PRIMARY GENERALIZED TONIC-CLONIC SEIZURES

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.

PREGABALIN

PREGABALIN

oral solution

20mg

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.
 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.

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.
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.

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 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.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.