the subject 
as noted above.  Lost to follow-up is defined by the inability to reach the subject after 
a minimum of three documented phone calls, faxes, or emails as well as lack of 
response by subject to one registered mail letter.  All attempts should be documented 
in the subject’s medical records.  If it is determined that the subject has died, the site 
will use permissible local methods to obtain the date and cause of death.  If 
investigator’s use of third-party representative to assist in the follow-up portion of the 
study has been included in the subject’s informed consent, then the investigator may 
use a Sponsor retained third-party representative to assist site staff with obtaining 
subject’s contact information or other public vital status data necessary to complete 
the follow-up portion of the study.  The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to 
obtain updated contact information.  If after all attempts, the subject remains lost to 
follow-up, then the last known alive date as determined by the investigator should be 
reported and documented in the subject’s medical records.

Lack of efficacy.

Pregnancy.

Non-compliance with study drug, protocol requirements, or study-related procedures.

Serious eligibility or on-study violations of the protocol (e.g., the subject does not 
have the disease under study).

Study termination by Sponsor or regulatory authorities.

Subject’s decision to withdraw/withdrawal of consent.
Note: Subjects who request to discontinue study treatment will remain in the study 
and must continue to be followed for protocol specified follow-up procedures.  The 
only exception to this is when a subject specifically withdraws consent for any further 
contact with him/her or persons previously authorized by subject to provide this 
information. Subjects should notify the investigator of the decision to withdraw 
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consent from future follow-up in writing, whenever possible.  The withdrawal of 
consent should be explained in detail in the medical records by the investigator, as to 
whether the withdrawal is from further treatment with study drug only or also from 
study procedures and/or post treatment study follow-up, and entered on the 
appropriate CRF page.  In the event that vital status (whether the subject is alive or 
dead) is being measured, publicly available information should be used to determine 
vital status only as appropriately directed in accordance with local law.

Investigator discretion in case of occurrence of any medical condition, requirement 
for prohibited concomitant medication or treatment, or circumstances that would 
expose the subject to substantial risk and/or would not allow the subject to adhere to 
protocol requirements.
For subjects who have participated in Study A0081105, subjects must be withdrawn at any 
time during Study A0081106 if any 1 of the following predetermined subject exit criteria is 
met:

An episode of status epilepticus.

A 28-day PGTC seizure rate during open-label treatment that is greater than 2-times 
the maximum 28-day study seizure rate during the Study A0081105 baseline phase (a 
28-day period is defined as a minimum of 4 consecutive study weeks).
Subjects with any of the following should be discussed with the Pfizer Study Clinician or 
representative for potential withdrawal:

An episode of a newly emergent generalized seizure type during open-label treatment 
compared with the subject’s history.

