Photosensitive epilepsy: Robust clinical efficacy of a selective GABA potentiator.

Authors

• Rachel Gurrell
• Donal Gorman
• Mark Whitlock
• Adam Ogden
• David S Reynolds
• Bree DiVentura
• Bassel Abou-Khalil
• Michael Gelfand
• John Pollard
• R Edward Hogan
• Gregory Krauss
• Michael Sperling
• Blanca Vazquez
• Robert T Wechsler
• Daniel Friedman
• Richard P Butt
• Jacqueline French

Publication/Presentation Date

4-9-2019

Abstract

OBJECTIVE: The objective of this phase 2a study was to assess the activity of PF-06372865, a positive allosteric modulator (PAM) of α2/3/5 subunit-containing GABA

METHODS: Seven participants with a photoparoxysmal response to intermittent photic stimulation (IPS) at baseline were randomized in a double-blind, 4-period cross-over study examining single doses of 17.5 and 52.5 mg PF-06372865, 2 mg lorazepam (active control), and placebo. Standardized photosensitivity ranges (SPRs) to IPS were recorded at screening, predose, and 1, 2, 4, and 6 hours postdose. The primary endpoint was the average least squares mean change in the SPR in the participant's most sensitive eye condition, across all time points.

RESULTS: Both doses of PF-06372865 produced a marked and statistically significant mean reduction in SPR compared to placebo, which was similar in degree to lorazepam. There was complete suppression of SPR in 6/7 participants following PF-06372865 or lorazepam administration. PF-06372865 was safe and well-tolerated.

CONCLUSION: PF-06372865 demonstrated highly robust efficacy. This demonstrates anticonvulsant activity of a novel α2/3/5-subtype selective GABA

CLINICALTRIALSGOV IDENTIFIER: NCT02564029.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for people with a stable photoparoxysmal response to intermittent photic stimulation, PF-06372865 reduces the SPR.

Volume

92

Issue

15

First Page

1786

Last Page

1786

ISSN

1526-632X

Published In/Presented At

Gurrell, R., Gorman, D., Whitlock, M., Ogden, A., Reynolds, D. S., DiVentura, B., Abou-Khalil, B., Gelfand, M., Pollard, J., Hogan, R. E., Krauss, G., Sperling, M., Vazquez, B., Wechsler, R. T., Friedman, D., Butt, R. P., & French, J. (2019). Photosensitive epilepsy: Robust clinical efficacy of a selective GABA potentiator. Neurology, 92(15), e1786–e1795. https://doi.org/10.1212/WNL.0000000000007271

Disciplines

Medicine and Health Sciences

PubMedID

30877186

Department(s)

Department of Medicine

Document Type

Article