None listed
Conditions
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
Interventions
ES-481 will be administered as 25 mg oral gelatin capsules.
The starting dose, dose administration schedule and the number of capsules of study medication (ES-481 or Placebo) to be administered per week in each 28-day treatment periods (Periods 1 and 2) are shown on the table below.
Week 1: 25 mg daily: 1 x 25 mg gelatin capsule Days 1 to 7 in Treatment
Period 1 and Days 43 to 49 in Treatment Period 2
Week 2: 25 mg twice a day: 2 x 25 mg gelatin capsules Days 8 to 14 in Treatment Period 1 and
ES-481 will be administered as 25 mg oral gelatin capsules. The starting dose, dose administration schedule and the number of capsules of study medication (ES-481 or Placebo) to be administered per week in each 28-day treatment periods (Periods 1 and 2) are shown on the table below. Week 1: 25 mg daily: 1 x 25 mg gelatin capsule Days 1 to 7 in Treatment Period 1 and Days 43 to 49 in Treatment Period 2 Week 2: 25 mg twice a day: 2 x 25 mg gelatin capsules Days 8 to 14 in Treatment Period 1 and Days 50 to 56 in Treatment Period 2 Week 3: 50 mg twice a day: 4 x 25 mg gelatin capsules Days 15 to 21 in Treatment Period 1 and Days 57 to 63 in Treatment Period 2 Week 4: 75 mg twice a day: 6 x 25 mg gelatin capsules Days 22 to 28 in Treatment Period 1 and Days 64 to 70 in Treatment Period 2 In the 14-day step-down and washout period (following the two Treatment Periods), subjects will be washout of the medication as follows: Day 1: 125 mg: 3 x 25 mg capsules in the morning and 2 x 25 mg capsules in the evening. Day 2: 100 mg: 2 x 25 mg capsules in the morning and 2 x 25 mg capsules in the evening. Day 3: 75 mg: 2 x 25 mg capsules in the morning and 1 x 25 mg capsules in the evening. Day 4: 50 mg: 1 x 25 mg capsules in the morning and 1 x 25 mg capsules in the evening. Day 5:50 mg: 1 x 25 mg capsules in the morning and 1 x 25 mg capsules in the evening. Day 6: 25 mg: 1 x 25 mg gelatin capsule in the morning. Day 7: 25 mg: 1 x 25 mg gelatin capsule in the morning. Days 8 – 14: 0 mg: 7-day washout period. Drug accountability will be performed on a weekly basis. A 36-week open-label extension for subjects who successfully completed both treatment periods and in the opinion of the Principal Investigator demonstrated efficacy to study drug will be treated with maximum dose of 75 mg bid of ES-481
Sponsors
ES Therapeutics Australia Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
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 anti-epileptic 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 approximately one (1) per hour on EEG recording. For continued enrollment into Treatment Period 1, this will be confirmed by continuous 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. Pregnant 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: o Hormonal contraception (birth control pills, injected hormones or vaginal ring) o Intrauterine device o Barrier methods (condom or diaphragm) combined with spermicide o Surgical sterilization (hysterectomy, tubal ligation, or vasectomy) 4. Current treatment for another significant medical disorder, such as diabetes, 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 last month) of illicit drug use or alcohol dependence, and a commitment not to take 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
Outcome results
None listed