A Phase 2 RCT Study of CX-8998 for Essential Tremor

NCT03101241 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CX-8998-CLN2-001
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 22

Brief 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.

Conditions

Essential Tremor

Keywords

Essential Tremor; Movement Disorders; thalamocortical dysrhythmias

Outcome Measures

Primary Outcomes (2)

• Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) Total Score

  The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) was used to assess the efficacy of CX-8998 in reducing essential tremor as scored by the independent video raters. TETRAS-PS quantifies tremor in the head, face, voice, limbs, and trunk. The overall subscale score ranges from a minimum of 0 to a maximum of 64. A lower score is indicative of improvement and a better outcome.

  Baseline and Day 28 post-dose.

• Change From Baseline to Day 28 on The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS)

  The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) was used to assess the efficacy of CX-8998 in reducing essential tremor as scored by the independent video raters. TETRAS-PS quantifies tremor in the head, face, voice, limbs, and trunk. The overall subscale score ranges from a minimum of 0 to a maximum of 64. A decrease or negative change in the score is indicative of improvement in outcome.

  Baseline up to Day 28 post-dose.

Secondary Outcomes (4)

• Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Activities of Daily Living (TETRAS-ADL) Subscale Score

  Baseline and Day 28 post-dose.

• Change From Baseline to Day 28 on The Essential Tremor Rating Assessment Scale Activities of Daily Living (TETRAS-ADL) Subscale Score

  Baseline up to Day 28 post-dose.

• Baseline and Day 28 in the Kinesia ONE Score

  Baseline and Day 28 post-dose.

• Change From Baseline to Day 28 in the Kinesia ONE Score

  Baseline up to Day 28 post-dose.

Study Arms (2)

CX-8998

EXPERIMENTAL

Drug: CX-8998

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

CX-8998 DRUG

T-type calcium channel blocker

CX-8998

Placebo DRUG

Placebo comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form indicating that the subject has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
• Men or non-pregnant, non-breastfeeding women 18 to 75 years-of-age who are able to read and understand English.
• Diagnosis of definite or probable essential tremor (ET) as defined by the Tremor Investigational Group with involvement of the hands and arms without present causes of enhanced physiologic tremor (Deuschl et al.,1998).
• Diagnosis of ET before the age of 65.
• Tremor severity score of at least 2 in at least one upper extremity on at least one of the three maneuvers on the TETRAS scale.
• Total TETRAS performance score of at least 15.
• One concomitant anti-tremor medication (other than primidone) is allowed. Note: Primidone is NOT an allowed anti-tremor medication. If on primidone, subjects are allowed to extend their screening period by 2 weeks (for a total of 6 weeks) and discontinue primidone under the supervision of the investigator.
• Subjects with reproductive capability including all males and women of child-bearing potential (WOCBP) must agree to practice continuous abstinence or adequate contraception methods (appropriate double barrier method or oral, patch, implant, or injectable contraception) from as soon as feasible during screening period until at least 30 days after the last dose.
• Approval by the sponsor medical personnel as to final suitability for the study.

You may not qualify if:

• Exposure to tremorigenic drugs or drug withdrawal states within the 30 days prior to the first planned dose of study drug.
• Direct or indirect trauma to the nervous system within 3 months preceding the onset of tremor
• History or clinical evidence of psychogenic tremor origin
• Known history of other medical or neurological conditions that may cause or explain subject's tremor, including, but not limited to: a. Parkinson's disease b. dystonia c. cerebellar disease, other than essential tremor d. Traumatic Brain Injury e. alcohol abuse or withdrawal f. mercury poisoning g. hyperthyroidism h. pheochromocytoma i. head trauma or cerebrovascular disease within 3 months prior to the onset of essential tremor j. multiple sclerosis k. polyneuropathy l. family history of Fragile X syndrome
• Prior MR-guided Focused Ultrasound or surgical intervention (e.g., deep brain stimulation, ablative thalamotomy or gamma knife thalamotomy).
• Botulinum toxin injection in the 6 months prior to screening.
• Currently using more than one anti-tremor medication.
• Experiencing clinical benefit from and/or is not willing to discontinue primidone
• Use of medication(s) in the past month that might produce tremor or interfere with the evaluation of tremor, such as, but not limited to: CNS-stimulants, lithium, amiodarone, metoclopramide, theophylline, and valproate
• Inability to refrain from use of medication/substance(s) that might produce tremor or interfere with the evaluation of tremor on study visit days, such as but not limited to stimulant decongestants, beta-agonist bronchodilators, caffeine, alcohol and tobacco, based on Investigator assessment at baseline.
• Positive urine drug screen.
• Regular use of more than two units of alcohol per day.
• Sporadic use of a benzodiazepine, sleep medication or anxiolytic to improve sleep performance. Stable use at a consistent dose is allowed as long as tremor persists against the background of regular medication use. Use on the evening prior to a study visit is prohibited.
• Use of prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study, including primidone.
• Concurrent illnesses that would be a contraindication to trial participation, including, but not limited to: a. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening b. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure c. Clinically significant ECG d. Known infection with HIV, hepatitis B, or hepatitis C, unless curative therapy completed for hepatitis C with negative PCR for HCV RNA e. Significant hepatic (AST/ALT \> 2X upper limit of normal) or renal disease (creatinine clearance \<39 mL/min) f. Significant psychiatric history including mood disorders and alcohol or substance abuse within the last year g. A current C-SSRS score of 4 or 5 at screening or history of suicide attempt at any time during the past year h. Clinically significant impaired balance or is considered at increased risk for falls i. Symptomatic orthostatic hypotension.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (22)

Tucson Neuroscience Research

Tucson, Arizona, 85710, United States

Location

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Pacific Research Network

San Diego, California, 92103, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Meridian Neurology Clinical Research

Savannah, Georgia, 31406, United States

Location

Northwestern Medical Group

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Henry Ford Hospital West Bloomfield

West Bloomfield, Michigan, 48322, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

St. Louis Clinical Trials

St Louis, Missouri, 63141, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Wake Research Associates, LLC

Raleigh, North Carolina, 27612, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Papapetropoulos S, Lee MS, Boyer S, Newbold EJ. A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of CX-8998, a Selective Modulator of the T-Type Calcium Channel in Inadequately Treated Moderate to Severe Essential Tremor: T-CALM Study Design and Methodology for Efficacy Endpoint and Digital Biomarker Selection. Front Neurol. 2019 Jun 11;10:597. doi: 10.3389/fneur.2019.00597. eCollection 2019.

  PMID: 31244760 DERIVED

MeSH Terms

Conditions

Essential Tremor; Movement Disorders

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Director, Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-870-9177

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a double-blind, placebo-controlled, parallel-group study.

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 5, 2017
• Study Start: August 29, 2017
• Primary Completion: July 16, 2018
• Study Completion: July 16, 2018
• Last Updated: November 23, 2021
• Results First Posted: October 22, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)