E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034089 |
E.1.2 | Term | Partial seizures NOS |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
The primary objective of this study is to evaluate the efficacy of 2 dose levels of pregabalin (Level 1: 2.5 mg/kg/day; maximum 150 mg day and Level 2: 10 mg/kg/day; maximum 600 mg day) compared to placebo as an adjunctive treatment in reducing the frequency of partial onset seizures in pediatric subjects 4 to 16 years of age. |
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E.2.2 | Secondary objectives of the trial |
-To characterize the efficacy of pregabalin vs. placebo on the frequency of partial onset seizures as determined by responder rate in pediatric subjects 4 to 16 years of age.
-To assess the safety and tolerability of pregabalin in pediatric subjects 4 to 16 years
of age with partial onset seizures. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 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) Please see appendix 1 of the protocol for additional siezure type inclusions.
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 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 clinical status has
occurred such that an imaging study would be
required, then a CT 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
randomization. Imaging 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 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. 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. |
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E.4 | Principal 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.
4. Exacerbation of POS due to fever occurring within
60 days of screening5.. Status epilepticus within 1 year
prior to screening.
6 . Seizures related to drugs, alcohol, or acute medical
illness.
7 . Any change in AED regimen (type of medication or
dose) within 28 days of the Screening Visit or during
the Baseline Phase.
8 . Progressive structural CNS lesion or a progressive
encephalopathy.
9 . Progressive errors of metabolism.
10 . 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).
11 . Estimated creatinine clearance (ClCR) <80
mL/min/1.73 m2.
12 . 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.
13 . 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.
14 . 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.
15 . The concomitant use of gabapentin is prohibited.
16 . 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.
17 . History of lack of efficacy for treatment of
epilepsy with pregabalin at presumed efficacious
doses.
18 . Known allergy or intolerance to pregabalin or its
excipients, including lactose, or other α2δ ligands (eg,
gabapentin).
19 . Prior participation in a pregabalin clinical trial.
20 . Treatment with pregabalin for any reason within
60 days prior to screening.
21 . History of sensitivity to heparin or heparin
induced thrombocytopenia.
22 . Unwilling or unable to comply with the Life Style
Guidelines.
23 . Not reasonably expected to complete the trial.
24 . Participation in other clinical studies within 30
days before the current study begins and/or during
study participation.
25 . Subjects whose parents/legally acceptable
representatives are investigational site staff members
or subjects whose parents/legally acceptable
representative are Pfizer employees directly involved
in the conduct of the trial.
26 . Any subjects considered at risk of suicide based
on the MINI-KID and C-SSRS Lifetime (subjects age
≥6 years) or CBCL (subjects <6 years) or likely to self
harm based on clinical judgment. Based on the
judgment of the investigator, 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
behaviour and if the subject has had suicidal ideation
in the last 6 months prior to screening, suicidal
behaviors or attempts within 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
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. For calculation see protocol. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Croatia |
Czech Republic |
Estonia |
Finland |
France |
Greece |
Guatemala |
Hungary |
India |
Italy |
Korea, Republic of |
Lithuania |
Malaysia |
Netherlands |
Panama |
Philippines |
Poland |
Romania |
Singapore |
Sweden |
Turkey |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 14 |