Efficacy, Safety and Pharmacokinetics of ES-481 in Adult Patients With Drug Resistant Epilepsy

March 1, 2023 updated by: ES Therapeutics Australia Pty Ltd

A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of ES-481 in Adult Patients With Drug Resistant Epilepsy

This is a Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study with cross-over to Evaluate the Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult Patients with Drug Resistant Epilepsy

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • Queensland
      • Herston, Queensland, Australia
        • Recruiting
        • Royal Brisbane and Women's Hospital
        • Contact:
          • David Reutens
    • Victoria
      • Heidelberg, Victoria, Australia
        • Recruiting
        • Austin Hospital
        • Contact:
          • Saul Mullen
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Alfred Health
        • Contact:
          • Terence O'Brien
      • Parkville, Victoria, Australia
        • Recruiting
        • Royal Melbourne Hospital
        • Contact:
          • John Paul Nicolo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The subject/legal guardian must be able to understand and sign the Human Research Ethics Committee-approved written Informed Consent Form (ICF) and privacy language as per national regulations (e.g., HREC and TGA requirement in Australia) prior to any study-related procedures being performed
  2. The subject is a male or female 18 to 70 years of age, inclusive
  3. The subject must have a history of drug resistant epilepsy (as per the ILAE definition)
  4. The subject must be taking 1 to 4 antiepileptic drugs (AED) and must be on a stable dose of the AEDs for at least four (4) weeks prior to entering the 28-day screening period
  5. If VNS implanted, the stimulation setting must have been stable for at least four weeks prior to entering the 28-day screening period
  6. The subject/legal guardian must be able to use the seizure dairy to record seizure throughout the study

  7. The subject must experience at least four (4) countable seizures within a 28-day period.

    For continued enrollment into Treatment Period 1, each subject will be confirmed to have experienced at least four (4) countable seizures in the 28-day screening period

  8. The subject must have interictal epileptiform discharges and/or seizure with an average frequency of at least one (1) per hour on EEG recording.

    For continued enrollment into Treatment Period 1, this will be confirmed by a 24-hour EEG performed during the 28-day screening period.

  9. The subject is willing and able to comply with the study requirements

Exclusion Criteria:

  1. Unwilling or inability to follow the procedures specified by the protocol
  2. Pregnancy or breast feeding

  3. 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 spermicideSurgical sterilization (hysterectomy, tubal ligation, or vasectomy)

  4. Current treatment for another significant medical disorder, such as diabetes, or heart disease or an untreated disorder, that is discovered during the 28-day screening period and might interfere with the study in the opinion of the Principal Investigator
  5. An abnormality on clinical laboratory tests, physical examination, EEG or ECG that might increase the risks associated with trial participation or investigational product administration, such as hepatic enzyme elevation greater than twice normal and/or a GFR < 60 mL/min/1.73 m2
  6. History (within the month) of illicit drug use or alcohol dependence, and a commitment by the subject to not take the illicit drugs during the study
  7. Concomitant treatment with more than four (4) AEDs
  8. Evidence for a potentially progressive neurologic disorder, such as a brain tumor, multiple sclerosis or dementia
  9. Planned epilepsy surgery within six months of enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo
Placebo on Week 1, Week 2, Week 3 and Week 4
Experimental: ES-481
Drug: ES-481

Treatment Period Week 1 - 25 mg qd, Week 2 - 25 mg bid, Week 3 - 50 mg bid, Week 4 - 75 mg bid.

Step-down and Washout Period Day 1 - 125 mg, Day 2 - 100 mg, Day 3 - 75 mg, Day 4 - 50 mg, Day 5 - 50 mg, Day 6 - 25 mg, Day 7 - 25 mg, Days 8 to 14 - 0 mg
Other: Open-Label Extension Study
Drug: Open-Label Extension Study
Dosing will be at the discretion of the Investigator with a minimum dose of 25 mg/day (25 mg qd) to a maximum dose of 150 mg/day (75 mg bid).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Seizure Frequency
Time Frame: Continuous and at Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
A change in seizure frequency and activity assessed using a patient diary and continuous 24-hour EEG monitoring (composite outcome)
Continuous and at Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hamilton Anxiety Rating Scale (HAM-A)
Time Frame: Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
To assess for changes in the HAM-A
Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
Hamilton Depression Rating Scale (HDRS)
Time Frame: Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
To assess for changes in HDRS
Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
Adverse Events
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Monitoring clinically for adverse events for both CNS and Cardiovascular events
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Laboratory Assessments - Hematology
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Assess changes in hematology and chemistry laboratories by blood and serum assays and analysis
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Laboratory Assessments - Chemistry
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Assess changes in hematology and chemistry laboratories by blood and serum assays and analysis
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Pharmacokinetics (PK) - Cmax
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: Cmax
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Pharmacokinetics (PK) - Tmax
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: Tmax
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Pharmacokinetics (PK) - AUC0-t
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: AUC0-t
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Pharmacokinetics (PK) - AUC0-inf. T1/2
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: AUC0-inf. T1/2
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Pharmacokinetics (PK) - CL/F
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: CL/F
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Pharmacokinetics (PK) - Vz/F
Time Frame: Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: Vz/F
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ES Therapeutics Australia Pty Ltd

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Terence O'Brien, The Alfred

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 30, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 13, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ES-481-C201

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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