A Relative Bioavailability Study of Three Dose Strengths and Four Dose Levels of SD-809, a Potential Treatment for Movement Disorders (P1.054)
Bibliographic record
Abstract
Introduction: SD-809 (deutetrabenazine) is a VMAT-2 inhibitor in clinical development for treatment of hyperkinetic movement disorders. Previous studies have shown that the active metabolites of SD-809, total (α+β)-dihydrodeutetrabenazine (HTBZ), have a half-life of approximately 9 hours, reducing the need for frequent dosing. Twice daily administration of dose strengths 6 mg, 12 mg, 18 mg and 24 mg has been developed as a potential treatment for treatment of chorea associated with Huntington’s disease. Objectives: Evaluate the relative bioavailability, dose proportionality and safety of single doses of 6-, 12-, 18- and 24-mg doses of SD-809 under fed conditions. Methods: Thirty-two healthy subjects, with either an extensive (EM) or intermediate (IM) CYP2D6 phenotype, were randomly assigned to an SD-809 treatment sequence in this open-label crossover study. Sequential plasma samples were collected in each period and assayed for SD-809, α-HTBZ, and β-HTBZ by validated LC-MS/MS methods. Exposure parameters for total d6-(α+β)-HTBZ were calculated as the sum of α-and β-HTBZ metabolites. Results: Based on regression models for evaluation of proportionality, total (α+β)-HTBZ increased linearly with doses between 6 and 24 mg and the dose normalized 90[percnt] CI for Cmax, AUC0-t, and AUCinf fell within 80[percnt] to 125[percnt] equivalence limits. Ten (31[percnt]) subjects experienced adverse events and no severe or serious adverse events were reported. Conclusions: Following single-dose administration of SD-809 from 6-24 mg, the active metabolites demonstrated dose proportional pharmacokinetics under fed conditions. SD-809 was well tolerated in healthy subjects.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.003 | 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 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".