Clinical Trial: Cantharidin-induced Skin Blister for Testing Anti-inflammatory Effects of Macrolides

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Utility of the Cantharidin-induced Skin Blister Assay for Evaluation of Anti-inflammatory Effects of Macrolides in Healthy Volunteers

Brief Summary: The purpose of this study is to investigate the utility of the cantharidin-induced skin blister assay for evaluation of the anti-inflammatory effects of macrolides in healthy male volunteers.

Detailed Summary: The study will consist of 3 parts. Part A of the study will assess the feasibility of different cantharidin blister induction/sampling timepoints (challenge options) ranging from 16/16 hours to 48/48 hours, including the ability to evaluate the acute and resolving phase of acute inflammation. In Part A, 4 to 8 healthy male volunteers will be included. This will be followed by Part B (in up to 12 subjects), aimed to select the optimum challenge option based on the reproducibility of read-outs across two challenge sessions. This option will be applied in Part C in up to 24 subjects in order to evaluate the utility of the assay to demonstrate anti-inflammatory effects of a standard macrolide (azithromycin). Part C is designed as a double-blind, placebo-controlled, parallel group trial. Following the first cantharidin challenge and blister evaluation, subjects will be randomised in a 1:1 ratio to receive azithromycin or placebo. Skin blister induction and assessment will be repeated immediately after treatment completion and, potentially, approximately 3 weeks later. The inflammatory response to cantharidin and its modulation by azithromycin will be evaluated by total and differential cell counts in blister fluid, monocyte/macrophage phenotyping and the measurement of selected inflammation mediators in blister fluid and serum.
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Tolerability and safety of cantharidin-induced skin blister assay (as determined by AEs, pain intensity, systemic inflammatory response, healing time, and cosmetic appearance of blister area) [ Time Frame: Study duration ]
  • Total cell count, neutrophil count and monocyte/macrophage count in blister fluid. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Monocyte/macrophage phenotype in blister fluid. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]
  • Inflammatory mediators in blister fluid. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]
  • Markers of neutrophil activation. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]
  • Inflammatory mediators in serum. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]
  • PK parameters for azithromycin in plasma and whole blood following the last dose of azithromycin, as well as azithromycin concentration in PMNs and, if possible, in peripheral blood mononuclear cells at selected time points. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]
  • Exploratory Outcome: Additional inflammatory mediators of interest may be determined. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ]


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: December 3, 2009
Date Started: June 2009
Date Completion:
Last Updated: January 4, 2013
Last Verified: February 2011