0861 A Phase 2a, Double-blind, Placebo-controlled Study of ORX750 in Patients with Narcolepsy (type 1 and 2) and Idiopathic Hypersomnia: Study Design
Bibliographic record
Abstract
Abstract Introduction Narcolepsy types 1 (NT1) and 2 (NT2), and idiopathic hypersomnia (IH) are rare, debilitating central disorders of hypersomnolence characterized by excessive daytime sleepiness (EDS). None of the currently available therapies target the orexin system, which is a core element of wake-promoting circuitries and specifically, of NT1 pathology. ORX750 is a novel, investigational oral orexin-2 receptor (OX2R) agonist that demonstrated strong wake-promoting effects in acutely sleep-deprived healthy volunteers (ongoing phase 1 study). An ongoing phase 2a study, ORX750-0201 will evaluate the safety, tolerability, efficacy, and PK of ORX750 in NT1, NT2, and IH patients. Methods This phase 2a study is a randomized, double-blind, placebo-controlled, cross-over basket study with separate cohorts for NT1, NT2, and IH. Initial dosing will be 1 mg (NT1) and 2 mg (NT2 and IH) with sequential dose escalation/de-escalation between cohorts. Within dosing cohorts, participants will be randomized to one of two blinded treatment sequences and receive ORX750 for 4 weeks and placebo for 2 weeks (6-week treatment duration total) in a crossover design. Efficacy endpoints will include the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS), and weekly cataplexy rate (NT1 only). Other exploratory assessments include measures of overall symptom improvement, sleep, cognition, attention, memory, and general health. Results This study plans to complete 78 participants (n=18 NT1; n=24 NT2; n=36 IH), with three dose cohorts per disorder. This 6-week crossover study has >87.5 % power within each dosing cohort to detect a 15 min change in mean sleep latency on the MWT relative to placebo (two-sided α=0.05). The study initiated with participating sites in the US, Canada, and EU. Data for all three disorders are expected in 2025. Conclusion This study will evaluate the safety, tolerability, efficacy, and PK of multiple doses of ORX750 for the first time in patients with NT1, NT2, and IH with results informing future clinical studies. Support (if any) Centessa Pharmaceuticals
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| 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".