Clinical Study to Assess the Effects of SRT2104 and Prednisolone on Biomarkers in Blood in Healthy Volunteers
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; 0.25g SRT2104; Prednisolone; 0.5g SRT2104; 1g SRT2104; 2g SRT2104
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Matching placebo is supplied containing microcrystalline cellulose (Avicel PH 105). Placebo will be administered as eight matched capsules.; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 0.25g SRT2104 treatment visit will be administered as one SRT2104 capsule with 7 placebo capsules. Dosing will take place during one of the 6 treatment visits.; During the last treatment period, subjects will receive 30 mg open-label prednisolone.; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 0.5g SRT2104 treatment visit will be administered as two SRT2104 capsules with 6 placebo capsules. Dosing will take place during one of the 6 treatment visits.; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 1g SRT2104 treatment visit will be administered as four SRT2104 capsules with four placebo capsules. Dosing will take place during one of the 6 treatment visits.; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 2g SRT2104 treatment visit will be administered as eight SRT2104 capsules. Dosing will take place during one of the 6 treatment visits.
Intervention MeSH terms: Prednisolone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science