| Outcome Measures: |
Primary: To evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state., AEs and clinically significant abnormal laboratory values will be recorded based upon investigator observation and subject reporting through a subject diary. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.|To examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy smokers in a fed state., Forearm venous occlusion plethysmography will be performed on Days -1, 28, and 56 to assess vasomotor and fibrinolytic function. Pulse wave analysis and pulse wave velocity will be measured to assess arterial stiffness on Days -1, 28, and 56. | Secondary: To investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates)., Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 and will be used to measure platelet activation (platelet-monocyte aggregates).|To evaluate SRT2104 effects on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine)., Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 to evaluate platelet and monocyte surface markers, inflammatory markers, and markers of oxidative stress.|To characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy smokers in a fed state., Plasma samples will be collected on Days 1, 28, and 56 at 0h, 15min, 30min, 1, 2, 3, 4, 8, and 12hrs post-dose. Samples will also be collected 24 and 27 hrs post-dose on Days 2, 29, and 57. Also, pre-dose samples will be collected on Days 15 and 43.|To explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation., Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 and will be used to measure potential biomarkers of activity for glucose control.
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