A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)

A Phase 2b, 12-week, Double-blind, Placebo-controlled, Randomized, Parallel Group, Multicenter Study of the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor

This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter study of the safety and efficacy of JZP385 in the treatment of adult participants with moderate to severe ET.

Study Overview

• Status: Completed
• Conditions: Essential Tremor
• Intervention / Treatment: Drug: JZP385; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bad Homburg, Germany, 61350
    • Zentrum for klinische Forschung Dr. med. Irma Schoell
  • Chemnitz, Germany, 09111
    • Pharmakologisches Studienzentrum Chemnitz
  • Dusseldorf, Germany, 40225
    • University Hospital Duesseldorf
  • Haag, Germany, 83527
    • Klinik Haag i. OB
  • Hannover, Germany, 30625
    • CRC Core Facility Medizinische Hochschule Hannover (MHH)
  • Wiesbaden, Germany, 65191
    • DKD Helios Klinik Wiesbaden
  • Wuerzburg, Germany, 97080
    • Klinikum der Julius-Maximilians-Universitaet Wuerzburg
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89081
      • Universitaetsklinikum Ulm
  • Hessen
    • Wiesbaden, Hessen, Germany, 65189
      • Velocity Clinical Research Germany GmbH
• Poland
  • Bydgoszcz, Poland, 85-065
    • Medicover Integrated Clinical Services (MICS) Centrum Medyczne Bydgoszcz
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
  • Krakow, Poland, 30-363
    • Centrum Medyczne Plejady
  • Krakow, Poland, 30-539
    • Specjalistyczne Gabinety Sp. z o.o
  • Krakow, Poland, 31-156
    • LANDA Specjalistyczne Gabinety Lekarskie
  • Krakow, Poland, 31-505
    • Krakowska Akademia Neurologii Sp. Z o.o
  • Krakow, Poland, 31-721
    • Linden Centrum Medyczne
  • Lublin, Poland, 20-080
    • Centrum Zdrowia i Urody Maxxmed
  • Lublin, Poland, 20-064
    • Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) Neuromed M. i M. Nastaj Spolka Partnerska( Sp.P.)
  • Plewiska, Poland, 62-064
    • Neurologiczny NZOZ Centrum Leczenia SM Osrodek Badan Klinicznych im. dr n. med. Hanki Hertmanowskiej
  • Poznan, Poland, 61-441
    • Rivermed Sp z o.o
  • Warsaw, Poland, 02-777
    • ETG Neuroscience
  • Warsaw, Poland, 03-505
    • MD Clinic Praga Spolka z o. o.
  • Slaskie
    • Katowice, Slaskie, Poland, 40-749
      • Neuro-Care Sp. Z.o.o. sp. Komandytowa
• Spain
  • Barakaldo, Spain, 48903
    • Hospital de Cruces
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • San Sebastian, Spain, 20014
    • Policlinica Gipuzkoa
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Hospital Universitario Virgen Macarena-merge
  • Vizcaya
    • Getxo, Vizcaya, Spain, 48993
      • CAE Oroitu (Centro de Atencion Especializada)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham (UAB)
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
    • Phoenix, Arizona, United States, 85032
      • Arizona Neuroscience Research, LLC
    • Scottsdale, Arizona, United States, 85258
      • Movement Disorders Center of Arizona
    • Scottsdale, Arizona, United States, 85258
      • Imaging Endpoints II, LLC
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research, LLC
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest, LLC
  • California
    • Fountain Valley, California, United States, 92708
      • The Parkinson's and Movement Disorder Institute
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine USC - Healthcare Consultation Center 2 (HCCII)
    • Los Angeles, California, United States, 90048
      • SC3 Research - Beverly
    • Pasadena, California, United States, 91105
      • SC3 Research Pasadena
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Neurology of Central Florida Research Center
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease And Movement Disorder Center Of Boca Raton
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research, LLC
    • Jacksonville, Florida, United States, 33217
      • Clinical Neuroscience Solutions, Inc.
    • Miami, Florida, United States, 33032
      • Homestead Associates in Research, Inc.
    • Tampa, Florida, United States, 33613
      • University of South Florida Parkinson's Disease and Movement Disorders Center
    • Tampa, Florida, United States, 33612
      • USF Carol and Frank Morsani Center for Advanced Healthcare
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research, Inc.
    • Atlanta, Georgia, United States, 30329
      • Brain Health Center, Emory University
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University - Feinberg School of Medicine - Parkinsonÿs Disease and Movement Disorders Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, Movement Disorder Clinic
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Nebraska Medical Center
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurological Institute
    • Patchogue, New York, United States, 11772
      • South Shore Neurology Associates, Inc.
    • Rochester, New York, United States, 14618
      • University of Rochester Medical Center
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Health System
  • Ohio
    • Beavercreek, Ohio, United States, 45432
      • American Clinical Research Institute LLC
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital - Movement Disorders Clinic
  • Washington
    • Kirkland, Washington, United States, 98034
      • Booth Gardner Parkinson's Care Center
  • West Virginia
    • Crab Orchard, West Virginia, United States, 25827
      • Vaught Neurological Services, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
2. Participants who are diagnosed with ET (including ET plus) according to the MDS Consensus Statement on the Classification of Tremors from the Task Force on Tremor of the International Parkinson's and Movement Disorder Society.
3. Participants have moderate to severe disability associated with tremor as determined by a score of ≥ 22 on the TETRAS-ADL subscale and a CGI-S rating of at least moderate for participants' ability to function.

