P2‐499: Safety and efficacy results of a phase II randomized, placebo‐controlled, dose‐ranging study of elnd005 (scyllo‐inositol) in mild‐to‐moderate Alzheimer's disease
Bibliographic record
Abstract
ELND005(scyllo-inositol), an orally-administered small molecule, has been shown to inhibit aggregation and the toxic effects of beta-amyloid (Abeta) in animal models of AD. This study explored safety, efficacy, and biomarker effects of ELND005 in mild/moderate AD. Of 353 patients randomized to ELND005 (250, 1000, or 2000 mg) or placebo twice daily for 78 weeks, 351 received study drug. Co-primary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The study was powered based on the average effect in the 3 active dose groups. After an imbalance of infections and deaths led to early discontinuation of the 2 high-dose groups, the primary analysis was based on the comparison of 250 mg to placebo at 78 weeks, using a mixed-effects model repeated measures analysis. There were no significant between group differences on the NTB or ADCS-ADL (n = 84/82 for 250mg/placebo). In protocol-specified subgroup analyses, mild patients on 250mg had higher NTB scores at Week 78 compared to placebo (mITT, p = 0.110), which were significant in the Per Protocol Set (PPS, p = 0.007). In mild patients, treatment differences on the ADCS-ADL, although numerically favorable, were not significant in mITT or PPS. The moderate group showed no significant differences on either primary endpoint. The adverse event (AE) incidence in mild/moderate patients was similar across the groups: placebo 91.6% versus 87.5, 90.1, and 88.4% of patients in the 250, 1000, and 2000 mg groups, respectively. The serious AE incidence was higher in the 3 ELND005 groups compared to placebo, and included 10 deaths (0 in placebo, 1 in 250mg, 5 in 1000mg, and 4 in the 2000mg); leading to discontinuation of the 2 high doses. The most common AEs in 250mg group with incidence of >5% (and double the placebo) were falls, depression, and confusional state. The safety and tolerability profile of ELND005 was similar in APOE ∊4 carriers compared with non-carriers.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".