Article ; Online: Photosensitive epilepsy: Robust clinical efficacy of a selective GABA potentiator.
2019 Volume 92, Issue 15, Page(s) e1786–e1795
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 ... ...
| 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. |
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| MeSH term(s) | Adolescent ; Adult ; Anticonvulsants/adverse effects ; Anticonvulsants/pharmacokinetics ; Anticonvulsants/therapeutic use ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Double-Blind Method ; Epilepsy, Reflex/drug therapy ; Female ; GABA Modulators/therapeutic use ; GABA-A Receptor Agonists/adverse effects ; GABA-A Receptor Agonists/pharmacokinetics ; GABA-A Receptor Agonists/therapeutic use ; Humans ; Imidazoles/adverse effects ; Imidazoles/pharmacokinetics ; Imidazoles/therapeutic use ; Lorazepam/therapeutic use ; Male ; Middle Aged ; Pyridazines/adverse effects ; Pyridazines/pharmacokinetics ; Pyridazines/therapeutic use ; Treatment Outcome ; Young Adult |
| Chemical Substances | Anticonvulsants ; GABA Modulators ; GABA-A Receptor Agonists ; Imidazoles ; PF-06372865 ; Pyridazines ; Lorazepam (O26FZP769L) |
| Language | English |
| Publishing date | 2019-03-15 |
| Publishing country | United States |
| Document type | Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 207147-2 |
| ISSN | 1526-632X ; 0028-3878 |
| ISSN (online) | 1526-632X |
| ISSN | 0028-3878 |
| DOI | 10.1212/WNL.0000000000007271 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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