Pharmacokinetics of XEN496, a Novel Pediatric Formulation of Ezogabine, Under Fed and Fasted Conditions: A Phase 1 Trial
Bibliographic record
Abstract
XEN496 is a novel, granular, immediate-release formulation of ezogabine intended for pediatric use. The objective of this study was to assess the effect of food on the pharmacokinetics (PK) of XEN496 and its N-acetyl metabolite (NAMR) in healthy volunteers. Twenty-four adult subjects were enrolled in this phase 1, single center, open-label, randomized, single-dose, two-way crossover study. Subjects received 400 mg XEN496 as an oral suspension in both fed and fasted states separated by a 6-day washout period. Serial blood samples were collected up to 48 h post-administration. PK parameters evaluated included maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration (Tmax), and area under the concentration–time curve (AUC(0–t) and AUCinf). Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. For XEN496, median Tmax was 3 and 2 h in the fed and fasted states, respectively. AUC parameters in the fed and fasted states were equivalent, whereas food decreased Cmax of XEN496 by 32% compared to the fasted state. The ratio of geometric means [90% CI] for Cmax was 72% [64–82%]. For NAMR, food delayed Tmax by 1 h, while Cmax and AUC parameters were equivalent in the fed and fasted states. The safety profile of XEN496 in this study appeared comparable to that previously reported for ezogabine tablets. The biopharmaceutical performance of XEN496 in this study was as expected for an immediate-release, granular dosage formulation, and generally comparable to that reported for ezogabine tablets. Future studies are needed to characterize the efficacy, safety, and PK of XEN496 in a pediatric population.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".