Amneal Announces New Data from Phase 3 Study Showing Significant Improvements in Sleep Quality with CREXONT® (Carbidopa and Levodopa) Extended-Release Capsules in Parkinson’s Disease

Rhea-AI Summary

Amneal Pharmaceuticals (AMRX) has announced new Phase 3 study data demonstrating significant improvements in sleep quality for Parkinson's disease patients using CREXONT® (Carbidopa and Levodopa) Extended-Release Capsules.

The RISE-PD study analysis revealed that patients who converted from immediate release (IR) carbidopa/levodopa to CREXONT showed statistically significant improvements in Parkinson's Disease Sleep Scale-2 (PDSS-2) scores, with a mean difference of -2.35 (p<0.0001). Patients experienced improvements across all PDSS-2 subdomains, including reduced disturbed sleep (-1.07), improved nighttime motor symptoms (-0.62), and PD symptoms at night (-0.65).

A separate analysis showed that CREXONT treatment resulted in more patients waking up in an 'On' state compared to IR CD/LD patients. Amneal has initiated a Phase 4 trial, ELEVATE-PD, to evaluate real-world efficacy and safety. The most common adverse reactions with CREXONT were nausea and anxiety.

Positive

• Significant improvement in sleep quality metrics (PDSS-2 scores)
• More patients waking up in 'On' state vs. traditional treatment
• Positive results across all sleep quality subdomains
• Advancement to Phase 4 trial indicating progression in clinical development

Negative

• Presence of adverse reactions including nausea and anxiety

Insights

Pharmaceutical Industry Analyst

The new Phase 3 data for CREXONT significantly strengthens Amneal's competitive positioning in the Parkinson's disease market by addressing a critical unmet need beyond motor symptom control. Sleep disturbances affect up to 80% of Parkinson's patients, making this statistically significant improvement in sleep quality (p<0.0001) a meaningful clinical differentiator.

What stands out is CREXONT's novel dual-release formulation combining immediate-release granules with extended-release pellets - enabling both rapid onset and sustained effects throughout the night. This addresses the common problem of patients waking in an "Off" state, which typically requires waiting for morning medication to take effect.

The initiation of the Phase 4 ELEVATE-PD trial demonstrates Amneal's commitment to generating real-world evidence, which is increasingly important for formulary placement and payer discussions. This expanded clinical profile should strengthen CREXONT's value proposition to clinicians, patients, and payers alike.

For Amneal (AMRX), this data expands CREXONT's potential market opportunity beyond basic symptom management to a more comprehensive treatment approach, potentially driving adoption in a competitive landscape where differentiation is crucial. The safety profile appears manageable with only nausea and anxiety noted as common adverse events occurring at higher rates than the immediate-release formulation.

Neurologist

The RISE-PD data reveals clinically meaningful improvements in sleep quality with CREXONT compared to immediate-release carbidopa/levodopa. The statistically significant -2.35 point difference in PDSS-2 total scores represents a substantial improvement in a vital aspect of Parkinson's management that often goes undertreated.

What's particularly valuable is the comprehensive improvement across all PDSS-2 subdomains - reduced disturbed sleep (-1.07, p<0.0001), improved nighttime motor symptoms (-0.62, p<0.0059), and decreased PD symptoms at night (-0.65, p<0.0017). This suggests CREXONT addresses multiple sleep-related issues simultaneously.

The higher percentage of patients waking up in an "On" state represents a significant quality-of-life improvement. Morning akinesia (difficulty moving upon waking) is extremely distressing for patients and complicates morning routines, medication timing, and caregiver assistance needs.

CREXONT's unique pharmacokinetic profile likely explains these benefits - the extended-release component maintains therapeutic levodopa levels overnight while the immediate-release component provides morning symptom control. This addresses the fundamental challenge in Parkinson's therapy: maintaining consistent dopaminergic stimulation without the peaks and troughs that lead to motor fluctuations and sleep disruptions.

- Analysis of RISE-PD presented at AAN 2025 showed CREXONT treatment significantly improved patients’ Parkinson’s Disease Sleep Scale-2 (PDSS-2) total and sub-scale scores

- Treatment with CREXONT also resulted in significantly more patients waking up in an “On” state compared to immediate-release CD/LD patients, as part of separate study analysis

- Sleep disturbances affect up to 80% of patients with Parkinson’s disease¹, highlighting the importance of extending treatment benefits beyond daytime symptoms

BRIDGEWATER, N.J.--(BUSINESS WIRE)-- Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX) (“Amneal” or the “Company”), a global biopharmaceutical company, today announced a new analysis of the pivotal RISE-PD Phase 3 study showed that patients who successfully converted to CREXONT 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 4 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 3 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.

About CREXONT®

CREXONT is an innovative formulation consisting of immediate-release granules with carbidopa and levodopa for rapid onset of action, and extended-release pellets with levodopa for long-lasting efficacy. CREXONT formulation and dosage strengths are different from RYTARY® (carbidopa and levodopa) extended-release capsules approved by the U.S. FDA in 2015. Learn more about CREXONT at crexont.com.

INDICATION

CREXONT (carbidopa and levodopa) extended-release capsules is a prescription medication for the treatment of Parkinson’s disease, Parkinson’s disease caused by infection or inflammation of the brain, or Parkinson’s disease-like symptoms that may result from carbon monoxide or manganese poisoning in adults.

