A Phase 1 randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability. and pharmacokinetics of single ascending doses and multiple ascending doses of SION-451 in healthy participants - Part C

Exclusion Criteria20

• Participants who meet any of the following criteria must be excluded from the study:
• Participant has clinically significant. in the opinion of the investigator, current or recurrent illness, such as cardiovascular (including but not limited to known structural cardiac abnormalities, family history of long QT syndrome, or cardiac syncope or recurrent. idiopathic syncope), neurologic, pulmonary, hepatic, renal. metabolic, gastrointestinal. urologic, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality which may affect safety or clinical laboratory evaluations.
• Participant has a history of malignancy, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of recurrence for at least 1 year.
• Participant has clinically significant abnormalities, in the opinion of the investigator, on ECG, physical examination, or vital sign assessment at Screening or Day -1.
• Participant has any single reading of QTcF >470 ms (females) or >450 ms (males) at Screening or Day -1.
• Chronic or habitual alcohol (>10 standard drinks per week) or tobacco (>10 cigarettes per week) use or use of recreational drugs (>1 use per month). The Investigator may exclude a participant with lower levels of alcohol, tobacco, or recreational drug use based on discretion and the pattern or history of use.
• Participant is positive for drug screen at Screening or Day -1. Of note, the drug screen does not include cannabis, cotinine or alcohol testing at Screening but does include this testing at study Check-in (Day -1).
• Participant has taken any prescription or over the counter medications within 14 days (or 5 half-lives of the medication, whichever is longer) prior to dosing or requires the use of these medications during the study, including herbal or homeopathic preparations excluding prophylactic doses of vitamin/mineral supplements and occasional paracetamol or ibuprofen, which are allowed.
• Participant has clinically significant abnormalities, in the opinion of the Investigator, at Screening or Day -1 on safety laboratory tests including serum chemistry, haematology, coagulation tests, and urinalysis.
• a. Participant must have an estimated glomerular filtration rate >90 ml/min/ 1.73 m2 using the CKD-EPI 2021 formula and based on individual body surface area at Screening and Day -1.
• b. Participant must have ALT, AST, alkaline phosphatase, and direct bilirubin less than or equal to the ULN at Screening and Day -1.
• , Participant has a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening. Healthy volunteers who have no evidence of cirrhosis and have completed a curative intent regimen for HCV, with a negative HCV polymerase chain reaction (PCR) test, will not be excluded.
• Participant has used any medication listed on the Flockhart table that is a substrate, inhibitor, or inducer of CYP3A4, or a substrate of CYP1A2 (with the exception of caffeine), CYP2B6, CYP2C8, CYP2C19 or CYP2D6 within 28 days or 10 half-lives (whichever is longer) prior to the planned first study drug administration. Additionally, participants must not have consumed other substances known to be potent inhibitors or inducers of CYP450 such as Seville orange, grapefruit or cranberry juice-containing products and herbal supplements such as St. John's Wort within 14 days before the planned first study drug administration.
• Participant has used any other prescription or over-the-counter medication that the Investigator judges is likely to interfere with the study or pose an additional risk in participating, within 14 days or 5 half-lives (whichever is longer) or has received any vaccinations within 14 days prior to the planned first study drug administration.
• Participant has received an investigational product within 30 days or 5 half-lives (whichever is longer) of the first study drug administration or will start any other investigational product before the planned End of Study Telephone Contact visit.
• Participant has been treated with an investigational device within 30 days prior to first study drug administration or will start an investigational device study before the planned End of Study Telephone Contact visit.
• Participant has donated or lost greater than 400 ml blood (or plasma) within the last 6 weeks preceding the first study drug administration.
• Participant has known or suspected intolerance or hypersensitivity to the investigational product, or any of the stated ingredients (including OraBlend and hypromellose polymer).
• Females who are breastfeeding or planning to breastfeed within go days of the End of Study Visit.
• Participant has an inability to follow a standardised meal schedule and diet or inability to fast. as required during the study.