4. Sex and Contraceptive/Barrier Requirements

   During the study intervention and for at least 30 days after the last dose of study intervention male participants must refrain from donating sperm. Non-abstinent males must agree to use a male condom in combination with female partner use of a highly effective contraceptive method with a failure rate of < 1% per year. All male participants must agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.

   Female participants must not be pregnant or breastfeeding, are either women of non-childbearing potential (WONCBP), or are women of childbearing potential (WOCBP) using a highly effective contraceptive method with a failure rate of < 1% during the study intervention period and for at least 30 days after the last dose of study intervention. Male partners of WOCBP are required to use barrier protection, eg, condoms, from the first dose of study intervention until 30 days after the last dose of study intervention.

   A WOCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1 and negative urine pregnancy tests (unless serum is required by local regulations) at the Screening Visit 2 (if applicable) and at the Baseline Visit

   - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

5. Prior/Concomitant Antitremor Medications

If currently treated with antitremor medications, potential participants must be on a stable dosage for at least 6 weeks prior to Screening and must not anticipate making any changes to their antitremor medication for the duration of the study. Note: Treatment with some antitremor medications (eg, primidone) is not allowed in accordance with other exclusion criteria.

Exclusion Criteria:

1. Known history or current evidence of other medical or neurological conditions that may cause or explain the participant's tremor.
2. Has evidence at Screening of severe cognitive impairment as defined by a Montreal Cognitive Assessment (MoCA; score < 20) or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures (including the ability to accurately self-report on study questionnaires) or the ability to provide informed consent.
3. Current suicidal risk as determined from history, by presence of active suicidal ideation as indicated by positive response to item 4 or 5 on the C-SSRS (within the past 24 months), or any history of suicide attempt; current or past (within 1 year) major depressive episode according to DSM-5 criteria.
4. History (within past 2 years at screening) or presence of a diagnosed substance use disorder (including alcohol, tobacco, and cannabis) according to DSM-5 criteria, known drug dependence, or seeking treatment for alcohol or substance abuse related disorder.
5. Prior magnetic resonance (MR)-guided focused ultrasound thalamotomy, surgical intervention (eg, deep brain stimulation, ablative thalamotomy, gamma knife thalamotomy), or inability to refrain from using a device for treatment of tremor for the duration of the treatment period.
6. Botulinum toxin injection for the treatment of upper limb tremor in the 6 months before screening or planned use at any time during the study.
7. Treatment with any medication that could produce tremor taken within 2 weeks or 5 half-lives (whichever is longer) before screening or anticipated use at any time during participation in the study.
8. Use of prescription of nonprescription drugs or other products known to be inducers of CYP3A4 that are known to decrease AUC by > 30% (eg, primidone) and which cannot be discontinued at least 4 weeks before Baseline or planned use at any time during the study.
9. Use of prescription or nonprescription drugs, or other products (eg, grapefruit, grapefruit juice, or Seville oranges) known to be strong or moderate inhibitors of CYP3A4, that cannot be discontinued 2 weeks or 5 half-lives, whichever is longer, before Baseline or planned use at any time during the study.
