Tavapadon Not Associated With Increased Daytime Sleepiness in 3 Parkinson Disease Studies
KEY TAKEAWAYS
- Daytime sleepiness scores remained stable with tavapadon across three phase 3 Parkinson disease trials.
- Epworth Sleepiness Scale outcomes were similar between tavapadon and placebo groups over 27 weeks.
- Findings support further evaluation of selective D1/D5 receptor targeting vs less selective dopamine agonist approaches.
Investigational tavapadon, an oral once-daily selective dopamine D1/D5 receptor agonist, was not associated with increased daytime sleepiness in people with Parkinson disease (PD) across 3 phase 3 clinical trials, according to findings presented at the 7th World Parkinson Congress. Across the TEMPO-1 (NCT04201093), TEMPO-2 (NCT04223193), and TEMPO-3 (NCT04542499) studies, daytime sleepiness scores remained generally stable over 27 weeks and were similar between tavapadon and placebo groups. The findings may be clinically relevant because currently approved dopamine agonists that target D2/D3 receptors have been associated with excessive daytime sleepiness in some individuals with PD.
Investigators evaluated daytime sleepiness using the Epworth Sleepiness Scale (ESS) in participants enrolled in the phase 3 TEMPO clinical program. TEMPO-1 and TEMPO-2 included individuals with early PD of less than 3 years’ duration receiving tavapadon monotherapy at fixed or flexible doses ranging from 5 mg to 15 mg daily. TEMPO-3 enrolled participants with PD and motor fluctuations receiving adjunctive tavapadon 5 mg to 15 mg daily added to levodopa. ESS total scores range from 0 to 24, with higher scores indicating greater daytime sleepiness.
What the Data Showed
- In TEMPO-1, least squares mean changes in ESS score at week 27 were −0.4 with placebo, −0.7 with 5-mg tavapadon (P=.44), and −0.4 with 15-mg tavapadon (P=.91).
- In TEMPO-2, ESS score changes were −0.3 in both placebo and tavapadon groups (P=.94)
- In TEMPO-3, ESS score changes were −0.7 with placebo and −0.9 with tavapadon (P=.53)
- No statistically significant differences vs placebo were observed across studies.
- Sleepiness-related item scores on the MDS-UPDRS and PDQ-39 were also similar between groups.
The investigators stated that tavapadon treatment did not increase daytime sleepiness compared with placebo over 27 weeks and suggested that selective D1/D5 receptor targeting may help avoid excessive daytime sleepiness.
Sources
Pahwa R, Mari Z, Ondo W, et al. Evaluation of daytime sleepiness with tavapadon in people with Parkinson’s disease. Presented at the 7th World Parkinson Congress; May 24-27, 2026; Phoenix, AZ.