First‐In‐Human Safety, Tolerability, and Pharmacokinetics of <scp>PPI</scp>‐1011, a Synthetic Plasmalogen Precursor
Bibliographic record
Abstract
PPI-1011 is a synthetic plasmalogen precursor designed to augment plasmalogen levels in patients with Rhizomelic chondrodysplasia punctata (RCDP), an ultra-rare genetic disorder caused by a plasmalogen deficiency that results in significant physical and mental delays. We report here a Phase I, randomized, double-blind, placebo-controlled study that evaluated the safety, tolerability, and pharmacokinetics (PK) of single (10-100 mg/kg) and multiple (75 and 100 mg/kg/day) ascending doses of PPI-1011 in healthy adults. All treatment-emergent adverse events (TEAEs) were mild, monitorable, and resolved without intervention, suggesting no significant safety concerns. The most common TEAEs were gastrointestinal in both the placebo and PPI-1011 groups, suggesting they were likely related to the oil-based nature of the formulation. PK analysis confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-dose (75 and 100 mg/kg, once daily) administration of PPI-1011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0/22:6). With a once-daily regimen, PPI-1011 administration resulted in a sustained increase of PlsEtn 16:0/22:6 serum concentrations in healthy participants over a duration of 14 days and beyond.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".