To evaluate the potential benefits of the COMT inhibitor opicapone (OPC) on sleep, when added to existing levodopa in Parkinson’s disease (PD) patients with end-of-dose motor fluctuations and associated sleep disturbances.

Levodopa remains the most effective symptomatic treatment for PD; however, as the disease progresses, patients experience end of dose wearing off and increasing frequency of non-motor symptoms. Sleep disturbance is among the most frequent non-motor symptoms in PD, affecting up to 80% of patients in all stages. OPC has been shown to be generally well tolerated and efficacious in reducing OFF-time in two pivotal Phase 3 studies in patients with PD and end-of-dose motor fluctuations (BIPARK I and II).

OASIS was an exploratory, open-label, single-arm pilot trial. All patients (N=16) received OPC 50mg once daily as add-on to levodopa therapy for 6 weeks. Primary endpoint was change from baseline in PD Sleep Scale-2 (PDSS-2). Secondary endpoints included tolerability, functional motor and non-motor assessments (Movement Disorder Society [MDS]-Unified Parkinson's Disease Rating Scale [UPDRS], MDS-Non-motor Scale [NMS], 8-item PD Questionnaire [PDQ-8], and 16-item PD Fatigue Scale [PFS-16], ON/OFF home diary).

At week 6, there was a significant reduction of -7.9 points (95% CI: -13.6,-2.2; p=0.0099) in total PDSS-2 score. The disturbed sleep domain of PDSS-2 also exhibited a significant mean change of -4.7 points (95% CI: -7.2,-2.3; p=0.0009), reflecting perceived improvements in sleep quality, initiation, maintenance, and restorative sleep. Significant reductions were also observed in PFS-16 (-9.6 [95% CI: -17.5,-1.7; p=0.0211]), MDS­NMS total score (-28.9 [95% CI: -44.7,-13.2; p=0.0015]), MDS-UPDRS-III and IV (-6.3 [95% CI: -11.6,-0.9; p=0.0253] and -1.2 [95% CI: -2.0,-0.4; p=0.0044], respectively) and PDQ-8 (-14.2 [95% CI: -23.3,-5.0; p=0.0051]). Absolute OFF-time was reduced (-142.1 mins), while ON-time without dyskinesia was increased (+127.1 mins).

Adding OPC 50mg to levodopa therapy improved sleep disturbances and other non-motor symptoms associated with PD.