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

Essential Tremor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05122650
• Other study ID #: JZP385-201
• Secondary ID: 2020-002463-61
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 6, 2021
• Est. completion date: May 31, 2024

Study information

• Verified date: May 2024
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 420
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Drug:
• JZP385
JZP385 capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.

Other:
• Placebo
Placebo capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.

Locations

Country	Name	City	State
Germany	Zentrum for klinische Forschung Dr. med. Irma Schoell	Bad Homburg
Germany	Pharmakologisches Studienzentrum Chemnitz	Chemnitz
Germany	University Hospital Duesseldorf	Dusseldorf
Germany	Klinik Haag i. OB	Haag
Germany	CRC Core Facility Medizinische Hochschule Hannover (MHH)	Hannover
Germany	Universitaetsklinikum Ulm	Ulm	Baden-Württemberg
Germany	DKD HELIOS Klinik Wiesbaden	Wiesbaden
Germany	Velocity Clinical Research Germany GmbH	Wiesbaden	Hessen
Germany	Klinikum der Julius-Maximilians-Universitaet Wuerzburg	Wuerzburg
Poland	Medicover Integrated Clinical Services (MICS) Centrum Medyczne Bydgoszcz	Bydgoszcz
Poland	Neuro-Care Sp. Z.o.o. sp. Komandytowa	Katowice	Slaskie
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis	Katowice
Poland	Centrum Medyczne Plejady	Krakow
Poland	Krakowska Akademia Neurologii Sp. z o.o	Krakow
Poland	Landa Specjalistyczne Gabinety Lekarskie	Krakow
Poland	Linden Centrum Medyczne	Krakow
Poland	Specjalistyczne Gabinety Sp. z o.o	Krakow
Poland	Centrum Zdrowia I Urody Maxxmed	Lublin
Poland	Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) Neuromed M. i M. Nastaj Spolka Partnerska( Sp.P.)	Lublin
Poland	Neurologiczny NZOZ Centrum Leczenia SM Osrodek Badan Klinicznych im. dr n. med. Hanki Hertmanowskiej	Plewiska
Poland	Rivermed Sp z o.o	Poznan
Poland	ETG Neuroscience	Warsaw
Poland	MD Clinic Praga Spolka z o. o.	Warsaw
Spain	Hospital de Cruces	Barakaldo
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	CAE Oroitu (Centro de Atencion Especializada)	Getxo	Vizcaya
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Majadahonda
Spain	Policlinica Gipuzkoa	San Sebastian
Spain	Hospital Universitario Virgen Macarena-merge	Sevilla	Andalucia
United States	Neurology of Central Florida Research Center	Altamonte Springs	Florida
United States	Dent Neurological Institute	Amherst	New York
United States	Brain Health Center, Emory University	Atlanta	Georgia
United States	Neurotrials Research, Inc.	Atlanta	Georgia
United States	JEM Research Institute	Atlantis	Florida
United States	American Clinical Research Institute LLC	Beavercreek	Ohio
United States	Pillar Clinical Research, LLC	Bentonville	Arkansas
United States	The University Of Alabama At Birmingham (Uab)	Birmingham	Alabama
United States	Parkinson's Disease And Movement Disorder Center Of Boca Raton	Boca Raton	Florida
United States	NeuroScience Research Center	Canton	Ohio
United States	Northwestern University - Feinberg School of Medicine - ParkinsonÃ'¿s Disease and Movement Disorders Center	Chicago	Illinois
United States	Innovative Research Of West Florida, Inc.	Clearwater	Florida
United States	Vaught Neurological Services, PLLC	Crab Orchard	West Virginia
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Duke University Health System	Durham	North Carolina
United States	QUEST Research Institute	Farmington Hills	Michigan
United States	The Parkinson's and Movement Disorder Institute	Fountain Valley	California
United States	Infinity Clinical Research, Llc	Hollywood	Florida
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Houston Methodist Hospital - Movement Disorders Clinic	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Booth Gardner Parkinson's Care Center	Kirkland	Washington
United States	Keck School of Medicine USC - Healthcare Consultation Center 2 (HCCII)	Los Angeles	California
United States	SC3 Research - Beverly	Los Angeles	California
United States	University of Louisville, Movement Disorder Clinic	Louisville	Kentucky
United States	Homestead Associates in Research, Inc.	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University Nebraska Medical Center	Omaha	Nebraska
United States	SC3 Research Pasadena	Pasadena	California
United States	South Shore Neurology Associates, Inc.	Patchogue	New York
United States	Arizona Neuroscience Research, LLC	Phoenix	Arizona
United States	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	University of Rochester Medical Center	Rochester	New York
United States	Woodland Research Northwest, LLC	Rogers	Arkansas
United States	Imaging Endpoints II, LLC	Scottsdale	Arizona
United States	Movement Disorders Center of Arizona	Scottsdale	Arizona
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	University of South Florida Parkinson's Disease and Movement Disorders Center	Tampa	Florida
United States	USF Carol and Frank Morsani Center for Advanced Healthcare	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion 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
Secondary	Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C)	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
Secondary	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).	Week 12
Secondary	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 higher scores representing more severe ET.	Change from baseline to week 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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) and a total score, plus 3 additional items relating to sexual function and satisfaction with tremor control and medication side effects. Each item is rated by frequency on a scale from 0 (never) to 4 (always), with higher scores indicating greater dissatisfaction or disability due to ET.	Change from baseline to week 12
Secondary	Change from Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) 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. Participants provide a simple response (disagree or agree) to each of the 14-items, the sum of which yields an initial score (Score A, range = 0 to 14). Participants then 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 (Score B, range = 0 to 70). Higher scores on both the simple and nuanced responses indicate greater embarrassment.	Change from Baseline to Week 12