Seizure Disorder Generalized Tonic Clonic Clinical Trial
Official title:
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures
| Verified date | November 2015 |
| Source | Eisai Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
This study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of perampanel on Primary Generalized Tonic Clonic (PGTC) seizure frequency in adolescents and adults maintained on one to two stable antiepileptic drugs.
| Status | Completed |
| Enrollment | 164 |
| Est. completion date | November 2015 |
| Est. primary completion date | May 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 12 Years and older |
| Eligibility |
Inclusion: 1. Clinical diagnosis of PGTC seizures (with or without other subtypes of primary generalized seizures) and experiencing greater than or equal to 3 PGTC seizures during the 8-week period prior to randomization 2. Have had a routine electroencephalogram (EEG) prior to or during the Baseline Period with electroencephalographic features consistent with primary generalized epilepsy; other concomitant anomaly should be explained by adequate past medical history 3. On a fixed dose of one to a maximum of three concomitant antiepileptic drugs (AEDs) for a minimum of 30 days prior to Baseline; only one inducer AED (i.e., carbamazepine, oxcarbazepine, or phenytoin) out of the maximum of two AEDs will be allowed 4. A vagal nerve stimulator (VNS) will be allowed, but it must have been implanted greater than or equal to 5 months prior to Baseline (stimulator parameters cannot be changed for 30 days prior to Baseline and for the duration of the study). 5. Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years (for adults) and 5 years (for adolescents) that ruled out a progressive cause of epilepsy 6. A ketogenic diet will be allowed as long as the participant has been on this diet for 5 weeks prior to randomization Exclusion: 1. A history of status epilepticus that required hospitalization within 12 months prior to Baseline 2. Seizure clusters where individual seizures cannot be counted 3. A history of psychogenic seizures 4. Concomitant diagnosis of Partial Onset Seizures (POS) 5. Progressive neurological disease 6. Clinical diagnosis of Lennox-Gastaut syndrome 7. If felbamate is used as a concomitant AED, participants must be on felbamate for at least 2 years, with a stable dose for 60 days prior to Baseline. They must not have a history of white blood cell (WBC) count below less than or equal to 2500/microL (2.50 1E+09/L), platelets less than 100,000/microL, liver function tests (LFTs) greater than 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate. 8. Concomitant use of vigabatrin: Participants who took vigabatrin in the past must be discontinued for approximately 5 months prior to Baseline, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test 9. Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline 10. Use of intermittent rescue benzodiazepines (i.e., one to two doses over a 24-hour period considered one-time rescue) two or more times within the 30 days prior to Baseline |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Eisai Inc. |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization)- for Core Study | Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days (as determined from participant diaries) was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change from baseline in PGTC seizure was analyzed over the Titration and Maintenance Periods combined, while baseline was defined as seizure frequency per 28 days based on all valid diary data during the Prerandomization Phase. | Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) | No |
| Primary | 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance-LOCF (for Core Study) | A responder is a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance-(last observation carried forward (LOCF) from prerandomization. The data is presented as percentage of participants. | Baseline (4 or 8 weeks) and Maintenance (13 weeks) | No |
| Secondary | Median Percent Change in All Seizure Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization)- for Core Study | Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change in seizure frequency relative to baseline (prerandomization) for all seizures (PGTC, myoclonic, absence and all other seizures that occur during the study) per 28 days during the Titration and Maintenance Periods combined was analyzed. | Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) | No |
| Secondary | Median Percent Change in Primary Generalized Seizure Subtype Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - for Core Study | Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change in seizure frequency relative to baseline (prerandomization) for primary generalized seizure subtype (myoclonic and absence) per 28 days during the Titration and Maintenance Periods combined was analyzed. | Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) | No |
| Secondary | 50% Responder Rate for All Seizure During Maintenance-LOCF (for Core Study) | All seizures includes PGTC, myoclonic, absence and all other seizures that occur during the study. A responder is a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance- LOCF from prerandomization. The data is presented as percentage of participants. | Baseline (4 or 8 weeks) and Maintenance (13 weeks) | No |
| Secondary | 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance-LOCF (for Core Study) | Primary generalized seizure subtype includes absence and myoclonic seizures. A responder is a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance-(last observation carried forward LOCF) from prerandomization. The data is presented as percentage of participants. | Baseline (4 or 8 weeks) and Maintenance (13 weeks) | No |
| Secondary | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events as a Measure of Safety and Tolerability of Perampanel in Subjects With Inadequately Controlled PGTC Seizures | An Adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational product. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening (ie, the subject was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect (in the child of a subject who was exposed to the study drug). In this study, treatment emergent adverse events (TEAEs) (defined as an AE that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed. | For each participant, from the first treatment dose till 30 days after the last dose or up to 21 weeks for core study and 142 weeks for extension phase. | Yes |