Objective: To evaluate motor states throughout the waking day when adding tavapadon to oral carbidopa/levodopa in adults with Parkinson’s disease experiencing motor fluctuations.

Background: Long-term treatment with levodopa may lead to dyskinesias and motor fluctuations that can be burdensome for some patients, and there is a need for additional adjunctive therapies to levodopa that can reduce motor fluctuations while minimizing troublesome dyskinesia. The phase 3 TEMPO-3 trial (NCT04542499) demonstrated that adjunctive tavapadon, an oral, once-daily, selective D1/D5 agonist, significantly increased total daily ON time without troublesome dyskinesia by 1.1 hours relative to placebo. Potential changes in motor states captured in the Hauser diary have not been assessed.

Method: Changes in motor states during the waking day (ON time without dyskinesia, ON time with troublesome dyskinesia, ON time with nontroublesome dyskinesia, and OFF time) were evaluated at baseline and Week 27 using the Hauser diary. Post hoc analyses compared changes in motor states normalized over the 16-hour waking day, and morning akinesia with tavapadon (5-15 mg once daily) versus placebo using a mixed effects model for repeated measures.

Results: Participants receiving adjunctive tavapadon (n=252) demonstrated a significant increase of 0.7 hours in ON time without dyskinesia during the normal waking day versus placebo (n=255; 1.6 hours vs 0.9 hours, respectively; P=0.0426). [figure1] Change from baseline in OFF time during the normal waking day also showed a significant reduction of 0.8 hours with tavapadon vs placebo (1.1 hours vs 1.9 hours, respectively; P=0.0022). Participants receiving tavapadon experienced a marginal decrease from baseline in ON time with troublesome dyskinesia versus placebo (−0.008 hours vs 0.1 hours; P=0.3397), and an increase in ON time with nontroublesome dyskinesia versus placebo (0.3 hours vs 0.05 hours; P=0.1815).

Conclusion: Improvement in ON time without troublesome dyskinesia with tavapadon was largely driven by an increase in ON time without dyskinesia and a decrease in OFF time.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/changes-in-motor-states-throughout-the-waking-day-with-tavapadon-in-people-with-parkinsons-disease/