AAN 2025: Crexont improves sleep quality in Parkinson’s patients
Data based on Phase 3 trial results show added benefits
Crexont, an extended-release oral formulation of carbidopa and levodopa, significantly improved sleep quality in people with Parkinson’s disease.
That’s according to data based on additional analysis of the Phase 3 RISE-PD trial (NCT03670953).
The results were detailed in a presentation, “Conversion to CREXONT in the RISE-PD Phase 3 Trial Improved Aspects of Sleep as Measured by the Parkinson’s Disease Sleep Scale-2 (PDSS-2),” at this year’s American Academy of Neurology (AAN) annual meeting, held April 5-9 in San Diego and online.
The findings build on earlier evidence demonstrating Crexont’s efficacy in extending good on time, or periods when motor symptoms are well controlled, with fewer daily doses than traditional formulations.
“It’s exciting to see the expanding body of research supporting CREXONT and its positive impact on patients,” Joe Renda, senior vice president and chief commercial officer at Amneal Pharmaceuticals, which markets Crexont, said in a company press release. “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 [Parkinson’s] patients,”
Sleep issues common in Parkinson’s
Parkinson’s is caused by the progressive loss of nerve cells that produce dopamine, a key chemical messenger in the brain that helps in movement control. As dopamine levels fall, patients experience a range of motor symptoms, while nonmotor symptoms arise from broader neuronal damage throughout the brain. Sleep disturbances are particularly common, affecting up to 80% of Parkinson’s patients.
Levodopa, combined with carbidopa, remains the gold standard for increasing dopamine levels and managing Parkinson’s disease symptoms. Traditional immediate-release formulations require frequent dosing, which, especially with long-term use, can lead to fluctuations in symptom control, known as off periods, and potential side effects like dyskinesia, or sudden, uncontrolled movements.
Crexont was developed as a dual-layer formulation that combines immediate-release granules with extended-release pellets of carbidopa and levodopa. This design aims to provide rapid onset and sustained symptom control, reducing the burden of frequent dosing.
The RISE-PD trial enrolled 506 Parkinson’s patients aged 40 and older experiencing off periods. It compared Crexont’s efficacy and safety to the traditional carbidopa/levodopa formulation.
The study began with a three-week, open-label phase, during which patients adjusted their doses of immediate-release carbidopa/levodopa to find the most effective amounts for their symptoms. This was followed by a four-week, open-label phase in which patients switched from immediate-release carbidopa/levodopa to Crexont.
After the conversion phase, patients entered a 13-week maintenance phase, during which they were randomly assigned to receive either Crexont or immediate-release carbidopa/levodopa. Crexont was administered orally two to four times per day.
Improved outcomes, including increased good on time with fewer daily doses and no significant increase in dyskinesia, led to Crexont’s U.S. Food and Drug Administration approval as a Parkinson’s treatment in August 2024.
The new analysis focused on patients who successfully made the switch to Crexont. Patients treated with Crexont saw statistically significant improvements in sleep quality, as observed by a 2.35-point decrease in the Parkinson’s Disease Sleep Scale-2 (PDSS-2) scores from study entry to end of dose conversion. The PDSS-2 is a 15-item questionnaire that assesses multiple dimensions of sleep disturbances in people with Parkinson’s, with higher scores indicating greater sleep difficulties.
Crexont was associated with less disturbed sleep, indicating fewer awakenings and more restful nights, along with a reduction in nighttime motor symptoms like rigidity and tremor, and overall decrease of Parkinson’s-specific symptoms at night.
“By addressing both nocturnal motor and non-motor symptoms, CREXONT has the potential to deliver substantial benefits that extend beyond daytime symptom management,” the researchers wrote.
More patients on Crexont woke up in an on state, and fewer reported waking up in an off state compared with those receiving immediate-release carbidopa/levodopa.
“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 study author Robert Hauser, MD, a professor of neurology at the University of South Florida and director of the university’s Parkinson’s Disease and Movement Disorders Center. “The new Phase 3 data analysis shows CREXONT’s ability to significantly improve sleep, in addition to its effects on daytime [Parkinson’s] symptoms, making it a valuable treatment option for patients dealing with the challenges of this debilitating condition.”
Amneal has begun a Phase 4 clinical trial, ELEVATE-PD, to further evaluate the real-world efficacy and safety of Crexont in Parkinson’s patients.
About the Author
