Epilepsy with partial onset seizures
Conditions
Interventions
Subjects will be randomized in a double-blind manner to a fixed dose of either
of the following:
* Placebo
* Level 1: Pregabalin 2.5 mg/kg/day (maximum 150 mg/day)
* Level 2: Pregabalin 10 mg/kg/day
Sponsors
Pfizer
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: 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 and/or parent/legally acceptable representative has been informed of all
 pertinent aspects of the study. When there are two parents or two 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 also be obtained.
 2. Subjects and/or parent(s)/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(s)/legally acceptable representative must be considered willing
 and able to complete daily seizure diaries and monitor seizure frequency.
 4. Male and female epilepsy subjects, 4 to 16 years of age inclusive on the date of the
 Screening Visit.
 5. Diagnosis of epilepsy with partial onset seizures classified as simple partial, complex
 partial or partial becoming secondarily generalized, according to the International
 League Against Epilepsy (ILAE)3 Diagnosis must be established by:
 - Subject*s history (eg, description of seizures excluding confounding disorders such as pseudoseizures, syncopes 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 EEG testing within 24 months of the Screening Visit. Results must be consistent with the
 diagnosis of focal-onset epilepsy and must demonstrate that no abnormality is
 likely to be progressive.
 - Confirmation of diagnosis by independent reviewer before randomization.
 6. Must have a partial onset seizure frequency of at least 3 seizures per 28-day period
 prior to screening. Must have a partial onset seizure frequency of *6 seizures and no
 continuous 4 week seizure free period during the 8 week baseline phase prior to
 randomization.
 7. Currently receiving a stable dose of 1 to 3 antiepileptic drugs (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. A previously
 implanted Vagus nerve stimulator (VNS) for the treatment of epilepsy is allowed and
 will be considered one of the 3 antiepileptic treatments.
 8. A 12-lead ECG at screening without significant abnormal findings as determined by
 the investigator and confirmed by the Central ECG Reader.
Exclusion criteria
Exclusion criteria: 1. Primary generalized seizures (including in the setting of co-existing partial onset
 seizures) which include for example:
 - Clonic, tonic and clonic-tonic seizures (note that partial onset seizures that become secondarily generalized are not exclusionary).
 - Absence seizures.
 - Infantile spasms.
 - Myoclonic, myoclonic atonic, myoclonic tonic seizures.
 2. Lennox-Gastaut syndrome, Benign Epilepsy with Centrotemporal Spikes (BECTS) and Dravet syndrome. 3. A current diagnosis of febrile seizures, or seizures related to an ongoing acute
 medical illness. Any febrile seizures within 1 year of screening. 4. Status epilepticus within 1 year prior to screening. 5. Seizures related to drugs, alcohol, or acute medical illness. 6. Any change in AED regimen (type of medication or dose) within 28 days of the Screening Visit or during the Baseline Phase. 7. Progressive structural CNS lesion or a progressive encephalopathy.
 8. Progressive errors of metabolism. 9. Known or suspected chronic hematologic, hepatic or renal disease (AST and ALT above 3 times the upper limit of normal (ULN); or bilirubin, BUN, or creatinine above 2 times the ULN within the previous 6 months prior to screening). 10. Estimated creatinine clearance (ClCR) <80 mL/min/1.73 m2. 11. Other severe acute or chronic medical or psychiatric condition (eg, current major depressive disorder;schizophrenia or other psychoses) or laboratory abnormality that may increase the risk associated with study participation or study medication administration or may interfere with the interpretation of the study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 12. Pregnant or nursing females (females who are menarchal must have a negative pregnancy test); menarchal females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least 14 days prior to the first dose of study medication until completion of the study.
 13. 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 will be permitted if medication doses are stable and remain so throughout the duration of study. A
 ketogenic diet will also be allowed given that the diet is adhered to for the duration of
 the study. 14. The concomitant use of gabapentin is prohibited. 15. Use of cocaine, phencyclidine (PCP), or other illegal or illicit drugs is prohibited. Use of amphetamines, barbiturates, opiates, or benzodiazepines without a valid current prescription is prohibited.
 16. History of lack of efficacy for treatment of epilepsy with pregabalin at presumed efficacious doses. 17. Known allergy or intolerance to pregabalin or other *2* ligands (eg, gabapentin).
 18. Prior participation in a pregabalin clinical trial.
 19. Treatment with pregabalin for any reason within 60 days prior to screening. 20. History of sensitivity to heparin or heparin induced thrombocytopenia. 21. Unwilling or unable to comply with the Life Style Guidelines. 22. Not reasonably expected to complete the trial.
 23. Participation in other clinical studies within 30 days before the current study begins
 and/or during study participation. 24. Subjects whose parents/legally
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be the log-transformed (loge) 28-day seizure rate for all partial onset seizures collected during the 12 week double-blind treatment phase. Data from the 1-week double-blind taper phase will not be used in the efficacy analyses. Results will be reported as *percent reduction in seizures* relative to placebo. The 28-day seizure rate will be calculated as follows for the double-blind period: # of seizures in the double-blind phase of study 28 day seizure rate = --------------------------------------------------------------------- X 28 # of days in period - # of missing diary days in period When the log-transformation is used, the quantity 1 is added to the 28-day seizure rate for all subjects to account for any possible "0" seizure incidence. This will result in the following primary efficacy measure: loge (28-day seizure rate +1). For example, a difference between one of the pregabalin doses and placebo of -0.400 on the log transformed scale for the 28-day seizure rate, translates into a 33% reduction in the 28-days seizure rate of the pregabalin group from the placebo group (ie, 100%*[exp-0.400-1]=-33%]). The 28-day seizure rate for the baseline phase will be calculated similarly. | — |
Secondary
| Measure | Time frame |
|---|---|
| Responder Rate, defined as subjects who have a * 50% reduction in partial seizure rate from baseline during the double-blind treatment phase. Subjects meeting this criterion will be considered a favorable outcome. | — |
Countries
Netherlands
Outcome results
None listed