A Phase 2 RCT Study of CX-8998 for Essential Tremor
Condition: Essential Tremor
MeSH terms: Tremor; Essential Tremor
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a multicenter, double-blind, placebo-controlled, parallel-group study consisting of a
      screening period of up to 4 weeks (with the exception of participants on primidone at
      baseline who will be allowed 6 weeks of screening to allow for safe discontinuation).
      Screening results from all patients meeting the eligibility requirements will be further
      assessed by the sponsor medical personnel for final approval of suitability for inclusion in
      the study. Randomized participants will enter a 4 week double-blind dose-titration treatment
      period, followed by a 1 week safety follow-up period following the last dose of study
      medication, and a scheduled follow-up safety telephone call one week later.
    

Detailed description: 
      This is a multicenter, double-blind, placebo-controlled, parallel-group study consisting of a
      screening period of up to 4 weeks (with the exception of participants on primidone at
      baseline who will be allowed 6 weeks of screening to allow for safe discontinuation).
      Screening results from all patients meeting the eligibility requirements will be further
      assessed by the sponsor medical personnel for final approval of suitability for inclusion in
      the study. Randomized participants will enter a 4 week double-blind dose-titration treatment
      period, followed by a 1 week safety follow-up period following the last dose of study
      medication, and a scheduled follow-up safety telephone call one week later.

      Participants will be randomized to one of two treatment groups. Group A will receive
      titrating doses of CX-8998 up to 10 mg BID and Group B will receive placebo. Participant
      randomization will be stratified by presence or absence of a single concomitant anti-tremor
      medication and by site-type (sub-study vs non sub-study).

      Tremor will be assessed via The Essential Tremor Rating Assessment Scale (TETRAS) and
      accelerometry. To reduce the potential for bias in the assessments of efficacy, all
      participants will be videotaped during the TETRAS performance scale testing according to a
      consistent script. The videotapes will be rated in a blinded manner by qualified, independent
      raters. A subset of participants will participate in a digital biomarker sub-study.

      Participants will be screened up to 4 weeks prior to initiation of dosing. Participants
      taking primidone at screening who are otherwise deemed eligible for participation and are
      willing to discontinue primidone will be allowed an additional 2 weeks of screening (a total
      of 6 weeks) to ensure safe primidone discontinuation. At Baseline, participants will undergo
      safety and tremor assessments prior to dosing, will receive their first dose of study drug
      and will be monitored for safety for one hour following dosing. For one week participants
      will receive 4 mg (or matching placebo) twice daily. Participants will return to the clinic
      on Day 8 for safety monitoring and dose up-titration to 8 mg (or matching placebo) twice
      daily. At Day 15 (Week 3) participants will return to clinic for safety and efficacy
      assessments and final dose up-titration to 10 mg (or matching placebo) twice daily. The final
      efficacy visit will occur at Day 28 (Week 4). A final safety visit will occur at Day 35 (Week
      5). Should participants experience intolerable adverse events (AEs) at 4 mg BID, 8 mg BID or
      10 mg BID, the dose may be decreased at Day 8 or Day 15 to the next lowest dose one time (or
      2 mg BID in the case of the 4 mg BID dose.

      Randomized participants will have the opportunity to participate in an optional exploratory
      sub-study designed to assess the utility of digital assessment tools for tremor (sub-study
      addendum #1). Participants with Parkinson's disease tremor will be enrolled in a second
      exploratory sub-study (addendum #2).
    

Intervention name(s): CX-8998; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): T-type calcium channel blocker; Placebo comparator
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a double-blind, placebo-controlled, parallel-group study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Essential Tremor; Movement Disorders; thalamocortical dysrhythmias