E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epilepsy: Partial Onset Seizures with or without 1) Secondarily Generalized Seizures 2) Primary Generalized Tonic-Clonic Seizures |
|
E.1.1.1 | Medical condition in easily understood language |
One part of brain affected called partial seizure. Partial seizures, encompass entire brain called generalized seizure. Disturbance in functioning of both sides of brain called Tonic-Clonic Seizures. |
|
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 | 24.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10085326 |
E.1.2 | Term | Parietal lobe epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 retention rate of perampanel when given as monotherapy or 1st adjunctive therapy in subjects with partial-onset seizures (POS) or primary generalized tonic-clonic seizures (PGTCS) |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of perampanel when given as monotherapy or 1st adjunctive therapy in subjects with POS or PGTCS as measured by seizure freedom; to assess the proportion of subjects with POS or PGTCS that are able to convert from 1st adjunctive therapy to perampanel monotherapy; to assess the safety of perampanel as initial monotherapy or 1st adjunctive therapy in subjects with POS or PGTCS; to assess dosing and titration of perampanel when administered as initial monotherapy or 1st adjunctive therapy in subjects with POS or PGTCS |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects will be male or female and no younger than 4 years of age and be able to swallow perampanel tablets. 2. Subjects must have a diagnosis of epilepsy with POS with or without secondarily generalized seizures (SGS) or with primary generalized tonic-clonic seizures (PGTCS). Either of the following must have occurred to support an epilepsy diagnosis: a. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart b. One unprovoked (or reflex) seizure with electroencephalography (EEG) evidence of seizures 3. Subjects who receive perampanel as a first adjunctive therapy must currently have been treated with stable doses of monotherapy with an anti-epileptic drug (AED) for 8 weeks prior to Visit 2 (Week 0), have not previously received adjunctive AED treatment, and must, in the investigator's judgement, be in need of initial adjunctive therapy after failure to control seizures with AED monotherapy, at the optimal dose and duration. 4. Subjects who receive perampanel as monotherapy, who were newly diagnosed (treatment naïve), following the defined diagnosis of epilepsy. 5. Subjects who are currently receiving monotherapy treatment may receive perampanel as monotherapy if, in the investigator's judgment, the participant may benefit from a change in monotherapy treatment. Subjects must not have previously received adjunctive AED treatment. 6. If antidepressants or antianxiety drugs are used, subjects must be on a stable dose regimen of these drugs during the 8 weeks before Visit 2 (Week 0). |
|
E.4 | Principal exclusion criteria |
1.Subjects should not have previously received or currently be receiving perampanel. 2.Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin [β-hCG] or hCG test with a minimum sensitivity of 25 International Units per liter [IU/L] or equivalent units of β-hCG or hCG); a separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 3.Females of childbearing potential who: •Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: •Total abstinence (if it is their preferred and usual lifestyle) •An intrauterine device or intrauterine hormone-releasing system •An oral contraceptive (with additional barrier method if using contraceptive containing levonorgestrel); subject must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation •Have a vasectomized partner with confirmed azoospermia •Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation -For sites outside of the European Union, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, i.e, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide. NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). 4.Presence of or previous history of Lennox-Gastaut syndrome 5.Presence of non-motor simple partial seizures only 6.A history of status epilepticus within 1 year before Screening Visit (Visit 1) 7.Subjects on antipsychotics or who have psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of attempted suicide within 1 year before Screening Visit (Visit 1) 8.Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors 9.Concomitant use of barbiturates (except for seizure control indication and premedication for electroencephalogram) and benzodiazepines (except for seizure control indication) within 8 weeks prior to Visit 2 (Week 0) 10.Use of intermittent rescue benzodiazepines (i.e, 1 to 2 doses over a 24-hour period is considered a one time rescue) 2 or more times in the 8-week period prior to Visit 2 (Week 0) 11.Severe renal insufficiency (defined by estimated glomerular filtration rate of < 30 milliliters per minute [mL/min]) or subjects who receive hemodialysis 12.Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the subject’s safety or study conduct NOTE: Stable elevation of liver enzymes, alanine aminotransferase and aspartate aminotransferase due to concomitant medication(s) will be allowed if they are less than 3 times the upper limits of normal. 13.Hypersensitivity to perampanel or any excipients 14.Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 15.Subjects who are participating in other interventional clinical trial 16.Subject who are judged to have inadequate cognitive ability for participation in the study (intelligence quotient < 80 or investigator judgment) 17.Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS) 18.Any lifetime suicidal behavior based on the C-SSRS 19.Concomitant use of any form of cannabidiol (CBD) 20.Planned brain surgery during study participation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Percentage of subjects remaining on perampanel at 3 months after the initiation of treatment (retention rate) 2. Percentage of subjects remaining on perampanel at 6 months after the initiation of treatment (retention rate) 3. Percentage of subjects remaining on perampanel at 9 months after the initiation of treatment (retention rate) 4. Percentage of subjects remaining on perampanel at 12 months after the initiation of treatment (retention rate) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Month 3 2. Month 6 3. Month 9 4. Month 12 |
|
E.5.2 | Secondary end point(s) |
1. Percentage of subjects who achieve seizure-free status for partial-onset seizures (POS), secondarily generalized seizures (SGS), and primary generalized tonic-clonic seizures (PGTCS) during the Maintenance Period 2. Percentage of subjects who achieve 3-month seizure-free status for POS, SGS, and PGTCS 3. Percentage of subjects who achieve 6-month seizure-free status for POS, SGS, and PGTCS 4. Percentage of subjects who receive perampanel as a first adjunctive therapy who are able to convert to perampanel monotherapy 5. Number of subjects with any treatment-emergent adverse event (AE) 6. Number of subjects with any treatment-emergent serious adverse event (SAE) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to 39 weeks 2. Up to Month 3 3. Up to Month 6 4. Up to 39 weeks 5. Up to approximately 24 months 6. Up to approximately 24 months |
|
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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
|
Last Visit Last Subject (LVLS) is when the final subject was examined or received an intervention for purposes of final collection of data for the primary and secondary outcome measures and adverse events. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 44 |