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

Primary Purpose

Drug Resistant Epilepsy

Status

Recruiting

Phase

Phase 2

Locations

Australia

Study Type

Interventional

Intervention

ES-481

Placebo

Open-Label Extension Study

About this trial

This is an interventional treatment trial for Drug Resistant Epilepsy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
The subject is a male or female 18 to 70 years of age, inclusive
The subject must have a history of drug resistant epilepsy (as per the ILAE definition)
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
If VNS implanted, the stimulation setting must have been stable for at least four weeks prior to entering the 28-day screening period
The subject/legal guardian must be able to use the seizure dairy to record seizure throughout the study
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
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.
The subject is willing and able to comply with the study requirements

Exclusion 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 spermicideSurgical sterilization (hysterectomy, tubal ligation, or vasectomy)
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
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
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
Concomitant treatment with more than four (4) AEDs
Evidence for a potentially progressive neurologic disorder, such as a brain tumor, multiple sclerosis or dementia
Planned epilepsy surgery within six months of enrollment

Sites / Locations

Royal Brisbane and Women's HospitalRecruiting
Austin HospitalRecruiting
Alfred HealthRecruiting
Royal Melbourne HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Other

Arm Label

ES-481

Placebo

Open-Label Extension Study

Arm Description

Outcomes

Primary Outcome Measures

Seizure Frequency

A change in seizure frequency and activity assessed using a patient diary and continuous 24-hour EEG monitoring (composite outcome)

Secondary Outcome Measures

Hamilton Anxiety Rating Scale (HAM-A)

To assess for changes in the HAM-A

Hamilton Depression Rating Scale (HDRS)

To assess for changes in HDRS

Adverse Events

Monitoring clinically for adverse events for both CNS and Cardiovascular events

Laboratory Assessments - Hematology

Assess changes in hematology and chemistry laboratories by blood and serum assays and analysis

Laboratory Assessments - Chemistry

Assess changes in hematology and chemistry laboratories by blood and serum assays and analysis

Pharmacokinetics (PK) - Cmax

Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: Cmax

Pharmacokinetics (PK) - Tmax

Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: Tmax

Pharmacokinetics (PK) - AUC0-t

Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: AUC0-t

Pharmacokinetics (PK) - AUC0-inf. T1/2

Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: AUC0-inf. T1/2

Pharmacokinetics (PK) - CL/F

Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: CL/F

Pharmacokinetics (PK) - Vz/F

Plasma concentration-time data will be analyzed using non compartmental methods to determine the following PK parameter: Vz/F

Full Information

NCT ID

NCT04714996

First Posted

January 13, 2021

Last Updated

March 1, 2023

Sponsor

ES Therapeutics Australia Pty Ltd

1. Study Identification

Unique Protocol Identification Number

NCT04714996

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 30, 2020 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ES Therapeutics Australia Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Drug Resistant Epilepsy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Double-blind, placebo-controlled

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ES-481

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Title

Open-Label Extension Study

Arm Type

Other

Intervention Type

Drug

Intervention Name(s)

ES-481

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo on Week 1, Week 2, Week 3 and Week 4

Intervention Type

Drug

Intervention Name(s)

Open-Label Extension Study

Intervention Description

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).

Primary Outcome Measure Information:

Title

Seizure Frequency

Description

A change in seizure frequency and activity assessed using a patient diary and continuous 24-hour EEG monitoring (composite outcome)

Time Frame

Continuous and at Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70

Secondary Outcome Measure Information:

Title

Hamilton Anxiety Rating Scale (HAM-A)

Description

To assess for changes in the HAM-A

Time Frame

Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70

Title

Hamilton Depression Rating Scale (HDRS)

Description

To assess for changes in HDRS

Time Frame

Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70

Title

Adverse Events

Description

Monitoring clinically for adverse events for both CNS and Cardiovascular events

Time Frame