A new analysis is announced of the pivotal RISE-PD Phase III study of Crexont (carbidopa XR + levodopa) which showed significant improvements in sleep quality for Parkinson's disease patients.- Amneal

Amneal Pharmaceuticals, Inc. announced a new analysis of the pivotal RISE-PD Phase III study showed that patients who successfully converted to Crexont (carbidopa XR +  levodopa) from immediate release (IR) carbidopa/levodopa (CD/LD) experienced statistically significant improvements in sleep quality. These improvements were measured by their Parkinson’s Disease Sleep Scale-2 (PDSS-2) total scores, showing a mean difference of -2.35 (p<0.0001). Crexont , which is indicated for the treatment of Parkinson’s disease (PD), is a novel formulation of CD/LD that combines both IR granules and extended-release pellets. This innovative design allows for rapid onset, while leveraging a sustained-release polymer for slow LD release, potentially enabling longer LD absorption in the gut.

The new analysis showed that patients on Crexont , compared to IR CD/LD, also experienced statistically significant improvements across all PDSS-2 subdomains, including reduced disturbed sleep (-1.07, p<0.0001), improved nighttime motor symptoms (‑0.62, p<0.0059) and PD symptoms at night (-0.65, p<0.0017). Full results will be presented at the American Academy of Neurology (AAN) 2025 Annual Meeting on April 9 at 8 a.m. PST.

"I’ve seen firsthand how common sleep disturbances are among patients with Parkinson's disease and the profound impact they have on daily life. Improving sleep quality is not only essential for effective disease management, but also critical for enhancing overall patient care and well-being," said Dr. Robert Hauser, a study author and Professor of Neurology at the Parkinson’s Disease and Movement Disorders Center, University of South Florida. "The new Phase 3 data analysis shows CREXONT’s ability to significantly improve sleep, in addition to its effects on daytime PD symptoms, making it a valuable treatment option for patients dealing with the challenges of this debilitating condition.”

A separate analysis of Hauser diary entries, which is a commonly used PD symptom tracking tool, from patients who completed the RISE-PD study will also be presented at AAN. Treatment with CREXONT compared to IR CD/LD resulted in significant increases in the number of patients who reported waking up in an “On” state and patients who never recorded being in an “Off” state upon awakening. Furthermore, the percentage of patients who never recorded “On” upon awakening decreased with CREXONT vs. IR CD/LD.

"It’s exciting to see the expanding body of research supporting CREXONT and its positive impact on patients. As we continue to explore the full benefits of CREXONT, we are optimistic that increased ‘On’ time throughout the day with fewer doses – and as now demonstrated, enhanced sleep quality – can help improve overall quality of life for more PD patients,” said Joe Renda, Senior Vice President, Chief Commercial Officer – Specialty at Amneal Pharmaceuticals. “The rising prevalence of Parkinson’s disease underscores the need for continued innovation, and Amneal remains dedicated to providing solutions that improve PD patient outcomes.”

Amneal has initiated a Phase IV clinical trial, ELEVATE-PD, to evaluate the real-world efficacy and safety of CREXONT in patients with PD.

The most common adverse reactions with CREXONT (incidence ≥3% and greater than IR CD/LD) are nausea and anxiety. See Important Safety Information below.

About the RISE-PD Phase III Trial; The multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group RISE-PD trial evaluated the efficacy and safety of Crexont  compared with IR CD/LD in the treatment of patients with PD who have motor fluctuations. The primary endpoint of the trial assessed the change from baseline in “On” time in hours per day at the end of the double-blind treatment period (Week 20 or early termination). Secondary endpoints assessed the change from baseline in “Off” time in hours per day, proportion of patients who were either “much improved” or “very much improved” in Patients' Global Impression of Change (PGI-C) scores, change from baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score, and the change from baseline in sum of MDS-UPDRS Parts II and III scores. The study included 506 patients who had received a PD diagnosis at age 40 or older.