Efficacy and safety of the novel GlyT1 inhibitor BI 425809 in Alzheimer’s dementia: a randomized controlled trial
Bibliographic record
Abstract
Abstract Background This phase II proof-of-concept study assessed the efficacy and safety of BI 425809, a novel selective glycine transporter-1 inhibitor, for the treatment of cognitive impairment associated with probable Alzheimer’s disease dementia. Methods This 12-week, multicenter, double-blind, placebo-controlled, parallel-group study randomized (1:1:1:1:1) patients with mild-to-moderate probable Alzheimer’s disease dementia to BI 425809 2, 5, 10, and 25 mg or placebo once daily. The primary efficacy endpoint was the change from baseline in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11-item total score after 12 weeks of treatment. Safety was also assessed. Results Six hundred and ten male and female patients were randomized to BI 425809 2 mg (n = 123), 5 mg (n = 122), 10 mg (n = 122), and 25 mg (n = 123) or placebo (n = 120). Approximately 47% (n = 286) were male; the mean (standard deviation) age was 72.9 (7.7) years. Treatment compliance was above 97% for all dose groups. The Mini-Mental State Examination category on the median score was < 22 in 47% (n = 287) of patients and ≥ 22 in 53% (n = 322) of patients. No significant, non-flat dose–response relationship was detected for the primary endpoint (adjusted p-value > 0.76 for all models). BI 425809 was generally well-tolerated. Overall, 47.9% (n = 292) of patients reported at least one adverse event during the trial; the frequency of patients with investigator-defined drug-related adverse events was similar in all treatment groups, ranging from 15.4 to 19.5% across the BI 425809 treatment groups and 15.8% for placebo. Conclusions No clinically meaningful changes from baseline were observed following treatment with BI 425809 in patients with mild-to-moderate probable Alzheimer’s disease dementia. Trial registration ClinicalTrials.gov NCT02788513 (1346-0023). Registered on June 2, 2016. EU Clinical Trials Register 2015-005438-24. Registered on May 6, 2016
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".