This is a prospective, single center, non-therapeutic clinical study of SRT2104 administered orally as 250 mg capsules. Randomized, double-blind study to evaluate and compare the sensitivity of systemic biomarkers, such as ex-vivo LPS-induced TNF-alpha, IL-6, IL-8, and IL-1beta, to treatment with four-single oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, and 2000 mg), prednisolone (30 mg), and placebo in healthy adult volunteers. Twenty (20) subjects (males and females of non-childbearing potential) aged 18-60, who fulfill the inclusion/exclusion criteria, will be enrolled in this study to achieve a minimum of 15 evaluable subjects. Each subject will participate in 6 treatment periods. For each treatment period subjects will fast for at least 10 hours overnight. After pre-dosing procedures, subjects will consume a standard, non-high-fat (approximately 650 kcal with approximately 30% of calories derived from fat) meal 15-30 minutes prior to receiving test material. During the first five treatment periods, subjects will receive a single dose of SRT2104 or matched placebo; during the last treatment period, subjects will receive 30 mg open-label prednisolone. Assessments will be performed until 24 hours post dose in each treatment period.~Subjects will be asked to sign the informed consent form(s) at the screening visit. If eligible and willing to participate, subjects will enter into the study. Subjects will be required to attend the research unit in a fasted state (at least 10 hours without food) on six separate occasions (treatment visits) during the study. There will be at least a 7-day washout period between treatment visits.~During the first five treatment visits, subjects will receive one of the following five treatments:~A. 250 mg SRT2104 administered as eight oral capsules (one active SRT2104 250 mg capsule + seven placebo capsules) B. 500 mg SRT2104 administered as eight oral capsules (two active SRT2104 250 mg capsules + six placebo capsules) C. 1000 mg SRT2104 administered as eight oral capsules (four active SRT2104 250 mg capsules + four placebo capsules) D. 2000 mg SRT2104 administered as eight oral capsules (eight active SRT2104 250 mg capsules + zero placebo capsules) E. Eight placebo capsules~During the last treatment visit, subjects will receive 30 mg of open-label prednisolone tablets.~Subjects will be required to return to the research unit 24 hours after dosing in each treatment period in order to gather the required PK and PD samples. Subjects will be asked to return to the study center for an End of Study safety assessment 7 to 10 days after the last treatment visit.
The primary purpose of this study is to assess the pharmacodynamic effect of single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, 2000 mg) and prednisolone as measured by levels of ex vivo LPS-induced TNF-alpha production in whole blood of healthy adult subjects.~The secondary purposes of this study are to assess the pharmacodynamic effects of single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, 2000 mg) and prednisolone (30mg) as measured by levels of IL-6, IL-8 and IL-1beta in whole blood of healthy adult subjects. In addition, plasma pharmacokinetics, safety and tolerability of SRT2104 following the administration of single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, 2000 mg) in healthy adult subjects will also be assessed. As exploratory endpoints, transcriptomic profiles, biomarker exploration, and relationships between plasma SRT2104 levels and ex vivo LPS-induced TNF-alpha production may also be examined.