Phase IV Vision Study Evaluates Retinal Structure and Function in Adult Patients with Refractory Complex Partial Seizures Treated with Vigabatrin (P07.255)

Objective: To evaluate change in retina structure and function in vigabatrin-naive patients, we initiated a prospective, 1-year open-label trial in patients requiring vigabatrin treatment. Background An important safety issue for vigabatrin is risk of bilateral concentric constriction of visual fields. Design/Methods: ∼80 patients with rCPS for ≥1 year (with ≥2 seizures/month averaged over prior 3 months) will be enrolled at ∼25 US sites. Patients must have failed ≥3 prior therapies for lack of efficacy and must be receiving concomitant AEDs. Vigabatrin-naive patients ≥18 years of age will have visual static perimetry and optical coherence tomography (OCT) assessments at baseline, and 3, 6, 9, and 12 months following vigabatrin initiation. Key endpoints include change from reference value in field width (static perimetry), and change from reference value in retinal nerve fiber layer thickness (OCT and macular thickness OCT). After commencing vigabatrin, patients are assessed every 3 months through automated static perimetry (both standard 30-2 and horizontal meridian full field), OCT, and ancillary exploratory visual endpoints such as visual acuity, color vision, and visual fields by Tangent Corner Test. If deficits are discovered, investigators conduct benefit/risk assessments with patients. Results: By October 2011, 8 sites had been initiated. Screening was initiated for 8 patients. Five were screen failures, and three patients were enrolled. Of these three, two are ongoing study participants, and one was an early termination (seizures returned to baseline rate and patient was discontinued following benefit/risk assessment). One patient had abnormal baseline OCT results (before vigabatrin therapy), emphasizing that patients may have pre-existing afferent visual system conditions. Conclusions: This study is designed to provide a better definition of onset and progression of peripheral visual field defects, to assess the risk of developing vision loss during first year of exposure, and to evaluate OCT for monitoring retinal changes. Supported by: Lundbeck Inc. Disclosure: Dr. Sergott has received personal compensation for activities with Pfizer, Serono, Lundbeck, and Centocor as a speaker and consultant. Dr. Sergott has received personal compensation in an editorial capacity for Current Opinion in Neuro-Opthamology. Dr. Faught has received personal compensation for activities with Pfizer Inc, UCB Pharma, Ortho-McNeil Pharmaceutical, Inc., Valeant Pharmaceuticals, Ovation Pharmaceuticals, Inc., GlaxoSmithKline, Inc., Abbott Laboratories, Inc., and Novartis as a consultant or speaker. Dr. Faught has received research support from Eisai Inc., Marinus, Ortho-McNeil Pharmaceutical, Inc., and Schwarz Biosciences. Dr. Torri has received personal compensation for activities with Lundbeck Research USA as an employee. Dr. Wesche has received personal compensation for activities with Lundbeck Research USA, Inc as an employee.