A Randomized, Double-Blind and Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SIR9900 after Oral Administrations in Healthy Adult Volunteers

Exclusion Criteria23

• Clinically significant haematological findings at screening.
• Abnormal findings indicating hepatic impairment, such as aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase greater than or equal to 1.5 times upper limit of normal (ULN), total bilirubin greater than ULN, albumin less than or equal to 3 g/dL, serum amylase or lipase greater than or equal to 1.5 times ULN at screening.
• Abnormal findings indicating renal impairment, such as creatinine greater than or equal to 1.5 times ULN, estimated glomerular filtration rate of 80 mL/minute/1.73m2 or less calculated by the Cockcroft-Gault formula, at screening.
• Clinically significant ECG findings including QTcF value greater than 450 ms for male or greater than 470 ms for female at screening/pre-dose day 1.
• Participants with a mean systolic blood pressure (SBP) of three measurements greater than 140 mmHg, or a mean diastolic blood pressure (DBP) of three measurements greater than 90 mmHg at screening. Blood pressure will be measured at sitting position at screening.
• Positive blood screen for human immunodeficiency virus (HIV), or hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) at screening or at any time during the screening period pre-dose.
• A history of seizure. However, a history of febrile seizure is allowed.
• Positive results of pregnancy test at screening or admission. Pregnant or breast feeding, lactating, or planning to become pregnant, breast feed or donate ova during the study and within 30 days after the study.
• A hospital admission or major surgery within 60 days prior to screening and/or planned surgery for the duration of the study and follow up period.
• Receipt of any other investigational drug product within 30 days or 5 half-lives of the other investigational drug (whichever is longer) prior to dosing.
• Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-V) substance use disorders and alcohol abuse within 12 months prior to screening and/or positive alcohol breath test at screening or admission.
• A positive result for drugs of abuse at screening or admission. One repeat test will be allowed if false positive is considered by the PI or designee.
• An unwillingness or inability to comply with food and beverage restrictions during study participation, including consumption of grapefruit (or pomelo or start fruit) or grapefruit juice, Seville oranges, Seville orange marmalade or other products containing grapefruit, pomelo, star fruit or Seville oranges within 7 days before dosing and until final discharge from the CRU.
• Donation or blood collection of more than 1 unit (approximately 450 mL) of blood (or blood products) or acute loss of blood during the 30 days prior to screening and/or planning to donate blood during the study and follow up period.
• For participants aged up to and including 64 years, use of prescription or non-prescription drugs (contraceptives are permitted), including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days, or 14 days if the drug is a potential index substrate for CYP450 isoform 1A2, or inhibitor/inducer of isoforms 3A4 or 2C8 enzymes, or 5 half- lives (whichever is longer) prior to dosing. These medications are also prohibited during the study except for those permitted, such as hormonal contraception.
• The following is not permitted prior to dosing: use of prescription medicines or other products that are potential index substrates for CYP450 isoform 1A2, or inhibitor/inducers of isoforms 3A4 or 2C8 enzymes within 14 days, or within 5 half-lives (whichever is longer).
• A history of suicide attempt in the past 12 months and/or judged by the Investigator as having a significant history of risk of suicide or homicide.
• Participant has a known or suspected hypersensitivity to SIR9900 and any components of the SIR9900 (or placebo) tablets.
• Participant who has lactose intolerance history.
• Participant has any other condition which makes the participant unsuitable for study participation in the opinion of the Investigator.
• Identified as a site employee of the Investigator or study centre, with direct involvement in the proposed study or other studies under the direction of the Investigator or study centre, and/or is an immediate family member (i.e., spouse, de facto, child) of site employees or Investigator.
• In addition to the general criteria above, potential adult participants (aged 18-64 years, inclusive) must not meet the following exclusion criterion:
• Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the Investigator or designee. Fully resolved childhood asthma and fully resected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with no reoccurrence, and all above with no medication taken is permitted.