EU Approves Modified-Release Carbidopa/Levodopa Capsules for Parkinson Disease Motor Fluctuations

The European Commission has granted marketing authorization for Hopledo (modified-release carbidopa/levodopa), an oral therapy for adults with Parkinson disease and motor fluctuations inadequately controlled by standard levodopa regimens. The approval follows a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) and mirrors the 2024 FDA approval of the same formulation, marketed in the US as Crexont.¹

Hopledo is indicated for adult patients with Parkinson disease and moderate to severe motor fluctuations not adequately controlled with oral levodopa/dopa decarboxylase inhibitor-based treatment regimens, per the approved European authorization.¹ The same formulation is marketed in the United States as Crexont, where the FDA-approved indication also extends to Parkinson disease caused by brain infection or inflammation and to parkinsonism following carbon monoxide or manganese poisoning; those indications are not included in the European label.²

The EC approval follows the CHMP's positive opinion, adopted in June 2026, and phased introduction across European markets is expected to begin in October 2026. Zambon holds exclusive commercialization rights for Hopledo across the EU, UK, and Switzerland under a 2024 licensing agreement with Amneal Pharmaceuticals. The same modified-release formulation received FDA approval in the US in August 2024 as Crexont, developed by Amneal subsidiary Impax Laboratories, with commercial launch following in September 2024.

Clinical evidence

Efficacy for both the EU and US approvals is supported by the phase 3 RISE-PD trial, a randomized, double-blind, active-controlled study that enrolled 506 patients with Parkinson disease and motor fluctuations. Compared with immediate-release carbidopa/levodopa, the modified-release capsule, which combines immediate-release granules with extended-release beads to maintain more stable plasma levodopa concentrations, produced a statistically significant increase in daily Good ON time (least squares mean difference, 0.53 hours; 95% CI, 0.09-0.97; P = .02) and required roughly 3 daily doses versus 5 for the immediate-release comparator.^3,4

A post hoc analysis of RISE-PD presented at the 2025 AAN Annual Meeting found the treatment effect varied by concomitant dopamine agonist dose. Patients on a levodopa-equivalent dopamine agonist dose of 200 mg or less gained 2.40 additional hours of daily Good ON time, compared with 1.45 hours among those on higher doses, roughly a 40% reduction in benefit at the higher dose threshold.⁵

READ MORE: TEMPO-2 Data Supports Tavapadon’s Efficacy in Early-Stage Parkinson Disease

Real-world data from the ongoing open-label phase 4 ELEVATE-PD study, presented at the 2026 AAN Annual Meeting, showed a similar pattern in patients switched to the modified-release formulation from other oral levodopa therapies. Among 111 patients evaluated 6 weeks after switching, daily Good ON time increased by 3.40 hours in those coming from immediate-release carbidopa/levodopa, 2.91 hours in those on immediate-release therapy plus a COMT inhibitor, and 3.07 hours in those switching from extended-release carbidopa/levodopa capsules (Rytary).^6,7

“These encouraging interim results underscore the real-world impact CREXONT can have in giving patients more 'Good On' time with fewer dosing interruptions,” Robert A. Hauser, MD, professor of neurology at the University of South Florida, said in a statement at the time of those results.⁶

Safety profile

Across RISE-PD, the modified-release formulation showed a safety profile broadly comparable to immediate-release carbidopa/levodopa; a full European product label with complete prescribing and safety information was not available at the time of this report.¹ In the ELEVATE-PD interim analysis, the most common treatment-emergent adverse events occurring in 3% or more of patients were dizziness (9.0%), nausea (7.2%), falls (7.2%), dyskinesia (4.5%), hallucination (3.6%), and headache (3.6%); investigators characterized all events as mild to moderate in severity.⁶

“Thanks to its unique modified-release formulation, Hopledo provides substantially more Good ON time per dose while maintaining a safety profile comparable to immediate-release levodopa/carbidopa,” said Günter Höglinger, MD, director of the Department of Neurology at LMU University Hospital Munich, calling it “an important advancement in levodopa therapy" for people with Parkinson disease and motor fluctuations.¹

REFERENCES
1. Zambon. Zambon announces European Commission approval of Hopledo for adults with Parkinson's disease and moderate to severe motor fluctuations. Published August 26, 2026. Accessed August 31, 2026. https://www.businesswire.com/news/home/20260826836384/en/Zambon-Announces-European-Commission-Approval-of-Hopledo-for-Adults-with-Parkinsons-Disease-and-Moderate-to-Severe-Motor-Fluctuations
2. Amneal Pharmaceuticals. 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. Published August 7, 2024. Accessed August 31, 2026. investors.amneal.com
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. 2023;80(10):1062-1069. doi:10.1001/jamaneurol.2023.2679
4. RISE-PD: efficacy, safety, and tolerability of IPX203 in Parkinson's disease patients with motor fluctuations. ClinicalTrials.gov identifier: NCT03670953. Updated 2023. Accessed August 31, 2026. clinicaltrials.gov/study/NCT03670953
5. Pahwa R, Isaacson SH, Espay AJ, et al. Impact of concomitant therapy with a dopamine agonist on converting Parkinson's disease patients from immediate-release carbidopa-levodopa to CREXONT (P7-5.024). Neurology. 2025;104(7 suppl 1). doi:10.1212/WNL.0000000000211199
6. Amneal Pharmaceuticals. Amneal announces additional positive interim phase 4 ELEVATE-PD results with CREXONT for Parkinson's disease, including over 3 more hours of daily "Good On" time when switching from RYTARY [press release]. Published April 20, 2026. Accessed August 31, 2026. investors.amneal.com
7. Open-label phase 4 study of CREXONT (carbidopa and levodopa) extended-release capsules in Parkinson's disease patients (ELEVATE-PD). ClinicalTrials.gov identifier: NCT06765668. Updated 2026. Accessed August 31, 2026. clinicaltrials.gov/study/NCT06765668