Complex Partial Seizures
Conditions
Keywords
Tuberous sclerosis, TS, Seizures
Brief summary
This is an open-label, phase 4 study to examine the safety and efficacy of vigabatrin (Sabril) in Tuberous Sclerosis patients, a subset of the larger refractory complex partial epilepsy population for which the drug is approved. While enrolled on this trial, subjects will continue to take all of their normally prescribed medications, including their other antiepileptic drugs (AEDs). Alternatively, there is a prospective observational arm that subjects who are about to take Sabril as treatment for seizures associated with Tuberous Sclerosis may join. Subjects who join this arm will not have any study visits and will not be asked to do anything specifically for the study. The study team will collect all study data from subjects' medical records only.
Interventions
DRUGvigabatrin
Subjects will begin taking vigabatrin (Sabril) during the third month of the study. Upward titration will happen at a rate of 500mg per week until subjects reach their maximum tolerated dose, or 3g per day (whichever is lower). This dose may be decreased if needed under the supervision of the study doctor. Subjects who need to lower their dose or who stop taking Sabril will have their dosage decreased at a rate of 1 gm/week for one month under the supervision of the study doctor.
Sponsors
H. Lundbeck A/S
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient or patient's legally authorized representative must sign and date the Institutional Review Board approved Informed Consent and HIPPA Authorization Form. * Male and female patients 18+ years of age with a clinical diagnosis of Tuberous Sclerosis who experience an average of at least three partial seizures every two months, of which one must be a complex partial seizure * Patient must be on at least one and a maximum of four AEDs. Patient must be on a stable AED dose regimen for at least 30 days prior to screening. Neither a Vagal Nerve Stimulator (VNS) nor the ketogenic diet will count as an AED * In the investigator's opinion, the patient or caregiver must be able to keep a seizure diary * An MRI in the last 5 years, or willingness to undergo an MRI as part of the screening process
Exclusion criteria
* Cause of patient's seizures is a neurologic disease that is not Tuberous Sclerosis * Current, clinical diagnosis of a major depressive episode or suicidal ideation * Patient is taking more than four concurrent AEDs. Note: VNS or ketogenic diet is allowed and will not be counted in the four allowed AEDs * Patient has a progressive CNS lesion confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan * Patient is currently abusing drugs or alcohol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Safely Tolerating Sabril | Outcome measures will be assessed at the initiation of Sabril (titration), and at three and five months after starting Sabril. After this time, the subjects will have completed the study. | * Antiepileptic Drug (AED) levels in blood * Comprehensive panel (blood test) * Complete Blood Count with differential (blood test) * Visual field tests testing * Ophthalmology exam assessment * Frequency and severity of adverse events reported by subjects throughout their involvement with the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Become Seizure Free While Taking Sabril | Seizure freedom will be assessed for the two month treatment phase of the study (months 4 and 5) | * Seizure freedom * Responder rate (complex partial seizures only) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited for the treatment arm from within the Tuberous Sclerosis (TS) clinical at the University of Pennsylvania. Recruitment begain on 8/19/2010 and continued through 2013. All potential subjects had to be eligible to take Sabril (vigabatrin) under the FDA-approved prescribing information.
Pre-assignment details
Before taking Sabril, subjects were required to undergo visual field and depression screenings in response to the FDA's black box warning about Sabril causing vision loss, and an increased risk of suicidal ideation among patients taking antiepileptic drugs like Sabril. No potential subjects were excluded due to screening assessments.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Sabril (Vigabatrin) This is a single arm study. All subjects who are eligible for treatment will begin taking vigabatrin (Sabril) during the third month of the study. Treatment will be in accordance with the FDA-approved prescribing information: upward titration will happen at a rate of 500mg per week until subjects reach their maximum tolerated dose, or 3g per day (whichever is lower). This dose may be decreased if needed under the supervision of the study doctor. Subjects who need to lower their dose or who stop taking Sabril will have their dosage decreased by 1 gm/week for one month under the supervision of the study doctor. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Treatment With Sabril (Vigabatrin) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 30 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Treatment Female | 1 Participants |
| Sex: Female, Male Treatment Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Number of Participants Safely Tolerating Sabril
* Antiepileptic Drug (AED) levels in blood * Comprehensive panel (blood test) * Complete Blood Count with differential (blood test) * Visual field tests testing * Ophthalmology exam assessment * Frequency and severity of adverse events reported by subjects throughout their involvement with the study
Time frame: Outcome measures will be assessed at the initiation of Sabril (titration), and at three and five months after starting Sabril. After this time, the subjects will have completed the study.
Population: One 30 year old female, Caucasian, non-Hispanic subject enrolled in the study. Due to adverse events, she did not complete the study, however, she completed all required follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Sabril (Vigabatrin) | Number of Participants Safely Tolerating Sabril | 0 Participants |
Secondary
Number of Patients Who Become Seizure Free While Taking Sabril
* Seizure freedom * Responder rate (complex partial seizures only)
Time frame: Seizure freedom will be assessed for the two month treatment phase of the study (months 4 and 5)
Population: One 30 year old female, Caucasian, non-Hispanic subject enrolled in the study. Due to adverse events, she did not complete the study, however, she completed all required follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Sabril (Vigabatrin) | Number of Patients Who Become Seizure Free While Taking Sabril | 0 Participants |