IPX203 Improves Daily Control Over Motor Fluctuations in Parkinson Disease

 In patients with advanced symptoms of Parkinson disease (PD), an oral, extended-release formulation of carbidopa-levodopa, IPX203, improved motor fluctuations and dyskinesia while decreasing treatment burden compared with immediate release carbidopa-levodopa, according to study findings published in JAMA Neurology.

An international team of researchers conducted a 20-week, randomized, double-blind, double-dummy, active-controlled, phase 3 clinical trial (RISE-PD; ClinicalTrials.gov Identifier: NCT03670953) from November 2018 to June 2021 across 105 academic and clinical centers throughout the United States and Europe. The first 3 weeks of the 20-week trial involved an open-label, dose-adjustment period for the immediate release carbidopa-levodopa. The next 4 weeks involved an open-label, IPX203 dose-conversion period. The last 13 weeks consisted of the double-blind, double-dummy treatment period.

Of the 770 individuals screened, the researchers enrolled 630 eligible patients with PD who were experiencing motor fluctuations in the study. Of these 630 participants, 506 completed the first 6 weeks of the trial period. The researchers randomly assigned 256 participants into the IPX203 group and 250 participants into the immediate release carbidopa-levodopa group. By the end of the last 13 weeks, 222 participants in the IPX203 group and 227 participants in the immediate release carbidopa-levodopa group completed the study.

Carbidopa-levodopa dosing depended on severity of motor fluctuations. Individuals in the IPX203 group received between 2 to 5 doses of 35 mg of carbidopa and 140 mg of levodopa every 8 hours or every 6 hours at minimum, but no more frequently. Individuals in the immediate release carbidopa-levodopa group fell into 4 dosing categories — receiving either 25 mg of carbidopa and 100 mg of levodopa (25/100 mg carbidopa-levodopa), between 25/100 and 37.5/150 mg carbidopa-levodopa, between 37.5/150 and 50/200 mg carbidopa-levodopa, and over 50/200 mg carbidopa-levodopa.  

The participants kept a daily diary of symptoms and side effects. They completed the Patient Global Impression of Change (PGI-C) scale and the Movement Disorders Society’s United Parkinson Disease Rating Scale (MDS-UPDRS) Parts II and III. At the end of the study, the researchers compared these scores to baseline measurements.

The researchers observed that individuals in the IPX203 group demonstrated significant improvements in their daily good on-time without dyskinesias or motor fluctuations compared with individuals in the immediate release carbidopa-levodopa treatment group (least squares mean, 0.53 hours; 95% CI, 0.09-0.97; P =.02). Participants in the IPX203 group reported an average of 1.55 hours of improved motor control compared with the immediate release carbidopa-levodopa group (95% CI, 1.37-173; P <.001).  

In addition to improved motor control, compared with the immediate release carbidopa-levodopa group, patients in the IPX203 treatment group did not have to dose as frequently. On average, compared to the immediate release carbidopa-levodopa group that required dosing 5 times daily, the IPX203 group received treatment 3 times daily.

Compared to baseline measurements, 29.7% patients in the IPX203 group demonstrated significant symptom improvement according to changes in their PGI-C scores compared with only 18.8% of patients in the immediate release carbidopa-levodopa treatment group (P =.002).

Overall, the IPX203 treatment demonstrated a good safety profile with patients tolerating the doses well. Compared with the immediate release carbidopa-levodopa group, the most commonly reported adverse events in the IPX203 group included nausea (4.3% vs 0.8%) and anxiety (2.7% vs 0%). The researchers did not observe any significant differences in baseline and final MDS-UPDRS scores between the 2 groups.

“In this study, IPX203 provided more hours of good on-time per day than immediate-release carbidopa-levodopa, even as IPX203 was dosed less frequently,” the researchers concluded.

As this trial only included participants with more advanced manifestations of PD, the researchers did not assess the efficacy and safety of IPX203 in individuals with early-onset PD and did not evaluate whether this treatment delayed onset of motor fluctuations and dyskinesia.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.

This article originally appeared on Neurology Advisor