Subgroup Analysis By Race in Perampanel Phase III Clinical Studies (P1.254)
Bibliographic record
Abstract
Objective: To evaluate potential differences in perampanel efficacy/safety based on race from pooled Phase III partial seizure clinical studies. Background: Perampanel is approved for adjunctive treatment of partial seizures in >40 countries. Pharmacokinetic properties of antiepileptic drugs (AEDs) can be affected by race/ethnicity.1 Desing/Methods: Patients (aged蠅12years) with refractory partial seizures receiving 1-3 concomitant AEDs enrolled in 3 double-blind Phase III studies were randomized to 19-weeks (6-week titration/13-week maintenance) of once-daily perampanel 2,4,8 or 12mg or placebo treatment. Patients were recruited from US, Canada, Australia and countries in Latin America, Africa, Asia and Europe. Pooled results (n=1478) were grouped by patient race: White (n=1114), Asian/Pacific-Islander (n=289 [Chinese: n=112]), Other (n=44), Black/African-American (n=31). Study endpoints included population pharmacokinetic and pharmacokinetic/pharmacodynamic analyses, percent change from baseline in seizure frequency/28 days, responder rate and safety. Due to small patient numbers in Black/African-American and Other subgroups, efficacy/safety analyses based on race compare Whites and Asian/Pacific-Islanders only. Results: In the population pharmacokinetic model developed for perampanel based on plasma concentrations from the Phase III studies, there was no significant difference in perampanel clearance or in concentration-response relationship for perampanel as a function of race. Improved seizure control was seen for perampanel therapeutic doses (4-12mg) compared to placebo in White and Asian/Pacific-Islander subgroups. Very common treatment-emergent adverse events (TEAEs) included dizziness, somnolence, headache, fatigue, irritability and fall, with no notable differences in TEAEs based on race. Patient study discontinuation proportion was similar among Whites (perampanel 16.8[percnt] vs placebo 10.1[percnt]) and Asian/Pacific-Islanders (perampanel 12.7[percnt] vs placebo 10.4[percnt]). Conclusions: Perampanel pharmacokinetics were similar between Whites and Asians/Pacific-Islanders, with improved seizure control observed for both subgroups. Incidence of very common TEAEs was also comparable. Sample size of Black/African-American or Other subgroups was too small to determine if efficacy or safety were different in these subgroups. Reference:1.Faught.Epilepsia2001;42(Supp4):19. Support: Eisai 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 | 0.028 | 0.030 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.019 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".