A Phase 1 study to evaluate safety and tolerability of ES-481 in healthy volunteers

Exclusion Criteria24

• Unwillingness or inability to follow the procedures specified by the protocol.
• History or family history of seizures.
• Major surgery within 3 months or minor surgery within 1 month prior to screening
• 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
• The subject has a history of severe allergic or anaphylactic reactions
• The subject has received a vaccine within 60 days prior to study drug administration
• 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
• Potential for suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) during the screening visit
• The subject has any clinically significant abnormality of the physical examination, ECG, EEG and protocol-defined clinical laboratory tests
• 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
• A QTc(B) interval of greater than 430 msec (for males) and greater than 450 msec (for females) at Screening or Day -1
• 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)
• 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
• The subject is suicidal or has a history of suicide attempt within the past 6 months as determined using the C-SSRS at screening.
• The subject has/had a symptomatic, viral, bacterial or fungal infection within 1 month prior to study drug administration
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements, and hormone replacement therapy within 7 days or 5 half-lives,
• 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
• Regular alcohol consumption,
• History of drug abuse within the previous 2 years
• The subject has a positive urine screen for drugs of abuse
• History of CYP3A4 inducer use in the 1 month prior to Day -1 and continuing throughout the study
• 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
• The subject has any other condition, which in the opinion of the Principal Investigator, precludes the subject’s participation in the study
• Subjects unwilling to abstain from consuming grapefruit, grapefruit juice, or Seville oranges