# Azetukalner cut focal seizure frequency in a phase 3 trial of 374 adults with epilepsy

- Published: 2026-11-13 08:15 UTC
- Section: Life & Health › Medicine
- Tags: azetukalner, X-TOLE2, focal epilepsy, KV7 channel opener, antiseizure medication, phase 3 trial, drug-resistant epilepsy, seizure frequency
- URL: https://realtech.media/news/rt-99c3c0132adcb1d46bd47a99_azetukalner_cut_focal/

**In the phase 3 X-TOLE2 trial, the KV7 channel opener azetukalner at 15 mg lowered median monthly focal seizure frequency by 34.5%, versus 10.4% on placebo.**

Azetukalner, a KV7 channel opener, reduced the frequency of focal seizures in adults in the phase 3 randomized trial X-TOLE2, according to a report in JAMA Neurology. [1] The double-blind period ran from November 18, 2022 to February 3, 2026 at 138 sites in North America, South America, Europe and Asia Pacific. [1] Of 607 adults screened, 374 were enrolled, randomized and treated. [1]

## Trial design

Participants had focal epilepsy and 4 or more focal seizures per month despite stable treatment with 1 to 3 antiseizure medications. [1] They were randomized 1:1:1 to placebo (125 participants), 15 mg azetukalner (125) or 25 mg azetukalner (124). The drug was taken once daily with the evening meal for 12 weeks, with no titration period. [1] Those who completed the double-blind period could enter an open-label extension.

The primary end point was the median percentage change from baseline in monthly (28-day) focal seizure frequency, azetukalner versus placebo. Safety was assessed by recording treatment-emergent adverse events, laboratory findings, vital signs and electrocardiogram.

The mean age was 40.0 years (SD 12.9), and 190 participants (50.8%) were female. At baseline the median was 12.75 seizures per month (IQR 7.56 to 32.97). Participants had previously tried and stopped a median of 5 antiseizure medications (IQR 3 to 8), and 336 (89.8%) were receiving 2 to 3 concomitant ones. [1]

## Results

The median change from baseline in monthly seizure frequency was -10.4% (IQR -39.1% to 8.3%) in the placebo group and -34.5% (IQR -61.6% to -12.3%) in the 15 mg azetukalner group. [1]

The authors concluded that azetukalner produced rapid and durable reductions in seizure frequency with a favorable benefit-risk profile. They described the effect as one of the largest median percentage reductions in seizure frequency versus placebo reported to date in drug-resistant epilepsy. [1] The trial is registered at ClinicalTrials.gov as NCT05614063.

## Sources

1. [JAMA neurology](https://doi.org/10.1001/jamaneurol.2026.4141)
2. [nplus1.ru](https://nplus1.ru/news/2026/11/09/more-potassium-less-seizures)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-99c3c0132adcb1d46bd47a99_azetukalner_cut_focal/