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Essential TremorPhase 2NCT03101241

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

A Phase 2 study testing CX-8998 in people with Essential Tremor, run by Jazz Pharmaceuticals at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Essential Tremor
What is being tested?
CX-8998
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
95 participants
Where
22 sitesUnited States
Study dates
29 Aug 2017to 16 Jul 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Treatment with an investigational agent within 30 days prior to the first dose of CX-8998 or planning to receive an investigational agent during the study.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University School of Medicine

    Atlanta, Georgia, 30329

  • Parkinson's Disease and Movement Disorders Center of Boca Raton

    Boca Raton, Florida, 33486

  • Boston University Medical Center

    Boston, Massachusetts, 02118

  • Northwestern Medical Group

    Chicago, Illinois, 60611

  • Midwest Clinical Research Center

    Dayton, Ohio, 45417

  • Quest Research Institute

    Farmington Hills, Michigan, 48334

  • Houston Methodist Neurological Institute

    Houston, Texas, 77030

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of California San Diego

    La Jolla, California, 92093

  • Woodland International Research Group

    Little Rock, Arkansas, 72211

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Columbia University

    New York, New York, 10032

  • Wake Research Associates, LLC

    Raleigh, North Carolina, 27612

  • Woodland Research Northwest

    Rogers, Arkansas, 72758

  • Pacific Research Network

    San Diego, California, 92103

  • Meridian Neurology Clinical Research

    Savannah, Georgia, 31406

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • St. Louis Clinical Trials

    St Louis, Missouri, 63141

  • University of South Florida

    Tampa, Florida, 33612

  • Tucson Neuroscience Research

    Tucson, Arizona, 85710

  • Henry Ford Hospital West Bloomfield

    West Bloomfield, Michigan, 48322

Other trials in United States

About this study

Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of CX-8998 for Essential Tremor

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.

Read the 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).

Being tested
CX-8998, Placebo
Keywords
Essential Tremor, Movement Disorders, thalamocortical dysrhythmias
Medical subject headings
Essential Tremor, Movement Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CX-8998Drug

    T-type calcium channel blocker

  • PlaceboDrug

    Placebo comparator

Study groups in NCT03101241
Study groupRoleWhat they receive
CX-8998ExperimentalNot described
Receives: Drug: CX-8998
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and Day 28 post-dose.

  2. 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.

    Measured: Baseline up to Day 28 post-dose.

Secondary outcomes (4)

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

    TETRAS-ADL subscale assesses items such as eating and drinking, dressing and personal hygiene, carrying items, and finer motor skills. Each item is rated on a scale for 0 to 4 on which 0 = normal activity and 4 = severe abnormality. The sum of the individual scores provides an overall score, which ranges from a minimum of 0 to a maximum of 48. A lower score is indicative of improvement or a better outcome.

    Measured: Baseline and Day 28 post-dose.

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

    TETRAS-ADL subscale assesses items such as eating and drinking, dressing and personal hygiene, carrying items, and finer motor skills. Each item is rated on a scale for 0 to 4 on which 0 = normal activity and 4 = severe abnormality. The sum of the individual scores provides an overall score, which ranges from a minimum of 0 to a maximum of 48. A decrease or negative change in score is indicative of improvement or a better outcome.

    Measured: Baseline up to Day 28 post-dose.

  3. Baseline and Day 28 in the Kinesia ONE Score

    Kinesia ONE was developed to provide a quantitative measurement of motor symptoms in individuals with Parkinson's disease. Scores are presented as the sum of the scores of the left and right hands. A total of 4 tasks were performed on the left side and then on the right side to assess resting, postural, kinetic, and lateral wing beating tremor. Values for each test range from 0 (no tremor) to 4 (severe tremor). The total overall score is the sum of all individual items and ranges from a minimum of 0 to a maximum of 32. A lower score is indicative of improvement or a better outcome.

    Measured: Baseline and Day 28 post-dose.

  4. Change From Baseline to Day 28 in the Kinesia ONE Score

    Kinesia ONE was developed to provide a quantitative measurement of motor symptoms in individuals with Parkinson's disease. Scores are presented as the sum of the scores of the left and right hands. A total of 4 tasks were performed on the left side and then on the right side to assess resting, postural, kinetic, and lateral wing beating tremor. Values for each test range from 0 (no tremor) to 4 (severe tremor). The total overall score is the sum of all individual items and ranges from a minimum of 0 to a maximum of 32. A decrease or negative change in score is indicative of improvement or a better outcome.

    Measured: Baseline up to Day 28 post-dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2017
  2. Study start29 Aug 2017
  3. Primary completion16 Jul 2018
  4. Study completion16 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a double-blind, placebo-controlled, parallel-group study.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03101241
Sponsor's protocol ID
CX-8998-CLN2-001
Status last verified
Oct 2021
First submitted
30 Mar 2017
Last updated
23 Nov 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31244760

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CX-8998 in people with Essential Tremor, run by Jazz Pharmaceuticals at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) Total Score (time frame: Baseline and Day 28 post-dose.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03101241, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.

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