Essential Tremor
Conditions
Keywords
JZP385, T-type calcium channels, Movement disorder, Tremor, Moderate to severe essential tremor
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.
Interventions
DRUGJZP385
JZP385 capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.
OTHERPlacebo
Placebo capsules will be administered orally (PO) once daily in the morning on an empty stomach for 12 weeks.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12 | 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). |
| Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12 | Change from baseline to 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 a total score ranging from 0 to 48. A higher score represents 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. |
| Percentage of Participants Who Improved (≥ 1-Point Improvement) 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 (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 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). 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 on the Essential Tremor Embarrassment Assessment (ETEA) Score A 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. 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 on the Essential Tremor Embarrassment Assessment (ETEA) Score B 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. 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 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. |
Countries
Germany, Poland, Spain, United States
Participant flow
Recruitment details
A total of 420 participants were randomized to treatment. These 420 participants are included in the Intent to Treat Analysis set (ITT). Of those 420 participants, only 416 received at least 1 dose of study intervention. Four participants did not receive any treatment. These 416 participants are included in the Safet Analysis Set
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will receive placebo from Day 1. | 104 |
| 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. | 105 |
| 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. | 104 |
| 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. | 107 |
| Total | 420 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 16 | 11 | 12 |
| Overall Study | Lack of Efficacy | 0 | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 3 | 0 |
| Overall Study | Non-compliance with study intervention | 0 | 0 | 0 | 2 |
| Overall Study | Other | 5 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 1 |
| Overall Study | Randomized by mistake | 0 | 0 | 3 | 2 |
| Overall Study | Sponsor request | 0 | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 7 | 4 | 8 |
Baseline characteristics
| Characteristic | Placebo | 10 Milligram (mg) JZP385 | 20 mg JZP385 | 30 mg JZP385 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 61 Participants | 54 Participants | 59 Participants | 59 Participants | 233 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 51 Participants | 45 Participants | 48 Participants | 187 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 10 Participants | 9 Participants | 11 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 95 Participants | 95 Participants | 96 Participants | 379 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 6 Participants | 9 Participants | 27 Participants |
| Race (NIH/OMB) White | 98 Participants | 96 Participants | 93 Participants | 92 Participants | 379 Participants |
| Sex: Female, Male Female | 41 Participants | 37 Participants | 33 Participants | 49 Participants | 160 Participants |
| Sex: Female, Male Male | 63 Participants | 68 Participants | 71 Participants | 58 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 104 | 0 / 104 | 0 / 103 | 0 / 105 |
| other Total, other adverse events | 20 / 104 | 35 / 104 | 35 / 103 | 46 / 105 |
| serious Total, serious adverse events | 3 / 104 | 3 / 104 | 4 / 103 | 4 / 105 |
Outcome results
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.
Time frame: Change from baseline to week 12
Population: The primary outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 TETRAS assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo | -6.3 score on a scale | Standard Deviation 6.22 |
| 10 Milligram (mg) JZP385 | Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo | -5.8 score on a scale | Standard Deviation 6.85 |
| 20 mg JZP385 | Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo | -6.7 score on a scale | Standard Deviation 6.88 |
| 30 mg JZP385 | Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo | -7.5 score on a scale | Standard Deviation 7.31 |
Secondary
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
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 ETEA assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score A as Summarized by Each Dose of JZP385 and Placebo | -0.6 score on a scale | Standard Deviation 2.84 |
| 10 Milligram (mg) JZP385 | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score A as Summarized by Each Dose of JZP385 and Placebo | -0.5 score on a scale | Standard Deviation 3.06 |
| 20 mg JZP385 | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score A as Summarized by Each Dose of JZP385 and Placebo | -0.6 score on a scale | Standard Deviation 3.6 |
| 30 mg JZP385 | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score A as Summarized by Each Dose of JZP385 and Placebo | -1.2 score on a scale | Standard Deviation 3.51 |
Secondary
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
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 ETEA assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score B as Summarized by Each Dose of JZP385 and Placebo | -4.2 score on a scale | Standard Deviation 12.87 |
| 10 Milligram (mg) JZP385 | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score B as Summarized by Each Dose of JZP385 and Placebo | -3.5 score on a scale | Standard Deviation 14.15 |
| 20 mg JZP385 | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score B as Summarized by Each Dose of JZP385 and Placebo | -4.6 score on a scale | Standard Deviation 14.42 |
| 30 mg JZP385 | Change From Baseline to Week 12 on the Essential Tremor Embarrassment Assessment (ETEA) Score B as Summarized by Each Dose of JZP385 and Placebo | -5.6 score on a scale | Standard Deviation 14.28 |
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). 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.
