Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult Patients With Essential Tremors

NCT05234762 | Unknown Phase 2

• 1 other identifier: ES-481-C203
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This Pilot Phase 2A study will investigate the safety, tolerability, and pharmacokinetics (PK) of ES-481 in adult patients with essential tremor.

Conditions

Tremor, Essential

Outcome Measures

Primary Outcomes (31)

• Performance Subscale of The Essential Tremor Rating Assessment Scale (TETRAS-P)

  To evaluate postural and kinetic tremor of body parts affected by ET, with emphasis on upper extremity tremor. Items are scored from 0 to 4, with 4 representing the highest severity.

  Collected during 6 days throughout the study, scores to be combined.

• Number of participants with abnormal laboratory test results

  Collection of: Total protein

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Sodium

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Potassium

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Calcium

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Chloride

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Albumin

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Glucose

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Blood urea nitrogen (BUN)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Creatinine

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Carbon dioxide (CO2)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Uric acid

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Total bilirubin

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Alkaline phosphatase (AP)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: AST

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: ALT

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Gamma-glutamyl transpeptidase (GGT)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Lactate dehydrogenase (LDH)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Creatine phosphokinase (CPK)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Hemoglobin

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Hematocrit

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Red blood cell (RBC) count

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: White blood cell (WBC) count with differential

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Mean corpuscular volume (MCV)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Mean corpuscular hemoglobin (MCH)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Mean corpuscular hemoglobin (MCHC)

  Through study completion, an average of 78 days.

• Number of participants with abnormal laboratory test results

  Collection of: Absolute platelet count

  Through study completion, an average of 78 days.

• Safety assessments through collection of serious adverse events

  Collection of Serious Adverse Events

  Through study completion, an average of 78 days.

• Safety assessments through collection of adverse events

  Collection of Adverse Events

  Through study completion, an average of 78 days.

• Safety assessments through collection of treatment emergent adverse events

  Collection of Treatment Emergent Adverse Events

  Through study completion, an average of 78 days.

• Plama samples for PK

  Will be collected to assess the plasma concentration of ES-481 during the 28-day treatment periods from both ES-481 and Placebo subjects to estimate the PK of ES-481 After the study blind is broken, only the samples from subjects who took ES-481 will be analyzed.

  Will be collected on Days 1, 22, 29, 44, 65, and 72

Secondary Outcomes (2)

• Activity of Daily Living

  Will be completed on Days 1 (baseline and prior to administration of study medication on Day 1 in Treatment Period 1), and Days 22, 29, 44 (baseline and prior to administration of study medication on Day 44 in Treatment Period 2), 65, and 72

• Subject Global Impression of Change Scale (SGIC)

  Will be completed on Days 1 (baseline and prior to administration of study medication on Day 1 in Treatment Period 1), and Days 22, 29, 44 (baseline and prior to administration of study medication on Day 44 in Treatment Period 2), 65, and 72

Study Arms (2)

ES-481

EXPERIMENTAL

Week 1 - 25 mg qd (2 x 25 mg capsule in the mornings Days 1 to 7 in Treatment Period 1 and Days 44 to 50 in Treatment Period 2) Week 2 - 50 mg bid (2 x 25 mg capsule in the mornings and 2 x 25 mg capsules in the evening on Days 8 to 14 in Treatment Period 1 and Days 51 to 57 in Treatment Period 2) Week 3 - 75 mg bid (2 x 25 mg capsule in the mornings and 2 x 25 mg capsules in the evening on Days 15 to 21 in Treatment Period 1 and Days 58 to 64 in Treatment Period 2) Week 4 - 75 mg bid (2 x 25 mg capsule in the mornings and 2 x 25 mg capsules in the evening on Days 22 to 28 in Treatment Period 1 and Days 65 to 71 in Treatment Period 2)

Drug: ES-481

Placebo

PLACEBO COMPARATOR

Placebo will be dosed at the same quantity and frequency as ES-481 just as Placebo HPMC capsules

Other: Placebo

Interventions

ES-481 DRUG

Dose escalation during two Treatment Periods

ES-481

Placebo OTHER

Placebo dosed at same dosing as ES-481

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written and Signed Informed Consent
• Age 18 to 75 years old
• The Subject must have Essential Tremor (ET). ET is defined as at least 1 upper extremity with a tremor score ≥ 1.5 in forward posture, wing beating posture, or finger-to-nose movement using the Performance subscale of The Essential Tremor Rating Assessment Scale (as per by the Tremor Investigation Group criteria).
• Subject has a diagnosis of essential tremor, as defined by all the following criteria: (a) isolated tremor syndrome consisting of bilateral upper limb action; (b) at least three years duration; (c) with or without tremor in other location (e.g., head, voice, or lower limb).
• The Subject must be on stable dose of anti-tremor medication in the four (4) weeks prior to screening and must willing to maintain their current dose for the duration of the study.
• The Subject had no prior surgery for tremor.
• The Subject had no botulinum injection for at least six (6) months prior to -screening.
• The Subject does not have a significant imbalance or risk fall.
• The Subject has not previously taken perampanel.

You may not qualify if:

• Subjects will be excluded from 7-day screening period or study enrollment into the Treatment Period 1, if they meet any of the following criteria:
• Unwilling or inability to follow the procedures specified by the protocol
• Pregnancy or breast feeding
• Women of child-bearing potential and men who are unable or unwilling to take adequate contraceptive precautions, including one of the following:
• Hormonal contraception (birth control pills, injected hormones, or vaginal ring)
• Intrauterine device
• Barrier methods (condom or diaphragm) combined with spermicide
• Surgical sterilization (hysterectomy, tubal ligation, or vasectomy)
• History (within the last year) of illicit drug use or alcohol dependence or a positive screen for alcohol on the Day 1 visit, or a positive screen for drugs of abuse at Screening or at the Day 1 visit
• Subject is unwilling or unable to refrain from alcohol 24 hours before and during clinical trial visits, or regular use of alcohol that would preclude abstinence from alcohol for time periods around visits.
• Subject has a history of substance use disorder consistent with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, in the opinion of the Principal Investigator,
• Concomitant treatment with more than three drugs to treat essential tremors
• Subject has had recent exposure (14 days prior to Day 1) to tremorgenic drugs.
• Subject has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
• Subject has a history or clinical evidence of other medical, neurological, or psychiatric conditions that may explain or cause tremors, including but not limited to Parkinson's disease, Huntington's disease, cerebellar disease (including spinocerebellar ataxias, primary dystonia, Fragile X Tremor/Ataxia syndrome or Family history of Fragile X syndrome, traumatic brain injury, psychogenic tremor, alcohol or benzodiazepines abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism or unstable treatment of hypothyroidism or medication, food, or supplement induced movement disorder (e.g., tremor related to beta agonists or caffeine), or other medical, neurological or psychiatric condition that may explain or cause tremors.

Sponsors & Collaborators

• ES Therapeutics Australia Pty Ltd: lead

Study Sites (1)

Clinique Neuro-Levis

Lévis, Quebec, Canada

RECRUITING

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Robert Niecestro, PhD

CONTACT

+1-917-733-5311; rniecestro@estherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2021
• First Posted: February 10, 2022
• Study Start: November 21, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 2, 2023

Record last verified: 2023-03

Locations

CA (1)