None listed
Conditions
Brief summary
This is a first-in-human, Phase 1 single center, open-label, randomized single ascending dose study of ES-481 to evaluate the PK, safety and tolerability of ES-481 in healthy subjects on a fixed dose.
Interventions
Oral gelatin capsule of ES-481 will be administered in total 10 Cohorts as below.
Cohort 1: total dose 3 mg; 1 capsule of 3 mg ES-481
Cohort 2: total dose 6 mg; 2 capsule of 3 mg ES-481
Cohort 3: total dose 12 mg; 4 capsule of 3 mg ES-481
Cohort 4: total dose 25 mg; 1 capsule of 25 mg ES-481
Cohort 5: total dose 37 mg; 1 capsule of 25 mg ES-481 + 4 capsules of 3 mg ES-481
Cohort 6: total dose 50 mg; 2 capsule of 25 mg ES-481
Cohort 7: total dose 62 mg; 2 capsule of 25 mg ES-481 + 4 capsules
Oral gelatin capsule of ES-481 will be administered in total 10 Cohorts as below. Cohort 1: total dose 3 mg; 1 capsule of 3 mg ES-481 Cohort 2: total dose 6 mg; 2 capsule of 3 mg ES-481 Cohort 3: total dose 12 mg; 4 capsule of 3 mg ES-481 Cohort 4: total dose 25 mg; 1 capsule of 25 mg ES-481 Cohort 5: total dose 37 mg; 1 capsule of 25 mg ES-481 + 4 capsules of 3 mg ES-481 Cohort 6: total dose 50 mg; 2 capsule of 25 mg ES-481 Cohort 7: total dose 62 mg; 2 capsule of 25 mg ES-481 + 4 capsules of 3 mg ES-481 Cohort 8: total dose 75 mg; 3 capsule of 25 mg ES-481 Cohort 9: total dose 87 mg; 3 capsule of 25 mg ES-481 + 4 capsules of 3 mg ES-481 Cohort 10: total dose 100 mg; 4 capsule of 25 mg ES-481 Cohorts will be mutually exclusive.
Sponsors
ES Therapeutics LLC
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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
Exclusion criteria
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
Outcome results
None listed