An increase in the rate or intensity of PGTC or other generalized seizure activity that, 
according to the investigator, is clinically significant.
Protocol-specified withdrawal procedures are the same as those to be performed at Visit 8 
and 9. 
Note: under certain circumstances, when subjects leave the study early (early termination), 
dosing with the taper medication may be inadvisable.  The decision not to taper the subject is 
upon agreement from the Sponsor's Study Clinician or Designee.  If the taper will not be 
utilized then all assessments required at Visit 8 should be conducted where possible.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome, if 
possible.  The investigator should inquire about the reason for withdrawal, request the subject 
to return all unused investigational product(s), request the subject to return for a final visit, if 
applicable, and follow-up with the subject regarding any unresolved adverse events.  If the 
subject withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
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collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol required tests and procedures are 
completed as described. However it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test (eg, a subject may not be able or willing to comply due to neurological 
compromise, motor deficits or cognitive impairment). In these cases if an assessment cannot 
be performed the investigator will take all steps necessary to ensure the safety and well being 
of the subject.  This may include gathering assessment data from a parent or legally 
acceptable representative who may answer assessment questions on behalf of the subject 
based upon their knowledge and observations of the subject. When a protocol required 
assessment cannot be performed the investigator will document the reason for this and any 
corrective and preventive actions which he/she has taken to ensure that normal processes are 
adhered to as soon as possible, if feasible. 
7.1. Physical and Neurological Examination
A physical examination will be performed and must be completed by a Medical Doctor 
(MD), Doctor of Osteopathy (DO), Nurse Practitioner (NP) or Physician Assistant (PA) or 
appropriate equivalent based upon normative country-specific practices.
Full physical and neurological exams will be performed at Visits 1A and 1B.  An abbreviated 
physical exam and full neurological exam will be performed at Visit 6 and 8 (i.e., at the 
completion of the study or early termination). 
Physical examinations will evaluate the following body systems/organs: general appearance; 
dermatological; head and eyes; ears, nose, mouth, and throat; pulmonary; cardiovascular; 
abdominal; genitourinary (optional); lymphatic; musculoskeletal/extremities.  For pediatric 
subjects Tanner Stage will also be assessed at screening (Visit 1A or 1B) and at 
completion/early termination (Visit 8).
Neurological exam will assess: level of consciousness, mental status, cranial nerve 
assessment, muscle strength and tone, reflexes, pin prick and vibratory sensation (the latter 
using a 128-Hz tuning fork), coordination and gait.
Any clinically significant changes from the entry physical or neurological examinations will 
be recorded as adverse events.  A physical and neurological exam will be performed at the 
screening and at the completion of study visit or early termination.
7.2. Vital Signs, Height and Weight
Sitting blood pressure and pulse are to be recorded at the Screening Visit (Visit 1A or 1B), 
Visits 4, 6, 7 and at the completion of the study.  Height (using stadiometer when 
appropriate) will also be recorded at the Screening Visit (Visit 1A or 1B), Visit 6 and at the 
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completion of the study.  Weight will be recorded at Visits 1A or 1B, 6, and 8.  Weight 
recorded at Visit 1A or 1B and Visit 6 will be used to calculate the dose for subsequent visits.  
7.3. Clinical Laboratory Assessments
Samples for clinical laboratory measurements will be analyzed by a central laboratory.
Estimated Creatinine Clearance (ml/min) 
Estimated Creatinine Clearance will be calculated at Screening (Visit 1A or 1B) only.  For 
subjects who previously participated in A0081041, A0081042 or A0081105, it is assumed 
the subjects have already met entry criteria, therefore, the Creatinine Clearance exclusion is 
based upon the Screening visit of A0081041, A0081042 or A0081105.  For those subjects 
directly enrolling into A0081106, this assessment is to be performed at Screening Visit 1B 
only.  The estimation will be calculated by the central laboratory using the following 
equation, the subject’s age in years and the serum creatinine value (mg/dL).
Converting Serum Creatinine Concentration from moles/L to mg/dL
Serum Creatinine (mg/dL) =
Serum Creatinine (M/L)
88.4
For subjects 12 years of age
Male CLCR =
(140 - age) Body Weight (kg)
x1.73m2/BSA
72 Serum Creatinine (mg/dL)
Female CLCR =
(140 - age) Body Weight (kg)
0.85 x1.73m2/BSA
72 Serum Creatinine (mg/dL)
BSA (Body Surface Area) = 0.007184 x Height(cm)0.725 x Weight(kg)0.425
For Subjects 1 year of age and <12 years of age
ClCR = 0.55 × length (cm)/serum creatinine (mg/dL) 
For Subjects 1 month of age and <1 year of age
ClCR = 0.45×length (cm)/serum creatinine (mg/dL), for infants 1 to <12 months old 
7.3.1. Pregnancy Test
A urine pregnancy test for female subjects who are menarchal will be collected at Screening 
(Visit 1A and B).  If the results of the urine pregnancy test are positive, the subject will not 
be eligible for study participation, or will need to withdraw from the study.  A urine 
pregnancy test will also be performed at Visits 6, 7, 8, and 9.  In the case of a positive urine 
pregnancy test, the subject can have a second confirmatory urine pregnancy test conducted 
locally prior to exclusion from the study.  Pregnancy tests may also be performed more 
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frequently as per Institutional Review Board (IRB’s)/Independent Ethics Committee (IEC’s) 
or as required based upon local regulations.
7.3.2. Hematology 
Blood samples will be collected at Screening Visit 1A and 1B (for direct enrolling subjects 
only), 6 and 8 to assess hematology parameters, including: red blood cell count (RBC), 
hemoglobin (HGB), hematocrit (HCT), platelets, and white blood cell count (WBC) (with 
differential), neutrophils, lymphocytes, monocytes, basophils, and eosinophils.
Blood volumes to be obtained, per visit, are as follows:
Screening:
10.5 mL
V6:
4.5 mL
V8/ET:
10.5 mL 
Unscheduled visit:
12.3 mL maximum (all testing optional)
7.3.3. Clinical Chemistry
Blood samples will be collected at Screening Visit 1A and 1B (for direct enrolling subjects 
only), 6 and 8 to assess clinical chemistries, including: total bilirubin, direct and indirect 
bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT/SGPT), aspartate 
aminotransferase (AST/SGOT), gamma glutamyl transferase (GGT), creatine phosphokinase 
(CPK) blood urea nitrogen (BUN), creatinine, glucose, total protein, albumin, total 
cholesterol, triglycerides, sodium, potassium, chloride and calcium.  In addition, Endocrine 
panel (free T4 and TSH, IGF-1, and IGFBP-3) and Hepatitis serology will be assessed at
Visit 1B and 8 only.  
7.3.4. Urinalysis
Urine samples will be collected at Visit 1A and 1B (for direct enrolling subjects only), 6 and 
8 to assess the following: pH, specific gravity, colorimetric urine protein, glucose and 
ketones.  Microscopic analysis will be performed only if the results of the urinalysis are 
abnormal and will include: red blood cells (RBCs), white blood cells (WBCs), casts, crystals, 
and bacteria. If it is not possible to collect a urine sample, despite appropriate efforts, the 
urine sample can be omitted for that visit.  The reason for the lack of a sample must be 
recorded and documented in source documentation. 
7.4. Electrocardiogram (ECG)
12-lead electrocardiographic assessments (ECG) will be performed at Visit 1B (for direct 
enrolling subjects only) and Visit 8 (Month 12/Early Termination).  The following 
parameters will be assessed: PR interval, RR interval, QRS complex/duration, QT interval, 
QTc, and heart rate.
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7.5. Seizure Counts
Subjects, parents or guardians will be responsible for completing a daily seizure diary 
throughout the subjects’ study participation.  The diary will enumerate the number of 
seizures experienced each day, and the seizure type for each seizure event.
7.6. Assessment of Suicidal Ideation and Behavior (SIB)
In addition to the information provided below, please refer to the study web-based workspace 
for additional details regarding the administration of the SIB assessments; training materials 
and instructions are located at the A0081106 workspace 
. All site personnel who require or request access to 
the workspace are granted access upon site activation.
7.6.1. Child Behavior Checklist (CBCL); Subjects 4 to <6 Years of Age
There are currently no validated scales to assess suicidal ideation and behavior in children 
below age 6, and suicidal ideation and behavior is an extremely rare occurrence in this age 
group. Children in this age group and young school-aged children are more likely to 
demonstrate aberrant behaviors that place them at-risk for self-injurious behaviors. 
Therefore, the Child Behavior Checklist (CBCL) will be implemented to assess behaviors in 
young children that may place them at-risk for self-injury.  The CBCL is a 100-item 
questionnaire designed to assess behavioral problems and social competency in children and 
has been used in studies of children with epilepsy.14  A parent or legally acceptable 
representative will complete the scale using pen and paper to rate the subject’s problem 
behaviors and competencies.  All items are rated on a 3-point scale (0 = Not true for that 
child; 1 = somewhat or sometimes true; and 2 = Very or often true) based on the subject’s 
behavior in the past 2 months at Screening, and then since last visit at all other study visits 
(Visit 2-10).  For this study, scores on the Withdrawn, Internalizing Problems subscales and 
the Total Problem scales will be obtained. Higher scores on the CBCL subscales indicate 
higher levels of problematic behaviors or dysfunction. The CBCL scoring algorithm allows 
for a subject’s scores to be standardized using scores from a normal population. These 
standardized scores are referred to as T-scores. CBCL T-scores will be obtained utilizing a 
standardized computerized scoring system provided to the Sponsor by 
.  For this study, 
a cut-off of ≥68 on the T-scores for the Withdrawn, Internalizing Problems subscales and the 
Total Problem scales will be used to determine whether a child is at-risk for SIB and requires 
a mental health risk assessment. 
The CBCL will be used in this study for children who are 4-<6 years of age beginning at 
Visit 1.  The CBCL will be completed at Visit 1 and for each subsequent visit through Visit 9 
or Early Termination.  The CBCL will be performed to assess for behavioral and emotional 
issues, including those that may be associated with suicidal ideation and behavior.  See the 
Schedule of Activities for the visits at which the CBCL will be completed by a parent or 
legally acceptable representative.
Please note that for Greek and Cebuano speaking subjects/parents, there is no available 
translation of the CBCL.  Therefore, subjects in the age range of 4-<6 years whose parents 
CCI
CCI
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are fluent only in these languages will be administered the CSSRS, which can be answered 
by the parents or legally acceptable representative.  
The CBCL, once administered, must be scanned and emailed or faxed to the designated 
Pfizer clinician for scoring as soon as possible, utilizing the CBCL study cover sheet 
provided to each site.  A subject should not be enrolled into the study until the site has 
received the CBCL scores and a signed approved cover sheet for study entry from the Pfizer 
clinician. Furthermore, the subjects’ CBCL scores must be obtained as soon as possible at 
each study visit for study continuation.  Sites should work with their study monitor to ensure 
that this process is followed correctly.
7.6.2. Mini International Neuropsychiatric Interview (MINI-KID) – Version 6.0 
(Subjects 6-<17 Years of Age)
The MINI-KID is a structured diagnostic interview evaluating 23 psychiatric conditions.15  It 
is divided into modules corresponding to different diagnostic categories.  The interview 
questions are designed to elicit information relevant to specific diagnostic criteria.  The 
questions should be read verbatim to the subject or the subject’s parent or legally acceptable 
representative.  If during an interview a particular word or concept is not understood, the 
rater may explain what it means or give examples that capture its essence.  If a responder is 
unsure if the subject has a particular symptom, the interviewer may ask for an explanation or 
example to determine if it matches the criterion being investigated.  If a subject is unwilling 
or unable to respond, the parent or legally acceptable representative may answer any or all 
questions based upon their knowledge of the subject and observations of the subject’s 
behavior. Subjects may be interviewed alone or with the parents or legally acceptable 
representative present based upon discretion of the interviewer. The MINI-KID is derived 
from the validated MINI and will be administered by the designated rater at Visit 1/Screening
only. Raters/interviewers must successfully complete required training and must have a valid 
rater training completion certificate in order to perform the assessment.
The MINI-KID will be used in this study to assess the presence or absence of psychiatric 
symptoms in subjects 6-<17 years of age at Screening (Visit 1B) for subjects who have not 
participated in Studies A0081041, A0081042, or A0081105 or for subjects ages 6-<17 who 
have not had the MINI-KID administered during prior participation in the studies above.  
However, subjects who have severe psychiatric illness (ie, current major depression, bipolar 
disorder, schizophrenia or other psychoses) based upon history or current diagnosis should be 
excluded from the study.  Since the C-SSRS is administered, the Suicidality Module of the 
MINI-KID does not have to be administered, unless there is indication of significant 
depression or other severe psychopathology, during the MINI-KID assessment.
7.6.3. Columbia-Suicide Severity Rating Scale (C-SSRS)- Subjects 6-65 Years of Age
The C-SSRS is a prospective semi-structured interview comprised of the following areas of 
assessment: Ideation, Intensity of Ideation, Behavior and Lethality. It has been used 
extensively in global clinical studies (academic and industry sponsored) and in a range of 
therapeutic areas, disorders and indications, including psychiatry, neurology, obesity, urology 
and endocrinology and is FDA-approved.  It has been translated into multiple languages.  
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The C-SSRS will be used to determine eligibility to enroll at Screening and at every 
follow-up visit to prospectively monitor suicidal ideation and behavior during the study. If a 
subject is unwilling or unable to respond, the parent or legally acceptable representative may 
answer any or all questions based upon their knowledge of the subject and observations of 
the subject’s behavior. Subjects may be interviewed alone or with the parents or legally 
acceptable representative present based upon discretion of the interviewer.
The C-SSRS will be utilized for all subjects who are 6-65 years of age at Visit 1.  The 
"Lifetime” version will be completed at Screening for those subjects who have not had it 
administered during participation to study A0081041 or at Visit 1B for direct enrolling 
subjects.  The “Since Last Visit” version of the C-SSRS will be completed at Visits 1A, 2, 3,
4, 5, 6, 7, 8, and 9 or Early Termination.  The “Since Last Visit” version will also be 
completed at any unscheduled clinic visits (ie, clinic visits not included in the Schedule of 
Activities).  C-SSRS raters must demonstrate successful completion of required training and 
must have a valid rater training completion certificate in order to perform the assessment.
7.6.4. Assessment of Suicidal Ideation and Behavior at Screening
Any subjects considered at risk of suicide based on the C-SSRS Lifetime (subjects 6-65 years 
of age), or demonstrating at-risk behaviors on the CBCL (subjects 4-<6 years of age) or 
MINI-KID (6-<17 years of age), or are likely to self harm based on clinical judgment of the 
investigator, should be excluded from the study or a risk assessment should be done by a 
qualified mental health professional (MHP – eg, licensed clinical psychologist or 
psychiatrist; psychiatric nurse practitioner; licensed clinical psychiatric social worker) to 
determine if the subject is appropriate for study inclusion.  A risk assessment should be 
performed based on responses to suicidal ideation and behavior assessments and if the 
subject has had suicidal ideation in the last 6 months prior to screening, suicidal behaviors or 
attempts in the past year, or current major psychiatric disorders that are not explicitly 
permitted in the inclusion/exclusion criteria.  Any positive response on the C-SSRS or a 
previous history of suicide behaviors should trigger a risk assessment.  A risk assessment 
should be performed in any child <6 years of age who the Investigator has knowledge of 
him/her exhibiting any potentially self-injurious or high-risk behaviors (eg, hurting himself 
or herself, running into traffic, or using potential weapons such as knives or bats for self or 
other injury).  A written risk assessment provided by a qualified mental health professional 
with approval for study participation must be documented prior to subject inclusion for 
at-risk subjects.
7.6.5. Assessment of Suicidal Ideation and Behavior During the Clinical Study
The correct age appropriate scale to assess suicidal ideation and behavior risk should be used 
based on the guidance in previous sections of this protocol.  At the interim baseline, 
randomization and post-baseline visits, if there are any positive responses on the C-SSRS or 
scores 68 on the Withdrawn, Internalizing Problems or Total Problems standardized scores 
from the CBCL (4-<6 years of age), a risk assessment should be done by a qualified MHP to 
determine whether it is safe for the subject to continue to participate in the study.  Subjects 
who meet these criteria (either CSSRS or CBCL) on more than one occasion during a study
must have their potential suicidal ideation and behavior managed appropriately by the 
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investigator together with a qualified MHP (or the investigator alone if the investigator is a 
qualified MHP), or be discontinued from the study.  The investigator should consult with the 
Pfizer medical monitor regarding this issue. 
For subjects <6 years of age , any lifetime history of exhibiting any potentially self-injurious 
or high-risk behaviors such as hurting himself or herself, should result in a risk assessment by 
a MHP to determine if it is safe for the subject to enroll in the study.  At post-baseline visits, 
if the subject has exhibited any potentially self-injurious or high-risk behaviors since the last
visit such as hurting himself or herself, a risk assessment by a qualified MHP should be 
obtained to determine if it is safe for the subject to continue in the study.  A written risk 
assessment from a qualified MHP with approval for study participation must be documented 
for study continuation for at-risk subjects.
7.7. Cognitive Testing
Measures of psychomotor and attentional function before and after treatment with pregabalin 
will be used to determine the extent to which the compound is associated with any adverse 
cognitive outcome.  Two tests will be used to measure psychomotor function and attention; 
these are the CogState Detection (psychomotor function) and CogState Pediatric 
Identification (Go-No Go: attention) tasks. Both of these tasks have demonstrated sensitivity 
to the effects of antiepileptic drugs, benzodiazepines and alcohol4, 5, 6 and can be used 
unchanged in children from ages 5 to adults,7, 8 they are rapid to administer, they can be 
given repeatedly without engendering practice effects7 and performance on these tests is not 
influenced by the cultural, language or educational background of patients.9, 10 Importantly, 
many children, adolescents and young adults with epilepsy do show impairments in 
attentional and psychomotor function prior to any treatment and these problems are 
associated with educational and behavioral difficulties. Therefore, tracking these functions is 
important.
7.7.1. The CogState Battery 
The CogState brief battery to be used in this study consists of 2 tasks.  Each task is 
summarized below.7, 11  The test battery is presented on a laptop computer with external 
response buttons.  At the beginning of each task, written instructions are presented on the 
screen to indicate the task rules.  Each subject is then given an interactive demonstration and, 
once they have successfully completed a sufficient number of practice trials to demonstrate 
their awareness of the rules, the task begins. The CogState tasks are in the form of card 
games.  For each task, subjects respond “yes” at the presentation of each stimulus using a 
response button.  “Yes” responses are made with the dominant hand.  At the beginning of 
each task subjects are instructed to “respond as fast and as accurately as possible.”  The tasks 
employed in this study, in their order of presentation, are described below:

Detection task:  The CogState Detection task is a measure of simple reaction time and 
has been shown to provide a valid assessment of psychomotor function in healthy 
children and adults.  For this test, the subject must press a “YES” response key as 
soon as they detect an event (ie, a card turning face up presented in the center of the 
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computer screen). The software measures the speed and accuracy of responses to 
each event. 

