Objective: To analyze all dyskinesia data from a Phase 2b trial of fluctuating Parkinson patients in order to understand the overall impact a study drug has on dyskinesias as measured by multiple endpoints, the temporal pattern of change, and whether the endpoints used to measure dyskinesias are consistent with one another.

Background: Treating motor fluctuations has the potential to worsen dyskinesias. The standard way to measure change in dyskinesias in a motor fluctuator study is to focus attention on adverse events (AEs) or patient reported diaries. AEs are typically presented as a comparison between active drug and placebo as a percentage of patients ever experiencing dyskinesias, but information regarding severity and duration is often overlooked. Rarely are all of the relevant data presented in sufficient detail to understand severity, temporal patterns and whether consistency exists between the multiple endpoints being used to quantitate dyskinesias.

Methods: All analyses were derived from a Phase 2b study of tozadenant in fluctuating Parkinson patients (Hauser et al. 2014). Dyskinesia measures were collected at baseline, Week 2, 6, and 12 for placebo and four active treatment arms including adverse events, patient reported diaries, and UPDRS Items 32, 33, and 34.

Results: Overall AE reporting for incidence of dyskinesias was 8.3% for placebo, compared with 14.1%, 15.9%, 20.0%, and 20.2% for tozadenant 60, 120, 180, and 240 mg BID, respectively. Analyzing by time the imbalance between placebo and tozadenant 60mg and 120mg BID was early and transient while the imbalance between placebo and the 180mg and 240mg BID treatment arms persisted. Patient reported diaries demonstrated a dose response such that ON time with troublesome dyskinesia was not increased in the lower dose arms (60mg & 120mg BID) but was increased in the higher dose arms (180mg & 240mg BID) compared to placebo. UPDRS Items 32, 33, and 34 indicated no difference in dyskinesias between placebo and active treatment arms. The measures used to quantitate dyskinesias were inconsistent with one another.

Conclusions: An analysis of dyskinesias from this Phase 2b study of tozadenant suggests that a thorough understanding of a Parkinson drug’s impact on dyskinesias requires a detailed presentation of all measures used to quantitate dyskinesias with a specific focus on temporal patterns.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/detailed-evaluation-of-dyskinesias-using-multiple-endpoints-in-a-randomized-placebo-controlled-trial-of-parkinsons-disease-patients-with-motor-fluctuations/