| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Epilepsy - partial-onset seizures with or without secondary generalisation |
|
| 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 | 10065336 |
|
| 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 efficacy of retigabine immediate release (IR) as adjunctive therapy to each of the following specified monotherapy AED treatments: carbamazepine/ oxcarbazepine, lamotrigine, levetiracetam or valproic acid in subjects with partial-onset seizures (POS) using a flexible dosing regimen. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the efficacy of retigabine IR adjunctive therapy to the pooled set of specified AED treatments using a flexible dosing regimen. • To evaluate the safety and tolerability of retigabine IR adjunctive therapy to each of the following specified monotherapy AED treatments: carbamazepine/ oxcarbazepine, lamotrigine, levetiracetam or valproic acid using a flexible dosing regimen. • To evaluate the safety and tolerability of retigabine IR adjunctive therapy to the pooled set of specified AED treatments using a flexible dosing regimen. • To evaluate the effect retigabine IR adjunctive therapy to each of the specified monotherapy AED treatments on functional status (worry, activity limitations) and productivity using a flexible dosing regimen. • To evaluate the effect retigabine IR as adjunctive therapy to the pooled set of specified AED treatments on functional status (worry, activity limitations) and productivity using a flexible dosing regimen. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the GW582892 Investigators Brochure. To be eligible for enrolment in the study, a subject must meet all of the following criteria: 1. Is ≥18 years of age (men or women). 2. Has a confident diagnosis of epilepsy with partial-onset seizures i.e., simple or complex partial seizures with or without secondary generalization (International League Against Epilepsy (ILAE) classification; 1981) for more than 24 weeks prior to the Baseline Visit. 3. Has experienced at least 4 partial-onset seizures (i.e., simple or complex partial seizures with or without secondary generalization) during an 8-week (i.e., 56 days) prospective Baseline Phase with at least one partial seizure occurring during each 4- week (i.e., 28-day) period. NOTE: With prior authorisation from the Sponsor, a maximum of 4 weeks (i.e., 28 days) of retrospective seizure data may replace up to the first 4 weeks (i.e., first 28 days) of the prospective Baseline Phase for subjects providing reliable documentation of the following (see Section 11, Appendix 3): • A complete daily seizure diary that includes the number, and type (i.e., simple or complex partial seizures with or without secondary generalization), of seizures experienced each day for up to 28 consecutive days immediately prior to the prospective Baseline Phase. • Stability of prescribed dosage of specified background AED • Compliance with background AED All subjects permitted to use retrospective seizure data must complete a minimum of 4 weeks (i.e., 28 days) of the prospective Baseline Phase. The retrospective Baseline Phase and prospective Baseline Phase must equal 56 consecutive days. 4. Is currently receiving a stable dose of one of the following AEDs: carbamazepine/oxcarbazepine, lamotrigine, levetiracetam or valproic acid. The AED dose must be stable 4 weeks prior to Baseline Visit (retrospective or prospective) and during the Baseline period. NOTE: Benzodiazepines used in any manner other than acute usage as defined in this protocol will be considered concurrent AED usage and will not be permitted (see Section 5.5.1.2). 5. Is able and willing to maintain an accurate and complete daily written seizure calendar and functional status diary or has a caregiver who is able and willing to maintain an accurate and complete daily written calendar/diary for the entire duration of the study. 6. Is able to comply with dosing of study drug, background AED and all study procedures. 7. Has given written informed consent, or has a legally authorized representative who has given written informed consent, prior to the performance of any study assessments. 8. A female subject is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal) . b. Child-bearing potential, has a negative pregnancy test at Screening, and agrees to satisfy one of the contraception methods as listed in Section 11, Appendix 4. c. Is not pregnant or lactating or planning to become pregnant during the study. |
|
| E.4 | Principal exclusion criteria |
| Has a history of generalised epilepsy (e.g. Lennox-Gastaut, Juvenile Myoclonic etc.) 2. Has had status epilepticus (other than simple partial status epilepticus) within the 24 weeks prior to Baseline Visit. 3. Has participated in a previous retigabine study (subjects with documented evidence of having received placebo will be eligible). 4. Is currently or has been abusing substance(s) or other medications in the 12 months prior to Baseline visit. 5. Has taken an investigational drug, or used an investigational device, within the previous 30 days prior to screening or plans to take an investigational drug anytime during the study. 6. Is currently following or planning to follow the ketogenic diet. 7. Has been treated with vigabatrin within the past 6 months prior to Baseline; if a subject has been previously treated with vigabatrin, a visual perimetry test after discontinuation of vigabatrin must show no visual field constriction that has been seen in some subjects taking vigabatrin. 8. Is planning surgery or implantation of Vagus Nerve Stimulator (VNS) to control seizures during the study. NOTE: Subjects with surgically implanted Vagus Nerve Stimulator (VNS) which is not functioning or has been switched off for at least 4 weeks prior to the Baseline Visit and remains non-functioning/off for the duration of the study will be eligible for the study. 9. Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that are likely to interfere with the objectives of the study. 10. Has any medical condition that, in the investigator’s judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs. 11. Has a QTc ≥450 millisecond (msec) or ≥480msec for subjects with Bundle Branch Block at the time of screening as calculated below. Note: If the initial ECG at screening indicates a QTc interval outside these limits, two further ECGs should be performed and the average QTc value of these triplicate ECGs calculated. If the average value exceeds the stated limits, the subject is not eligible. 12. Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects experiencing a ≥ 50% reduction in 28-day partial-onset seizure frequency from Baseline during the combined Titration and Flexible Dose Evaluation Phases stratified by concurrent AED. |
|
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| multicentrico, in aperto, a dosi flessibili |
|
| 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 |
| no terapia confronto,specifiche monoterapie conAED |
|
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 41 |
| 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
|
| Il termine dello studio sar� alla fine delle 16 sett.della fase di valutazione della dose flessibile, i cui soggetti potranno entrare in uno studio di estensione.Contrariamente i soggetti entreranno in "taper/follow-up" |
|
| 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 | 27 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 27 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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