Pediatric Identification task (Go-No Go task: GONG):  The CogState Pediatric 
Identification task is a measure of choice reaction time and has been shown to provide 
a valid assessment of visual attention.  In this task an event (a card turning face up) 
occurs in the center of the computer screen and the subject must decide whether this 
event meets a predefined and unchanging criterion (is the color of the card black?) 
and answer “YES” when the criterion is met.  The software measures the speed and 
accuracy of each response.  

Total administration time is approximately 10 min.
The time required for performance of these tests is given in Table 4: 
Table 4.
Trials and Timing of each task in CogState- Cognitive Battery
Task
N Trials/
screens
Maximum Time 
allowed
Average time req’d in 
pediatric clinical trials
Subject demographic screen
1
Unlimited
1 min
Detection task instructions
1
Unlimited
0.5 min
Detection task practice
3
1 min
0.5 min
Detection task
30
5 min
3 min
Identification task instructions
1
Unlimited
0.5 min
Identification task practice
6
1 min
0.5 min
Pediatric Identification Task (GONG)
50
7.5 min
4 min
The CogState battery will be performed twice at Visit 1A and 1B and once at Visit 8 
(Month 12/Early Termination) for POS pediatric subjects 4-16 years of age.  
The CogState battery is easy enough to perform for the majority of subjects participating in 
this study.  For those subjects who are uncooperative or incapable of performing the task, for 
example due to motor or cognitive impairments, the task does not need to be administered.  
The reason for task omission should be appropriately documented.
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered adverse events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all adverse events, the investigator must pursue and obtain information adequate both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as a serious adverse event requiring immediate notification to Pfizer or its 
designated representative.  For all adverse events, sufficient information should be obtained 
by the investigator to determine the causality of the adverse event.  The investigator is 
required to assess causality.  Follow-up by the investigator may be required until the event or 
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its sequelae resolve or stabilize at a level acceptable to the investigator, and Pfizer concurs 
with that assessment.
As part of ongoing safety reviews conducted by the Sponsor, any non-serious adverse event 
that is determined by the Sponsor to be serious will be reported by the Sponsor as an SAE.  
To assist in the determination of case seriousness further information may be requested from 
the investigator to provide clarity and understanding of the event in the context of the clinical 
trial.
8.2. Reporting Period
For serious adverse events, the active reporting period to Pfizer or its designated 
representative begins from the time that the subject provides informed consent, which is 
obtained prior to the subject’s participation in the study, ie, prior to undergoing any 
study-related procedure and/or receiving investigational product, through and including 
28 calendar days after the last administration of the investigational product.  Serious adverse 
events occurring for a subject after the active reporting period has ended should be reported 
to the Sponsor if the investigator becomes aware of them; at a minimum, all serious events 
that the investigator believes have at least a reasonable possibility of being related to study 
drug are to be reported to the Sponsor.
AEs (serious and non-serious) should be recorded on the CRF from the time the subject has 
taken at least one dose of study treatment through last subject visit.  
8.3. Definition of an Adverse Event
An adverse event is any untoward medical occurrence in a clinical investigation subject 
administered a product or medical device; the event need not necessarily have a causal 
relationship with the treatment or usage.  Examples of adverse events include but are not 
limited to:  

Abnormal test findings;

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency. 
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;
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
Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy;

Exposure via breast feeding;

Medication error;

Occupational exposure.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong drug, by the wrong subject, at the wrong time, or at the wrong dosage strength.  Such 
medication errors occurring to a study participant are to be captured on the medication error 
case report form (CRF) which is a specific version of the adverse event (AE) page, and on 
the SAE form when appropriate.  In the event of medication dosing error, the sponsor should 
be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error should be captured on the medication error version of the 
adverse event (AE) page and, if applicable, any associated AE(s) are captured on an AE CRF 
page. 
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows: 

Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or
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
Test result leads to a change in study dosing (outside of protocol-stipulated dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy, and/or

Test result is considered to be an adverse event by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event.
8.6. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires in subject hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect;

Lack of efficacy should be reported as an adverse event when it is associated with a 
serious adverse event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject, or may require intervention to prevent one of the other adverse event outcomes, 
the important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
8.6.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections, and will be handled as SAEs in the safety 
database (see Section on Serious Adverse Event Reporting Requirements).
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate transaminase (AST) and/or alanine transaminase (ALT) 
concurrent with abnormal elevations in total bilirubin that meet the criteria outlined below in 
the absence of other causes of liver injury are considered potential cases of drug-induced 
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liver injury (potential Hy’s Law cases) and should always be considered important medical 
events.  
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions. Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT 3 times the upper limit of normal 
(X ULN) concurrent with a total bilirubin 2 X ULN with no evidence of hemolysis 
and an alkaline phosphatase 2 X ULN or not available.

For subjects with preexisting ALT OR AST OR total bilirubin values above the 
upper limit of normal, the following threshold values should be used in the definition 
mentioned above:

For subjects with pre-existing AST or ALT baseline values above the normal 
range: AST or ALT 2 times the baseline values and 3 X ULN, or 
8 X ULN (whichever is smaller).

Concurrent with

For subjects with pre-existing values of total bilirubin above the normal range: 
Total bilirubin increased by one time the upper limit of normal or 3 times the 
upper limit of normal (whichever is smaller).
The subject should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history and physical assessment. In addition to repeating 
AST and ALT, laboratory tests should include albumin, creatine kinase, total bilirubin, direct 
and indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/INR, and 
alkaline phosphatase.  A detailed history, including relevant information, such as review of 
ethanol, acetaminophen, recreational drug and supplement consumption, family history, 
occupational history, sexual history, travel history, history of contact with a jaundiced 
subject, surgery, blood transfusion, history of liver or allergic disease, and work exposure, 
should be collected. Further testing for acute hepatitis A, B, or C infection and liver imaging 
(eg, biliary tract) may be warranted.  All cases confirmed on repeat testing as meeting the 
laboratory criteria defined above, with no other cause for LFT abnormalities identified at the 
time should be considered potential Hy’s Law cases irrespective of availability of all the 
results of the investigations performed to determine etiology of the abnormal LFTs. Such 
potential Hy’s Law cases should be reported as serious adverse events.
8.7. Hospitalization
Adverse events reported from studies associated with hospitalization or prolongations of 
hospitalization are considered serious.  Any initial admission (even if less than 24 hours) to a 
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healthcare facility meets these criteria.  Admission also includes transfer within the hospital 
to an acute/intensive care unit (eg, from the psychiatric wing to a medical floor, medical floor 
to a coronary care unit, neurological floor to a tuberculosis unit).
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Routine emergency room admissions;

Same day surgeries (as out-patient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
adverse event is not in itself a serious adverse event.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new adverse event or with a worsening of the preexisting condition 
(eg, for work-up of persistent pre-treatment lab abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical exam);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical adverse event (eg, for 
elective cosmetic surgery);

Hospitalization for observation without a medical AE;

Pre-planned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not 
be reported as adverse events.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an adverse event.  For example, an 
acute appendicitis that begins during the adverse event reporting period should be reported as 
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the adverse event, and the resulting appendectomy should be recorded as treatment of the 
adverse event
8.8. Severity Assessment
If required on the adverse event case report forms, the investigator will use the adjectives 
MILD, MODERATE, or SEVERE to describe the maximum intensity of the adverse event.  
For purposes of consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an adverse event.  A severe 
event is not necessarily a serious event.  For example, a headache may be severe (interferes 
significantly with subject's usual function) but would not be classified as serious unless it met 
one of the criteria for serious adverse events, listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all adverse events (serious 
and non-serious); the investigator must record the causal relationship in the CRF, as 
appropriate, and report such an assessment in accordance with the serious adverse reporting 
requirements if applicable.  An investigator’s causality assessment is the determination of 
whether there exists a reasonable possibility that the investigational product caused or 
contributed to an adverse event; generally the facts (evidence) or arguments to suggest a 
causal relationship should be provided.  If the investigator does not know whether or not the 
investigational product caused the event, then the event will be handled as “related to
investigational product” for reporting purposes, as defined by the Sponsor (see section on 
Reporting Requirements).  If the investigator's causality assessment is "unknown but not 
related to investigational product", this should be clearly documented on study records. 
In addition, if the investigator determines a serious adverse event is associated with study 
procedures, the investigator must record this causal relationship in the source documents and 
CRF, as appropriate, and report such an assessment in accordance with the serious adverse 
event reporting requirements, if applicable.
8.10. Exposure During Pregnancy
For investigational products and for marketed products, an exposure during pregnancy (also 
referred to as in-utero [EIU] occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or being 
exposed to (eg, due to treatment or environmental exposure) or after discontinuing or 
having been directly exposed to the investigational product;
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2. A male has been exposed (eg, due to treatment or environmental exposure), to the 
investigational product prior to or around the time of conception or is exposed during 
his partner’s pregnancy.
If any study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer Drug Safety Unit on a Serious Adverse Event Form and Exposure 
in Utero (EIU) Supplemental Form, regardless of whether an SAE has occurred.  In addition, 
the investigator must submit information regarding environmental exposure to a Pfizer 
product in a pregnant woman (eg, a subject reports that she is pregnant and has been exposed 
to a cytotoxic product by inhalation or spillage) using the Exposure in Utero Form.  This 
must be done irrespective of whether an adverse event has occurred and within 24 hours of 
awareness of the exposure.  The information submitted should include the anticipated date of 
delivery (see below for information related to termination of pregnancy).
Follow-up is conducted to obtain pregnancy outcome information on all EIUreports with an 
unknown outcome.  The investigator will follow the pregnancy until completion or until 
pregnancy termination and notify Pfizer of the outcome as a follow up to the initial EIU 
Form.  In the case of a live birth, the structural integrity of the neonate can be assessed at the 
time of birth.  In the event of a termination, the reason(s) for termination should be specified 
and, if clinically possible, the structural integrity of the terminated fetus should be assessed 
by gross visual inspection (unless pre-procedure test findings are conclusive for a congenital 
anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as serious adverse events 
follows: 

Spontaneous abortion includes miscarriage and missed abortion.