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 QUEST assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Physical Subscale Total Score | -11.0 score on a scale | Standard Deviation 17.65 |
| Placebo | 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 | Work and Finance Subscale Total Score | -5.8 score on a scale | Standard Deviation 16.44 |
| Placebo | 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 | Psychosocial Subscale Total Score | -6.8 score on a scale | Standard Deviation 14.93 |
| Placebo | 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 | Hobbies and Leisure Subscale Total Score | -1.1 score on a scale | Standard Deviation 29.35 |
| Placebo | 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 | Communication Subscale Total Score | -5.5 score on a scale | Standard Deviation 15.35 |
| 10 Milligram (mg) JZP385 | 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 | Hobbies and Leisure Subscale Total Score | -8.9 score on a scale | Standard Deviation 31.66 |
| 10 Milligram (mg) JZP385 | 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 | Physical Subscale Total Score | -5.1 score on a scale | Standard Deviation 17.6 |
| 10 Milligram (mg) JZP385 | 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 | Psychosocial Subscale Total Score | -2.9 score on a scale | Standard Deviation 16.57 |
| 10 Milligram (mg) JZP385 | 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 | Work and Finance Subscale Total Score | 1.0 score on a scale | Standard Deviation 17.26 |
| 10 Milligram (mg) JZP385 | 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 | Communication Subscale Total Score | -3.3 score on a scale | Standard Deviation 15.62 |
| 20 mg JZP385 | 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 | Hobbies and Leisure Subscale Total Score | -3.5 score on a scale | Standard Deviation 36.5 |
| 20 mg JZP385 | 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 | Communication Subscale Total Score | -3.5 score on a scale | Standard Deviation 14.67 |
| 20 mg JZP385 | 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 | Work and Finance Subscale Total Score | -6.1 score on a scale | Standard Deviation 15.61 |
| 20 mg JZP385 | 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 | Physical Subscale Total Score | -10.1 score on a scale | Standard Deviation 16.85 |
| 20 mg JZP385 | 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 | Psychosocial Subscale Total Score | -6.1 score on a scale | Standard Deviation 15.79 |
| 30 mg JZP385 | 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 | Physical Subscale Total Score | -13.4 score on a scale | Standard Deviation 20.24 |
| 30 mg JZP385 | 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 | Work and Finance Subscale Total Score | -6.7 score on a scale | Standard Deviation 15.11 |
| 30 mg JZP385 | 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 | Communication Subscale Total Score | -7.8 score on a scale | Standard Deviation 16.18 |
| 30 mg JZP385 | 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 | Hobbies and Leisure Subscale Total Score | -10.2 score on a scale | Standard Deviation 33.81 |
| 30 mg JZP385 | 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 | Psychosocial Subscale Total Score | -6.2 score on a scale | Standard Deviation 15.4 |
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 a total score ranging from 0 to 48. A higher score represents more severe ET.
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 TETRAS-ADL assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 on the TETRAS-ADL Subscale as Summarized by Each Dose of JZP385 and Placebo | -6.4 score on a scale | Standard Deviation 6.4 |
| 10 Milligram (mg) JZP385 | Change From Baseline to Week 12 on the TETRAS-ADL Subscale as Summarized by Each Dose of JZP385 and Placebo | -6.3 score on a scale | Standard Deviation 7.55 |
| 20 mg JZP385 | Change From Baseline to Week 12 on the TETRAS-ADL Subscale as Summarized by Each Dose of JZP385 and Placebo | -7.1 score on a scale | Standard Deviation 7.88 |
| 30 mg JZP385 | Change From Baseline to Week 12 on the TETRAS-ADL Subscale as Summarized by Each Dose of JZP385 and Placebo | -8.7 score on a scale | Standard Deviation 8.49 |
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.
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 TETRAS-PS subscale assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo | -5.4 score on a scale | Standard Deviation 5.73 |
| 10 Milligram (mg) JZP385 | Change From Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo | -5.3 score on a scale | Standard Deviation 6.57 |
| 20 mg JZP385 | Change From Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo | -5.1 score on a scale | Standard Deviation 6.15 |
| 30 mg JZP385 | Change From Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo | -5.5 score on a scale | Standard Deviation 6.27 |
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.
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 TETRAS Total assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo. | -11.8 score on a scale | Standard Deviation 10.18 |
| 10 Milligram (mg) JZP385 | Change From Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo. | -11.6 score on a scale | Standard Deviation 11.54 |
| 20 mg JZP385 | Change From Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo. | -12.3 score on a scale | Standard Deviation 11.95 |
| 30 mg JZP385 | Change From Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo. | -14.4 score on a scale | Standard Deviation 12.2 |
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.
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 Upper limb score on the TETRAS-PS assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | -2.3 score on a scale | Standard Deviation 2.68 |
| 10 Milligram (mg) JZP385 | 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 | -2.4 score on a scale | Standard Deviation 2.78 |
| 20 mg JZP385 | 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 | -2.0 score on a scale | Standard Deviation 2.61 |
| 30 mg JZP385 | 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 | -2.4 score on a scale | Standard Deviation 2.81 |
Secondary
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).
Time frame: Change from baseline to week 12
Population: Inferential analysis results were based on multiple imputations (impute missing values) on all study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S) | 50.0 Percentage of participants |
| 10 Milligram (mg) JZP385 | Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S) | 49.8 Percentage of participants |
| 20 mg JZP385 | Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S) | 55.7 Percentage of participants |
| 30 mg JZP385 | Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S) | 62.8 Percentage of participants |
Secondary
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).
Time frame: Week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 CGI-C assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12 | 22 Participants |
| 10 Milligram (mg) JZP385 | Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12 | 18 Participants |
| 20 mg JZP385 | Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12 | 19 Participants |
| 30 mg JZP385 | Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12 | 30 Participants |
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).
Time frame: Change from baseline to week 12
Population: The outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 PGI-C assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12 | 16 Participants |
| 10 Milligram (mg) JZP385 | Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12 | 11 Participants |
| 20 mg JZP385 | Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12 | 20 Participants |
| 30 mg JZP385 | Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12 | 32 Participants |