Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of NBI-827104 in Subjects With Essential Tremor

The main objective of this study is to evaluate the efficacy, safety, and tolerability of NBI-827104 in adults with essential tremor.

Study Overview

• Status: Completed
• Conditions: Essential Tremor
• Intervention / Treatment: Drug: NBI-827104; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • CL
    • Leiden, CL, Netherlands, 2333
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects, 18 to 75 years of age, inclusive at screening.
2. Body mass index (BMI) between 18 and 35 kg/m², inclusive, at screening.
3. Diagnosis of Essential Tremor (inclusive of Essential Tremor plus) as defined by the Movement Disorders Society Consensus Criteria for Tremor.
4. Confirmation of bilateral upper limb action tremor in the absence of overt dystonia, ataxia, or parkinsonism.
5. History of onset of tremor before 65 years of age.
6. 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.
7. 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.

Exclusion Criteria:

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.
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.
4. Have had prior magnetic resonance guided focused ultrasound or surgical intervention (e.g., deep brain stimulation, ablative thalamotomy or gamma knife thalamotomy).
5. Have a history or evidence of clinically significant cardiac conduction abnormality, uncontrolled bradyarrhythmia, heart failure, or long QT syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; In treatment period 1 participants will receive increasing doses of NBI-827104 for 28 days. After a 14-day washout period, participants will receive matching placebo for 28 days in treatment period 2.	Drug: NBI-827104; Capsules for oral administration; Drug: Placebo; Capsules matching NBI-827104 for oral administration
Experimental: Sequence 2; In treatment period 1 participants will receive matching placebo for 28 days. After a 14-day washout period, participants will receive increasing doses of NBI-827104 for 28 days in treatment period 2.	Drug: NBI-827104; Capsules for oral administration; Drug: Placebo; Capsules matching NBI-827104 for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline to Day 28 of Each Treatment Period in Amplitude at Peak Frequency of Postural Tremor	Baseline and Day 28 of each treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Score	Baseline up to Day 28 of each treatment period
Change from Baseline in TETRAS Activities of Daily Living (ADL) Score	Baseline up to Day 28 of each treatment period
Clinical Global Impression of Change (CGI-C)	Up to Day 28 of each treatment period

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Actual): May 25, 2022
• Study Completion (Actual): June 8, 2022

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Movement disorder; Tremor syndrome
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: NBI-827104-ET2016; 2020-006012-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No