10. Use of proton pump inhibitors that cannot be discontinued at least 2 weeks before Baseline, or planned use at any time during the study. Occasional use of antacids or histamine-2 receptor antagonists will be permitted, but antacids should be taken at least 4 hours before or after study intervention; and histamine-2 receptor antagonists should be taken at least 4 hours after and at least 12 hours before study intervention.
11. Inability to refrain from use of medication/substance(s) that might produce tremor or interfere with the evaluation of tremor on study visit days prior to discharge such as, but not limited to, stimulant decongestants, beta-agonist bronchodilators, and alcohol.
12. Regular use of more than 3 units of alcohol per day.
13. Regular consumption of caffeine > 400 mg/day or > 4 cups of coffee per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 milligram (mg) JZP385; Participants will initially receive 5 mg/day from Day 1 through Day 7, and 10 mg/day starting on Day 8.	Drug: JZP385; JZP385 capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.
Experimental: 20 mg JZP385; Participants will initially receive 5 mg/day from Day 1 through Day 7, 10 mg/day from Day 8 through Day 14, and 20 mg/day starting on Day 15.	Drug: JZP385; JZP385 capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.
Experimental: 30 mg JZP385; Participants will initially receive 5 mg/day from Day 1 through Day 7, 10 mg/day from Day 8 through Day 14, 20 mg/day from Day 15 through Day 21, and 30 mg/day starting on Day 22.	Drug: JZP385; JZP385 capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.
Placebo Comparator: Placebo; Participants will receive placebo from Day 1.	Other: Placebo; Placebo capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo	The TETRAS composite outcome score is the sum of modified items 1 - 11 of the TETRAS-ADL subscale and modified items 6 - 7 of the TETRAS-PS. The TETRAS-ADL subscale is a patient-rated scale administered by a trained interviewer that assesses the impact of tremor on day-to-day functioning, such as eating, drinking, dressing, and other fine motor skills. The TETRAS-PS is a clinical rating scale that quantifies tremor in the head, face voice, limbs and trunk. Items 6 (drawing an Archimedes spiral using left and right hands) and 7 (handwriting) of the TETRAS-PS evaluate the impact of upper limb tremor on performance. Each item from the modified subscales ranges from 0 - 3, with 0 representing normal or slightly abnormal and 3 representing severely abnormal. The sum of the 14 items provides the TETRAS composite outcome score, which ranges from 0 - 42, with higher scores representing more severe ET.	Change from baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S)	The CGI-S is a 5-point Likert-type rating scale that a qualified medical personnel (ie, a clinician)will use to rate the severity of the participants' ability to function due to their ET. The responses to this scale range from 1 (no limitations) to 5 (severe).	Change from baseline to week 12
Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12	The CGI-C is a 5-point Likert-type rating scale that a qualified medical personnel (ie, a clinician) will use to rate the change in severity of the participants' ability to function due to their ET since baseline. The responses to this scale range from 1 (Much improved) to 5 (Much worse).	Week 12
Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12	The PGI-C is a 5-point Likert-type rating scale that participants use to rate the change in severity of their ability to function due to ET since baseline. The responses to this scale range from 1 (Much improved) to 5 (Much worse).	Change from baseline to week 12
Change From Baseline to Week 12 on the TETRAS-ADL Subscale as Summarized by Each Dose of JZP385 and Placebo	The TETRAS-ADL subscale is a patient-rated scale of the impact of tremor on day-to-day functioning administered by a trained interviewer. The TETRAS-ADL subscale directly measures how a patient functions by assessing activities impacted by tremor, such as eating and drinking, dressing and personal hygiene, carrying items and fine motor skills. The TETRAS-ADL has 12 items, and each item is rated on a 0 (normal) to 4 (severe) scale with a total score ranging from 0 to 48. A higher score represents more severe ET.	Change from baseline to week 12
