| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Partial onset seizures and Primary Generalised Tonic Clonic Seizures |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10034089 |
| E.1.2 | Term | Partial seizures NOS |
| E.1.2 | System Organ Class | 100000004852 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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.
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| E.2.2 | Secondary objectives of the trial |
| There are no Secondary Objectives in this study |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For Subjects who have Participated in Studies A0081041, A0081042, or A0081105
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. The diagnosis must be established by:
•Subject’s history 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 with PGTC seizures and who continue to satisfy seizure related inclusion criteria for that study. 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.
For Directly Enrolling 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. see item 1 above
2. see item 2 above
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. The diagnosis must be established by:
•see subitem 4.1 above
•Subjects must have had a contrast enhanced CT or 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 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 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. |
|
| E.4 | Principal exclusion criteria |
1. Lennox-Gastaut syndrome, Infantile Spasms, Absence seizures for Direct Enrolling subjects, BECT 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 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 CNS lesion or a progressive encephalopathy. Progressive inborn errors of metabolism.
5. Known or suspected chronic hematologic, hepatic or renal disease (AST and 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 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)
8. Taking any 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 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 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 C-SSRS Lifetime (subjects >=6 years of age) or CBCL(subjects <6 years of age) or responses obtained during the 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. 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 alpha2delta ligands.
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 |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
• 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).
• Clinical laboratory data (hematology, chemistry, urinalysis).
• Electrocardiograms (ECGs).
• 28 day seizure rate (number of seizures per 28 day period).
• Suicidality assessments.
•Cognitive assessment battery (POS pediatric subjects 4 16 years of age only). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Various endpoints throughout the study |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 116 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Belgium |
| Bulgaria |
| China |
| Croatia |
| Czech Republic |
| Estonia |
| Finland |
| France |
| Germany |
| Greece |
| Hungary |
| India |
| Israel |
| Italy |
| Korea, Republic of |
| Lithuania |
| Malaysia |
| Netherlands |
| Philippines |
| Poland |
| Portugal |
| Romania |
| Serbia |
| Singapore |
| Slovakia |
| South Africa |
| Spain |
| Sweden |
| Switzerland |
| Taiwan |
| Thailand |
| Turkey |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 28 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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