BackgroundSAGE‐324/BIIB124 is an investigational positive allosteric modulator of GABAA receptors.ObjectiveKINETIC (NCT04305275), a double‐blind, randomized, placebo‐controlled, phase 2 study, evaluated SAGE‐324/BIIB124 in individuals with essential tremor (ET).MethodsIndividuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE‐324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale‐Performance Subscale (TETRAS‐PS) Item 4 (upper‐limb tremor) at day 29 with SAGE‐324/BIIB124 versus placebo.ResultsBetween May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE‐324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS‐PS Item 4 at day 29 with SAGE‐324/BIIB124 versus placebo (least squares mean [standard error]: –2.31 [0.401] vs. –1.24 [0.349], P = 0.0491). The most common treatment‐emergent adverse events included somnolence, dizziness, fatigue, and balance disorder.ConclusionThese results support further development of SAGE‐324/BIIB124 for potential ET treatment. © 2024 Sage Therapeutics, Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.