Epilepsy
Conditions
Keywords
Epilepsy, Epilepsy, partial onset, Epilepsy, generalized onset, Fycompa, perampanel
Brief summary
This study will aim to improve retention and tolerability by slowing the initial titration rate of perampanel from a standard up-titration rate of 2 week intervals to a slower up-titration rate consisting of 3 week intervals. Subjects will be randomized to either perampanel, standard titration interval rate (Group A) or perampanel, slower titration interval rate (Group B).
Detailed description
A total of 60 subjects with a confirmed diagnosis of either partial onset or primary generalized epilepsy will be recruited into the trial. 30 subjects will initiate perampanel at a dose of 2 mg/day and titrate upwards every 2 weeks to a target dose of 6 mg/day. Subjects in this group will be designated Group A. The remaining 30 subjects will also begin perampanel at a dose of 2 mg/day but will titrate upwards every 3 weeks to a target dose of 6 mg/day and will be designated Group B.
Interventions
DRUGPerampanel Oral Tablet
Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.
Sponsors
Eisai Inc.
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Must provide written informed consent signed by the subject or legal guardian prior to entering the study in accordance with ICH and GCP guidelines. 2. Subject has a confirmed diagnosis of medically refractory epilepsy with or without secondary generalization for at least 12 months prior to visit 1. 3. Subjects currently being treated with 1 to 3 antiepileptic medications with or without VNS (does not count as an AED). 4. Subjects aged 18 to 75. 5. Subject's requiring an additional epilepsy medication due to either uncontrolled seizures and/or lack of tolerability with current epilepsy medications. 6. Can be safely treated, in the opinion of the investigator, with Fycompa. 7. Able and agrees to follow the specified titration schedule. 8. Subjects or a legal guardian who is able to communicate effectively with study personnel and considered reliable, able, willing and cooperative with regard to complying with protocol-defined requirements, including completion of the study diary.
Exclusion criteria
1. Any history of non-epileptic or psychogenic seizures. 2. Women who are currently pregnant, lactating or have plans to become pregnant in the immediate future. 3. Subjects with active suicidal ideation or behavior as evidenced by positive answers on the Columbia Suicide Severity Rating Scale (C-SSRS) or subject's with a history of suicidal ideation or attempt within 12 months. 4. Subjects with a suicidal attempt in the 12 months prior to Visit 1 5. Any clinically significant medical or psychiatric illness, psychological or behavioral problems, which in the opinion of the investigator would interfere with the subject's ability to participate in the study. 6. Subjects with severe hepatic impairment or severe renal impairment or on hemodialysis. 7. Any use of concomitant medication as listed in the drug insert, including medications known to be inducers of cytochrome P450 (CYP3A).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Completing 52 Weeks of Adjunctive Therapy During the Maintenance Phase [Retention Rate]. | Up to 52 weeks | Retention rate, which indirectly measures the therapeutic tolerance, will be measured at 52 weeks in each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject or Observed by the Investigator [Safety and Tolerability]. | Up to 52 weeks | Adverse events experienced in each group will be tabulated and the total percentage of subjects reporting adverse events will be calculated. |
| Seizures Frequency Per Week | Up to 52 weeks | The average of seizures per week will be calculated starting at initial titration through final maintenance \[Efficacy\]. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fycompa 2 Week Titration Intervals Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control.
Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures. | 10 |
| Fycompa 3 Week Titration Intervals Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control.
Perampanel Oral Tablet: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Total | Fycompa 2 Week Titration Intervals | Fycompa 3 Week Titration Intervals |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 10 Participants | 10 Participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 11 | 33 years STANDARD_DEVIATION 11 | 43 years STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 8 Participants | 10 Participants |
| Region of Enrollment United States | 20 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 4 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 |
Outcome results
Primary
The Percentage of Subjects Completing 52 Weeks of Adjunctive Therapy During the Maintenance Phase [Retention Rate].
Retention rate, which indirectly measures the therapeutic tolerance, will be measured at 52 weeks in each group.
Time frame: Up to 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fycompa 2 Week Titration Intervals | The Percentage of Subjects Completing 52 Weeks of Adjunctive Therapy During the Maintenance Phase [Retention Rate]. | 2 Participants |
| Fycompa 3 Week Titration Intervals | The Percentage of Subjects Completing 52 Weeks of Adjunctive Therapy During the Maintenance Phase [Retention Rate]. | 3 Participants |
Secondary
Incidence of Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject or Observed by the Investigator [Safety and Tolerability].
Adverse events experienced in each group will be tabulated and the total percentage of subjects reporting adverse events will be calculated.
Time frame: Up to 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fycompa 2 Week Titration Intervals | Incidence of Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject or Observed by the Investigator [Safety and Tolerability]. | 4 participants |
| Fycompa 3 Week Titration Intervals | Incidence of Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject or Observed by the Investigator [Safety and Tolerability]. | 3 participants |
Secondary
Seizures Frequency Per Week
The average of seizures per week will be calculated starting at initial titration through final maintenance \[Efficacy\].
Time frame: Up to 52 weeks
Population: 2 participants in Group A were discontinued due to adverse events and 3 were lost to follow-up. In group B, 3 participants were discontinued due to adverse events and 2 were lost to follow-up. Therefore, only 5 participants remained in each treatment group for determination of seizure frequency during the final maintenance phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fycompa 2 Week Titration Intervals | Seizures Frequency Per Week | 0.912 Seizures per week | Standard Deviation 0.647 |
| Fycompa 3 Week Titration Intervals | Seizures Frequency Per Week | 0.508 Seizures per week | Standard Deviation 0.887 |