Objective: Analysis of dyskinesia as reported by PD diary, adverse events, UPDRS part IV dyskinesia score and examiner rated observation, during a phase 3 study of CVT-301 (levodopa inhalation powder) for the intermittent treatment of OFF periods in patients with Parkinson’s disease (PD) on a carbidopa/levodopa regimen.

Background: In a 12-week, randomized, double-blind, placebo-controlled study of 339 patients with PD experiencing OFF periods (SPAN-PD™), CVT-301 84 mg significantly improved motor function, measured by an improvement in UPDRS part III motor score pre-dose to 30 minutes post-dose at 12 weeks compared to placebo (LS mean change from baseline of -9.83 vs. -5.91 respectively; P=0.009). In addition, 58% of patients in the CVT-301 84-mg group turned ON and remained ON at the 60-minute assessment compared with 36% in the placebo group (P=0.003).

Method: Dyskinesia data were collected as: patient reported ON time with troublesome dyskinesia by PD diary for 3 consecutive days prior to each study visit, adverse events (AE) by standard reporting methods, UPDRS part IV dyskinesia score in clinic (questions 32-35), and examiner rated occurrence and severity (mild, moderate, or severe) of dyskinesia during the 60-minute post-dose period in the clinic.

Results: With an average usage of 2 doses per day, which remained consistent throughout the 12 weeks for both treatment groups, least squares (LS) mean change from baseline in patient diary-reported ON time with troublesome dyskinesia was 0.17h for CVT-301 84 mg and 0.17h for placebo at week 12. An AE of dyskinesia was reported by 4 (3.5%) patients in the CVT-301 84-mg group and none in the placebo group. No patient withdrew due to dyskinesia. UPDRS part IV dyskinesia average score at week 12 was 2.0 for 84 mg CVT-301 and 1.8 for placebo, representing changes from baseline of 0 and -0.2, respectively. Examiner rated dyskinesia during the 1-hour post-dose period was 16.7% in the 84-mg CVT-301 group and 8% in the placebo group at week 12; throughout the study, all were rated mild to moderate except 1 severe report in the placebo group.

Conclusion: 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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dyskinesia-rates-in-patients-with-parkinsons-disease-on-cvt-301-levodopa-inhalation-powder/