Design of a Phase 2 Study of Suvecaltamide in Moderate-to-severe Parkinson’s Disease Tremor
Tara Skarpaas1, Robert Hauser2, Charles Adler3, Guenther Deuschl4, Michelle Baladi1, Patricia Chandler1, Kevin Xu1, Peter LeWitt5
1Jazz Pharmaceuticals, 2Parkinson’s Disease and Movement Disorders Center, University of South Florida, 3Department of Neurology, Mayo Clinic Arizona, 4Department of Neurology, Christian Albrecht University, 5Wayne State University School of Medicine
Objective:

Describe the design of a phase 2 study (NCT05642442) of a once-daily, extended-release formulation of suvecaltamide to treat moderate to severe residual Parkinson’s disease tremor (PDT).

Background:
Suvecaltamide, a T-type calcium channel modulator, is a nondopaminergic medication in development for PDT. Clinical assessments primarily focus on tremor amplitude, but the functional impact of tremor may represent a more clinically meaningful measure. This study will evaluate the efficacy of suvecaltamide on the functional impact of PDT using a composite of The Essential Tremor Rating Assessment Scale (TETRAS, activities of daily living items 1–11, and performance subscale items 6 and 7), among other secondary and exploratory scales.
Design/Methods:

This double-blind, placebo-controlled, flexible-dosing, parallel-group, multicenter study will enroll participants with PD (aged 40−85 years) with inadequately controlled tremor despite optimized treatment with PD medications. Participants will be randomized 1:1 to placebo or suvecaltamide, stratified by baseline TETRAS composite score (>17 or ≤17). In a 5-week titration period, participants will receive suvecaltamide 5 mg/day for 1−2 weeks, increasing to 10 mg/day for 1 week, then increasing by 10 mg/day once weekly up to 30 mg/day to optimize efficacy and tolerability. A 12-week maintenance period follows. The primary endpoint is change from baseline at week 17 on a TETRAS composite score. Additional endpoints assess PD symptoms, clinician and participant global impressions, embarrassment/quality of life due to tremor, and safety and tolerability.

Results:

Target enrollment is 160 participants (128 evaluable) with 80% power to detect a 3-point change from baseline to week 17 on the primary endpoint between suvecaltamide and placebo (common σ=6.0, 2-sided α=0.05). Enrollment is ongoing.

Conclusions:

The phase 2 proof-of-concept study for the efficacy of suvecaltamide to treat the functional impact of PDT represents the first large clinical study informing the use of TETRAS to assess tremor in this population.

10.1212/WNL.0000000000206381