Objective:

Background:

Sleep disturbances affect up to 80% of individuals with PD and are among the most disabling non-motor symptoms. CREXONT is a novel extended-release CD-LD formulation. In RISE-PD, CREXONT significantly increased “Good On” time per day and per dose vs IR CD-LD.

Design/Methods:

RISE-PD was a 20-week phase 3 study with a 3-week open-label IR CD-LD dose-optimization period, 4-week open-label dose-conversion to CREXONT, and a 13-week randomized, double-blind maintenance phase with two arms: IR CD-LD and CREXONT. The current analysis included patients with clinically relevant sleep disturbances at study entry (PDSS-2 total score ≥18). Outcome measures were changes in PDSS-2 total and subscale scores, and nighttime and early morning ‘Off’ per Hauser diary data.

Results:

In the prespecified subgroup of patients with clinically relevant sleep disturbances (n=199), total PDSS-2 scores significantly improved during the open-label period (mean change = –6.99, p<0.001). Domain-specific analyses showed significant improvements: Disturbed Sleep Score improved from 11.94 ± 0.23 to 9.06 ± 0.28 (–2.88, p<0.001); Motor Symptoms at Night Score from 7.73 ± 0.24 to 5.56 ± 0.25 (–2.17, p<0.001); and PD Symptoms at Night Score from 6.62 ± 0.24 to 4.69 ± 0.22 (–1.93, p<0.001). Compared with study entry (V1), CREXONT treatment reduced nighttime “Off”: 2.5% reported none at V1, 4.5% at V2, and 18.6% by the end of CREXONT dose conversion. Early morning motor function also improved: 6.5% reported never experiencing early morning “Off” at V1, rising to 8% at V2 and 20.1% after CREXONT conversion.

Conclusions:

These findings suggest that in PD patients with clinically relevant sleep disturbances, IR CD-LD optimization followed by conversion to CREXONT improves patient-reported sleep quality. CREXONT may also enhance nighttime and early morning motor control.