Safety and efficacy of an investigational drug for essential tremor
- Conditions
- Essential tremorMedDRA version: 21.1Level: PTClassification code 10015496Term: Essential tremorSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2020-006012-24-NL
- Lead Sponsor
- eurocrine Biosciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 28
1. Signed informed consent prior to any study-mandated procedure.
2. Male or female subjects, 18 to 75 years of age, inclusive at screening.
3. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, at screening.
4. Diagnosis of Essential Tremor (inclusive of Essential Tremor plus) as defined by the Movement Disorders Society Consensus Criteria for Tremor.
5. Confirmation of bilateral upper limb action tremor in the absence of overt dystonia, ataxia, or parkinsonism by an independent rating based on the video recorded at screening of the standardized exam following the TETRAS Performance Subscale.
6. History of onset of tremor before 65 years of age.
7. Tremor Performance score of =2 on at least 2 of the 6 upper limb manoeuvres (Item 4) on the TETRAS Performance Subscale and a total TETRAS Performance score =15 at screening (investigator and independent video rating).
8. All women of childbearing potential and all males must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study drug.
9. Has the ability to communicate well with the Investigator in the Dutch or English language and is willing to comply with the study procedures and restrictions.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14
1. Evidence of any acute (at screening or prior to first dose) or chronic disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs [systolic and diastolic blood pressure, pulse rate, body temperature] and 12-lead ECG). For example, neurological conditions other than ET [plus] like cognitive impairment or myasthenia gravis, uncontrolled psychiatric disorders or malignancy. Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance.
2. Have direct or indirect trauma to the nervous system within 3 months preceding the onset of tremor.
3. Have known history of other medical or neurological conditions that may cause or explain subject's tremor, including, but not limited to: Parkinson's disease, dystonia, cerebellar disease other than ET, traumatic brain injury, alcohol abuse or withdrawal, mercury poisoning, hyperthyroidism, pheochromocytoma, head trauma or cerebrovascular disease (within 3 months prior to the onset of ET), multiple sclerosis, and family history of Fragile X syndrome.
4. Have had prior magnetic resonance guided focused ultrasound or surgical intervention (e.g., deep brain stimulation, ablative thalamotomy or gamma knife thalamotomy).
5. Clinically significant impaired balance or at increased risk for falls, including the inability to ambulate safely unaided.
11. Are currently taking any of the prohibitive medications listed in the protocol Appendix 2. Subjects who have received these medications in the past, must have been off them for at least 30 days prior to first dose. Stable dosage of 1 other anti-tremor medication, excluding primidone, is allowed from 30 days before screening if anticipated to be stable from screening until end of study. If on primidone, subjects are allowed to extend the screening period by 2 weeks (for a total of 6 weeks) and discontinue primidone under the supervision of the investigator.
22. Have a significant risk of suicidal or violent behaviour. Subjects will be excluded if they have:
• Any lifetime history of suicidal behaviour or
• Any lifetime history of suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: - To evaluate efficacy of NBI-827104 in subjects with Essential Tremor (ET)<br>- To evaluate safety and tolerability of NBI-827104 in subjects with ET<br>;Secondary Objective: -To evaluate pharmacokinetics of NBI-827104 and metabolite (if quantified) for each treatment in subjects with ET<br>;Primary end point(s): 1.<br>• Change from baseline in amplitude at peak frequency (mg2/Hz) of postural tremor (extended hand position) in the more severely affected hand measured using laboratory tremography at the last day of each treatment period<br><br><br>2.<br>• Incidence of: <br>o Adverse Events (AEs) <br>o Suicidality measured by Columbia Suicide Severity Rating Scale (C-SSRS)<br>• Absolute values and changes from baseline values in: <br>o clinical laboratory tests (haematology, chemistry)<br>o vital signs<br>o 12-lead ECGs ;Timepoint(s) of evaluation of this end point: 1. Baseline till last day of each treatment period<br>2. Baseline to follow up
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: 1. Baseline till end of treatment. <br>2. 0h (dosing) till 24h post dose (for each treatment period);Secondary end point(s): 1.<br>Change from baseline by timepoint in the following:<br>• The Essential Tremor Rating Assessment Scale (TETRAS) Performance score (independent blinded video rating)<br>• TETRAS ADL score<br>• Clinical Global Impression of Change (CGI-C).<br><br>2.<br>• Plasma NBI-872104 and metabolite concentrations at each sampling timepoint<br>• PK parameters for NBI-827104 and metabolites will be determined by standard non-compartmental analysis of the plasma concentration-time data, including but not limited to:<br>o AUCtau, CL/F, Cmax, Ctrough, lambdaz, t1/2, tmax<br>o Dose-normalized PK parameters: AUCtau, Cmax, Ctrough<br>