E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adjunctive treatment of partial seizures, with and without secondary generalization. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015037 |
E.1.2 | Term | Epilepsy |
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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 compare the efficacy of pregabalin and levetiracetam, at doses up to the maximal ones used in pivotal registration trials, as adjunctive therapy in subjects with refractory partial seizures, under randomized, parallel-group, flexible-dose conditions. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of pregabalin and levetiracetam in this subject population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects (male or female) must be > 18 years of age, with a diagnosis of epilepsy with partial seizures, as defined in the International League Against Epilepsy (ILAE) classification of seizures. Partial seizures may be simple or complex, with or without secondary tonic-clonic generalization. 2. Subjects must be have been diagnosed with epilepsy for at least 2 years, and must have been unresponsive to treatment with at least two but no more than five prior antiepileptic drugs (AEDs), and at the time of study enrollment are on stable dosages of 1 or 2 standard AEDs. 3. They must have had a 12-lead electrocardiogram (ECG) without clinically significant abnormal findings prior to randomization. 4. Subjects must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy. 5. Women of childbearing potential must be established on an effective method of contraception during the study. Women should also have a negative pregnancy test prior to study entry. 6. During the 6-week baseline period, subjects must have had a minimum of four partial seizures, with no 28-day period free of partial seizures with or without secondary generalization. A caregiver or witness must be with the subject for a sufficient duration to accurately chronicle the occurrence of seizures. These seizures must have been documented in the subject’s diary. 7. Subjects with electroencephalograph (EEG) testing done within 2 years of randomization. EEG abnormalities should be consistent with a diagnosis of focal-onset epilepsy; 8. Signed and dated informed consent will be obtained from each subject (only include those able to consent) in accordance with the local regulatory and legal requirements 9. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Subjects who are willing, but need assistance for self administered questionnaires may be considered acceptable, but must first be discussed on a case-by-case basis with the Pfizer monitor prior to any to any screening tests or procedures for the study. |
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E.4 | Principal exclusion criteria |
1. Females who are pregnant, breastfeeding, or intend to become pregnant during the course of the trial will be excluded; 2. Subjects with other neurologic illness that could impair endpoint assessment, or subjects with Lennox-Gastaut syndrome, absence seizures, status epilepticus within the 12 months prior to trial entry, or with seizures due to an underlying medical illness or metabolic syndrome, will be excluded 3. Subjects with clinically significant liver disease or with a calculated creatinine clearance of <60mL/min will be excluded. 4. Subjects with a history of retinal abnormalities or treatment with retinotoxic agents will be excluded. Refer to Section 5.5. 5. Subjects with a history of lack of response to levetiracetam or pregabalin or hypersensitivity or poor tolerability to levetiracetam, gabapentin or pregabalin will be excluded. 6. Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol. 7. Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study. 8. Previous use of levetiracetam (less than one month), gabapentin or pregabalin within 30 days prior to randomization or likelihood of engaging in these treatments during the study period. 9. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial. 10. Any patients who are not suitable to be treated with pregabalin or levetiracetam according to the respective local labeling. 11. In the judgment of the investigator the subject is unable or unlikely to follow the protocol, drug administration procedure or otherwise might not be suitable for the study. 12. In the judgment of the investigator, any subject unable to understand the nature, scope, procedures and possible consequences of the study and/or evidence of an uncooperative attitude. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoint:The primary efficacy parameter will be the responder rate, defined as the proportion of subjects who had at least a 50% reduction in 28-day seizure rate during the maintenance phase, as measured from baseline (data collected during 6 weeks screening phase). (see Protocol Section 9.3)
Exploratory Endpoints:Time to drop out due to AE Time to dose reduction during the maintenance phase. Time to dose maintenance following seizure freedom;
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 | Information not present in EudraCT |
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 |
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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
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |