Objective: Evaluate the efficacy and safety of IPX203 vs. immediate-release (IR) carbidopa-levodopa (CD-LD) and vs. extended-release (ER) CD-LD (IPX066, RYTARY^®) in patients with advanced Parkinson’s disease (PD).

Background: IR CD-LD treatment is often accompanied by motor fluctuations and dyskinesias in advanced PD. ER reduces “off” time and improves “on” time without troublesome dyskinesia vs. IR. IPX203 is an investigational extended-release capsule formulation of CD-LD aimed at further improving the clinical response over that from ER.

Methods: An open-label, rater-blinded, randomized, crossover study compared the response to single doses of IR, ER, and IPX203 during three separate periods. Advanced PD patients on a stable IR regimen (≥400 [max 1600] mg LD/day, given ≥4x/day) were rated by trained personnel as “off” or as “on” with or without troublesome dyskinesia every 30 min after dosing. The Unified PD Rating Scale (MDS-UPDRS) Part III was completed hourly for 10 hours after dosing. Adverse events (AEs) were recorded throughout the study.

Results: Twenty-five of 26 patients completed all 3 periods. The proportion of patients turning “on” by hour 1 was similar between IR, ER, and IPX203. IPX203 decreased mean (±SD) “off” time (4.5±2.0 hr) vs. IR (7.2±1.3 hr, p<.0001) and vs. ER (5.4±1.9 hr, p<.05). IPX203 increased “on” time vs. both comparators without significantly increasing troublesome dyskinesia. The proportion of patients in an “off” state was significantly lower for IPX203 between 3-8 hr than IR (p<.05), and 2.5-6 hr vs. ER (p<.05). The maximum improvement in MDS-UPDRS Part III scores was similar across treatments; however, the mean (SD) change from baseline was greater for IPX203 [-12.7(7.2)] than for IR [-6.6(3.7), p<.0001], and ER [-9.3(5.1), p<.05]. IPX203 increased the duration of a 4-point improvement [IPX203: 6.1 hr; IR: 3.7 hr (p<.0001); ER: 5.2 hr (p<.05)] and 13-point improvement [IPX203: 4.8 hr; IR: 2.2 hr (p<.0001); ER: 3.6 hr (p<.05)] in the MDS-UPDRS Part III. AEs were reported by 28.0% (IR), 8.0% (ER), and 19.2% (IPX203) of patients. AEs reported by ≥2 patients in any treatment were nausea, dizziness, and hypertension; no serious AEs were reported.

Conclusions: IPX203 significantly improved motor symptoms over a longer duration compared to both IR and ER CD-LD in advanced PD patients, without increasing troublesome dyskinesia.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-effects-and-safety-of-ipx203-an-investigational-extended-release-formulation-of-carbidopa-levodopa-in-advanced-parkinsons-disease-a-single-dose-study/