IMPORTANT SAFETY INFORMATION

• Do not take CREXONT with antidepressant medications known as nonselective monoamine oxidase (MAO) inhibitors.
• Do not take CREXONT with other carbidopa-levodopa preparations without consulting your healthcare provider.
• CREXONT may cause falling asleep during activities of daily living, somnolence, or dizziness. Avoid activities that require alertness such as driving and operating machinery, until you know how CREXONT affects you.
• The most common side effects that may occur with CREXONT are nausea and anxiety.
• Avoid sudden discontinuation or rapid dose reduction with CREXONT. If you are discontinuing CREXONT, work with your healthcare provider to taper the dose over time to reduce the risk of fever or confusion.
• You may take CREXONT with or without food; but taking it with food may decrease or delay its effect. Consider taking the first dose of the day about 1 to 2 hours before eating.
• Swallow CREXONT whole. Do not chew, divide, or crush the capsules.
• Do not take CREXONT with alcohol.

Tell your healthcare provider if you:

• Have any heart conditions, especially if you have had a heart attack or irregular heartbeats.
• Experience hallucinations or abnormal thoughts and behaviors.
• Have an inability to control urges to gamble, have increased sexual urges, or experience other intense urges.
• Have thoughts of suicide or have attempted suicide.
• Have abnormal involuntary movements that appear or get worse during treatment.
• Have ever had a peptic ulcer or glaucoma.
• Become or intend to become pregnant. Based on animal data, CREXONT may cause fetal harm.
• Are breastfeeding during therapy.
• Have side effects; your doctor can adjust your dose.

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Specialty, a division of Amneal Pharmaceuticals, LLC at 1-877-835-5472 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please read the full Prescribing Information. For more information talk to your healthcare provider.

About Parkinson’s Disease

Parkinson’s disease (PD) has become the fastest growing neurological disorder worldwide, with approximately 1 million people diagnosed in the U.S.^2,3 It is a progressive disorder of the central nervous system (CNS) that affects dopamine-producing neurons in the brain that affect movement. PD is characterized by slowness of movement, stiffness, resting tremor and impaired balance.⁴ While PD is not considered a fatal disease, it is associated with significant morbidity and disability.⁵ The average age at diagnosis for people with PD is 60; as people live longer, the number of people living with PD is predicted to grow significantly over the coming decades.^2,6

About Amneal

Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX), headquartered in Bridgewater, NJ, is a global biopharmaceutical company. We make healthy possible through the development, manufacturing, and distribution of a diverse portfolio of over 280 pharmaceuticals, primarily within the United States. In its Affordable Medicines segment, the Company is expanding across a broad range of complex product categories and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceuticals focused primarily on central nervous system and endocrine disorders. Through its AvKARE segment, the Company is a distributor of pharmaceuticals and other products for the U.S. federal government, retail, and institutional markets. For more information, please visit www.amneal.com and follow us on LinkedIn.

Forward-Looking Statements

Certain statements contained herein, regarding matters that are not historical facts, may be forward-looking statements (as defined in the U.S. Private Securities Litigation Reform Act of 1995). Such forward-looking statements include statements regarding management’s intentions, plans, beliefs, expectations, financial results, or forecasts for the future, including among other things: discussions of future operations; expected or estimated operating results and financial performance; and statements regarding our positioning, including our ability to drive sustainable long-term growth, and other non-historical statements. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates,” and similar words, or the negatives thereof, are intended to identify estimates and forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. Forward-looking statements included herein speak only as of the date hereof and we undertake no obligation to revise or update such statements to reflect the occurrence of events or circumstances after the date hereof.

References:
1.	Chahine LM, Amara AW, Videnovic A. A systematic review of the literature on disorders of sleep and wakefulness in Parkinson's disease from 2005 to 2015. Sleep Med Rev. 2017;35:33-50.
2.	Dorsey ER et al. JAMA Neurol. 2018;75(1):9-10.
3.	Marras et al. NPJ Parkinson’s Dis. 2018;4:21.
4.	NINDS. Parkinson’s disease: challenges, progress, and promise. Reviewed August 2019.
5.	Data Monitor: Gibrat et al., 2009; Goldenberg, 2008; Muangpaisan et al., 2009; Pringsheim et al., 2014.
6.	John Hopkins Medicine. Young-Onset Parkinson’s disease.

 

View source version on businesswire.com: https://www.businesswire.com/news/home/20250407981059/en/

Investor Contact

Anthony DiMeo

VP, Investor Relations

anthony.dimeo@amneal.com

Media Contact

Randi Kahn

SVP, Corporate Affairs, Syneos Health

randi.kahn@syneoshealth.com

Amneal Medical Affairs

888-990-AMRX (2679)

askamrx@amneal.com

Source: Amneal Pharmaceuticals, Inc.

FAQ

What are the key findings of AMRX's Phase 3 RISE-PD study for CREXONT in Parkinson's disease?

The study showed significant improvements in sleep quality with PDSS-2 scores (-2.35, p<0.0001), including reduced disturbed sleep, improved nighttime motor symptoms, and PD symptoms at night.

How does CREXONT's formulation differ from traditional Parkinson's medications?

CREXONT combines immediate-release granules and extended-release pellets, allowing rapid onset and sustained levodopa release for longer absorption in the gut.

What percentage of Parkinson's patients are affected by sleep disturbances?

Sleep disturbances affect up to 80% of patients with Parkinson's disease.

What are the most common side effects reported in CREXONT clinical trials?

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

What is the status of AMRX's Phase 4 ELEVATE-PD trial for CREXONT?

Amneal has initiated the Phase 4 ELEVATE-PD trial to evaluate real-world efficacy and safety of CREXONT in Parkinson's disease patients.