All neonatal deaths that occur within 1 month of birth should be reported, without 
regard to causality, as serious adverse events.  In addition, infant deaths after 1 month 
should be reported as serious adverse events when the investigator assesses the infant 
death as related or possibly related to exposure to investigational product.
Additional information regarding the exposure during pregnancy may be requested by the 
investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis 
(eg, follow-up on preterm infants to identify developmental delays).  
In the case of paternal exposure, the investigator will provide the study subject with the 
Exposure in Utero Pregnant Partner Release of Information Form to deliver to his partner.  
The Investigator must document on the Exposure in Utero Form that the subject was given 
this letter to provide to his partner.
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8.11. Occupational Exposure
An occupational exposure occurs when during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an adverse event.
An occupational exposure is reported to safety within 24 hours of Investigator’s awareness, 
using the SAE Report form, regardless of whether there is an associated AE/SAE. Since the 
information does not pertain to a subject enrolled in the study, the information is not reported 
on a Case Report Form (CRF), however a copy of the completed SAE Report form is 
maintained in the study master file.
8.12. Withdrawal Due to Adverse Events (See also section on Subject Withdrawal)
Withdrawal due to adverse event should be distinguished from withdrawal due to insufficient 
response, according to the definition of adverse event noted earlier, and recorded on the 
appropriate adverse event CRF page.  
When a subject withdraws due to a serious adverse event, the serious adverse event must be 
reported in accordance with the reporting requirements defined below.
8.13. Eliciting Adverse Event Information
The investigator is to report all directly observed adverse events and all adverse events 
spontaneously reported by the study subject.  In addition, each study subject will be 
questioned about adverse events.
8.14. Reporting Requirements
Each adverse event is to be assessed to determine if it meets the criteria for serious adverse 
events.  If a serious adverse event occurs, expedited reporting will follow local and 
international regulations, as appropriate.
8.14.1. Serious Adverse Event Reporting Requirements
If a serious adverse event occurs, Pfizer is to be notified within 24 hours of investigator
awareness of the event.  In particular, if the serious adverse event is fatal or life-threatening, 
notification to Pfizer must be made immediately, irrespective of the extent of available 
adverse event information.  This timeframe also applies to additional new information 
(follow-up) on previously forwarded serious adverse event reports as well as to the initial and 
follow-up reporting of exposure during pregnancy and exposure during breast feeding cases.  
In the rare event that the investigator does not become aware of the occurrence of a serious 
adverse event immediately (eg, if an outpatient study subject initially seeks treatment 
elsewhere), the investigator is to report the event within 24 hours after learning of it and 
document the time of his/her first awareness of the adverse event.
For all serious adverse events, the investigator is obligated to pursue and provide information 
to Pfizer in accordance with the timeframes for reporting specified above.  In addition, an 
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investigator may be requested by Pfizer to obtain specific additional follow-up information in 
an expedited fashion.  This information collected for serious adverse events is more detailed 
than that captured on the adverse event case report form.  In general, this will include a 
description of the adverse event in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality.  Information on 
other possible causes of the event, such as concomitant medications and illnesses must be 
provided.  In the case of a subject death, a summary of available autopsy findings must be 
submitted as soon as possible to Pfizer or its designated representative. 
8.14.2. Non-Serious Adverse Event Reporting Requirements
All adverse events will be reported on the adverse event page(s) of the CRF.  It should be 
noted that the form for collection of serious adverse event information is not the same as the 
adverse event CRF.  Where the same data are collected, the forms must be completed in a 
consistent manner.  For example, the same adverse event term should be used on both forms.  
Adverse events should be reported using concise medical terminology on the CRFs as well as 
on the form for collection of serious adverse event information.
8.14.3. Sponsor Reporting Requirements to Regulatory Authorities
Adverse events reporting, including suspected unexpected serious adverse reactions, will be 
carried out in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
A detailed methodology for summary and statistical analyses of the data collected in this 
study will be documented in a Statistical Analysis Plan, which will be maintained by the 
sponsor.  This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment.
Data will be summarized into 3 groups defined by a combination of the subject’s randomized 
treatment group in one of the previously participated studies (subjects previously on 
pregabalin will be combined across treatment groups) and the treatment received during this 
study.  All subjects in this study will receive pregabalin.  The 3 summary treatment groups 
will be described as: 
18. Pregabalin-Pregabalin: any dose of pregabalin from the previous study and pregabalin 
in this study.
19. Placebo-Pregabalin: placebo in the previous study, and pregabalin in this study.
20. Direct Pregabalin: pregabalin only in this study.
Additionally, all pregabalin data in this study will be combined “Overall”.
Other than baseline, where relevant, information will be presented only for this study.  
Baseline values will be the last observation made prior to initiating double-blind dosing in 
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Studies A0081041, A0081042, and A0081105. Subjects entering Study A0081106 directly 
will have baseline observations made at screening (Visit 1B).
Cohort analysis will consist of an age cohort defined as either pediatric (1 month to 16 years 
of age) or non-pediatric; and a primary seizure type cohort (partial onset seizures or PGTC 
seizures).
9.1. Sample Size Determination
This study will enroll a sufficient number of subjects to ensure that 100 pediatric subjects 
(1 month to 16 years of age) complete one year of adjunctive treatment.  Pediatric subjects 
with partial onset seizures (who have participated in Studies A0081041, A0081042, or 
directly enrolled into this study) or with PGTC seizures (who have participated in Study 
A0081105) are included.
9.2. Efficacy Analysis
All seizure information will be addressed in safety.
9.2.1. Analysis of Primary Endpoint
Not applicable.
9.2.2. Analysis of Secondary Endpoints
Not applicable.
9.3. Analysis of Other Endpoints
Not applicable.
9.4. Safety Analysis
Summaries will include data for all subjects who took at least one dose of study medication 
in this study (Safety population).
The safety data (including adverse events, clinical laboratory assessments, ECGs, vital signs, 
height/weight/Tanner stage, suicidality assessments, cognitive assessments, and 
physical/neurological examinations) will be summarized by treatment group and overall 
through standard data tabulations, descriptive statistics, and/or graphical presentations.  
Twenty-eight-day seizure rate will be calculated from the seizure diaries and will be 
reviewed as a means of determining seizure control.  Seizure frequency for each seizure type 
will be summarized using descriptive statistics every 4 weeks thereafter until the end of the 
study by treatment group and overall.  No statistical inferences will be performed. 
Subgroup analysis will be done on the safety data and seizures rates for each age cohort and 
primary seizure type.
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9.5. Data Monitoring Committee 
This study will not use a Data Monitoring Committee.
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Pratices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs is accurate.  The 
investigator and institution will allow Pfizer monitors or its agents and appropriate regulatory 
authorities direct access to source documents to perform this verification.
The study site may be subject to review by the institutional review board (IRB)/independent 
ethics committee (IEC), and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term case report form (CRF) should be understood to refer to 
either a paper form or an electronic data record or both, depending on the data collection 
method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true. Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry.” 
In most cases, the source documents are the hospital's or the physician's subject chart.  In 
these cases data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
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identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent forms, copies of all CRFs, safety reporting forms, source documents, and detailed 
records of treatment disposition, and adequate documentation of relevant correspondence 
(eg, letters, meeting minutes, telephone calls reports).  The records should be retained by the 
investigator according to International Conference on Harmonisation (ICH), local 
regulations, or as specified in the Clinical Study Agreement, whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer.  The 
investigator must obtain Pfizer's written permission before disposing of any records, even if
retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent forms, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for Good Clinical Practice (International Conference on 
Harmonization 1996), and the Declaration of Helsinki (World Medical Association 1996 and 
2008). 
In addition, the study will be conducted in accordance with the protocol, the International 
Conference on Harmonisation guideline on Good Clinical Practice, and applicable local 
regulatory requirements and laws.
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12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law. 
When study data is compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study subjects.  The study 
site will maintain a confidential list of subjects who participated in the study linking their 
numerical code to the subject’s actual identity.  In case of data transfer, Pfizer will maintain 
high standards of confidentiality and protection of subject personal data consistent with 
applicable privacy laws.
The informed consent/assent documents must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy laws.
The informed consent/assent documents used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB/EC before use, and available for inspection.  
The investigator must ensure that each study subject, or his or her legally acceptable 
representative, or parent(s) or legal guardian if a minor, is fully informed about the nature 
and objectives of the study and possible risks associated with participation.  
Whenever consent is obtained from a subject’s legally acceptable representative/parent(s) or 
legal guardian, the subject’s assent (affirmative agreement) must subsequently be obtained 
when the subject has the capacity to provide assent, as determined by the IRB/EC.  If the 
investigator determines that a subject’s decisional capacity is so limited he/she cannot 
reasonably be consulted, as permitted by the IRB/EC and consistent with local regulatory and 
legal requirements, then the subject’s assent may be waived with source documentation of 
the reason assent was not obtained.  If the study subject does not provide his/her own 
consent, the source documents must record why the subject did not provide consent 
(eg, minor, decisionally impaired adult), how the investigator determined that the person 
signing the consent was the subject’s legally acceptable representative, the consent signer’s 
relationship to the study subject (eg, parent, spouse) and that the subject’s assent was 
obtained, or waived.  If assent is obtained verbally it must be documented in the source 
documents.
If the study includes minor subjects who reach the age of majority during the study, as 
recognized under local law, they must be re-consented as adults to remain in the study.  If the 
enrollment of ‘emancipated minors’ is permitted by the study age criteria, the IRB/EC, and 
local law, they must provide documentation of legal status to give consent without the 
permission of a parent or legal guardian.   
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject's legally acceptable representative, parent(s) or legal 
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guardian and the subject’s assent, before any study-specific activity is performed. The 
investigator will retain the original of each subject's signed consent/assent document.
12.4. Subject Recruitment
Advertisements approved by ethics committees and investigator databases may be used as 
recruitment procedures.
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of the 
investigational product, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State
End of Trial in a Member State of the European Union is defined as the time at which it is 
deemed that sufficient subjects have been recruited and completed the study as stated in the 
regulatory application (ie, Clinical Study Application (CTA)) and ethics application in the 
Member State.  Poor recruitment (recruiting less than the anticipated number in the CTA) by 
a Member State is not a reason for premature termination but is considered a normal 
conclusion to the study in that Member State.
13.2. End of Trial in all Participating Countries
End of Trial in all participating countries is defined as Last Subject Last Visit.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of pregabalin at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within 1 week.  As directed by Pfizer, all study 
materials must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov) www.pfizer.com, and/or the 
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European Clinical Trials Database (EudraCT), and other public registries in accordance with 
applicable local laws/regulations. 
www.clinicaltrials.gov
Pfizer registers study protocols and posts Basic Results on ClincialTrials.gov for 
Pfizer-sponsored interventional studies that evaluate the safety and/or efficacy of a Pfizer 
product.  For studies involving a Pfizer product, the timing of the posting depends on 
whether the Pfizer product is approved for marketing in any country at the time the study is 
completed:

For studies involving products applicable under the US Food and Drug 
Administration Amendments Act of 2007 (FDAAA) ie, FDA-approved products.  
Pfizer posts results within one year of the primary completion date (PCD).  For 
studies involving products approved in any country, but not FDA approved, Pfizer 
posts results one year from last subject, last visit (LSLV).

For studies involving products that are not yet approved in any country, Pfizer posts 
the results of already-completed studies within 30 days after US regulatory approval.  
or one year after the first ex-US regulatory approval of the product (if only submitted 
for approval ex-US).

