Clinical Data

The XEN1101 interim Phase 1 results include data from five SAD cohorts (n=28, placebo=6) ranging in dose from 5 to 30 mg, and one MAD cohort at a 15 mg dose (n=6, placebo=2).

Pharmacokinetic data confirms a half-life consistent with once daily dosing. Based on data generated from the MAD cohort, it is anticipated that steady state could be achieved at approximately seven days, and food enhances the exposure of XEN1101. Drug exposure levels in the Phase 1 clinical trial were observed above the EC50 in preclinical models.

The preliminary XEN1101 interim Phase 1 data suggest that overall XEN1101 is safe and well tolerated, with no serious adverse events, and no clinically significant laboratory findings. The majority of adverse events were mild and resolved spontaneously. The most common adverse events were headache, dizziness and drowsiness. One severe adverse event, a vasovagal reaction, was observed following a blood draw and standing. Importantly, no urinary retention or hesitation adverse events were noted, which was one of the adverse events observed in historical clinical trials with ezogabine.

The TMS Phase 1a pilot study included 8 male subjects where three doses were tested (10 mg, n=2; 15 mg, n=3; 20 mg, n=3). When measuring the resting motor threshold (RMT) in the TMS-EMG assay, the mean change (standard deviation) in RMT was 1.5% (±2.1), 1.33% (±0.58) and 4.33% (±0.58) for the 10 mg, 15 mg and 20 mg doses, respectively. This compares to a literature publication of ezogabine (Ossemann et. al) where in a double-blind, placebo-controlled cross-over study in 15 healthy subjects at a single dose of 400 mg, ezogabine increased the RMT by 2.4% (±3.6).

In the TMS-EEG portion of the study, all three subjects at the 20 mg dose showed statistically significant (p<0.01) modulating activity at 4 hours post dose when compared to baseline. The effects of ezogabine within a TMS-EEG have not been tested.

Based on pre-clinical in vitro metabolism studies, it is anticipated that there is a low risk of drug-drug interactions with XEN1101.