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

Sponsor

Jazz Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05122650

Collaborator

(none)

400

Enrollment

Locations

Arms

24.1

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Tremor	Drug: JZP385 Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 6, 2021

Anticipated Primary Completion Date :

Nov 13, 2023

Anticipated Study Completion Date :

Dec 11, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Change from Baseline to Week 12 on the TETRAS composite outcome score as summarized by each dose of JZP385 and placebo [Change from baseline to week 12]
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.

Secondary Outcome Measures

Change from Baseline to Week 12 on the Clinical Global Impression - Severity scale CGI-S [Change from Baseline to Week 12]
The CGI-S is a 5-point Likert-type rating scale that a qualified medical personnel 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).
Percentage of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) [Week 12]
The CGI-C is a 5-point Likert-type rating scale that a qualified medical personnel 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).
Percentage of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12 [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 on the TETRAS-ADL subscale as Summarized by Each Dose of JZP385 and Placebo [Change from baseline to week 12]
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 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo [Change from baseline to week 12]
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 on the Upper Limb Score (item 4) of the TETRAS-PS as Summarized by Each Dose of JZP385 and Placebo [Change from baseline to week 12]
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 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo. [Change from baseline to week 12]
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 on the Quality of Life in Essential Tremor Questionnaire (QUEST) as Summarized by Each Dose of JZP385 and Placebo [Change from baseline to week 12]
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 on the Essential Tremor Embarrassment Assessment (ETEA) as Summarized by Each Dose of JZP385 and Placebo [Change from Baseline to Week 12]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
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.
Participants have moderate to severe disability associated with tremor as determined by a score of ≥ 22 on the TETRAS-ADL subscale; and a score of > 5 on the sum of items 6 and 7 of the TETRAS-PS; and a CGI-S rating of at least moderate for participants' ability to function.
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, over the same 30 day period.

Exclusion Criteria:

Known history or current evidence of other medical or neurological conditions that may cause or explain the participant's tremor.
Severe cognitive impairment as defined by a Montreal Cognitive Assessment (MoCA; score <23), or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent.
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.
History (within past 2 years at screening) or presence of substance use disorder (including alcohol) according to DSM-5 criteria, known drug dependence, or seeking treatment for alcohol or substance abuse related disorder. Nicotine use disorder is excluded if it impacts tremor.
Prior magnetic resonance (MR)-guided focused ultrasound, 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.
Botulinum toxin injection in the 6 months before screening or planned use at any time during the study.
Treatment with any medication that could affect the evaluation of tremor within 2 weeks or 5 half-lives (whichever is longer) before screening or planned use at any time during the study.
Use of prescription of nonprescription drugs or other products known to be inducers of CYP3A4 that are known to decrease AUC by > 30%, which cannot be discontinued at least 4 weeks before Baseline, or planned use at any time during the study.
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.
Use of proton pump inhibitors and histamine-2 receptor antagonists, which cannot be discontinued at least 2 weeks before Baseline, or planned use at any time during the study (occasional use of antacids will be permitted, but antacids should be taken at least 4 hours apart from study intervention).
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, and alcohol.
Regular use of more than 3 units of alcohol per day.
Regular consumption of caffeine > 400 mg/day or > 4 cups of coffee per day.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph's Hospital and Medical Center - Barrow Neurological Institute	Phoenix	Arizona	United States	85013
2	Woodland Research Northwest	Rogers	Arkansas	United States	72758
3	Keck School of Medicine USC - Healthcare Consultation Center 2 (HCCII)	Los Angeles	California	United States	90033
4	SC3 Research - Beverly	Los Angeles	California	United States	90048
5	SC3 Research Pasadena	Pasadena	California	United States	91105
6	JEM Research Institute	Atlantis	Florida	United States	33462
7	Parkinson's Disease And Movement Disorder Center Of Boca Raton	Boca Raton	Florida	United States	33486
8	Innovative Research Of West Florida, Inc.	Clearwater	Florida	United States	33756
9	Infinity Clinical Research, Llc	Hollywood	Florida	United States	33024
10	Homestead Associates in Research, Inc.	Miami	Florida	United States	33032
11	USF Carol and Frank Morsani Center for Advanced Healthcare	Tampa	Florida	United States	33612
12	USF Parkinson's Disease and Movement Disorders Center	Tampa	Florida	United States	33613
13	Neurotrials Research, Inc.	Atlanta	Georgia	United States	30328
14	Hawaii Pacific Neuroscience	Honolulu	Hawaii	United States	96817
15	Northwestern Medical Group, Department of Neurology	Chicago	Illinois	United States	60611
16	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
17	University of Louisville, Movement Disorder Clinic	Louisville	Kentucky	United States	40202
18	South Shore Neurology Associates, Inc.	Patchogue	New York	United States	11772
19	Richmond Behavioral Associates	Staten Island	New York	United States	10312
20	Duke University Health System	Durham	North Carolina	United States	27705
21	Midwest Clinical Research	Dayton	Ohio	United States	45417
22	Booth Gardner Parkinson's Care Center	Kirkland	Washington	United States	98034
23	Vaught Neurological Services, PLLC	Crab Orchard	West Virginia	United States	25827
24	Curiositas-ad-sanum Beratungs-und Studien GmbH	Haag In Oberbayern	Bavaria	Germany	83527
25	NZOZ Neuromed M.iM.Nastaj Sp.	Lublin	Lubelskie	Poland	20-064