Clinical trial NCT05122650: A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor
Keywords: JZP385
T-type calcium channels
Movement disorder
Tremor
Moderate to severe essential tremor
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-11-17
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline to Week 12 on the TETRAS composite outcome score as summarized by each dose of JZP385 and placebo
timeFrame: Change from baseline to week 12
Secondary outcomes:
measure: Proportion of Participants who Improved (≥ 1-Point Improvement) from Baseline to Week 12 on the Clinical Global Impression- Severity scale (CGI-S)
timeFrame: Change from Baseline to Week 12
measure: Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C)
timeFrame: Week 12
measure: Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12
timeFrame: Week 12
measure: Change from Baseline to Week 12 on the TETRAS-ADL subscale as Summarized by Each Dose of JZP385 and Placebo
timeFrame: Change from baseline to week 12
measure: Change from Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo
timeFrame: Change from baseline to week 12
measure: 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
timeFrame: Change from baseline to week 12
measure: Change from Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo.
timeFrame: Change from baseline to week 12
measure: 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
timeFrame: Change from baseline to week 12
measure: Change from Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) as Summarized by Each Dose of JZP385 and Placebo
timeFrame: Change from Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University Of Alabama At Birmingham (Uab)
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Neuroscience Research, LLC
state: Arizona
city: Scottsdale
country: United States
facility: Imaging Endpoints II, LLC
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Bentonville
country: United States
facility: Pillar Clinical Research, LLC
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest, LLC
state: Arkansas
city: Fountain Valley
country: United States
facility: The Parkinson's and Movement Disorder Institute
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine USC - Healthcare Consultation Center 2 (HCCII)
state: California
city: Los Angeles
country: United States
facility: SC3 Research - Beverly
state: California
city: Pasadena
country: United States
facility: SC3 Research Pasadena
state: California
city: Altamonte Springs
country: United States
facility: Neurology of Central Florida Research Center
state: Florida
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease And Movement Disorder Center Of Boca Raton
state: Florida
city: Clearwater
country: United States
facility: Innovative Research Of West Florida, Inc.
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, Llc
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Miami
country: United States
facility: Homestead Associates in Research, Inc.
state: Florida
city: Tampa
country: United States
facility: USF Carol and Frank Morsani Center for Advanced Healthcare
state: Florida
city: Tampa
country: United States
facility: University of South Florida Parkinson's Disease and Movement Disorders Center
state: Florida
city: Atlanta
country: United States
facility: Neurotrials Research, Inc.
state: Georgia
city: Atlanta
country: United States
facility: Brain Health Center, Emory University
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine - ParkinsonÃÂ¿s Disease and Movement Disorders Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville, Movement Disorder Clinic
state: Kentucky
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Omaha
country: United States
facility: University Nebraska Medical Center
state: Nebraska
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Patchogue
country: United States
facility: South Shore Neurology Associates, Inc.
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Beavercreek
country: United States
facility: American Clinical Research Institute LLC
state: Ohio
city: Canton
country: United States
facility: NeuroScience Research Center
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital - Movement Disorders Clinic
state: Texas
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center
state: Washington
city: Crab Orchard
country: United States
facility: Vaught Neurological Services, PLLC
state: West Virginia
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden-Württemberg
city: Wiesbaden
country: Germany
facility: Velocity Clinical Research Germany GmbH
state: Hessen
city: Bad Homburg
country: Germany
facility: Zentrum for klinische Forschung Dr. med. Irma Schoell
city: Chemnitz
country: Germany
facility: Pharmakologisches Studienzentrum Chemnitz
city: Dusseldorf
country: Germany
facility: University Hospital Duesseldorf
city: Haag
country: Germany
facility: Klinik Haag i. OB
city: Hannover
country: Germany
facility: CRC Core Facility Medizinische Hochschule Hannover (MHH)
city: Wiesbaden
country: Germany
facility: DKD HELIOS Klinik Wiesbaden
city: Wuerzburg
country: Germany
facility: Klinikum der Julius-Maximilians-Universitaet Wuerzburg
city: Katowice
country: Poland
facility: Neuro-Care Sp. Z.o.o. sp. Komandytowa
state: Slaskie
city: Bydgoszcz
country: Poland
facility: Medicover Integrated Clinical Services (MICS) Centrum Medyczne Bydgoszcz
city: Katowice
country: Poland
facility: NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Krakow
country: Poland
facility: Specjalistyczne Gabinety Sp. z o.o
city: Krakow
country: Poland
facility: Landa Specjalistyczne Gabinety Lekarskie
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o.o
city: Krakow
country: Poland
facility: Linden Centrum Medyczne
city: Lublin
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) Neuromed M. i M. Nastaj Spolka Partnerska( Sp.P.)
city: Lublin
country: Poland
facility: Centrum Zdrowia I Urody Maxxmed
city: Plewiska
country: Poland
facility: Neurologiczny NZOZ Centrum Leczenia SM Osrodek Badan Klinicznych im. dr n. med. Hanki Hertmanowskiej
city: Poznan
country: Poland
facility: Rivermed Sp z o.o
city: Warsaw
country: Poland
facility: ETG Neuroscience
city: Warsaw
country: Poland
facility: MD Clinic Praga Spolka z o. o.
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena-merge
state: Andalucia
city: Getxo
country: Spain
facility: CAE Oroitu (Centro de Atencion Especializada)
state: Vizcaya
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
city: San Sebastian
country: Spain
facility: Policlinica Gipuzkoa
Study officials:
References: