Efficacy and safety of extended-release carbidopa–levodopa (IPX203) versus immediate-release carbidopa–levodopa for Parkinson's disease: A systematic review

Objective IPX203 is a newly approved oral carbidopa–levodopa formulation designed to prolong the therapeutic effect and reduce complications associated with the standard immediate-release formulation. Immediate-release carbidopa–levodopa remains the current standard of care but has a short duration of action. This study aimed to evaluate the efficacy and safety of IPX203 compared with immediate-release carbidopa–levodopa in patients with advanced Parkinson's disease. Methods This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42024623230). A comprehensive search of PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, ScienceDirect, Scopus, and Embase identified randomized controlled trials comparing IPX203 with immediate-release carbidopa–levodopa. The primary outcomes were changes from baseline in “Good On-time” (periods of effective symptom control with minimal dyskinesia) and “Off-time” (periods when medication effects wear off and symptoms return). Secondary outcomes included scores on Part III of the Movement Disorder Society–Unified Parkinson's Disease Rating Scale and adverse events. Results A total of 466 records were screened, resulting in the inclusion of three randomized controlled trials involving 560 participants. Compared with immediate-release carbidopa–levodopa, IPX203 increased total “Good On-time” and reduced “Off-time.” Scores on Part III of the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale demonstrated greater improvement in motor function with IPX203. The incidence of adverse events was comparable between the two groups, although treatment-emergent adverse events and treatment discontinuations were more frequent in the IPX203 group. Conclusion Compared with immediate-release carbidopa–levodopa, IPX203 increased “Good On-time,” reduced “Off-time,” improved motor function as measured by Part III of the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale, and demonstrated a comparable safety profile.