Zuranolone as an oral adjunct to treatment of Parkinsonian tremor: A phase 2, open-label study.

Abstract

Parkinson's disease (PD) is characterized by both motor and nonmotor deficits. Among cardinal symptoms of this disorder, tremor is the least responsive to dopamine replacement therapy and is often undertreated. Zuranolone (SAGE-217) is an investigational oral neuroactive steroid (NAS) gamma-aminobutyric acid A (GABAA) receptor-positive allosteric modulator (PAM) that has been investigated for its safety and efficacy in patients with PD. In the current open-label study, zuranolone capsules (20 to 30 mg) were administered for 7 days in 14 patients (mean age, 65.1 years; mean time since PD diagnosis, 9 years). The primary efficacy endpoint was reduction in tremor symptoms, as assessed by change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Tremor Scores on Day 8. Additional endpoints included improvements in overall motor symptoms, and motor and nonmotor aspects of daily living. Adverse events (AEs) were also monitored. The MDS-UPDRS Part II/III Tremor Score improved by 40% (P < 0.0001) from baseline on Day 8. The motor score, and nonmotor experiences of daily living (nM-EDL), and motor experiences of daily living (m-EDL) scores (MDS-UPDRS Parts I and II, respectively), also improved on Day 8. No serious AEs were reported, and no patients discontinued treatment. The most common AEs were dizziness, sedation, and somnolence. Zuranolone was generally well tolerated and improved tremor symptoms in patients with PD who were on stable doses of concurrent dopaminergic agents. These data support the further investigation of NAS GABAA receptor PAMs as adjunctive treatments for tremor in patients with PD.

• Authors: Amy Bullock, Inder Kaul, Sigui Li, Christopher Silber, James Doherty, Stephen J Kanes
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 421 Pg. 117277 (Feb 15 2021) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 33387701 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Pregnanes
• Pyrazoles
• zuranolone

Topics

• Aged
• Humans
• Parkinson Disease (complications, drug therapy)
• Pregnanes
• Pyrazoles
• Severity of Illness Index
• Tremor (drug therapy, etiology)