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Acorda Therapeutics’ Inbrija, an inhalation powder formulation of levodopa, was associated with no significant increases in troublesome dyskinesia for patients being treated with carbidopa/levodopa.
Emmanuelle Pourcher, MD, MSc
CVT-301 (Inbrija, Acorda Therapeutics), an inhalation powder formulation of levodopa as a treatment for intermittent off periods, was found to have no increase in troublesome dyskinesia in patients with Parkinson disease who were on a carbidopa/levodopa regimen.
The phase 3 study, dubbed SPAN-PD, included 12 weeks of randomized, placebo-controlled analysis of 339 patients with Parkinson treated with either placebo or 84 mg CVT-301. Ultimately, patients in the CVT-301 group experienced no change in the Unified Parkinson’s Disease Rating Scale (UPDRS) part IV dyskinesia average score, compared to -0.2 for placebo. In total, CVT-301 improved UPDRA part III motor scores by -9.83 compared to -5.91, respectively (P = .009).
The data were presented at the 2019 International Congress of Parkinson’s Disease and Movement Disorders, in Nice, France. Acorda’s inhalation powder was approved by the FDA for the treatment of off periods in this patient population in December 2018, based on data from SPAN-PD.
“In this phase 3 study of CVT-301, adverse events and examiner ratings of mild to moderate dyskinesia were reported more frequently for CVT-301 compared to placebo, but there was no increase in troublesome dyskinesia according to the patient-reported diary and the overall impact on UPDRS part IV dyskinesia score was minimal,” study author Emmanuelle Pourcher, MD, MSc, DEM, neurologist, faculty of medicine, Laval University, and colleagues wrote.
Patients had an average of 2 doses used per day, which was consistent throughout the 12 weeks for both groups. The least-squares mean change from baseline in patient-reported on time with troublesome dyskinesia was 0.17 hours for CVT-301, compared to 0.17 hours for placebo at week 12.
Examiner rated dyskinesia during the first hour after dosing was 16.7% in the treatment group, compared to 8% in the placebo group, at week 12. All bouts of dyskinesia were rated mild to moderate, save for a single report in the placebo group. In total 3.5% (n = 4) patients on CVT-301 reported a dyskinesia-like event lasting 3 days, in contrast to none in the placebo group. Although, no patients withdrew from the study due to dyskinesia.
The SPAN-PD study assessed 2 doses of CVT-301, with the higher dose of 84 mg being selected for the FDA application. All patients had PD diagnosed between the ages of 30 and 85 years and were stage 1 to 3 in an on state. Patients were on a levodopa dose of <1600 mg per day and could perform a spirometry maneuver in the on and off states.
There were improvements in key secondary endpoints with CVT-301 at 84 mg over placebo. Overall, at 60 minutes, 21.6% more patients switched from off to on with CVT-301 compared with placebo (P = .003). Overall, 57.7% of patients in the CVT-301 arm switched from off to on compared with 36.1% with placebo. Additionally, 71.4% of patients had an improvement in PGI-C scale versus 46.4% for placebo, which was a 25% improvement (P <.001). An improvement in UPDRS part III at 20 minutes and 10 minutes was also seen with CVT-301 compared with placebo. At 20 minutes, there was a -2.55 drop and at 10 minutes there was a -2.26 decline.
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Pourcher D, Corbin A, Qian J, Kenney C. Dyskinesia Rates in Patients with Parkinson’s Disease on CVT-301 (levodopa inhalation powder). Mov Disord. 2019;34(suppl 2). Presented at: MDS 2019; September 22-26; Nice, France. Abstract 1035.