Phase 1 Study to Investigate SIR2501 in Healthy Adult Participants

SIR2501-AU-101 is a two-part study containing parts 1 and 2 with Part 2 also containing three parts -Part 2A, 2B and 2C. Each study part and stage will involve unique participants. Part 1: Single ascending dose cohorts Part 1 evaluates the single-dose administration of SIR2501 or matched placebo (a tablet that looks the same as the study drug but has no active substances): 10mg, 30mg, 100mg, 300mg, 450mg and 600mg respectively in cohorts 1-6. Each cohort will consist of 8 participants who will each receive a single dose of investigational drug or matched placebo under fasted state (after an overnight fast of at least 10 hours prior to dosing), Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. Part 1 cohort 3 - Participants in Cohort 3 who complete the assigned SAD dosing will continue to remain in the clinical research unit to receive an additional assigned study intervention. The second dosing will occur after a washout period of 7 days from their first dose and upon consumption of a high-fat breakfast participants will receive the same assigned study intervention as a part of the Food Effect study. Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. Each of the SAD cohorts will be observed for 10 days after the Day 1 dosing. Safety, tolerability, and available PK data will be reviewed by the SRC for dose escalation and the actual doses to be administered may be adjusted accordingly. Part 2: Multiple dose cohorts Part 2 of the study consists of three parts. Part 2A: Multiple ascending dose cohorts Each cohort will consist of 10 participants who will each receive SIR2501 or matched placebo (a tablet that looks the same as the study drug but has no active substances): 30mg, 100mg, and 150mg respectively in cohorts 1-3 given by oral administration once daily for 10 days. Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. In Part 2A, after an observation and follow-up period of 20 days from the first day of dosing) and review of the safety, tolerability, and available PK data of all participants enrolled in the previous cohorts, the next actual dose cohort may be adjusted by the SRC. Part 2B: Drug-Drug Interaction Study Ten (10) healthy male and female adult volunteers will be enrolled to Part 2B of the study which aims to characterize the drug-drug interaction (DDI) potential of SIR2501 as a perpetrator of midazolam. For all participants: • Part 2B will be an open label design where each participant will receive SIR2501 and midazolam, . On Day 1,5 and 12 participants will each receive a single oral dose of midazolam 2 mg. • On Days 3 through 12, participants will each receive SIR2501 30mg given by oral administration once daily. Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. The actual SIR2501 dose including dose regimen for Part 2B and conditions for the administration of the study intervention will be determined by SRC after reviewing of the safety, tolerability, and available PK data of Part 1 and Part 2A. In Part 2B, after a dosing period of 12 days, participants will be observed and followed for safety for a further 10 days. Part 2C: China Cohort Part 2C of the study will be conducted in China. One cohort of 14 participants will each receive SIR2501 or matched placebo (a tablet that looks the same as the study drug but has no active substances): 100mg given by oral administration once daily for 10 days. Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff. After an observation and follow-up period of 20 days from the first day of dosing) participants will return to the clinical research unit for an End of Study Visit. Completion of this follow up visit by the last participant in Part 2C will mark the end of the active study. Part 2C will commence after the same dose level is reviewed by the SRC in Part 2A. however the planned 100mg dose for Part 2C maybe adjusted based on the outcome of SRC review of Part 2A. In all study parts adherence to the intervention will be done via supervised drug administration.