Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04714996




Registration number
NCT04714996
Ethics application status
Date submitted
13/01/2021
Date registered
20/01/2021
Date last updated
2/03/2023

Titles & IDs
Public title
Efficacy, Safety and Pharmacokinetics of ES-481 in Adult Patients With Drug Resistant Epilepsy
Scientific 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
Secondary ID [1] 0 0
ES-481-C201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drug Resistant Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ES-481
Treatment: Drugs - Placebo
Treatment: Drugs - Open-Label Extension Study

Experimental: ES-481 -

Placebo Comparator: Placebo -

Other: Open-Label Extension Study -


Treatment: Drugs: 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

Treatment: Drugs: Placebo
Placebo on Week 1, Week 2, Week 3 and Week 4

Treatment: Drugs: 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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Seizure Frequency
Timepoint [1] 0 0
Continuous and at Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [1] 0 0
Hamilton Anxiety Rating Scale (HAM-A)
Timepoint [1] 0 0
Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [2] 0 0
Hamilton Depression Rating Scale (HDRS)
Timepoint [2] 0 0
Collected at screening, Days 1, 8, 15, 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [3] 0 0
Adverse Events
Timepoint [3] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [4] 0 0
Laboratory Assessments - Hematology
Timepoint [4] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [5] 0 0
Laboratory Assessments - Chemistry
Timepoint [5] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [6] 0 0
Pharmacokinetics (PK) - Cmax
Timepoint [6] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [7] 0 0
Pharmacokinetics (PK) - Tmax
Timepoint [7] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [8] 0 0
Pharmacokinetics (PK) - AUC0-t
Timepoint [8] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [9] 0 0
Pharmacokinetics (PK) - AUC0-inf. T1/2
Timepoint [9] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [10] 0 0
Pharmacokinetics (PK) - CL/F
Timepoint [10] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70
Secondary outcome [11] 0 0
Pharmacokinetics (PK) - Vz/F
Timepoint [11] 0 0
Collected at screening, Days 1, 8, 15 22, 28, 43, 50, 57, 64 and 70

Eligibility
Key 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
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2023
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Alfred Health - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment postcode(s) [2] 0 0
- Heidelberg
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
- Parkville

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ES Therapeutics Australia Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT04714996
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Terence O'Brien
Address 0 0
The Alfred
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Robert Niecestro, PhD
Address 0 0
Country 0 0
Phone 0 0
917-733-5311
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04714996