For studies involving products whose drug development is discontinued before 
approval, Pfizer posts the results within one year after such discontinuation of the 
program (if there are no plans for outlicensing or within 2 years if outlicensing plans 
have not completed).
Primary Completion Date (PCD) is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome,
whether the clinical trial concluded according to the prespecified protocol or was terminated.
www.pfizer.com
Pfizer posts clinical trial results on www.pfizer.com for all Pfizer-sponsored interventional 
studies in patients that assess the safety and/or efficacy of an FDA-approved Pfizer product 
with a LSLV on or after 27-Sep-2007 for which Basic Results were posted on 
www.clinicaltrials.gov.
EudraCT
Pfizer posts clinical trial results on EudraCT in accordance with Commission Guideline 
2012/C 302/03 Guidance on posting and publication of result-related information on clinical 
trials in relation to the implementation of Article 57(2) of Regulation (EC) No 726/2004 and 
Article 41(2) of Regulation (EC) No 1901/2006 for studies with centers in the European 
Economic Area and with LSLV on or after 01-May-2004, regardless of the marketing status 
of the compound.
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15.2. Publications by Investigators
Pfizer has no objection to publication by Investigator of any information collected or 
generated by Investigator, whether or not the results are favorable to the Investigational 
Drug.  However, to ensure against inadvertent disclosure of Confidential Information or 
unprotected Inventions, Investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure before it is submitted or otherwise disclosed.
Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer 
at least 30 days before they are submitted for publication or otherwise disclosed.  If any 
patent action is required to protect intellectual property rights, Investigator agrees to delay 
the disclosure for a period not to exceed an additional 60 days.
Investigator will, on request, remove any previously undisclosed Confidential Information 
(other than the Study results themselves) before disclosure.
If the Study is part of a multi-centre study, Investigator agrees that the first publication is to 
be a joint publication covering all centers.  However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the Study at all 
participating sites, Investigator is free to publish separately, subject to the other requirements 
of this Section.
For all publications relating to the Study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the institution.  In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement.
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16. REFERENCES
1.
Hermann BP, Austin J. Psychosocial status of children with epilepsy and the effects of 
epilepsy surgery. In: Wylie E, editor. The treatment of epilepsy: principles and 
practices. Philadelphia: Lea & Febiger; 1993: p. 1141-8.
2.
Ott D, Siddarth P, Gurbani S, et al. Behavioral disorders in pediatric epilepsy: unmet 
psychiatric need. Epilepsia 2003; 44(4):591-7.
3.
Berg AT, Berkovic SF, Brodie MJ, et al. Revised Terminology and Concepts for 
Organization of Seizures and Epilepsies. Epilepsia 2010; 51: 676-685.
4.
Pietrzak RH, Fredrickson A, Snyder PJ, Maruff P. A comparison of statistical 
approaches used to evaluate change in cognitive function following pharmacologic 
challenge: an example with lorazepam. Hum Psychopharmacol. 2010 Jun;25(4):335-41. 
5.
Cromer JR, Cromer JA, Maruff P, Snyder PJ. Perception of alcohol intoxication shows 
acute tolerance while executive functions remain impaired. Exp Clin Psychopharmacol. 
2010 Aug;18(4):329-39.
6.
Maruff  P, Werth J, Giordani B, Caveney AF, Feltner D, Snyder PJ,. A statistical 
method for measuring cognitive response to treatment in individual patients. 
Psychopharmacology.2006; 186:7-17.
7.
Maruff P, Thomas E, Cysique L, Brew B, Collie A, Snyder P, Pietrzak RH. Validity of 
the CogState brief battery: relationship to standardized tests and sensitivity to cognitive 
impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. 
Arch Clin Neuropsychol. 2009 Mar;24(2):165-78.
8.
Mollica CM, Maruff  P, Collie A, Vance A (2005)  Repeated assessment of cognition in 
children and the measurement of performance change. Neuropsychol Dev Cogn C Child 
Neuropsychol. 11, 303-10. 
9.
Dingwall KM, Lewis MS, Maruff P, Cairney S. Assessing cognition following petrol 
sniffing for Indigenous Australians. Aust N Z J Psychiatry. 2010 Jul;44(7):631-9.
10.
Yamashita Y,  Mukasa A, Anai C, Honda Y, Kunisaki C, Koutaki J Tada Y, Egami C, 
Kodama N, Nakashima N, Nagamitsu S and , Matsuishi T (in press) Summer treatment 
program for children with attention deficit hyperactivity disorder: Japanese experience 
in 5 year.  Brain and Development DOI: 0.1016/j.braindev.2010.09.005.
11.
Collie A, Maruff  P, Snyder PJ, Darekar MA, Huggins JP.  Cognitive testing in early 
phase clinical trials: outcome according to adverse event profile in a Phase I study.  
Hum Psychopharmacol. 2006 Oct;21(7):481-8.
12.
Vartanian, M.G., Radulovic, L.L., Kinsora, J., Serpa, K.A., Vergnes, M., Bertram, E. & 
Taylor, C.P. Activity profile of pregabalin in rodent models of epilepsy and ataxia. 
Epilepsy research 68, 189-205 (2005).
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13.
Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J. Glossary 
of Descriptive Terminology for Ictal Semiology: Report of the ILAE Task Force on 
Classification and Terminology. Epilepsia 2001 42(9): 1212-1218. 
14.
Achenbach, T. M. (1991). Manual for the Child Behavior Checklist/4-18 and 1991 
Profile. Burlington, VT: University of Vermont, Department of Psychiatry.
15.
The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and 
validation of a structured diagnostic psychiatric interview for DSM-IV and ICD. 
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, 
Baker R, Dunbar GC. J Clin Psychiatry. 1998; 59 Suppl 20:22-33.
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Appendix 1. International League Against Epilepsy 2010 and Revised 1981 
Classification
2010 ILAE criteria:
"Descriptors of focal seizures. For pragmatic reasons and to facilitate continuity with the 
1981 classification of seizures, descriptors of focal seizures may be used, individually or in 
combination with other features depending on the purpose.  We have listed examples chosen 
to facilitate continuity with the 1981 seizure document and which have been drawn from the 
glossary of ictal semiology (Blume et al 200113) (Table 2)."
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Revised 1981 criteria:
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Appendix 2. Clinical Dosing Instructions for Administration of the Liquid Oral 
Solution Formulation:
Oral solution
Pregabalin 20 mg/mL and matching placebo oral solutions are provided as clear, colorless, 
flavored solutions bottles.  To accommodate the broad dose range that may be encountered 
during clinical studies, pregabalin 20 mg/mL and matching placebo oral solutions can be 
administered using a variety of oral dosing syringes (1, 3, and 10 mL).  An example of the 
syringes and dosing tables are provided in this document for reference.  
Subjects/parents/guardians should receive training on dose preparation, administration, 
storage, and disposal prior to release for outpatient dosing.
DOSING:
Dosing is accommodated by the use of either a 1, 3, or 10 mL oral dosing syringe depending 
on the required dose.  The 1 mL oral dosing syringe can accommodate 0.1-1 mL doses in 
0.1 mL  The 3 mL oral dosing syringe can accommodate doses from 1.25-3.0 mL in 0.25 mL 
increments. The 10 mL oral dosing syringe can accommodate doses from 3.5-10.0 mL in 
0.5 mL increments.
Illustrations of the oral dosing syringes are provided in Figure 2.
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Figure 2.
Oral Dosing Syringes (1, 3, and 10 mL left to right)
DOSING AND ADMINISTRATION PROCEDURE:
1. Insert the appropriate oral dosing syringe into the bottle. 
2. Pull back on the plunger of the oral dosing syringe to the appropriate measurement 
mark on the oral dosing syringe barrel.
3. Measure the dose by aligning the fin on the plunger to the appropriate marking on the 
barrel (Figure 2).  Note: the plunger on the 1 mL oral dosing syringe has 2 fins on the 
plunger and the fin closest to the syringe tip should be used to measure the dose.
4. Place the oral dosing syringe down onto a clean surface and securely close the bottle.
5. Deliver the dose by placing the tip of the oral dosing syringe into the mouth of the 
subject with the subjects head tilted slightly back and pushing the plunger to expel the 
liquid.  Be careful to not expel the dose directly into the back of the throat, to avoid 
choking. Alternatively dose can be transferred into a cup for administration.
6. Remove the plunger from the oral dosing syringe and rinse the barrel and plunger 
under warm water.  Allow the plunger and barrel to air dry or use a fresh paper towel 
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or clean cloth to dry.  When dry, push the plunger back into the barrel prior to the 
next dose. 
Figure 3.
Dosing Example
DOSE CALCULATIONS/SUPPLIES:
Subjects will be supplied with a suitable oral dosing syringe for self-administration.  
STABILITY AND STORAGE:
A single dose that has been prepared in an oral dosing syringe should be administered within 
1 hour.  Bottles containing the dosing solution should be stored at room temperature.
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Appendix 3. List of Abbreviations:
A
AE
Adverse Event
AED
Antiepileptic Drug
2-
Alpha-2-Delta
ALT
alanine aminotransferase
AST
aspartate aminotransferase
B
BID
Twice Daily
BP
Blood Pressure
C
CBCL
Child Behavioral Check List
CLcr
Creatinine Clearance
Cmax
Maximum Concentration
CNS
Central Nervous System
CP
Complex Partial
CRF
Case Report Form
C-SSRS
Columbia Suicidality Rating Scale
CT
CAT Scan (Computerized Tomography Scan)
CTA
Clinical Trial Application or Clinical Study Application
D
DMC
Data Monitoring Committee
DSM-IV
Diagnostic and Statistical Manual of Mental Disorders, Version IV
E
ECG
Electrocardiogram
EEG
Electroencephalogram
EIU
Exposure in Utero
ET
Early Termination
F
FSFV
First Subject First Visit
G
GCP
Good Clinical Practice
I
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IRB
Institutional Review Board
L
LSLV
Last Subject Last Visit
M
MHP
Mental Health Professional
MINI-KIDS
Mini International Neuropsychiatric Interview 
mL
Milliliter
MRI
Magnetic Resonance Imaging
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P
PBO
Placebo
PGTC
Primary Generalized Tonic-Clonic Seizure
PI
Principal Investigator
PK
Pharmacokinetic/Pharmacokinetics
R
RBC
Red Blood Cell
S
SAP
Statistical Analysis Plan
SAE
Serious Adverse Event
SE
Status Epilepticus
SGTC
Secondarily Generalized Tonic-Clonic Seizures (a type of Partial Epilepsy 
Seizure)
SP 
Simple Partial
SSID
Single Subject Identification Number
T
TID
Three Times A Day
V
V
Visit
VNS
Vagus Nerve Stimulation
W
WBC
White Blood Cell
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SAP_001.pdf: 
Protocol A0081106
Statistical Analysis Plan
Page 1
Protocol A0081106
A 12-MONTH OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND 
TOLERABILITY OF PREGABALIN AS ADJUNCTIVE THERAPY IN PEDIATRIC
SUBJECTS 1 MONTH TO 16 YEARS OF AGE WITH PARTIAL ONSET SEIZURES 
AND PEDIATRIC AND ADULT SUBJECTS 5 TO 65 YEARS OF AGE WITH 
PRIMARY GENERALIZED TONIC-CLONIC SEIZURES
Statistical Analysis Plan 
(SAP)
Version:
1.0 Final
Author:
 (Study Statistician -
)
Date:
August 15, 2011
Version:
2.0 Final
Author:
 (Study Statistician -
)
Date:
05 OCTOBER 2015
Version:
3.0 Final 
Author:
Pfizer Inc
Date:
03 September 2019
PPD
PPD
PPD
PPD
PPD
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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
Version 2.0 Amendment 1:
Status of study when amendment made: Study is still ongoing.
Reason for amendment: Clarified safety endpoints. (Section 6.2).
Reason for amendment: Detailed for subjects participated in previous studies how ongoing 
AEs were handled from their previous study. (Section 6.2.1).
Reason for amendment: Explained handling of concomitant medication data, including for 
subjects participated in previous studies ongoing data from their previous study.
(Section 6.2.3).
Reason for amendment: Seizure rates will be determined by visit rather than 28-day period as 
seizure data is collect from diaries at each visit. Detailed that seizure types will be computed 
based on previous study enrollment and added specifications in regards to handling of special 
cases of the seizure diary. (Section 6.2.3 and Appendix 1).
Reason for amendment: Suicidality is changed to suicidal ideation and behavior. 
(Section 6.2.4 and Appendix 2).
Reason for amendment: Age cohorts will be defined based on the Pediatric Written Request 
(PWR). Added how age and seizure cohorts will be determined. (Section 8).
Reason for amendment: Added safety analysis sections for Treatment and Disposition of 
Subjects (Section 8.3.1); Demographic Data and Clinical Examination data (Section 8.3.2); 
Discontinuations(s) (Section 8.3.3); Laboratory, Vital Signs (including height/weight), and 
ECG Data (Section 8.3.7); Physical and Neurological Examinations (Section 8.3.8); and 
Exposure and Compliance (Section 8.3.11).
Reason for amendment: AE presentations will also be done by primary seizure type cohort. 
(Section 8.3.5).
Reason for amendment: Specified how seizure frequency presentations should be handled, 
which is separated by previous study and age cohorts within the study. (Section 8.3.6).
Reason for amendment: All safety (excluding seizure frequency and cognitive function) will 
use age cohort only for their summary presentations (ie, no combined across age cohort 
summaries). AEs and Physical/Neurological examinations will be additionally presented 
combined across the age cohorts. (Section 8.3.5, Section 8.3.8).
Reason for amendment: Stated how to handle subjects who completed the CBCL but outside 
the range (listings only). Explained the handling of subjects who are unable to complete the 
CBCL due to translation issue for their language, they completed the C-SSRS (listings only). 
(Section 8.3.9).
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Reason for amendment: Clarified that CogState information (cognitive function) is relevant 
for subject previously in A0081041 who participated in study A0081106 and A0081106 
Direct Enrollers. Subgroup analysis will be done by age cohort (within this study type) and 
primary seizure type cohort. (Section 8.3.10).
Version 3.0 Amendment 2:
General Reason: To fulfill study A0081106 protocol requirements and to streamline 
some of the analyses that were previously required by PWR and PREA. Since PWR and 
PREA obligations have met previously, this version of the SAP addresses study 
A0081106 protocol requirements only, whereas previous versions of the SAP had also 
addressed PWR and PREA specified analyses.
Results for study A0081106 subjects will be reported 1) overall and 2) by primary 
diagnosis of POS or PGTC seizures and 3) by 2 age cohorts (1 month to 16 years of age, 
17 years of age and older) for majority of the endpoints.  For cases where the endpoint 
summarization does not lend itself to the 3 sets of analysis above, more details will be 
provided at the endpoint level in the specific section. 
Section 6.2.1 was modified to clarify reporting of AEs for subjects in previous studies 
who participated in study A0081106.
Section 6.2.2 was modified to clarify reporting of prior medications and nondrug 
treatment/procedures for subjects in previous studies who participated in study 
A0081106. 
Section 6.2.3 Seizure Frequency was modified to clarify the reporting of the following:

