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
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 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 | 0.013 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".