1285 Rationale and Study Design of Samelisant (SUVN-G3031) for the Treatment of Cataplexy in Type 1 Narcolepsy Patients
Bibliographic record
Abstract
Abstract Introduction Samelisant (SUVN-G3031) is potent and selective histamine 3 receptor inverse agonist, which works by modulating the histamine system, a key part of the brain’s sleep-wake regulation. Samelisant demonstrated wake-promoting and anticataplectic effects, in animal models relevant to narcolepsy. Methods Samelisant was evaluated in orexin knockout mice and orexin-B SAP lesioned rats for its effects on sleep/ wake and cataplexy using electroencephalography (EEG). Samelisant produced significant reduction in cataplectic like episodes in orexin knockout mice, similarly significant decrease in direct wake to REM sleep (DREM) episodes was observed in orexin-B SAP lesioned rats. Based on the evidence from animal studies, Samelisant is being evaluated in a Phase 2 proof-of-concept study in the USA and Canada to treat cataplexy in NT1 patients. Results This study is a placebo-controlled, double blind randomized, parallel-group study. The study will recruit about 129 NT1 patients with an established diagnosis of NT1 according to the ICSD-3 or DSM-5-TR. After a prescreening period of 4-weeks, eligible patients will follow a titration schedule to gradually increase their dose of the investigational product for initial three weeks followed by stable dose treatment for additional five weeks. The primary endpoint of the study will be to evaluate change from Baseline in weekly cataplexy rate on Day 56. Secondary endpoints will include change from Baseline in Clinical Global Impression Scale-Severity (CGI-S) score and Epworth Sleepiness Scale (ESS) score on Day 56. Other exploratory endpoints will be change from Baseline in Clinical Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), Narcolepsy Severity Scale (NSS) score and 5-level EQ-5D version (EQ-5D-5L) on Day 56. Conclusion Outcomes from animal models of narcolepsy suggest that Samelisant may have anticataplectic effects. The Phase-2 study results may inform the therapeutic utility of Samelisant for the treatment cataplexy in NT1 patients. Support (if any)
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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 | 0.011 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.015 | 0.004 |
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".