Duration of benefit per Dose: Carbidopa-Levodopa immediate release vs. extended release capsules (Rytary?)

Background: For patients with Parkinson's disease, clinicians commonly assess duration of benefit for individual doses of levodopa in order to consider medication changes. Objective: To determine the mean duration of ON time per dose and mean duration of ON time without troublesome dyskinesia (WoTD) per dose of CD-LD IR vs. CD-LD ER in the ADVANCE-PD trial. Methods: We performed a post hoc analysis of the ADVANCE-PD trial. Mean ON time per dose and ON time WoTD was calculated at baseline and end-of-study (EOS). Changes were compared between CD-LD IR and CD-LD ER (Rytary (R)) treatment groups using an ANCOVA model. Results: Mean (SD) baseline ON time per dose of CD-LD IR (n = 393) was 2.20 h. Patients randomized to double-blind treatment with CD-LD IR (n = 192) experienced an increase in mean ON time per dose from baseline to EOS from 2.24 h to 2.38 h. In comparison, patients randomized to double-blind treatment with CD-LD ER (n = 201) experienced an increase in mean ON time per dose from baseline (on CD-LD IR) to EOS (on CD-LD ER) from 2.17 h to 3.55 h. Conversion and optimization with CD-LD ER increased ON time per dose by 1.21 h more than optimization of CD-LD IR (p < 0.0001). Similarly, CD-LD ER increased ON time WoTD per dose by 1.16 h more than CD-LD IR (p < 0.0001). Conclusion: In the ADVANCE-PD trial, CD-LD ER significantly increased ON time per dose compared to CD-LD IR (+1.21 h, p < 0.0001) and provided significantly more ON time per dose (3.55 h vs 2.38 h, p < 0.0001).