Evaluation of OM3-PL/FFA Pharmacokinetics After Single and Multiple Oral Doses in Healthy Volunteers
Bibliographic record
Abstract
Purpose The US Food and Drug Administration has approved several omega-3 (OM3)-containing prescription drugs for the treatment of severe hypertriglyceridemia (HTG). However, there is still a need to develop formulations with high bioavailability irrespective of the fat content and time of the meal. OM3-phospholipid (PL)/free fatty acid (FFA) is an investigational drug for the treatment of severe HTG containing naturally derived krill oil mixture of OM3, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as PL esters and as FFA. Both forms in OM3-PL/FFA are believed to be readily bioavailable. Per gram, OM3-PL/FFA contains a lower dose of EPA/DHA in comparison with already approved prescription drugs. The study aim was to evaluate OM3-PL/FFA pharmacokinetic (PK) properties after single and multiple oral doses of 1, 2, and 4 g in healthy subjects when receiving a Therapeutic Lifestyle Change (TLC) diet. The dose proportionality of the study drug, the effect of a high-fat (HF) meal on its PK properties and its safety profile after multiple administration were also explored. Methods In this Phase I, open-label, randomized, multiple-dose, single-center, parallel-design study, 42 healthy volunteers following a TLC diet were randomly assigned into 1 of 3 treatment groups in a 1:1:1 ratio to receive a single dose at day 1, followed by multiple oral doses of 1, 2, and 4 g/d for 14 days. At day 15, all subjects received a HF breakfast. Findings After once-daily dosing, based on graphic assessment, OM3-PL/FFA levels reached steady state within 7–10 days. Exposure of total EPA + DHA, total DHA, and total EPA (C max and AUC) appeared to be approximately proportional over the 1–4 g/d dose range. After 14 days of repeated daily dosing, accumulation was observed and was greater at the higher dose of the study product. When administered after a HF breakfast on day 15, median t max , the geometric mean of AUC 0–24 and C max were comparable with the values on day 14 across the 3 dose levels. Implications OM3-PL/FFA was found to be well tolerated in healthy subjects. The study drug PK properties appeared to be approximately dose proportional over the 1–4 g/d dose range. The bioavailability of OM3-PL/FFA did not appear to be meaningfully affected by the fat content of the meal consumed before dose administration. This is clinically relevant because a low-fat diet is part of the management of patients with HTG.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".