Amneal Pharmaceuticals has announced promising new data from its Phase 3 RISE-PD study demonstrating that CREXONT, a novel extended-release formulation of carbidopa and levodopa, significantly improves sleep quality in patients with Parkinson's disease (PD).
The analysis, presented at the American Academy of Neurology (AAN) 2025 Annual Meeting, showed that patients who successfully converted to CREXONT from immediate-release (IR) carbidopa/levodopa experienced statistically significant improvements in their Parkinson's Disease Sleep Scale-2 (PDSS-2) total scores, with a mean difference of -2.35 (p<0.0001).
Comprehensive Sleep Benefits Demonstrated
Sleep disturbances affect up to 80% of patients with Parkinson's disease, significantly impacting quality of life. The new analysis revealed improvements across all PDSS-2 subdomains for patients on CREXONT compared to those on IR carbidopa/levodopa:
- Reduced disturbed sleep (-1.07, p<0.0001)
- Improved nighttime motor symptoms (-0.62, p<0.0059)
- Decreased PD symptoms at night (-0.65, p<0.0017)
"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, study author and Professor of Neurology at the Parkinson's Disease and Movement Disorders Center, University of South Florida.
Improved Morning "On" State
A separate analysis of Hauser diary entries from the RISE-PD study revealed additional benefits. Treatment with CREXONT resulted in significant increases in the number of patients who reported waking up in an "On" state compared to those on IR carbidopa/levodopa. Additionally, more CREXONT patients never recorded being in an "Off" state upon awakening.
This finding is particularly significant as many Parkinson's patients struggle with morning akinesia, often waking up in an "Off" state with limited mobility.
Innovative Formulation Approach
CREXONT's novel formulation combines immediate-release granules of carbidopa and levodopa for rapid onset with extended-release pellets utilizing a sustained-release polymer. This design potentially enables longer levodopa absorption in the gut, addressing the pharmacokinetic limitations of traditional formulations.
"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.
About the RISE-PD 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 carbidopa/levodopa in PD patients experiencing motor fluctuations. The study included 506 patients diagnosed with PD at age 40 or older.
The primary endpoint assessed the change from baseline in "On" time in hours per day at the end of the 20-week treatment period. Secondary endpoints included changes in "Off" time, Patients' Global Impression of Change scores, and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores.
Future Research
Amneal has initiated a Phase 4 clinical trial, ELEVATE-PD, to evaluate the real-world efficacy and safety of CREXONT in patients with PD. This study will provide additional insights into the medication's performance in clinical practice.
Safety Profile
The most common adverse reactions with CREXONT (incidence ≥3% and greater than IR carbidopa/levodopa) were nausea and anxiety. As with other dopaminergic medications, healthcare providers should monitor patients for potential side effects including somnolence, dizziness, and falling asleep during activities of daily living.
Parkinson's Disease Burden
Parkinson's disease has become the fastest-growing neurological disorder worldwide, affecting approximately 1 million people in the United States alone. It is a progressive disorder of the central nervous system characterized by slowness of movement, stiffness, resting tremor, and impaired balance.
As the global population ages, the prevalence of Parkinson's disease is expected to continue rising, underscoring the need for innovative treatment approaches that address both motor and non-motor symptoms of the condition.
