Objective: To evaluate the efficacy of NBI-827104 in patients with essential tremor (ET).
Background: NBI-827104 is a T-type calcium channel blocker that demonstrated tremorolytic activity in preclinical studies.
Method: This Phase 2 study (NCT04880616) was designed to assess the safety, tolerability, and efficacy of NBI-827104 in adults (ages 18 to 75 years) with ET (plus). Study participants were randomized 1:1 to one of two treatment sequences: NBI-827104 capsules (28 days) followed by washout (14 days) then placebo (28 days), or placebo followed by washout then NBI-827104. In both sequences, the dose of NBI-827104 was increased over time. In each treatment period, the primary endpoint was change from baseline to last day of treatment in amplitude squared at peak frequency of postural tremor, assessed with a triaxial accelerometer. Secondary endpoints were The Essential Tremor Rating Assessment Scale Performance and Activities of Daily Living subscales (TETRAS-P and TETRAS-ADL) and Clinical Global Impression of Change (CGI-C) score. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, and Columbia-Suicide Severity Rating Scale.
Results: In the full analysis set (N=31), 23 (74.2%) participants were male and 30 (96.8%) were white; mean age (±standard deviation) was 58.1±15.3 years. Mean amplitude at peak frequency of postural tremor was not significantly different between NBI-827104 and placebo (least squares mean difference: -0.04 mg2/Hz; p=0.7805). Additionally, no significant differences were found between NBI-827104 and placebo for the TETRAS-P, TETRAS-ADL, and CGI-C endpoints (all p>0.05). NBI-827104 was generally well tolerated. There were no severe or serious adverse events and no notable differences from placebo in other safety parameters.
Conclusion: NBI-827104 did not meet the primary or secondary efficacy endpoints. No statistically significant differences between treatment groups were observed using accelerometry and clinical scales.
To cite this abstract in AMA style:C. de Cuba, L. Smits, P. Kremer, R-J. Doll, J. Heuberger, R. Helmich, A F. van Rootselaar, R. Elble, W. Ondo, L. Rees, N. Wedick, G. Liang, D. Haubenberger. An evaluation of NBI-827104 for essential tremor: results from a randomized, double-blind, placebo-controlled, dose-escalation, crossover study [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/an-evaluation-of-nbi-827104-for-essential-tremor-results-from-a-randomized-double-blind-placebo-controlled-dose-escalation-crossover-study/. Accessed September 23, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-evaluation-of-nbi-827104-for-essential-tremor-results-from-a-randomized-double-blind-placebo-controlled-dose-escalation-crossover-study/