To evaluate the efficacy of ND0612 compared with placebo or current oral therapy in patients with Parkinson’s disease (PD).

Motor fluctuations in advanced PD remain challenging despite optimized oral therapy. ND0612, a continuous subcutaneous levodopa/carbidopa infusion, aims to provide stable plasma levels and reduce OFF time.

A systematic review of PubMed and meta-analysis of randomized controlled trials comparing ND0612 with placebo or current oral regimens was conducted. Outcomes included OFF-time (hours/day), ON-time without troublesome dyskinesia, PDQ-39, PDSS, and UPDRS-III. Standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI) were pooled using inverse variance methods under fixed and random-effects models.

Three trials (n = 327) were included. ND0612 significantly reduced OFF time versus comparators (SMD = –0.55; 95% CI: –0.77 to –0.33; p < 0.0001; I² = 0%). ON time without dyskinesia increased (SMD = 0.54; 95% CI: 0.17 to 0.92; p = 0.0047). Quality of life improved (PDQ-39 MD = –2.89; 95% CI: –4.90 to –0.88; p = 0.0049). Sleep quality (PDSS) showed benefit under fixed-effect model (MD = –2.11; p = 0.021) but not random-effects (p = 0.096; I² = 75.5%). UPDRS-III changes were not significant (random-effects MD = –2.15; p = 0.687; I² = 80.8%). Subgroup analysis revealed no significant differences between placebo and current regimen comparators.

ND0612 significantly reduces OFF time and improves ON time and quality of life in PD patients with motor fluctuations, with consistent effects across comparator types. Benefits on sleep and motor scores require further confirmation. ND0612 represents a promising non-surgical alternative for continuous dopaminergic delivery.