Phase 3 & Safety
Name the two 12-week Phase 3 studies of oveporexton in narcolepsy type 1.
First Light (FirstLight) and Radiant Light (RadiantLight).
Which H3 antagonist/inverse agonist is indicated in the US for adult narcolepsy EDS or cataplexy?
Pitolisant (WAKIX).
What cerebrospinal-fluid molecule is characteristically low in orexin-deficient NT1?
Hypocretin-1 (orexin-A).
Which narcolepsy-specific PRO assesses functional impact?
Functional Impacts of Narcolepsy Instrument (FINI); includes cognition and everyday activities.
Which overnight test is generally performed before a diagnostic daytime MSLT?
Polysomnography (PSG).
Osaka is in which region of Japan?
Kansai.
Which three pivotal-trial measures captured objective wakefulness, subjective sleepiness and cataplexy?
MWT mean sleep latency (primary); ESS score and weekly cataplexy rate (key secondary).
Name the once-nightly extended-release sodium oxybate product for narcolepsy EDS or cataplexy.
LUMRYZ.
Where are orexin-producing neurons located?
The hypothalamus (including lateral hypothalamic regions).
MSLT and MWT are both sleep studies, which measures propensity to fall asleep and which measures ability to stay awake?
MSLT tests sleep propensity; MWT tests the ability to remain awake.
Sleepiness improves, but sleep stays fragmented and thinking remains difficult. Which two other domains show NT1’s 24-hour impact?
Nighttime sleep quality and cognitive/daytime functioning (or quality of life).
Which Swiss national language is spoken mainly in parts of Graubünden and is the country’s smallest language group?
Romansh (Rumantsch).
At week 12, roughly how many minutes did MWT latency change with oveporexton versus placebo?
+14.3 to +19.8 minutes versus −0.4 to −0.8 minutes.
Which investigational OX2R agonist is being studied in the Phase 3 Brilliance NT1/NT2 program?
Alixorexton (previously ALKS 2680).
Orexin neurons are lost in NT1. Why might a selective OX2R agonist still enhance wake signaling?
It directly activates downstream OX2R despite deficient endogenous orexin; it does not regrow neurons.
ESS focuses on sleepiness. What Phase 3 severity tool measures broader NT1 symptoms, and name two non-EDS symptoms it captures?
NSS-CT; e.g., cataplexy and disrupted nighttime sleep (also sleep paralysis or hallucinations).
An NT1 patient on treatment struggles at work and feels socially isolated. Suggest one supportive step for EACH impact.
Work/school accommodations for function; peer or psychological support for social/emotional burden.
Which former federal penitentiary sits on an island in San Francisco Bay and is now managed by the National Park Service?
Alcatraz Island.
Name one labeled safety warning AND the class of drugs contraindicated with oveporexton per the FDA label
Warning: insomnia, urinary frequency/urgency, or CPK elevations. Contraindicated: strong CYP3A inhibitors.
Which investigational orexin agonist is studied in CRYSTAL-1 across NT1, NT2 and idiopathic hypersomnia?
Cleminorexton (ORX750).
Which orexin-responsive hypothalamic nucleus releases histamine to promote wakefulness?
The tuberomammillary nucleus (TMN); its histaminergic neurons promote wakefulness.
What MSLT mean sleep latency and SOREMP count can support a narcolepsy diagnosis?
Mean latency ≤8 minutes and at least 2 sleep-onset REM periods.
Someone diagnosed with NT2 later reports laughter-triggered jaw weakness. Which diagnosis merits reevaluation, and why?
Reevaluate for NT1 with proper clinical/test criteria; cataplexy may emerge after EDS or initially be missed.
The Terracotta Army is part of the First Qin Emperor’s mausoleum near which Chinese city?
Xi’an (Lintong District, Shaanxi Province).
Across the 12-week First Light and Radiant Light trials, approximately what proportion of oveporexton-treated participants reported an adverse event, and how many participants discontinued because of an adverse event across both trials?
86–89% of oveporexton-treated participants reported an adverse event. Six participants discontinued because of an adverse event across both trials—five receiving oveporexton and one receiving placebo.
Which dopamine/norepinephrine reuptake inhibitor is US-labeled for narcolepsy-related EDS, but not for cataplexy?
Solriamfetol (SUNOSI). Its labeled narcolepsy indication is improvement in wakefulness; do not infer cataplexy benefit.
How does orexin deficiency contribute to excessive daytime sleepiness and cataplexy in NT1?
Less activation of arousal pathways contributes to EDS; reduced restraint of REM atonia during wake contributes to cataplexy.
Before interpreting a PSG–MSLT result, name two pre-test checks that help prevent misleading findings.
Confirm sufficient habitual sleep (sleep diary/actigraphy); review medications and substances that alter REM or alertness.
HLA-DQB1*06:02 is positive. Why can that finding not, by itself, establish a diagnosis of NT1?
It indicates susceptibility, not disease: healthy people can carry it. Use clinical and PSG–MSLT or CSF criteria.
Which real-life musketeer associated with The Three Musketeers died at the Siege of Maastricht in 1673?
D’Artagnan (Charles de Batz de Castelmore).