Sabril Clinical Data for IS
Below is the infantile spasms (IS) data from the 2 pivotal trials showing that Sabril achieved spasm freedom.1,2
Click any of the links below to learn more about the Sabril clinical trials:
Or, click here to see safety data.
Study 1 Design1,2
- N=221
- Multicenter, randomized, low-dose/high-dose, parallel group study in patients <2 years of age with new-onset IS
- Partially blinded (parents blinded to arm but not to dose; EEG reader blinded but investigators not blinded)
- Study included patients with both symptomatic and cryptogenic etiologies
- Patients were randomized to receive low or high doses of Sabril for 14 to 21 days
- Following the 14- to 21-day, partially blinded, randomized phase, patients entered a flexible-dosing, open-label, long-term follow-up phase of up to 3 years
- Primary efficacy endpoint was proportion of patients who were spasm-free for 7 consecutive days beginning within the first 14 days of Sabril therapy
- Patients considered spasm-free were defined as those patients who remained free of spasms (evaluated according to caregiver response to direct questioning
regarding spasm frequency) and who had no indication of spasms or hypsarrhythmia during 8 hours of CCTV EEG recording (including at least one sleep-wake-sleep
cycle) performed within 3 days of the 7th day of spasm freedom and interpreted by a blinded EEG reader
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Study 2 Design1,2
- N=40
- Multicenter, randomized, double-blind, placebo-controlled, parallel group study
- A pretreatment (baseline) period of 2 to 3 days was followed by a 5-day double-blind treatment phase
- Patients received Sabril (initial dose of 50 mg/kg/day with titration allowed to 150 mg/kg/day) or placebo
- Primary efficacy endpoint was the average percent change in daily spasm frequency assessed during a predefined and consistent 2-hour window of
evaluation, comparing baseline to the final 2 days of the 5-day double-blind treatment phase
The onset of vision loss from Sabril is unpredictable and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after
months or years. Sabril should be used at the lowest dose and shortest exposure that is consistent with clinical objectives.
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Study Results1,2
Study 1: Sabril Achieved Spasm Freedom
- Primary efficacy evaluations based on caregiver assessment confirmed by CCTV EEG within 3 days of the 7th day of spasm freedom
- High-dose Sabril was significantly superior to low-dose Sabril for patients achieving spasm freedom (P=0.0375)
Study 2: Sabril Decreased Daily Spasm Frequency1,2
- No statistically significant differences were observed using the 2-hour window of evaluation
- Post-hoc alternative efficacy analysis used a 24-hour clinical evaluation window that found a statistically significant difference in the overall percentage of reductions in spasms between the Sabril group (68.9%) and the placebo group (17.0%) (P=0.030)
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Adverse Events in Study 1
- Adverse Events were similar in both groups
- No clear correlation was observed between dose and indication of adverse events
Adverse Events in Study 2
- The adverse events reported by >5% of Sabril Patients and that occurred more frequently than in placebo patients were
somnolence (Sabril 45%, placebo 30%), bronchitis (Sabril 30%, placebo 15%), ear infection (Sabril 10%, placebo 5%), and acute otitis
media (Sabril 10%, placebo 0%)
Permanent Vision Loss
- Sabril causes permanent vision loss in infants, children, and adults. Because assessing vision loss is difficult in children, the frequency and extent of vision loss in infants and children is poorly characterized. For this reason, the data described below is primarily based on the adult experience
- In adults, Sabril causes permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe, including tunnel vision to within 10° of visual fixation, and can result in disability. In some cases, Sabril also can damage the central retina and may decrease visual acuity
- The onset of vision loss from Sabril is unpredictable and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years
- The lowest dose and shortest exposure to Sabril should be used that is consistent with clinical objectives
Click the button below to see the safety data from the trials.
Important Safety Information
SABRIL® (vigabatrin) Tablets
SABRIL® (vigabatrin) for Oral Solution
Indication
SABRIL is indicated as adjunctive therapy for adult patients with refractory complex partial seizures (CPS) who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. SABRIL is not indicated as a first line agent for complex partial seizures.
SABRIL is indicated as monotherapy for pediatric patients 1 month to 2 years of age with infantile spasms (IS) for whom the potential benefits outweigh the potential risk of vision loss.
