Objective: To evaluate daytime sleepiness in people with Parkinson’s disease (PD) treated with tavapadon as monotherapy (TEMPO-1; NCT04201093) or adjunctive to levodopa (TEMPO-3; NCT04542499).

Background: Tavapadon, an oral, once-daily, selective D1/D5 agonist, demonstrated improvements in PD motor symptoms with a generally tolerable safety profile in phase 3 trials. Currently approved dopamine agonists are associated with increased risk of daytime sleepiness, in part due to D2/D3 receptor activation in extrastriatal brain regions. It is hypothesized that selective activation of D1/D5 receptors with tavapadon may avoid the adverse event of excessive daytime sleepiness; however, this has not been well established.

Method: In TEMPO-1, people with early PD (<3 years’ PD duration) were randomized to monotherapy with placebo or 1 of 2 fixed doses of tavapadon (5 or 15 mg). TEMPO-3 evaluated flexible-dose tavapadon (5 to 15 mg) adjunctive to levodopa in people with PD experiencing motor fluctuations (≥2.5 hours of daily OFF time). Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS), which assesses the likelihood of dozing off or falling asleep in common situations. Total scores range from 0 to 24; higher scores indicate greater sleepiness.

Results: Mean ESS total scores were stable over time and did not differ between tavapadon (TEMPO 1: n=177 for both doses; TEMPO-3: n=252) and placebo groups (TEMPO 1: n=175; TEMPO-3: n=255) [figure 1]. In TEMPO-1, least squares mean (LSM) changes from baseline to Week 27 (end of study) in ESS total score were −0.4 with placebo, −0.7 with 5-mg tavapadon, and −0.4 points with 15-mg tavapadon (LSM difference from placebo [95% CI], −0.2 [−0.9, 0.4]; P=0.44 for 5 mg and 0.0 [−0.6, 0.7]; P=0.91 for 15 mg). In TEMPO-3, LSM decrease in ESS total score from baseline was 0.9 with tavapadon and 0.7 points with placebo (LSM difference from placebo [95% CI], −0.2 [−0.8, 0.4]; P=0.53). Item-level scores related to sleepiness on the Movement Disorder Society-Unified Parkinson’s Disorder Rating Scale and Parkinson’s Disease Questionnaire-39, including frequency of unexpectedly falling asleep during the day, did not differ from placebo.

Conclusion: Tavapadon is not associated with increased daytime sleepiness compared to placebo when used as monotherapy or adjunctive to levodopa in people with PD.

Figure

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tavapadon-is-not-associated-with-increased-daytime-sleepiness-in-people-with-parkinsons-disease/