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

Tavapadon is an investigational, oral, once-daily, selective D1/D5 partial dopamine agonist that may improve PD motor symptoms while potentially minimizing adverse events (AEs) associated with D2/D3 receptor activation.

TEMPO-1 (NCT04201093) is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, 27-week trial evaluating 2 fixed doses of tavapadon as monotherapy for adults with early PD (aged 40-80 years; modified Hoehn and Yahr stage 1-2; disease duration from diagnosis <3 years). Participants were randomly assigned (1:1:1) to receive placebo, 5-mg tavapadon, or 15-mg tavapadon (once daily, titrated to dose) for 27 weeks. Change from baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II+III combined score was the primary endpoint. The MDS-UPDRS Part II score was a key secondary endpoint. Safety and tolerability were also assessed.

529 adults were enrolled; key participant demographics and baseline disease characteristics were balanced across groups and consistent with the target population. Change from baseline in the MDS-UPDRS Parts II+III combined score was significantly reduced in participants treated with 5-mg (-11.5; 95% CI: -13.8, -9.2) and 15-mg tavapadon (-12.1; 95% CI: -14.4, -9.8) compared with placebo (both P<0.0001). Tavapadon reduced the MDS-UPDRS Part II score versus placebo (5 mg: -2.5, 95% CI: -3.3, -1.7; 15 mg: -2.6, 95% CI: -3.4, -1.7; both P<0.0001). Safety data demonstrated a profile consistent with prior tavapadon trials; most AEs were non-serious and mild to moderate in severity.

In individuals with early PD, tavapadon as monotherapy was effective with an acceptable safety profile. Other trials evaluating tavapadon as flexible-dose monotherapy (TEMPO-2) or adjunctive therapy (TEMPO-3) are completed, and an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing.