P1‐062: A PHASE II STUDY EVALUATING EFFICACY, SAFETY, AND TOLERABILITY OF ORAL BI 425809 IN PATIENTS WITH COGNITIVE IMPAIRMENT DUE TO ALZHEIMER'S DISEASE DEMENTIA
Bibliographic record
Abstract
Although currently approved therapies for Alzheimer's disease dementia (ADD) are used to treat impairments in memory and function, there is an unmet need for additional symptomatic therapies in mild-to-moderate ADD. As N-methyl-D-aspartate (NMDA) receptor hypofunction has been hypothesized to be associated with cognitive impairment in ADD, improving post-synaptic NMDA receptor signaling through glycine transporter 1 (GlyT1) inhibition may improve cognitive function. This proof of clinical concept study aims to investigate the efficacy and safety of BI 425809, a GlyT1 inhibitor, in mild-to-moderate ADD. This study will provide dose-ranging data to define a suitable dose of BI 425809 in this population. This ongoing Phase II, multicenter, double-blind, parallel-group study includes patients aged ≥55 years with mild-to-moderate ADD according to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for AD, a mini mental state exam score of 15–26 at screening, and a reliable study partner who is in close contact with the patient and can contribute to the neuropsychological rating scales. Concomitant use of acetylcholinesterase inhibitors is allowed but not required. Eligible patients are being randomized (1:1:1:1:1) to receive BI 425809 2, 5, 10, 25 mg, or placebo once daily for 12 weeks. The primary endpoint is change from baseline in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog11) total score at Week 12. Secondary endpoints include change from baseline in the Alzheimer's Disease Cooperative Study/Activities of Daily Living score and Clinician's Interview-Based Impression of Change at Week 12. Further endpoints include Neuropsychiatric Inventory and change from baseline in the derived composite endpoint of selected tests from ADAS-Cog11 and further cognitive tests at Week 12. Pharmacokinetic parameters are being investigated and safety is being evaluated throughout the study. Study completion is currently planned in March 2020 with topline Results available in Q2 2020. Preliminary recruitment and baseline characteristic data will be presented. The Results will be used to test for a positive proof of clinical concept and to define a suitable dose of BI 425809 regarding efficacy and safety in mild-to-moderate ADD for further studies. Funding: Boehringer Ingelheim: Study 1346.23 (NCT02788513).
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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) | 0.002 | 0.001 |
| 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 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".