Did patients with advanced Parkinson disease switched to extended release carbidopa-levodopa experience clinical benefits?
Many patients with advanced Parkinson disease (PD) who are on controlled release (CR) or CR plus immediate release (IR) carbidopa-levodopa (CD-LD) may safely switch to an extended release formulation, according to a study published in the Journal of Neurological Science.1
“The results of this small, open-label study suggest that advanced PD patients using CR CD-LD, alone or with IR CD-LD, can be safely switched to a stable IPX066 regimen with reduction of dosing frequency and improvement in overall clinical benefit,” wrote first author James Tetrud, MD, of The Parkinson’s Institute and Clinical Care Center, Stanford University, and colleagues.
IPX066 (Rytary®) is an extended release oral form of CD-LD (ER CD-LD). IPX066 offers decreased dosing frequency and prolonged duration, which is maintained for four to five hours. Clinical trials have suggested that IPX066 can decrease off time, increase on time, and has a similar safety profile as IR CD-LD in patients with advanced PD, according to background information in the article.
The open label study included 43 patients at eight clinical sites in the US. Participants underwent six weeks of conversion to IXP066 from CR CD-LD with or without IR CD-LD, followed by a six-month extension phase of maintenance therapy. In some patients, IPX066 was extended for an additional six months. Thirty-two patients entered the first extension phase, and 12 patients entered the second extension phase. The LD conversion ratio was defined as the LD dose of IPX066 after conversion divided by the baseline LD dose.
• 76.7% of patients completed the conversion
♦ 87.9% reached a stable dosage in an average of 5 days
• Mean LD conversion ratio:
♦ Previously on LD as CR + IR: 1.8
♦ LD as CR alone: 1.5
• Mean daily dosing frequency decreased
♦ IPX066: 3.5 times/day
♦ Previously on LD as CR plus IR: 2.6 times/day (CR) and 4.6 times/day (IR)
♦ Previously on LD as CR alone: 4.7â times/day
• At the end of extension phase 2, 83.3% were on IPX066 ≤4 times/day
• Patient and clinician global improvement ratings after 6-month maintenance:
♦ Much or very much improved: ≥43.8%
♦ At least minimally improved: ≥68.8%
♦ 62.8% preferred IPX066 over their prior treatment
• Adverse events: reported by over 10% of patients
♦ Severe AEs: 7%
♦ Serious AEs: 14%
♦ No new suicidal ideation or behavior
The authors noted that adverse events were consistent with past studies of IPX066. They added that the length of the study and its lack of restrictions on dose conversion may simulate real-world clinical practice more closely than randomized, controlled clinical trials.
Limitations include the open-label design and small population. Additionally, the study was not designed to directly compare IPX066 to a standard CR formulation because only three patients used CR as their only LD therapy.
The authors concluded: “The study suggests that the initial dose conversion table tested for switching from IR CD-LD can also be used for patients on CR CD-LD alone or in combination with IR CD-LD, with dose adjustment as needed during the individual patient's conversion.”
• A small open-label trial showed that the majority of participants with advanced PD treated with CR or CR plus IR carbidopa-levodopa may safely switch to extended release CD-LD.
• Switching to ER CD-LD decreased dosing frequency.
• Over 40% of patients showed global clinical improvement.
• Adverse events were similar to past studies of ER CD-LD.
The study was funded by Impax Laboratories, Inc. Several authors report financial relationships or grant support from multiple pharmaceutical companies.
Drs Hsu, Kell, Khanna, Rubens and Gupta are employees of Impax Laboratories, Inc. Dr Ellenbogen is an employee of the Quest Research Institute.
Reference: Tetrud J, , et al. Conversion to carbidopa and levodopa extended-release (IPX066) followed by its extended use in patients previously taking controlled-release carbidopa-levodopa for advanced Parkinson's disease. J Neurol Sci. 2017 Feb 15;373:116-123.