Phase 1 Study to Investigate SIR4156 in Healthy Adult and Elderly Participants

SIR4156-AU-101 is a two-part study containing parts 1 and 2 with Part 2 also containing 3 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 SIR4156 capsules or matched placebo (a capsule that looks the same as the study drug but has no active substances): 3 mg, 10 mg, 30 mg 100 mg, 300 mg, 600 mg, and 1000 mg respectively. 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). Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take the study drug under direct supervision of the clinical research unit staff. Part 1 Cohort 4: Participants in Cohort 4 who complete the assigned fasted SAD capsule dosing will continue to remain in the clinical research unit to receive two additional assigned study intervention. The second fasted dosing of SIR4156 tablet or matched placebo (a tablet that looks the same as the study drug but has no active substances) will occur after a washout period of at least 5 days from their first dose and under fasted state. The third dosing of SIR4156 tablet or matched placebo will occur after a washout period of 5-10 days from their second dose and upon consumption of a high-fat breakfast. The High-Fat breakfast will be as per the FDA Guidance, e.g. two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk). Participants will receive the same assigned study intervention as a part of the Food Effect and Relative Bioavailability study, Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under the direct supervision of the clinical research unit staff. Each of the SAD cohorts (except Cohort 4) will be observed for 11 days since the Day 1 dosing. Cohort 4 will be observed for 21 days (+5 days window) since the Day 1 dosing. Safety, tolerability, and available PK data will be reviewed by the Safety Review Committee (SRC) for dose escalation and the actual dose to be administered may be adjusted accordingly. Part 2: Multiple ascending dose cohorts Part 2 of the study consists of three parts. Part 2A: Multiple ascending dose cohorts in Healthy Volunteers First three cohorts will consist of 13 participants each and Cohort 4 will consist of 10 participants who will each receive SIR4156 tablets or matched placebo: 30 mg, 100 mg, 200 mg and 400 mg respectively given by oral administration twice daily for 28 days (except Day 28, where only 1 morning dose will be given). 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 38 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. These dose adjustments may involve either an increase or decrease in the planned dose or a change in the dosing frequency or a change in the fasting conditions (either fasted or fed). Part 2B: Elderly Cohort Part 2B consists of one cohort of 13 healthy elderly participants will each receive SIR4156 tablets or matched placebo; 200 mg given by oral administration twice daily for 28 days (except Day 28, where only 1 morning dose will be given). 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 2B will commence after the same dose level is reviewed by the SRC in Part 2A, however the planned 200 mg dose for Part 2B may be adjusted based on the outcome of SRC review of Part 2A. . In Part 2B, participants will be observed and followed for safety for 38 days (from the first day of dosing). Part 2C: China Cohort Part 2C of the study will be conducted in China. One cohort of 14 participants will receive SIR4156 or matched placebo; 400 mg given by oral administration twice daily for 28 days (except Day 28, where only 1 morning dose will be given). 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 38 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 400 mg dose for Part 2C may be 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.