A Phase 1 study to evaluate safety and tolerability of ES-481 in healthy volunteers
- Conditions
- EpilepsyNeurological - Epilepsy
- Registration Number
- ACTRN12619001591145
- Lead Sponsor
- ES Therapeutics LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 80
1.Written informed consent obtained
2.The subject is a healthy male or non-childbearing or breast-feeding female or male, 18 to 55 years of age, inclusive
3.Body weight 45 to 85 kg, and body mass index (BMI) 18 to 29.9 kg/m2, inclusive.
4.If female, is of non-childbearing potential with documentation provided by healthcare professional or post-menopausal [defined as at least 2 years at Screening without menses and with follicle stimulating hormone
5.If male, the subject agrees to sexual abstinence, or is surgically sterile or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from screening until 30 days after the last dose administration
6.The subject must have screening and Day -1 clinical laboratory test results within normal limits or, if abnormal, the results are not clinically significant as determined by the Principal Investigator
7.Healthy as determined by the Principal Investigator based on Medical History, Physical Examination, Normal Electrocardiograms (ECG) and Normal Electroencephalogram (EEG) recordings done during the screening visit
8.Creatinine clearance (CrCL) > 60 mL/min as estimated by the Cockcroft-Gault equation.
9.The subject is willing and able to comply with the study requirements
1.Unwillingness or inability to follow the procedures specified by the protocol.
2.History or family history of seizures.
3.Major surgery within 3 months or minor surgery within 1 month prior to screening
4.The subject has a positive serology test for human immunodeficiency virus, antibody, hepatitis C virus (HCV) antibody or hepatitis B surface antigen (HbsAg) at screening
5.The subject has a history of severe allergic or anaphylactic reactions
6.The subject has received a vaccine within 60 days prior to study drug administration
7.The subject has a history of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, excluding non-melanoma skin cancer
8.Potential for suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) during the screening visit
9.The subject has any clinically significant abnormality of the physical examination, ECG, EEG and protocol-defined clinical laboratory tests
10.Heart rate less than 40 or greater than 90 bpm; systolic blood pressure greater than 140 mm Hg; diastolic blood pressure greater than 90 mm Hg
11.A QTc(B) interval of greater than 430 msec (for males) and greater than 450 msec (for females) at Screening or Day -1
12.A history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS)
13.Participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives prior to the initiation of screening
14.The subject is suicidal or has a history of suicide attempt within the past 6 months as determined using the C-SSRS at screening.
15.The subject has/had a symptomatic, viral, bacterial or fungal infection within 1 month prior to study drug administration
16.Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements, and hormone replacement therapy within 7 days or 5 half-lives,
17.Regular use of tobacco or nicotine-containing products within 4 weeks prior to screening or urinary continine level indicative of active smoking at screening and/or at Day -1
18.Regular alcohol consumption,
19.History of drug abuse within the previous 2 years
20.The subject has a positive urine screen for drugs of abuse
21.History of CYP3A4 inducer use in the 1 month prior to Day -1 and continuing throughout the study
22.The subject has donated or lost greater than or equal to 450 mL of blood or received a transfusion of any blood or blood products within 90 days prior to screening, or has donated plasma within 7 days prior to Day -1
23.The subject has any other condition, which in the opinion of the Principal Investigator, precludes the subject’s participation in the study
24.Subjects unwilling to abstain from consuming grapefruit, grapefruit juice, or Seville oranges
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the pharmacokinetics of Oral ES-481[Blood for PK analysis will be collected at 8 AM (time 0 hours, prior to the oral dose of study drug /placebo and after an overnight fast, at 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours following the oral administration of study drug/placebo on Day 1 and at 36 and 48 (Day 2) hours after the oral administration of study drug/placebo on Day 2. <br><br>Below PK parameters will be assessed derived from plasma data.<br><br>Peak concentration in plasma (Cmax);<br>Time to peak concentration in plasma (Tmax);<br>Area under the plasma concentration-time curve (AUC) from time zero to last quantifiable concentration (AUClast);<br>AUC from time zero to infinity (AUCinf);<br>Apparent total body clearance from plasma (CL)<br>Apparent renal clearance from plasma (CLr);<br>Elimination half-life (t½);]
- Secondary Outcome Measures
Name Time Method