Reporting of PGTC and POS 28-day seizure rate and time point to reflect study 
A0081106 timepoints.

Other types of seizure that were not part of 28-day PGTC or POS seizure rate 
(unclassified epileptic seizure, status epilepticus, myoclonic, tonic/atonic, & 
clonic) and time point to reflect study A0081106 timepoints. 
Section 8. Statistical methodology was modified to define the 3 sets of analysis and 
analyses cohorts and to clarify which cohorts were used for the different endpoints. 
Additionally, language was added to clarify that all analyses will be conducted for each 
of the 3 treatment groups and combined.  Definition of treatments and cohorts used for 
the analysis described in Section 8.1-Section 8.3.11 were subsequently removed from 
these sections.  
Section 8.3.6 Seizure Frequency was modified to clarify the following:

POS and PGTC seizure cannot be reported as combined due the different nature 
of seizure.

To distinguish between other seizure types which are not part of 28-day seizure 
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rate for PGTC or POS

To clarify the method of analysis for other types of seizure that are not part of 28-
day PGTC or POS seizure rate.

To clarify reporting of baseline 28-day seizure rate for PGTC seizure and to 
provide the reason for not presenting baseline 28-day seizure rate for POS 
seizure.  
Section 8.3.9- Suicidal Ideation and Behavior: Added or removed wording for 
clarification.
Section 8.3.10 Cognition was modified as follows:

Added the age cohort for analysis of CogState data as 4 -11 years 12-16 years.

CogState will perform the analysis of the CogState Detection and CogState 
Pediatric Identification.
Section 8.3.11 – Exposure was modified to add compliance definition for TID dosing. 
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TABLE OF CONTENTS
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................2
APPENDICES ...........................................................................................................................6
2. INTRODUCTION .................................................................................................................7
2.1. Study Design .............................................................................................................7
2.2. Statistical Power and Sample Size ............................................................................8
2.3. Study Objectives .......................................................................................................8
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................8
4. HYPOTHESES AND DECISION RULES...........................................................................8
4.1. Statistical Hypotheses ...............................................................................................8
4.2. Statistical Decision Rules..........................................................................................8
5. ANALYSIS SETS .................................................................................................................9
5.1. Full Analysis Set (Safety Population) .......................................................................9
5.2. ‘Per Protocol’ Analysis Set (PP Population).............................................................9
5.3. Safety Analysis Set....................................................................................................9
5.4. Other Analysis Sets ...................................................................................................9
5.5. Treatment Misallocations..........................................................................................9
5.6. Protocol Deviations...................................................................................................9
6. ENDPOINTS AND COVARIATES .....................................................................................9
6.1. Efficacy Endpoint(s) .................................................................................................9
6.2. Safety Endpoints .......................................................................................................9
6.2.1. Adverse Events...........................................................................................10
6.2.2. Prior and Concomitant Treatments and Medications .................................10
6.2.3. Seizure Frequency ......................................................................................10
6.2.4. Suicidal Ideation and Behavior (SIB) Assessments During the 
Clinical Trial....................................................................................................11
6.2.5. Cognitive Testing During the Clinical Trial...............................................12
6.3. Other Endpoints.......................................................................................................13
6.3.1. PK/PD Endpoints........................................................................................13
6.4. Covariates................................................................................................................13
6.4.1. Exploratory Endpoint..................................................................................13
7. HANDLING OF MISSING VALUES ................................................................................13
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................13
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8.1. Analysis of Primary Efficacy Endpoint ..................................................................14
8.2. Analysis of Secondary Efficacy Endpoints.............................................................14
8.3. Safety Analyses.......................................................................................................14
8.3.1. Treatment and Disposition of Subjects.......................................................15
8.3.2. Demographic Data and Clinical Examination Data....................................15
8.3.3. Discontinuation...........................................................................................15
8.3.4. Subject discontinuations, temporary discontinuations or dose 
reductions due to adverse events will be summarized.....................................15
8.3.5. Adverse Events...........................................................................................15
8.3.6. Seizure Frequency ......................................................................................15
8.3.7. Laboratory, Vital Signs, Height, Weight, and ECG Data...........................16
8.3.8. Physical and Neurological Examinations...................................................16
8.3.9. Suicidal Ideation and Behavior...................................................................16
8.3.10. Cognitive Function ...................................................................................17
8.3.11. Exposure and Compliance........................................................................17
8.4. Summary of Efficacy Analyses...............................................................................17
APPENDICES
Appendix 1. Data Derivation Details.......................................................................................18
Appendix 2. C-SSRS Mapped to C-CASA - Suicidal Ideation and Behavior Events and 
Codes ........................................................................................................19
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2. INTRODUCTION
This is a 12-month open-label, flexible-dose study in pediatric subjects 1 month through 
16 years of age with partial-onset seizures (POS), who have participated in Study A0081041
(4-16 years of age) or Study A0081042 (1 month-3 years of age) and pediatric and adult 
subjects 5-65 years of age with Primary Generalized Tonic-Clonic (PGTC) seizures who 
have participated in Study A0081105. Subjects who have completed the studies cited above 
will be eligible for screening for this study. For subjects who have participated in, but did 
not complete Studies A0081041, A0081042, or A0081105, eligibility for Study A0081106 will 
be considered on a case by case basis. A minimum of 4 weeks in the double-blind treatment 
phase of either Study A0081041 or Study A0081105 will be required for consideration of 
enrollment into Study A0081106.
Selected sites that are not participating in studies A0081041 or A0081042 may screen and 
enroll pediatric subjects (1 month to 16 years of age) with partial onset seizures directly into 
Study A0081106 provided they meet the study inclusion/exclusion criteria. When subject 
enrollment for Studies A0081041 and A0081042 is complete, sites that were enrolling 
subjects in Studies A0081041 or A0081042 may screen and enroll pediatric subjects 
(1 month to 16 years of age) with partial onset seizures directly into Study A0081106 until 
enrollment into Study A0081106 is closed by Pfizer.
2.1. Study Design
The day of the last visit (completion of taper phase) of Studies A0081041, A0081042, and 
A0081105 is designated as Day 1 (Visit 1A) of this study. Baseline values for analysis of 
change in safety endpoints will be the assessments made prior to initiating double-blind 
dosing at Visit 1 of Studies A0081041, A0081042, or A0081105. For subjects directly 
entering Study A0081106 without participation in one of the studies above, baseline values 
for analysis of change in safety endpoints will be the assessments made at the first visit 
(Screening Visit 1B) of this study.
Subjects will return for the designated assessments of safety, tolerability, and drug 
accountability at Week 1 (Visit 2), Month 1 (Visit 3), Month 2 (Visit 4), Month 4 (Visit 5), 
Month 6 (Visit 6), Month 9 (Visit 7), Month 12/Early Termination (Visit 8), and Follow-up 
(Visit 9). Investigator site staff will contact the subject and/or parent/caregiver by telephone 
at least monthly between visits, to address questions, assess safety and adverse events, and 
ensure compliance with study directives.
At Visit 2 and subsequent visits thereafter, the investigator or designee will review seizure 
diary data and tolerability with the subject and may adjust the dose at his/her discretion. 
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Study Design Diagram:
2.2. Statistical Power and Sample Size
This study will enroll a sufficient number of subjects to ensure that 100 pediatric subjects (1 
month to 16 years of age) complete one year of adjunctive treatment. Pediatric subjects with 
partial onset seizures (who have participated in Studies A0081041, A0081042, or directly 
enrolled into this study) or with PGTC seizures (who have participated in Study A0081105) 
are included.
2.3. Study Objectives 
To evaluate the long-term safety and tolerability of pregabalin in pediatric subjects 1 month 
through 16 years of age with partial onset seizures and pediatric and adult subjects 
17-65 years of age with PGTC seizures.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING 
Not applicable. This is an open-label trial.
4. HYPOTHESES AND DECISION RULES 
4.1. Statistical Hypotheses
Not applicable. No formal statistical analysis will be performed.
4.2. Statistical Decision Rules
Not applicable. No formal statistical analysis will be performed.
Study 
A0081041
A0081
042
A0081
Study A0081106 
  V2
Week 
    1
     V3
Month 
      1
      V4
   Month 
       2
  V6
Month   
    6
       V7
    Month 
         9
          V8
     Month 12/ 
      Early Term 
      End of   
       study/Initiate
     Taper
    V9
    End 
    Taper
    V1A
    Day 1
  V5
Month
   4
   V1B
   Day 1
  Directly 
  Enrolling
  Pediatric 
  POS
  Subjects 
Open Label Flexible Treatment Phase 2.5-10 mg/kg/day
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5. ANALYSIS SETS
5.1. Full Analysis Set (Safety Population)
The primary analysis set will be the Safety population which will include subjects who took 
at least one dose of the study medication in this study.
5.2. ‘Per Protocol’ Analysis Set (PP Population)
None.  Protocol Deviations will be addressed (See Section 5.6) but no PP analyses are 
planned. 
5.3. Safety Analysis Set
The primary analysis set for safety will be the Safety population which will include subjects 
who took at least one dose of the study medication in this study.  
5.4. Other Analysis Sets
Not applicable.
5.5. Treatment Misallocations 
Not applicable.
5.6. Protocol Deviations
The list of protocol deviations will be compiled and evaluated for major deviation prior to 
database closure and the listing will be provided.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
All seizure information will be addressed in safety. 
6.2. Safety Endpoints
Safety and tolerability will be evaluated at each study visit.  Data on the following endpoints 
will be collected:

