Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SKI-O-703 in Healthy Volunteers

Exclusion Criteria

• •History of any clinically significant disease or disorder that may put the subject at risk due to study participation, impact the subject's ability to participate in the study, or influence the study results.
• •History or presence of any gastrointestinal, hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• •Any surgical or medical condition that could possibly affect drug absorption, distribution, metabolism, and excretion (e.g. bariatric procedure).
• •Any medical/surgical procedure or trauma within 4 weeks prior to Day -1 as determined by the investigator.
• •Any clinically significant infection within 3 months prior to Day -1 as determined by the investigator.
• •Any of the following abnormal laboratory values upon repeat testing at Screening or Check-in (Day -1):
• •1. Hemoglobin \< lower limit of normal (LLN),
• •2. Platelet count \<LLN,
• •3. Absolute neutrophil count \<LLN or \>upper limit of normal (ULN),
• •4. Alanine aminotransferase or aspartate aminotransferase \>ULN,
• •5. Creatinine or blood urea nitrogen \>ULN, or
• •6. Any other clinically significant, in the opinion of the investigator, abnormal laboratory result.
• •Use of concomitant medications from 30 days or 5 half-lives prior to Day -1 (whichever is longer) through completion of the End of Study (EOS) visit, including prescription medications, nutritional supplements, herbal remedies, and over-the-counter medications (note: use of vitamin supplements should be stopped at least 7 days prior to Screening through completion of the EOS visit).
• •Receipt of any investigational medication within 30 days or 5 half-lives prior to Day -1, whichever is longer.
• •Use of tobacco or nicotine-containing products within 30 days prior to Day -1 through the EOS visit.
• •Use of CYP3A inducers and inhibitors (including St. John's wort) within 30 days prior to dosing.
• •Intake of food or beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g. kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), or charbroiled meats within 1 week prior to dosing.
• •History of substance abuse, drug addiction, or alcoholism.
• •Positive urine drug or urine alcohol test at Screening or Day -1 or unable to abstain from alcohol from 72 hours prior to study entry through the EOS visit.
• •Unable to abstain from caffeine- and xanthine-containing products from 72 hours prior to dosing through discharge from the study center.
• •Female subjects who are pregnant or lactating or have a positive pregnancy test at Screening or Day -1.
• •Positive result at Screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus antibody or positive result for hepatitis B core antibody with a negative result for hepatitis B surface antigen.
• •Recent (within the past 5 years) history of malignancy, except successfully treated basal cell carcinoma.
• •High blood pressure, defined as \>140 mm Hg systolic blood pressure or \>90 mm Hg diastolic blood pressure upon repeat confirmation (repeated up to 4 times).
• •Cardiac arrhythmias or clinically significant electrocardiogram (ECG) findings.
• •Corrected QT interval \>450 milliseconds or deemed clinically significant by the investigator (may be repeated for confirmation).
• •Family history of long QT syndrome.
• •Blood loss or blood donation \>450 mL within 4 weeks prior to study drug dosing.
• •History of sensitivity to drugs with chemical similarity to the study medication, its components, or the excipients.