Category: Tremor
Objective: Evaluate efficacy and safety of CX-8998 in essential tremor (ET) as a function of baseline tremor severity.
Background: CX-8998, a selective modulator of T-type calcium channels, was evaluated for treatment of ET in a 4-week, randomized, double-blind, placebo-controlled phase 2a trial (NCT03101241).
Method: Adults with ET and score ≥15 on The Essential Tremor Rating Assessment Scale performance subscale (TETRAS-PS) based on independent video raters were randomly assigned to CX-8998 titrated to 10 mg BID or placebo. Changes from baseline to day 28 on TETRAS-PS, rated in real time by the investigators (evaluated post hoc), and the activities of daily living subscale (TETRAS-ADL) were evaluated using analysis of covariance in the full analysis set (FAS), which included all participants who received study drug and had baseline and ≥1 post-baseline assessments. A prespecified analysis evaluated outcomes in subgroups defined by baseline independent video-rated TETRAS-PS scores at or below (less severe) and above (more severe) the median score of 22.5.
Results: Investigator-rated TETRAS-PS improved with CX-8998 treatment vs placebo: least squares (LS) mean differences from placebo (95% confidence interval [CI]) in change from baseline to day 28 were −2.0 (−4.0, 0.0) in the FAS population (n=83); −1.2 (−3.1, 0.6) in the less severe subgroup (n=44) and −3.5 (−7.4, 0.4) in the more severe subgroup (n=39). For TETRAS-ADL, LS mean differences from placebo (95% CI) in change from baseline to day 28 were −2.9 (−5.8, −0.1) in the FAS population; −1.6 (−4.7, 1.4) in the less severe subgroup and −5.8 (−11.2, −0.5) in the more severe subgroup. In both subgroups, adverse events were mostly mild to moderate.
Conclusion: For participants with more severe tremor at baseline, the treatment effect with CX8998 may be larger in absolute value relative to those with less severe baseline tremor.
To cite this abstract in AMA style:
H. Jinnah, S. Papapetropoulos, M. Lee, S. Versavel, E. Newbold, R. Pahwa, K. Lyons, R. Elble, W. Ondo, T. Zesiewicz, P. Hedera, A. Handforth, J. Elder, M. Versavel. Efficacy and safety of CX-8998 in T-CALM, a randomized, double-blind, placebo-controlled, phase 2a trial in participants with essential tremor: subgroup analysis by baseline tremor severity [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-cx-8998-in-t-calm-a-randomized-double-blind-placebo-controlled-phase-2a-trial-in-participants-with-essential-tremor-subgroup-analysis-by-baseline-tremor-severity/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-cx-8998-in-t-calm-a-randomized-double-blind-placebo-controlled-phase-2a-trial-in-participants-with-essential-tremor-subgroup-analysis-by-baseline-tremor-severity/