E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Essential tremor is a nervous system (neurological) disorder that causes involuntary and rhythmic shaking |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015496 |
E.1.2 | Term | Essential tremor |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of JZP385 to improve the functional impact of tremor when administered once daily for up to 12 weeks at fixed doses of 10, 20, and 30 mg/day. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of JZP385 to improve the clinician’s assessment of the ability to function due to ET when administered once daily for up to 12 weeks at fixed doses of 10, 20, and 30 mg/day.
To evaluate the efficacy of JZP385 to improve overall ET when administered once daily for up to 12 weeks at fixed doses of 10, 20, and 30 mg/day.
To evaluate the safety and tolerability of JZP385 administered once daily for up to 12 weeks at fixed doses of 10, 20, and 30 mg/day in the treatment of adult participants with ET. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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. 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. |
|
E.4 | Principal exclusion criteria |
1. Known history or current evidence of other medical or neurological conditions that may cause or explain the participant's tremor. 2. 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. Nicotine use disorder is excluded if it impacts tremor. 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 or 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 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 or histamine-2 receptor antagonists will be permitted, but antacids should be taken at least 4 hours before and 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Difference in the mean Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) composite outcome score(a) from Baseline to Week 12 between each dose of JZP385 and placebo.
(a) The TETRAS composite outcome score consists of the sum of modified items 1 to 11 of the TETRAS Activities of Daily Living (TETRAS-ADL) subscale and modified items 6 and 7 of the TETRAS Performance Subscale (TETRAS-PS).
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Efficacy -Difference in the proportion of participants who improved (≥ 1-point improvement) from Baseline to Week 12 on the CGI-S, between each dose of JZP385 and placebo -Proportion of participants reported as much improved at Week 12 relative to baseline on the: -Clinical Global Impression of Change (CGI-C) -Patient Global Impression of Change (PGI-C) -Change from Baseline to Week 12, as summarized by each dose of JZP385 and placebo, on the: -TETRAS-ADL -TETRAS-PS -Upper limb score (item 4) of the TETRAS-PS -TETRAS total score -Quality of Life in Essential Tremor (QUEST) -Essential Tremor Embarrassment Assessment (ETEA)
Safety The occurrence of and/or change in: -Treatment-emergent adverse events (TEAEs) -Safety laboratory assessments -Vital signs -12-lead electrocardiogram (ECG) -Columbia Suicide Severity Rating Scale (C-SSRS) -Physical exam
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Germany |
Poland |
Spain |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |