Objective:

This post hoc analysis of a phase 3 trial (NCT03030599) assessed low-sodium oxybate (LXB; Xywav^®) efficacy and safety in narcolepsy participants with or without psychiatric/neurologic comorbidities. 

Background:

Prior studies report high incidences of psychiatric/neurologic comorbidities in narcolepsy patients. LXB is an FDA-approved treatment for cataplexy or excessive daytime sleepiness in patients ≥7 years old with narcolepsy and for adults with idiopathic hypersomnia. 

Design/Methods:

Adults (18‒70 years) with narcolepsy with cataplexy optimized/titrated their LXB dose (≤12 weeks) before a 2-week stable-dose period. During a 2-week double-blind randomized-withdrawal period, participants switched to placebo or continued LXB. Epworth Sleepiness Scale (ESS) scores, average weekly number of cataplexy attacks, Patient Global Impression of Change (PGIc) scores, Patient Health Questionnaire-9 (PHQ-9) scores, and treatment-emergent adverse events (TEAEs) were evaluated in participants with or without psychiatric/neurologic comorbidities.

Results:

Of 201 participants, 84 reported baseline comorbidities (most commonly depression, migraine headaches, anxiety, and headache [non-migraine]). Imbalances between subgroups were observed regarding sex, race, ethnicity, and BMI. Compared with participants continuing LXB, participants randomized to placebo in both subgroups showed worsening (increases) in ESS scores (least squares mean differences, LXB vs placebo [95% CI], with comorbidities: −3.7 [−5.6, −1.9], P=0.0001; without comorbidities: −2.0 [−3.5, −0.6]; P=0.0050). Participants randomized to placebo in both subgroups had increased weekly cataplexy attacks (location shift, LXB vs placebo [95% CI], with comorbidities: −4.0 [−7.0, −1.1], P=0.0026; without comorbidities: −3.5 [−9.1, −1.1], P<0.0001). Participants randomized to placebo in both subgroups showed worsening in PGIc scores (P<0.0001, for both). PHQ-9 scores, indicating depressive symptoms, remained stable in both subgroups. TEAEs and serious TEAEs occurred in 69 (82.1%) and 1 (1.2%) participants with comorbidities, and 84 (71.8%) and 3 (2.6%) without comorbidities, respectively.

Conclusions:

The efficacy and safety of LXB in narcolepsy participants with psychiatric/neurologic comorbidities were similar to those in participants without psychiatric/neurologic comorbidities.