A Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)

Multicenter, prospective open-label study with approximately 25 sites in the US that specialize in caring for adult patients with refractory CPS

* Sites must have access to Humphrey static perimetry and to Spectralis SD-OCT.
* All vision test results will be sent to the central readers for evaluation.
* Additional study tests:

* The Columbia Suicide Severity Rating Scale (C-SSRS)
* The National Eye Institute Visual Field Questionnaire-39 (NEI VFQ-39)
* A whole blood sample for specific analysis of DNA characteristics
* An optional whole blood sample for exploratory analysis of DNA characteristics
* Plasma samples for bioanalytical analysis of vigabatrin and blood samples for taurine biomarker analysis

• Sabril (Drug), also known as Vigabatrin: Sabril: 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.

Primary outcomes

• Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB) [Baseline (Month 0), Month 3, Month 6, Month 9, Month 12]: Mean change from the reference value in 30-2 SITA mean deviation, which was generated using the University of Iowa Visual Field Reading Center (VFRC) normative database and the Humphrey Field Analyzer (HFA) normative database. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). The mean change from the reference value are presented for Months 3, 6, 9 and 12. A negative change from the reference value indicates a decrease in the central visual field.
• Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography) [Baseline (Month 0), Month 3, Month 6, Month 9, Month 12]: Mean change from the reference value in average RNFL thickness (µm) as measured by SD-OCT. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). Thinning of the RNFL, that is, a negative change from the reference value, has been associated with ophthalmological disease.

Sex: All, ages: 18 Years to any

Important Inclusion Criteria:

1. The patient speaks English or Spanish.
2. The patient has had no prior exposure to Sabril.
3. To begin Sabril therapy for the treatment of CPS.
4. Male or female ≥18 years of age.
5. The patient has refractory CPS:

   1. The patient has complex partial epilepsy of more than 1 year duration and no other seizure type within the past year except for partial seizures secondarily generalized.
   2. The patient has failed because of lack of efficacy 3 or more prior or concurrent treatment trials including 3 or more anti-epileptic drugs (AEDs) of differing pharmacologic mechanisms administered as monotherapy or polytherapy.
   3. The patient is taking at least 1 AED. A vagal nerve stimulator is not counted as an AED.
   4. The patient reports an average of 2 or more seizures per month averaged over the prior 3 months.
6. The patient is deemed by the treating neurologist and ophthalmologist to be able to reliably complete perimetry testing.
7. The initial (Visit 1) SD-OCT and static perimetry readings tests must be performed and assessed for technical adequacy by the SD-OCT and perimetry central readers prior to the first dose of Sabril. The initial (Visit 1) tangent corner test must be performed prior to the first dose of Sabril.

Exclusion Criteria:

1. Prior exposure to Sabril.
2. Pre-existing ocular or neurological disease that might affect bilateral visual fields or interfere with perimetry (e.g., aphakia, visually significant cataract, glaucoma, diabetes mellitus, ischemic optic neuropathy, multiple sclerosis). Patients with stable visual field defects from CNS lesions (e.g., epilepsy surgery more than 6 months prior to receiving Sabril) may be enrolled.
3. Concurrent exposure to medications with known or suspected retinal or optic nerve toxicity.
4. Concurrent use of an investigational agent or device or such use within 30 days of entering the study.
5. Concurrent use of the ketogenic or similar diet.
6. For any reason, the patient is considered by the investigator to be an unsuitable candidate for the study.

Participant flow

Outcome results

• Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB) (Primary), Mean, dB: Sabril -0.28 +/- 1.06
• Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography) (Primary), Mean, µm: Sabril 0.70 +/- 2.56

Adverse events

Time frame: Baseline to end of study

Serious adverse events by term

Other adverse events by term

• Email contact via H. Lundbeck A/S, Study director, LundbeckClinicalTrials@lundbeck.com