Adverse event (AE) data (occurrence, nature, intensity, and relationship to study 
drug). 

Physical and neurological examinations.

Vital signs.

Growth and development parameters (height and weight) including Tanner stage
(Tanner stage not applicable for subject from study A0081042) for pediatric subjects.

Clinical laboratory data (hematology, chemistry, urinalysis).
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
Electrocardiograms (ECGs).

28-day seizure rate (number of seizures per 28-day period).

Assessment of suicidal ideation and behavior.

Cognitive testing (Only A0081041 subjects who participated in study A0081106 and 
A0081106 Direct Enrollers).
In addition, identification of subjects meeting the definition of Hy’s law will be evaluated.
6.2.1. Adverse Events
All AEs will be coded using the MedDRA coding dictionary.  All AEs (serious and non-
serious) reported from onset of the first day of A0081106 study treatment through and 
including 999 calendar days after the last administration of the study drug will be considered 
treatment emergent AEs (TEAEs). For subjects who participated in the previous studies, 
AEs that were ongoing from their previous study were recorded in A0081106 and were 
considered treatment-emergent only if the severity worsened. 
6.2.2. Prior and Concomitant Treatments and Medications
Concomitant medications, defined as medications that are ongoing or started on or after the 
first day of A0081106 study treatment up to the last dose of study treatment, and prior 
medications, defined as medications that stopped prior to the first day of study treatment, will 
be summarized using the WHO-drug coding dictionary. In addition, concomitant and prior 
non-drug treatments/procedures will be summarized using the MedDRA coding dictionary.
6.2.3. Seizure Frequency
The seizure frequency for PGTC and POS seizure will be based on the 28-day seizure rate at 
each visit and overall (all treatment days during the treatment phase, excluding the taper 
phase), calculated as follows:
28 day seizure rate
=
# of seizures since last visit
X 28
[# of days since last visit - # of missing diary days since last visit]

Number of days since last visit is defined as: Date of last diary data entry since last visit – Date of first diary data entry
since last visit +1.
Calculations will be made, using A0081106 visit schedule, for Week 1 (Visit 2), Month 1 
(Visit 3), Month 2 (Visit 4), Month 4 (Visit 5), Month 6 (Visit 6), Month 9 (Visit 7), Month 
12 (Visit 8) and Overall.
The 28-day seizure rate for all POS will be computed for subjects from Studies A0081042, 
A0081041, and direct enrollers, for each visit in study A0081106 and overall. Since these 
subjects were all <17 years of age at the time of entry to the previous studies, there will be 
only one age cohort.
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The 28-day seizure rate for PGTC seizures will be computed for subjects from Study 
A0081105 for each visit in Study A0081106 and overall. The 28-day PGTC seizure rate will 
also be summarized by age cohort (5 to 16 years and >=17 years).
Number and percent of subjects who experienced at least one unclassified epileptic seizure,
status epilepticus, myoclonic, absence seizure, tonic/atonic & clonic seizure will be 
computed for all subjects for each visit in study A0081106 by primary seizure type cohorts 
(PGTC, POS). These seizure types are not part of the PGTC or POS 28-day seizure rate. 
The following specifications in regard to the handling of special cases for the seizure diary
are also considered:
1. Any unplanned diary records will be mapped to planned visits by comparing the diary 
date against the dosing visits and assigned to the first visit that occurs after the 
unplanned diaries date.
2. If the subject has multiple diary records on the same date, then the below algorithm 
will be used to select the record for analysis:
a.
Select 'DONE' records over 'NOT DONE'.
b. If one of the repeated records has 'NO Seizures' and the other is with some 
positive number as result, then select record with positive number of seizures.
c.
If both/multiple repeated records have positive number of seizure, then include all 
seizures from both pages.
3. The data is collected in two ways due to CRF amendment. Per earlier version of 
CRF, the diary data is collected daily. Per the revised CRF, diary start and end dates 
are collected and the data are entered only when a seizure has occurred. If the data 
are collected on the revised CRF, then dates collected on CRF are used. Otherwise 
the minimum/maximum dates per visit from daily collection dates are used.
6.2.4. Suicidal Ideation and Behavior (SIB) Assessments During the Clinical Trial
The correct age appropriate scale to assess suicidal ideation and behavior risk was used 
based on the guidance in the protocol, specifically the use of the Child Behavior Checklist 
(CBCL) for subjects <6 years of age) and the Columbia-Suicide Severity Rating Scale 
(C-SSRS) for subjects 6 - 65 years of age.
C-SSRS responses will be mapped to the Columbia Classification Algorithm of Suicide 
Assessment (C-CASA). (see Appendix 2).
The following 3 endpoints are key endpoints for suicidal ideation and behavior data analysis 
and evaluation: 
1. Suicidal Behavior.
2. Suicidal Ideation.
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3. Suicidal Behavior or Ideation.
Suicidal behavior: A subject is said to have suicidal behavior if the subject has experienced 
any of the following events (C-CASA event codes 1-3, according to the 2010 FDA draft 
guidance to industry): 
1. Completed suicide.
2. Suicide attempt; or
3. Preparatory acts toward imminent suicidal behavior.
Suicidal ideation: Any observed suicidal ideation maps to a single C-CASA category.  The 
C-SSRS, for example, includes five ideation questions (that map to C-CASA category 4) 
with increasing severity.  
There are currently no validated scales to assess suicidal ideation and behavior in children 
below age 6, and suicidal ideation and behavior is an extremely rare occurrence in this age 
group.  Children in this age group and young school-aged children are more likely to 
demonstrate aberrant behaviors that place them at-risk for self-injurious behaviors. The 
CBCL will be used in this trial for children <6 years of age at Screening and follow-up visits 
to assess for behavioral and emotional issues, including those that may be related to suicidal 
ideation and behavior. For this trial, scores on the Withdrawn, Internalizing Problems 
subscales and the Total Problem scales will be examined.  Higher scores on the CBCL 
indicate higher levels of problematic behaviors or dysfunction.  The CBCL scoring algorithm 
allows for a subject’s scores to be standardized using scores from a normal population.  
These standardized scores are referred to as T-scores on the CBCL report.  For this study, a 
cut-off of ≥68 on the T-scores for the Withdrawn, Internalizing Problems subscales and the 
Total Problem scales will be used. The CBCL in this study is used for subjects age 4 to 
<6 years of age.
6.2.5. Cognitive Testing During the Clinical Trial
The CogState Battery will be completed for pediatric partial onset seizure subjects 
4-16 years of age only (subjects from A0081041 and A0081106 Direct Enrollers).
Measures of psychomotor function and attention before and after treatment with study 
medication will be used to determine the extent to which the compound is associated with any 
adverse cognitive outcome.  Two tests will be used to measure psychomotor function and 
attention; these are the CogState Detection (psychomotor function) and CogState Pediatric 
Identification (Go-No Go: attention) tasks.  
CogState Detection and CogState Pediatric Identification will assess task speed and accuracy, 
with faster task speeds and higher accuracy an indicator of a higher-level of cognition.
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6.3. Other Endpoints 
6.3.1. PK/PD Endpoints 
Not applicable.
6.4. Covariates 

Not applicable.
6.4.1. Exploratory Endpoint 
Not applicable.
7. HANDLING OF MISSING VALUES
Missing data will be handled based on the nature of the endpoint and the proposed statistical 
methods for summarizing the data.  
For all endpoints that include seizure rate, number of days with missing seizure diary data 
will be subtracted from the denominator of the 28-day seizure rate calculations. If seizure 
rate for a given subject and for any phase cannot be calculated due to missing information, 
the endpoint that involves seizure rate during that phase will be also missing.
For scales used in this study (eg, CBCL, C-SSRS), scores will be imputed according to the 
imputation rules and algorithms for missing component scores, that are provided in the data 
standard documents. Partial dates for AEs and concomitant medications will be imputed 
according to Pfizer standard algorithms.
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
All subject in this study will receive pregabalin, and all doses of pregabalin will be 
combined. Data will be summarized into 3 groups defined by a combination of the subject’s 
randomized treatment group in one of the previously participated studies (subjects previously 
on pregabalin will be combined across treatment groups) and the treatment received during 
this study. The 3 summary treatment groups will be described as: 
1. Pregabalin-Pregabalin: any dose of pregabalin from the previous study and pregabalin 
in this study.
2. Placebo-Pregabalin: placebo in the previous study and pregabalin in this study. 
3. Direct Pregabalin: pregabalin only in this study and did not participate in any 
previous study.
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Additionally, all pregabalin data in this study will be combined “Overall”.  Other than 
baseline, where relevant, information will be presented only for this study.  Baseline values 
will be the last observation made prior to initiating double-blind dosing in Studies 
A0081041, A0081042, and A0081105.  Subjects entering Study A0081106 directly will have 
baseline observations made at screening (Visit 1B).
There will be 3 sets of analyses performed for most of safety endpoints where it is relevant.
1) Overall; 2) age cohorts); 3) primary seizure type. The three sets are described below.
1. Overall (all subjects in A0081106). This analysis is not applicable for seizure related 
endpoints due to nature of primary seizure type (PGTC, POS) and for some other 
safety endpoints where the assessment is not required for all subjects due to age 
differences.
2. Age cohorts: This cohort analysis will consist of an age cohort defined as: 1 month to 
16 years of age or age >=17. For subjects from previous studies entering study 
A0081106, the age at randomization from their previous study will be used to 
determine the age cohort.  For direct enrollers, age at screening/baseline of the 
present study will be used.  

