Interim analysis of the long‐term efficacy and safety of azetukalner in an ongoing open‐label extension study following a phase 2b clinical trial (X‐<scp>TOLE</scp>) in adults with focal epilepsy
Bibliographic record
Abstract
OBJECTIVE: To report interim data from an ongoing, open-label extension (OLE) of a Phase 2b study (X-TOLE) of azetukalner in adults with focal onset seizures (FOS) receiving 1-3 antiseizure medications. METHODS: Eligible participants enrolled in the 7-year OLE at 20 mg azetukalner once daily with food. Long-term seizure outcomes included median percentage change (MPC) in monthly (28 days) FOS frequency from the double-blind phase (DBP) baseline and achievement of ≥50%, ≥75%, ≥90%, and 100% seizure reductions. RESULTS: 285 participants completed the DBP, and 275 (96.5%) enrolled in the OLE. At the 24-month interim analysis (September 5, 2023), 182 participants had been treated for ≥12 months and 165 for ≥24 months; 152 (55.3%) continued in the study. The median (range) treatment duration in the OLE was 26.3 (0.1-46.6) months. MPC reduction was 83.2% at 24 months in the OLE vs. DBP baseline. For all participants who entered the OLE, 56.4% (155/275) and 44.4% (122/275) achieved a ≥50% seizure reduction, 28.4% (78/275) and 19.6% (54/275) achieved a ≥90% seizure reduction, and 22.2% (61/275) and 14.9% (41/275) achieved seizure freedom (100% seizure reduction) for any consecutive ≥6- and ≥12-month period, respectively. For those who reached ≥24 months in the OLE, seizure freedom was achieved by 34.5% (57/165) and 23.6% (39/165) for any consecutive ≥6- and ≥12-month period, respectively. The majority of treatment-emergent adverse events (TEAEs) were mild or moderate. The most common TEAEs were dizziness (21.8%), headache (15.3%), coronavirus infection (15.3%), somnolence (12.7%), fall (12.7%), and memory impairment (10.9%). Serious AEs were reported in 35 (12.7%) participants. SIGNIFICANCE: The efficacy demonstrated by azetukalner in reducing FOS seizure frequency in the DBP was sustained in this interim analysis. Azetukalner was generally well tolerated, with no new safety signals compared to the DBP. These data suggest sustained long-term efficacy and safety of azetukalner in a difficult-to-treat population. PLAIN LANGUAGE SUMMARY: This long-term study assessed the safety and efficacy of azetukalner to treat focal seizures. Patients taking azetukalner daily with food for about 2 years had far fewer focal seizures with azetukalner than before taking the medication. For those who had been treated for 24 months, about a third were seizure-free for a consecutive 6-month period, and about a quarter were seizure-free for a consecutive 12-month period. Most side effects were mild or moderate, and these included dizziness, headache, and somnolence (sleepiness).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".