Change From Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo	The TETRAS-PS is a clinical rating scale performed by a blinded rater that quantifies tremor in the head, face, voice, limbs, and trunk. Each item will be rated on a scale of 0 (normal) to 4 (severe). The sum of the individual scores provides the overall score, ranging from 0 to 64, with higher scores representing more severe ET.	Change from baseline to week 12
Change From Baseline to Week 12 on the Upper Limb Score (Item 4) of the TETRAS-PS as Summarized by Each Dose of JZP385 and Placebo	Item 4 of the TETRAS-PS measures upper limb tremor, and includes 3 maneuvers for each arm that assess postural and kinetic tremor. Each item is rated on a scale of 0 (normal) to 4 (severe) in 0.5-point increments. The total score is the sum of each of the 6 items and ranges from 0 to 24, with higher scores representing more severe ET. The TETRAS-PS is performed by a blinded rater.	Change from baseline to week 12
Change From Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo.	The TETRAS total score is the sum of the scores of the full TETRAS-ADL and TETRAS-PS subscales. Each item is rated on a 0 (normal) to 4 (severe) scale, and total scores range from 0 to 112, with higher scores representing more severe ET. The TETRAS-PS is performed by a blinded rater.	Change from baseline to week 12
Change From Baseline to Week 12 on the Quality of Life in Essential Tremor Questionnaire (QUEST) as Summarized by Each Dose of JZP385 and Placebo	The Quality of Life in Essential Tremor Questionnaire (QUEST) was developed to specifically assess the impact of ET on health-related quality of life. The QUEST is a 30-item questionnaire comprising 5 subscales (physical, psychosocial, communication, hobbies/leisure, and work/finance). Each item is rated by frequency on a scale from 0 (never) to 4 (always). Each dimension had been standardized to a range of 0 to 100 with higher scores indicating greater dissatisfaction or disability due to ET.	Change from baseline to week 12
Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score A as Summarized by Each Dose of JZP385 and Placebo	The Essential Tremor Embarrassment Assessment (ETEA) is a participant-rated questionnaire administered by a health care provider or researcher that contains 14-items assessing embarrassment related to tremor. For Score A, participants provide a simple response (disagree or agree) to each of the 14-items, the sum of which yields an initial score range = 0 to 14. Higher scores indicate greater embarrassment	Change from baseline to week 12
Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score B as Summarized by Each Dose of JZP385 and Placebo	The Essential Tremor Embarrassment Assessment (ETEA) is a participant-rated questionnaire administered by a health care provider or researcher that contains 14-items assessing embarrassment related to tremor. For Score B, participants provide a more nuanced response to each question on a 0 to 5 point Likert scale ranging from disagree (0) to agree strongly (5). The sum of the nuanced responses yields a second score (range = 0 to 70). Higher scores indicate greater embarrassment	Change from baseline to week 12

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2021
• Primary Completion (Actual): May 30, 2024
• Study Completion (Actual): May 30, 2024

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 6, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Tremor; JZP385; T-type calcium channels; Movement disorder; Moderate to severe essential tremor
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: JZP385-201; 2020-002463-61 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No