Efficacy and Safety of Tavapadon, an Orally Administered, Once-daily, Selective D1/D5 Partial Dopamine Agonist, Adjunctive to Levodopa for Treatment of Parkinson’s Disease with Motor Fluctuations
Hubert Fernandez1, Stuart Isaacson2, Robert Hauser3, Pinky Agarwal4, William Ondo5, Ariane Park6, Lawrence Elmer7, Daniel Kremens8, Matthew Leoni9, Sridhar Duvvuri9, Cari Combs9, Erica Koenig9, Ih Chang9, Gina Pastino9, Stacey Tringali9, Nicole Golonski9, Raymond Sanchez9
1Center for Neurological Restoration, Cleveland Clinic, 2Parkinson's Disease & Movement Disorders Center of Boca Raton, 3USF Parkinson's Disease and Movement Disorders Center, 4Evergreen Health, 5Houston Methodist Neurological Institute, 6The Ohio State University Wexner Medical Center, 7Division of Movement Disorders, Department of Neurology, University of Toledo, 8Thomas Jefferson University, 9Cerevel Therapeutics
Objective:
To evaluate the efficacy, safety, and tolerability of tavapadon adjunctive to levodopa in adults with Parkinson’s disease (PD) and motor fluctuations.
Background:
Tavapadon is an investigational, oral, once-daily selective D1/D5 partial dopamine agonist. Selective, partial D1/D5 agonism may provide a balance of dopamine signaling that improves PD motor symptoms while potentially minimizing certain adverse events (AEs) associated with activation of D2/D3 receptors.
Design/Methods:
TEMPO-3 (NCT04542499) is a phase 3, placebo-controlled, double-blind clinical trial evaluating adjunctive therapy with tavapadon in adults experiencing motor fluctuations (modified Hoehn and Yahr stage 2-3 in the ON state, minimum 2.5 h of OFF time on 2 consecutive diary days) while receiving stable levodopa treatment. Participants were randomly assigned (1:1) to receive adjunctive tavapadon (titrated to maximum tolerated flexible dose: 5–15 mg once daily) or placebo. Change from baseline in total daily ON time without troublesome dyskinesia (Hauser diary 2-day average) was the primary endpoint. Key secondary endpoints included change from baseline in total daily OFF time and AEs.
Results:
Adults aged 40-80 years (N=507) were enrolled. Treatment with tavapadon (5–15 mg once daily) significantly increased total daily ON time without troublesome dyskinesia by 1.1 hours relative to placebo (1.7 hours vs 0.6 hours, respectively; P<0.0001). A significant reduction versus placebo in change from baseline in daily OFF time was also observed. Tavapadon’s safety profile was consistent with prior clinical trials and the majority of AEs were mild to moderate in severity.
Conclusions:
These findings in adults with PD and motor fluctuations demonstrate the efficacy and acceptable safety profile of tavapadon as adjunctive therapy to levodopa. Tavapadon as monotherapy in early PD (TEMPO-1 and TEMPO-2) and the long-term use of tavapadon (open-label extension; TEMPO-4) are being evaluated in ongoing phase 3 trials.
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