IPX203 Boosts “Good ON” Time in Parkinson Disease, Especially in Patients on Lower Dopamine Agonist Doses

Rajesh Pahwa, MD

(Credit: University of Kansas Medical Center)

In recently presented results from a phase 3 trial, investigators reported that patients with Parkinson disease (PD) who switched from immediate-release (IR) carbidopa-levodopa (CD-LD) to the extended-release formulation IPX203 (Crexont; Amneal Pharmaceuticals) improved good ON time, with the most notable gains seen in those on lower dopamine agonist doses.¹

The findings stemmed from the RISE-PD study (NCT0300788), a randomized, double-blind, active-controlled trial that evaluated IPX203’s efficacy and safety versus IR CD-LD. In the full study population, conversion to IPX203 improved good ON time by 1.74 hours and reduced average dosing frequency from 5 to 3 times per day. A subgroup analysis explored the role of concomitant dopamine agonist (DA) use, revealing that DA dose significantly influenced treatment outcomes.

Subgroup results showed good ON time increases of 2.35 hours in patients not taking DA and 2.72 hours in those on DA doses of 1–100 mg levodopa-equivalent-daily-dose (LEDD). For patients taking 101–200 mg DA LEDD, good ON time improved by 2.36 hours, whereas those in the 201–300 mg group had a gain of 1.50 hours. The smallest improvement—1.37 hours—was observed in patients taking more than 300 mg DA LEDD. Authors noted that an ANOVA analysis confirmed a significant effect of DA dose on good ON time improvement (P <.01).

An unbiased thresholding algorithm identified 200 mg DA LEDD as the key cut off point. Patients receiving 200 mg or less experienced a good ON time gain of 2.40 hours, compared with 1.45 hours in those above that threshold—a 40% reduction in benefit (P <.01). These results were recently presented by lead author Rajesh Pahwa, MD, the Laverne and Joyce Rider professor of neurology at the University of Kansas Medical Center, at the 2025 American Academy of Neurology (AAN) Annual Meeting, held April 5-9, in San Diego, California.

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In August 2024, the FDA approved IPX203 as a treatment for for PD, PD caused by infection or inflammation of the brain, or PD-like symptoms that may result from carbon monoxide or manganese poisoning in adults. It is not recommended in combination with nonselective monoamine oxidase inhibitors, nor with other CD/LD preparations without consultation with a healthcare provider.²

Amneal’s CD/LD ER capsule product was approved based on data from the RISE-PD trial, which showed that those treated with IPX203 at least 3 times per day (n = 256) had a statistically significant improvement of 0.53 hours (95% CI, 0.09-0.97; P = .02) in daily good ON time relative to those on IR CD/LD (n = 250), who were dosed 5 times per day.³ In addition to meeting its primary end point, IPX203 performed well on the secondary end point of change in OFF time hours per day.

All told, treatment with the agent resulted in significantly less OFF time compared with IR CD/LD (difference in least square [LS] means, –0.48; 95% CI, –0.90 to –0.06; P = .03). In addition, 29.7% and 18.8% of patients on IPX203 and IR CD/LD, respectively, rated themselves as much improved or very much improved on Patient Global Impression of Change (P = .002).

Treatment-emergent adverse events (TEAEs) for IPX203-treated participants were most frequent in the double-blind period (42.2%) than the dose-conversion (38.9%) or dose-adjustment (18.7%) periods. Within this group, the most common TEAEs were nausea (4.3%), anxiety (2.7%), and dizziness (2.3%), while those on IR CD/LD mostly experienced fall (3.6%), urinary tract infection (3.2%), and back pain (2.8%). During the double-blind period, 8 patients treated with IPX203 (3.1%) and 4 treated with IR CD/LD (1.6%) experienced serious TEAEs.

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REFERENCES
1. Pahwa R, Patel N, Falconer R, et al. Impact of Concomitant Therapy with a Dopamine Agonist on Converting Parkinson’s Disease Patients from Immediate-release Carbidopa-levodopa to CREXONT®. Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA.
2. Amneal Receives U.S. FDA Approval for IPX203 for Treatment of Parkinson’s Disease to Be Launched as CREXONT® (Carbidopa and Levodopa) Extended-Release Capsules. News release. Amneal. August 7, 2024. Accessed April 5, 2025. https://investors.amneal.com/news/press-releases/press-release-details/2024/Amneal-Receives-U.S.-FDA-Approval-for-IPX203-for-Treatment-of-Parkinsons-Disease-to-Be-Launched-as-CREXONT-Carbidopa-and-Levodopa-Extended-Release-Capsules/default.aspx
3. Hauser RA, Espay AJ, Ellenbogen AL, 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. Published online August 14, 2023. doi:10.1001/jamaneurol.2023.2679