Important Safety Information
WARNING: VISION LOSS
See full Prescribing Information for complete boxed warning
- SABRIL causes progressive and permanent bilateral concentric visual field constriction in a high percentage of patients. In some cases, SABRIL may also reduce visual acuity
- Risk increases with total dose and duration of use, but no exposure to SABRIL is known that is free of risk of vision loss
- Risk of new and worsening vision loss continues as long as SABRIL is used, and possibly after discontinuing SABRIL
- Unless a patient is formally exempted, periodic vision assessment is required for patients on SABRIL. However, this assessment cannot always prevent vision damage
- Because of the risk of permanent vision loss, SABRIL is available only through a special restricted distribution program
SABRIL causes permanent vision loss in infants, children, and adults. Because assessing vision loss is difficult in children, the frequency and extent of vision loss in infants and children is poorly characterized.
In adults, SABRIL causes permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe, including tunnel vision to within 10° of visual fixation, and can result in disability. In some cases, SABRIL also can damage the central retina and may decrease visual acuity. The onset of vision loss from SABRIL is unpredictable and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years. The lowest dose and shortest exposure to SABRIL should be used that is consistent with clinical objectives.
Because of the risk of permanent vision loss, SABRIL should be withdrawn from patients with IS who fail to show substantial clinical benefit within 2 to 4 weeks of initiation, or sooner if treatment failure becomes obvious, or adult patients treated for refractory CPS as adjunctive therapy who fail to show substantial clinical benefit within 3 months of initiation, or sooner if treatment failure becomes obvious. Patient response to and continued need for SABRIL should be periodically reassessed.
Unless a patient is formally exempted from periodic ophthalmologic assessment as documented in the SHARE program, vision assessment is required at baseline (no later than 4 weeks after starting SABRIL), at least every 3 months while on therapy and about 3-6 months after the discontinuation of SABRIL therapy. Once detected, vision loss is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss. Drug discontinuation should be considered, balancing benefit and risk, if visual loss is documented.
Symptoms of vision loss from SABRIL are unlikely to be recognized by the patient, parent or caregiver before vision loss is severe. Vision loss of milder severity, although unrecognized by the patient, parent or caregiver may still adversely affect function. The possibility that vision loss from SABRIL may be more common, more severe, or have more severe functional consequences in infants and children than in adults, cannot be excluded.
SABRIL should not be used in patients with, or at high risk of, other types of irreversible vision loss or with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks. The interaction of other types of irreversible vision damage with vision damage from SABRIL has not been well characterized, but is likely adverse.
In adult patients treated for CPS, dose adjustment is necessary in patients with renal impairment.
Abnormal MRI signal changes have been observed in some infants treated for IS with SABRIL. These changes generally resolved with discontinuation of treatment and in a few patients the lesion resolved despite continued use.
Antiepileptic drugs (AEDs), including SABRIL, increase the risk of suicidal thoughts or behavior. Adult patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior and/or any unusual changes in mood or behavior.
As with all AEDs, SABRIL should be discontinued gradually to avoid withdrawal seizures.
Vigabatrin is excreted in human milk and may cause serious adverse events in nursing infants. SABRIL should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Pregnancy Registry: To provide information regarding the effects of in utero exposure to SABRIL, physicians are advised to recommend that pregnant patients taking SABRIL enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
SABRIL has been shown to cause neurotoxicity, anemia, somnolence and fatigue, peripheral neuropathy, weight gain and edema. The most commonly observed adverse reactions reported in 2 add-on clinical studies of adults with refractory CPS treated with SABRIL as adjunctive therapy with the recommended dose of 3 g/day (≥10% and at least 5% greater than placebo, respectively) were dizziness (24% vs 17%), fatigue (23% vs 16%), somnolence (22% vs 13%), tremor (15% vs 8%), blurred vision (13% vs 5%), and arthralgia (10% vs 3%). A 6 g/day dose has not been shown to confer additional benefit compared to the 3 g/day dose and is associated with an increased incidence of adverse events.
The most common adverse events reported by >5% of infants taking SABRIL for IS occurring more frequently than placebo, respectively, in a randomized, placebo-controlled IS study with a 5-day double-blind treatment phase (n=40) were somnolence (45% vs 30%), bronchitis (30% vs 15%), ear infection (10% vs 5%), and acute otitis media (10% vs 0%).
Oral Solution: For more information, please see the full Prescribing Information including Boxed Warning, Medication Guide, and Dosing Instructions.
Solución oral: Para más información, vea por favor la información que prescribe completa incluyendo la advertencia encajonada, guía de la medicación, y las instrucciones de la dosificación.
Tablets: For more information, please see the full Prescribing Information including Boxed Warning and Medication Guide.
Tabletas: Para más información, vea por favor la información que prescribe completa incluyendo la advertencia encajonada, y guía de la medicación.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
- Sabril full Prescribing Information for IS, February 2010, Deerfield, IL, Lundbeck.
- Data on file. Lundbeck.