Objective: To conduct the efficacy and safety of IPX203, an extended-release carbidopa-levodopa formulation, and LCIG, a continuous levodopa infusion, compared to Immediate-Release Carbidopa-Levodopa (IR CD-LD) in addressing motor fluctuations in Parkinson’s disease (PD).

Background: Motor fluctuations, including OFF periods and dyskinesia, restrict the effectiveness of IR CD-LD. Optimized levodopa delivery strategies are essential to address these limitations. IPX203 and LCIG represent two different approaches; both provide steady levodopa levels. Unlike other formulations, these two have powerful RCT data, allowing direct comparison with IR CD-LD. This study aims to provide evidence for their clinical impact.

Method: A systematic search was conducted on PUBMED, SCOPUS, and WOS to find eligible RCTs comparing IPX203 or LCIG to IR CD-LD. The risk of bias 2 tool was used for quality assessment. The study was conducted using random-effects models. Sensitivity analyses and subgrouping assessed the strength of the evidence.

Results: Four RCTs with 682 patients met inclusion criteria. IPX203 did not significantly reduce OFF time (MD: -0.40 hours; 95% CI: -1.09, 0.29; p = 0.26), while LCIG significantly reduced OFF time (MD: -1.29 hours; 95% CI: -2.53, -0.05; p = 0.04). The overall pooled estimate showed a moderate reduction in OFF time (MD: -0.77 hours; 95% CI: -1.49, -0.04; p = 0.04). Sensitivity analysis excluding Slevin 2015 confirmed OFF time reduction (MD: -0.52; p = 0.04) with reduced heterogeneity (I² = 0%) [Figure1]. ON time with troublesome dyskinesia showed no significant difference between groups (MD: 0.10; 95% CI: -0.40, 0.59; p = 0.70) [Figure2]. After sensitivity analysis, LCIG confirmed a favorable safety profile, with fewer treatment-emergent adverse events (OR: 0.36; p < 0.0001).[Figure3]

Conclusion: LCIG was efficacious in reducing off-time and was recommended for PD patients with severe motor fluctuations. For patients preferring noninvasive therapy, IPX203 can be a good oral alternative but did not significantly outperform IR CD-LD. Both drugs showed a comparable safety profile with low adverse effects. Further large-scale RCTs are needed to compare IPX203 and LCIG and modify patient selection criteria.

[Figure1] : OFF Time

[Figure2] : On time with troublsome dyskinesia

Treatment Emerging Adverse Effects

References: [1] R. A. Hauser et al., “IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease: The RISE-PD Randomized Clinical Trial,” JAMA Neurol, vol. 80, no. 10, pp. 1062–1069, Oct. 2023, doi: 10.1001/JAMANEUROL.2023.2679.
[2] N. B. Modi, A. Mittur, P. Dinh, R. Rubens, and S. Gupta, “Pharmacodynamics, Efficacy, and Safety of IPX203 in Parkinson Disease Patients With Motor Fluctuations,” Clin Neuropharmacol, vol. 42, no. 5, pp. 149–156, Sep. 2019, doi: 10.1097/WNF.0000000000000354.
[3] C. W. Olanow et al., “Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study,” Lancet Neurol, vol. 13, no. 2, pp. 141–149, Feb. 2014, doi: 10.1016/S1474-4422(13)70293-X.
[4] J. T. Slevin et al., “Long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal gel: an open-label extension of the double-blind pivotal study in advanced Parkinson’s disease patients,” J Parkinsons Dis, vol. 5, no. 1, pp. 165–174, 2015, doi: 10.3233/JPD-140456.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-ipx203-and-levodopa-carbidopa-intestinal-gel-lcig-compared-to-immediate-release-carbidopa-levodopa-in-parkinsons-disease-a-systematic-review-and-meta-analysis/