J10 Analysis of integrated safety data from pridopidine clinical trials demonstrates a favorable safety and tolerability profile at the clinically relevant dose of 45 mg bid
Bibliographic record
Abstract
<h3></h3> Pridopidine is a highly selective Sigma-1 receptor (S1R) agonist, being evaluated in the PROOF-HD Ph3 trial. Pooled safety data from 22 trials assessing pridopidine at doses 10-112.5 mg bid was analyzed, encompassing safety data from 1300 patients (~1300 patient-years of exposure, including long-term data >5 years); 1100/1300 (85%) HD patients, and 981/1300 (75%) treated with 45 mg bid, the dose assessed in PROOF-HD. Due to different placebo and pridopidine exposures, AE rate analyses, corrected for patient-years of exposure, were performed. The rate of common AEs was similar for placebo vs. 45 mg bid (rate=2.35 vs.1.82 events/patient years). Serious adverse events (SAEs) were reported in placebo and 45 mg bid groups (rate=0.07 and 0.18, respectively). Most SAEs were common for HD; 1 case of subdural hematoma was considered drug-related. Concentration-QTc analysis was performed using PK sampling and ECG monitoring data from 402 PRIDE-HD Ph2 trial participants, for 52 weeks. Pridopidine shows a concentration dependent effect on QTcF interval (slope=0.012 ms/ng/mL; 90% CI: 0.0109-0.0127). The, predicted QTc effect at 45 mg bid is 6.6 ms, with a two-sided 90% CI below 8 ms, that is of no regulatory concern (FDA considers QTc <10 ms low risk for Torsade de Pointes, TdP). Across the integrated safety database, the rate of AEs for QT prolongation was higher in placebo vs 45 mg bid (rate=0.013 vs. 0.005). No cases of TdP, and no increased risk for pro-arrhythmic events reported at the clinical dose. As of June 16th, 2022, PROOF-HD has low dropout (23/499, 4.6%) and discontinuation (19/499, 3.8%) rates. In February 2022, an independent safety monitoring committee reported no safety signals of concern, and recommended PROOF-HD continue as planned.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.013 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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 teacher head, 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".