Objective: To examine the safety of levodopa-carbidopa intestinal gel treatment (LCIG, carbidopa-levodopa enteral suspension in the US) in advanced Parkinson’s disease (PD) patients that received ≥2000 mg/day dose of levodopa during clinical studies.

Background: LCIG is a treatment option for advanced PD patients with severe motor fluctuations despite optimized medical therapy.  Published data on levodopa safety by dose is limited, especially for ≥2000 mg.

Methods: Adverse events (AEs) from patients in the phase 3 program who received open-label LCIG were summarized through October 1, 2016. Patients were divided post-hoc into 2 dose groups of <2000 mg (N=340) ≥2000 mg (N=72) mean total levodopa per day.  Device/procedure AEs were excluded from the analysis. Real world safety data from the GLORIA observational study was also summarized.

Results: Approximately 17% (n=72/412) of the advanced PD patients in the phase 3 program required ≥2000 mg/day of levodopa for symptom control. Real world data from the GLORIA observational study reflects a similar percentage of patients receiving ≥2000 mg (100 ml) levodopa per day (n=47/356 [13%]). Mean baseline (BL) patient characteristics were comparable across dose groups from the phase 3 program.[table1] Mean (SD) BL oral levodopa daily dose was higher for the ≥2000 mg/day group than patients receiving <2000 mg/day (<2000mg: 1000.3[499.6] mg; ≥2000mg: 1464.8[693.3]). AEs were reported by 93% of patients in the <2000 mg/day group and 97% of patients in the ≥2000 mg/day group.[table2]  AEs with the highest incidence rates overall were insomnia (<2000mg: 24%, ≥2000mg: 24%) and fall (<2000mg: 22%, ≥2000mg: 8%). AEs reported in ≥15% of patients in the ≥2000 mg dose group with incidence rates ≥ twice that of the <2000 mg dose group included PD, or the return/worsening of PD symptoms (<2000mg: 14%, ≥2000mg: 31%), and vomiting (<2000mg: 9%, ≥2000mg: 22%). Serious AEs were reported by 44% of patients in the <2000 mg/day group and 64% of the patients receiving ≥2000 mg/day, with pneumonia, PD, and fall having the highest incidence rates overall.

Conclusions: Patients that required ≥2000 mg/day of levodopa for PD symptom control had higher BL oral levodopa doses and higher AE rates compared to the patients who received <2000 mg/day levodopa dose. However, baseline characteristics and discontinuation due to AE were relatively similar between groups.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-of-levodopa-carbidopa-intestinal-gel-treatment-in-advanced-parkinsons-disease-patients-receiving-%e2%89%a5-2000-mg-daily-dose-of-levodopa/