| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061334 |
| E.1.2 | Term | Partial seizures |
|
| 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 assess the efficacy of pregabalin as monotherapy in the treatment of patients with partial seizures who are not well controlled on current antiepileptic drug (AED) treatment. Safety data will also be collected and analyzed. |
|
| E.2.2 | Secondary objectives of the trial |
| There are no secondary objectives, just the one main objective in E.2.1 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Diagnosis of epilepsy with partial seizures, as defined in the International League
Against Epilepsy (ILAE) classification of seizures (Appendix 3). Partial seizures may be simple or complex, with or without secondary tonic-clonic generalization. Diagnosis must be established by the following: patient’s medical history (eg, seizures), excluding confounding disorders such as pseudo seizures, syncopes, etc., family history and the results of electroencephalograph (EEG) testing done within 2 years of the first patient visit. Results must be consistent with the diagnosis of focal-onset epilepsy;
2. Males or females, age 18 years or older;
3. Women must be nonpregnant and nonlactating, and must be using a barrier or
hormonal method of contraception; or must be post-menopausal, or surgically sterilized. All women must have a negative pregnancy test at Screening. Females who become pregnant will be discontinued from the study;
4. Minimum body weight of 90 lbs;
5. Documented history of at least 4 partial seizures in the 8 weeks prior to the
Screening Visit (V1);
6. Stable treatment with 1-2 AEDs in the 8 weeks prior to the Screening Visit (V1);
7. Seizure frequency of at least 4 partial seizures in the 8-week Baseline phase, with
no 4-week seizure-free period;
8. Electrocardiogram (ECG) without significant abnormal findings (Section 7.2.4.);
9. A computed tomography (CT) or magnetic resonance imaging (MRI) scan within
2 years of the Screening Visit (V1) demonstrating no progressive structural abnormality;
10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
study procedures, diary completion and other trial procedures;
11. Willing and able to give written informed consent by 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 the trial. |
|
| E.4 | Principal exclusion criteria |
1. Current diagnosis of febrile seizures or seizures related to an ongoing acute medical illness;
2. Seizures occurring only in cluster patterns, or seizures of a metabolic, toxic or infectious origin;
3. Primary generalized epilepsy (eg, absence epilepsy);
4. Progressive structural CNS lesion or a progressive encephalopathy;
5. Status epilepticus within the previous year;
6. Any significant psychiatric disorder or recurrent episodes of severe depression (defined as any pharmacologic treatment or hospitalization for the illness within 1 year prior to the Screening Visit, V1). Patients with mild, chronic depression without recent hospitalization who are being maintained on a stable dose of a single antidepressant are acceptable;
7. Current or within the last 6 months, white blood cell (WBC) count of <2500 cells/µL or a neutrophil count of <1500 cells/µL or a platelet count of <100 x 103 cells/µL, or a history of bone marrow suppression;
8. History or clinical evidence of cardiovascular, hematologic, hepatic, or renal disease;
9. CLcr ≤60 mL/min (estimated from serum creatinine);
10. Current treatment with benzodiazepines and/or barbiturates if used for any indication other than epilepsy
11. Concomitant non-antiepileptic medication (eg, neuroleptic drugs) that could alter
the effectiveness of the study medication response or affect seizure frequency;
12. Alcohol or substance abuse or dependence unless in full remission for at least 12 months;
13. Participation in any clinical trial within the 30 days before the Screening Visit (V1);
14. 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.
15. Previous use of pregabalin.
16. History of poor compliance with AED therapy. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this trial is the percent of subjects who meet at least one of the following predetermined exit criteria listed below.
1. An episode of status epilepticus;
2. A secondarily generalized tonic-clonic seizure if none had been experienced within 2 years of study entry;
3. A 28-day study seizure rate during the double-blind treatment phase that was greater than two times the maximum 28-day study seizure rate during the baseline phase (a 28-day period is defined as 28 consecutive study days);
4. A 2-day study seizure rate during the double-blind treatment phase that was greater than two times the maximum 2-day study seizure rate during the baseline phase (a 2-day period is defined as 2 consecutive study days);
5. An unacceptable increase in the frequency or intensity of seizure activity that,
according to the investigator, is clinically significant. |
|
| 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 | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 75 |
| 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 |
|
| 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
| |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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