0649 Samelisant Improves the Symptoms of Excessive Daytime Sleepiness in Narcolepsy: Results from a Phase-2 Study
Bibliographic record
Abstract
Abstract Introduction Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness (EDS) with irresistible sleep attacks, cataplexy, hypnagogic hallucination, and sleep paralysis. The currently available treatments suffer from major limitations like side effects, modest efficacy or they must be prescribed in combination. Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of narcolepsy. Safety and tolerability studies in animals and healthy human volunteers suggest a favorable risk/benefit profile for samelisant. Methods Samelisant had been evaluated as monotherapy in a Phase-2 proof of concept study in the USA and Canada for the treatment of EDS in patients with narcolepsy (ClinicalTrials.gov Identifier: NCT04072380). Patients diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of < 12 min were recruited in the study. A total of 190 patients were randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio and received either placebo or samelisant, once daily for 2 weeks. The primary efficacy endpoint was change in ESS score from baseline to Day 14. Secondary endpoints were changes from baseline to week 2 in Clinical Global Impression - Severity (CGI-S) and MWT scores. The medical monitor and the data safety monitoring committee monitored safety throughout the study. Results The baseline characteristics and demographics were consistent with the general narcolepsy population and equally distributed between treatment groups. The study met the pre-specified primary efficacy endpoint. In comparison against placebo, samelisant as monotherapy demonstrated statistically significant (p< 0.024) and clinically meaningful reduction (-2.1 point) in EDS measured by ESS. Samelisant was generally safe and well tolerated. Conclusion Samelisant holds promise as a monotherapy treatment of EDS in narcolepsy. Support (if any)
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".