For some of vital signs and ECGs data where mean and standard deviation of the 
measurement are reported, the age cohorts will be (1 month to <2 years, 2 years to 
<4 years, 4 years to <10 years, 10 years to 16 years and >=17 years) and the 
“overall” summary and by seizure cohort summary will not be performed due to 
differences in normal range in younger age group.
3. Primary seizure type cohorts are POS or PGTC seizures).  The partial onset seizure 
cohort consists of subjects from studies A0081041, A0081042, and A0081106 Direct 
Enrollers. The PGTC seizure cohort includes subjects from Study A0081105.
8.1. Analysis of Primary Efficacy Endpoint
Not applicable.
8.2. Analysis of Secondary Efficacy Endpoints
Not applicable.
8.3. Safety Analyses
Summaries will include data for all subjects who took at least one dose of study medication 
in this study (Safety population).
The safety data (including adverse events, clinical laboratory assessments, ECGs, vital signs, 
height/weight, and physical/neurological examinations) will be summarized through 
standard data tabulations, descriptive statistics, and/or graphical presentations. 
The 3-tier safety analysis approach will not be utilized as this is not a comparative study. 
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8.3.1. Treatment and Disposition of Subjects
Subject evaluation groups will show subject disposition and number of subjects analyzed for 
safety (adverse events and laboratory data). Frequency counts will be supplied for subject 
discontinuation(s) 
Data will be reported in accordance with the sponsor reporting standards.
8.3.2. Demographic Data and Clinical Examination Data
A breakdown of demographic data will be provided for age, race, weight and height.  Each 
will be summarized by sex at birth.
8.3.3. Discontinuation
8.3.4. Subject discontinuations, temporary discontinuations or dose reductions due to 
adverse events will be summarized.
8.3.5. Adverse Events
AEs will be reported in accordance with the sponsor reporting standards, including frequency 
and severity.
8.3.6. Seizure Frequency
Twenty-eight-day seizure rate will be calculated from the seizure diaries and will be 
reviewed as a means of determining seizure control.  Seizure frequency for each seizure type 
will be summarized using descriptive statistics by visit until the end of the trial by treatment 
group and overall.  No statistical inferences will be performed. PGTC and POS seizure 
types will be summarized separately.
PGTC Seizure Frequency: will be summarized for subjects from study A0081105 with 
primary diagnosis of PGTC, and age range from 5 to 65 years. Baseline 28-day seizure rates
for PGTC subjects will be the diary data collected prior to initiating double-blind dosing 
study A0081105.  Other than baseline, time points are relative to study A0081106 open-label 
treatment phase. The 28-day PGTC seizure rate during treatment phase will be reported 
descriptively for each visit in study A0081106 and overall and will be also reported by age 
cohorts (5 to 16 years, >=17 years). For other types of seizure which are not part of the 
28-day PGTC rate (ie, myoclonic, absence seizure, tonic/atonic, clonic, unclassified, status 
epileptic) percent of subjects who experienced at least one myoclonic, absence seizure, 
tonic/atonic, clonic, unclassified, status epileptic will be summarized.
POS Seizure Frequency: will be summarized for subjects from study A0081041, A0081042 
and from direct enrollers with primary diagnosis of POS, and age range from 1 month to 
16 years.  Baseline is not represented for POS subjects as only a subset of these subjects 
(those from Study A0081041) had seizure diary observations prior to the initiation of study 
treatment. Baseline seizure data were collected using V-EEG for subjects previously in Study 
A0081042, which are not comparable to seizure data collected in Study A0081106 using 
diaries. Direct enrollers into Study A0081106 did not have observation of seizures prior to 
initiation of study treatment. 
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The 28-day POS seizure rate during treatment phase will be reported descriptively for each 
visit in study A0081106 and overall. For other types of seizure which are not part of the 
28-day POS rate (ie, unclassified, status epileptic) percent of subjects who experienced at 
least one unclassified, status epileptic will be summarized.
8.3.7. Laboratory, Vital Signs, Height, Weight, and ECG Data
Laboratory, vital signs, height, weight and ECG data will be reported in accordance with the 
sponsor reporting standards for cohorts described in Section 8 by treatment group and 
overall.
8.3.8. Physical and Neurological Examinations
Physical and neurological examination data will be presented for cohorts described in 
Section 8 by treatment group and overall.
8.3.9. Suicidal Ideation and Behavior
C-CASA/C-SSRS
The denominator used in the percentages will be the number of subjects assessed for suicidal 
ideation and behavior (6 to 65 years of age). 
The number and percent of subjects within each C-CASA category by treatment group and 
overall at baseline screening (lifetime) and at any time post-baseline without regard to 
baseline will be reported.  
A subject listing of C-CASA categories as well as the underlying C-SSRS scale data will be 
presented.  
CBCL
For the CBCL (4 to <6 years of age), the denominator used in the percentages will be the 
number of subjects assessed.  Only subjects who fall within the age range for CBCL will be 
summarized. For subjects who falls outside of this age range and have CBCL data collected, 
CBCL data will only be displayed in the listing. 
Additionally, some subjects <6 years are unable to have the CBCL administered due to 
translation issues (eg, Greek and Cebuano speaking subjects) and are administered the 
C-SSRS, which can be answered by the parents/caregivers. These children who have the 
C-SSRS administered will be displayed in listings only, ie, not summarized within the C-
SSRS table.
A subject listing of CBCL scale data will be presented. Also, a summary table with the 
number and percent of subjects with a cut-off  68 on the T-scores for the Withdrawn, 
Internalizing Problems subscales and the Total Problem scales by treatment group at baseline
screening (lifetime), and at any time post-baseline without regard to baseline will be 
reported. 
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C-CASA and CBCL will be presented combined for all subjects and subgroup summaries for 
each age cohort (for C-CASA only; see Section 8) and primary seizure type.
8.3.10. Cognitive Function
CogState Detection task speed and accuracy, and CogState Pediatric Identification speed and 
accuracy will be summarized using descriptive statistics for subjects who participated in 
previous study 1041 and Study A0081106 direct enrollers, overall and by age group 
(4 to 11 years, 12 to 16 years). 
CogState will perform the analysis of the CogState Detection and CogState Pediatric 
Identification.  CogState SAP will be a separate document and developed by CogState.
8.3.11. Exposure and Compliance
Exposure will be calculated as (date of last dose – date of first dose + 1) across the open-label 
treatment phase and categorized using Pfizer Data Standards. 
Compliance will be based on frequency (BID or TID) of dosing recorded on the dosing 
record and calculated as:
Compliance = (Actual Dosing/Expected dosing) X 100%.
Study medication compliance algorithm:
1. Open-label treatment phase: date of last dose – date of first dose + 1 (excluding taper 
phase).
2. Actual Dosing over the open-label treatment phase (excluding taper phase): Using the 
dosing record to determine the doses reported taken: count number of capsules/doses 
taken per day (capsule or liquid, as relevant) during the open-label treatment phase
and add any recorded extra doses or subtract any recorded missed doses. 
3. Expected BID dosing over the open-label treatment phase (excluding taper phase): 
open-label treatment phase duration *2; adjusting for AM/PM dosing on first and last 
days of dosing period. 

Example of BID dosing: If a subject took only PM dose on the first day of dosing 
and AM on the final day of dosing, subtract two from expected dosing.

Expected TID dosing over the open-label treatment phase (excluding taper phase): 
open-label treatment phase duration *3 (excluding first and last day of dosing in 
addition to the taper phase). 
Compliance will be calculated and summarized by liquid dosing, capsule dosing and overall 
across the whole open-label treatment phase (excluding taper phase), and by visit.
8.4. Summary of Efficacy Analyses 
Not applicable.
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Appendix 1. Data Derivation Details
This table describes how seizure related endpoints have been defined. 
Endpoint 
Derivation
PGTC 28-day seizure rate at baseline: 
Baseline 28-day seizure rates will be 
observation made prior to initiating 
double-blind dosing in studies 
A0081105 during the 8 weeks baseline 
period)
There will not be baseline seizure rate 
for POS subject for reason described in 
Section 8.   
28-day seizure rateb= [(# of seizuresb) ÷ (#of 
daysb - # of missing diaryb)] × 28, where #of 
daysb is defined as (first dose date-1) – screening 
date +1.
28-day seizure rate during treatment 
phase (excluding taper phase) POS, 
PGTC
28-day seizure ratet = [(# of seizurest) ÷ (#of 
dayst- # of missing diaryt)] × 28, where #of dayst
is defined as date of last diary data entry for that 
visit – date of first diary data entry for that visit
+1.
Seizure frequency for other type of 
seizure (ie, myoclonic, absence seizure, 
tonic/atonic, clonic, unclassified, status 
epileptic) which are not part of 28-day 
seizure rate. 
n (%) of subject experienced at least each other 
type of seizure will be calculated for POS 
population and PGTC population separately
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Appendix 2. C-SSRS Mapped to C-CASA - Suicidal Ideation and Behavior Events and 
Codes
C-CASA 
Event Code
C-CASA Event
C-SSRS Response
1
Completed suicide
As captured in the safety database
2
Suicide attempt
“Yes” on “Actual Attempt”
3
Preparatory acts towards 
imminent suicidal behavior
“Yes” on any of the following:

“Aborted attempt”, or

“Interrupted attempt”, or

“Preparatory Acts or Behavior”
4
Suicidal ideation
“Yes” on any of the following:

“Wish to be dead”, or

“Non-Specific Active Suicidal 
Thoughts”, or

“Active Suicidal Ideation with Any 
Methods (Not Plan) without Intent 
to Act”, or

“Active Suicidal Ideation with 
Some Intent to Act, without 
Specific Plan”, or

“Active Suicidal Ideation with 
Specific Plan and Intent”
7
Self-injurious behavior, no 
suicidal intent
“Yes” on “Has subject engaged in Non-
suicidal Self-Injurious Behavior?”
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