Mortality in Phase III Studies of Adjunctive and Monotherapy Eslicarbazepine Acetate (ESL) in Patients with Partial-Onset Seizures (POS) (P2.058)
Bibliographic record
Abstract
Objective: To conduct an exploratory analysis of mortality in adults with refractory POS treated with ESL in Phase III adjunctive or monotherapy studies. Background: Mortality and Sudden Unexplained Death in Epilepsy (SUDEP) are important issues in epilepsy. Risk factors for SUDEP are not fully understood, but may include inadequate seizure control. Methods: Mortality data from six studies were included: adjunctive studies, BIA-2093-301/-302/-304 (including open-label [OL] extension phases); monotherapy studies, -045/-046, and the related OL extension, -050. Patients with refractory POS (≥4 seizures/month) during stable treatment with ≥1 antiepileptic drug (AED) received adjunctive ESL (400mg, 800mg or 1200mg once-daily [QD], plus stable doses of baseline AEDs), or ESL monotherapy (1200mg or 1600mg QD [studies -045 and -046; previous AEDs withdrawn], or 800-2400mg QD [study -050; flexible dosing schedule, ≤2 additional non-oxcarbazepine AEDs allowed]). Results: Numbers of patients who received ≥1 dose of ESL were: adjunctive trials, 1021 double-blind; 639 OL; monotherapy trials, 365 double-blind; 274 OL. As of 09/22/2014, overall ESL exposure (patient-years) was 1877.3 for adjunctive therapy and 627.0 for monotherapy (double-blind and OL periods combined), while a total of 19 deaths had occurred: two during pre-randomization; 13 during double-blind or OL treatment with placebo (n=2) or ESL (n=13); and four after ESL discontinuation. Six deaths were potentially due to SUDEP; three occurred while patients were taking ESL (adjunctive, n=2; monotherapy, n=1). SUDEP rates were 0.11 per 100 patient-years in patients taking adjunctive ESL (double-blind and OL phases) (upper 90[percnt] confidence limit [CL]=0.34) and 0.12 per 100 patient-years for those taking ESL as either monotherapy or adjunctive therapy (upper 90[percnt] CL=0.31). Conclusions: Deaths, including those potentially due to SUDEP, were rare among adults with refractory POS taking ESL (adjunctive or monotherapy) in Phase III studies. Study Supported by Sunovion Pharmaceuticals Inc.
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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 | 0.017 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.006 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".