A new soluble formulation of levodopa-cardiopa delivered via a continuous subcutaneous infusion (CSCI) and portable pump is showing promise as a treatment for advanced Parkinson’s disease.
A phase 3 RCT compared the safety and efficacy of 24-h/day foslevodopa-foscarbidopa with the oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in 145 patients with advanced Parkinson’s disease.
Patients were aged ≥30 years, on a minimum of 400 mg/day levodopa equivalents, and with inadequately controlled motor fluctuations with an average off time of at least 2·5 h/day over 3 consecutive days.
The study, conducted across 65 centres in the US and Australia, found foslevodopa-foscarbidopa provided a significant increase in on time without troublesome dyskinesia at week 12 compared with the oral levodopa–carbidopa (p=0·0083).
Similarly, in a key secondary outcome, treatment with foslevodopa-foscarbidopa showed a significant decrease in off time at week 12 compared with oral levodopa-carbidopa (p=0.0054).
“The improvements in on and off times were observed as early as the first post-baseline assessment and continued to the end of the double-blind treatment period at week 12,” the study said.
“On time without dyskinesia showed a 25% (3·96 [3·77] h) increase from baseline in the foslevodopa-foscarbidopa group compared with a 7% (1·15 [3·63] h) increase in the oral levodopa–carbidopa group as a percentage of the waking day.”
The study, published in The Lancet Neurology [link here], did not find a significant difference between groups in another key secondary endpoint of the Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) part II score.
Regarding safety, the study found adverse events were more common with the continuous infusion (85% v 63%) but most were mild or moderate in severity. They included infusion site reactions (72% v 12%) which were typically erythema, pain, cellulitis and oedema.
Hallucinations or psychosis were more common with foslevodopa-foscarbidopa (15% v 3%) while falls and associated injuries were less common (18% v 25%).
Adverse events leading to discontinuation of treatment was more common with foslevodopa-foscarbidopa (22% v 1%) while serious AEs were similar in both groups (8% v 6%).
The study investigators including Associate Professor Victor Fung, Associate Professor Thomas Kimber and Dr Daniel O’Neill, said the findings suggested foslevodopa-foscarbidopa was an effective alternative treatment to deep brain stimulation and levodopa-carbidopa intestinal gel.
They noted the study also showed the capability of the foslevodopa-foscarbidopa drug–device combination to provide a wide range of therapeutically relevant doses of levodopa equivalents from 600 mg to 4250 mg over a 24-h period.
“Importantly, foslevodopa-foscarbidopa infusion rates could be adjusted in small increments, equivalent to approximately 1·7 mg of levodopa per h, enabling individual fine-tuning and optimisation of therapy.”
“As a 24-h/day CSCI, foslevodopa-foscarbidopa delivers a wide range of therapeutically relevant doses that can control motor symptoms and reduce motor fluctuations in patients with advanced Parkinson’s disease, and offers a potentially safe and effective, individualised, and non-surgical alternative to available treatments,” they concluded.
An accompanying Comment in the journal [link here] said clinically useful therapies for PD had to improve both motor and non-motor symptoms.
Given there was no significant change in the MDS-UPDRS part II, an activity of daily living score, the author said the overall effectiveness of foslevodopa-foscarbidopa for advanced PD was still unclear.
“The logistical set-up and maintenance of foslevodopa-foscarbidopa infusions is potentially simpler than those for levodopa-carbidopa intestinal gel. However, caregiver and financial support will still be required, which might limit such options to certain regions of the world,” it concluded.