To evaluate the efficacy, safety, and tolerability of flexible-dose tavapadon in adults with early Parkinson’s disease (PD).

Tavapadon is an investigational, oral, once-daily, selective D1/D5 partial dopamine agonist. Selective agonism at D1/D5 receptors may provide a balance of dopamine signaling that improves motor symptoms in PD while potentially minimizing specific adverse events (AEs) associated with activation of D2/D3 receptors.

TEMPO-2 (NCT04223193) is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, 27-week trial evaluating flexible-dose tavapadon as monotherapy for adults with early PD (aged 40-80 years; modified Hoehn and Yahr stage 1-2; Movement Disorder Society-Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] Part II score ≥3 and Part III score ≥10). Participants were randomized (1:1) to receive placebo or tavapadon (5-15 mg once daily; titrated to maximum tolerated dose) for 27 weeks. The primary endpoint was change from baseline in MDS-UPDRS Parts II+III combined score. Key secondary endpoints included change from baseline in MDS-UPDRS Part II score and AEs. 

304 adults were enrolled; key participant demographics and baseline disease characteristics were consistent with the target population and balanced across treatment arms. Tavapadon showed a significant improvement in MDS-UPDRS Parts II+III combined score compared with placebo (least squares mean [LSM] difference, -9.1, 95% CI: -11.7, -6.5; P<0.0001). MDS-UPDRS Part II score was also significantly improved in the tavapadon versus placebo cohorts (LSM difference, -1.5, 95% CI: -2.4, -0.6; P=0.0007). Safety data showed a profile consistent with prior tavapadon trials; most AEs were non-serious and mild to moderate in severity. 

TEMPO-2 results demonstrate the efficacy and acceptable safety profile of flexible-dose tavapadon as monotherapy in adults with early PD. Trials evaluating tavapadon as fixed-dose monotherapy (TEMPO-1) or adjunctive therapy (TEMPO-3) are completed; an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing.