Cantharidin-induced Skin Blister for Testing Anti-inflammatory Effects of Macrolides - Full Text View

Purpose

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.

Condition	Intervention	Phase
Inflammation	Other: Cantharidin Drug: Azithromycin Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	Utility of the Cantharidin-induced Skin Blister Assay for Evaluation of Anti-inflammatory Effects of Macrolides in Healthy Volunteers

Resource links provided by NLM:

Drug Information available for: Azithromycin Azithromycin dihydrate Azithromycin monohydrate

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
Total cell count, neutrophil count and monocyte/macrophage count in blister fluid. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Monocyte/macrophage phenotype in blister fluid. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ] [ Designated as safety issue: No ]
Inflammatory mediators in blister fluid. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ] [ Designated as safety issue: No ]
Markers of neutrophil activation. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ] [ Designated as safety issue: No ]
Inflammatory mediators in serum. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Exploratory Outcome: Additional inflammatory mediators of interest may be determined. [ Time Frame: Part C: end of treatment and potentially 3 weeks later ] [ Designated as safety issue: No ]

Enrollment:	44
Study Start Date:	June 2009
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part C- Azithromycin 2 x 250 mg once daily over 3 days	Other: Cantharidin Cantharone topical liquid containing 0.7% cantharidin (blistering agent) is applied as 25 µL of 0.1% cantharone solution in acetone Drug: Azithromycin Zithromax (250 mg oral capsule).
Placebo Comparator: Part C- Placebo Once daily over 3 days	Other: Cantharidin Cantharone topical liquid containing 0.7% cantharidin (blistering agent) is applied as 25 µL of 0.1% cantharone solution in acetone Drug: Placebo Matching placebo

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy as determined by a responsible and experienced physician.
Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.
The subject has a body weight of more than or equal to 50 kg and a BMI 18.5 to 30 kg/m2.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

Subjects with very fair skin type.
Presence on either forearm of tattoos, naevi, scars, keloids, hyperpigmentation, excessive hair or any skin abnormalities that may, in the opinion of the investigator, interfere with study assessments.
Subjects with a history of keloids, skin allergy, hypersensitivity or contact dermatitis, including previous reactions to dressings to be used in the study.
Subjects with a history of lymphangitis and/or lymphoedema.
Subjects with a history of HIV infection, hepatitis B or C.
A positive pre-study drug/alcohol screen.
Use of prescription or non-prescription drugs, including ergot derivatives e.g. dihydroergotamine (Dihydergot), vitamins, herbal and dietary supplements (including St John's Wort) within whichever is the longer period of 14 days or 5 half-lives (if known) prior to the first challenge day, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56-day period.

For part C only:

QTcB or QTcF >450 msec, based on average QTc value of triplicate ECGs obtained over a brief recording period, if the first measurement shows abnormal QTc value.
History of sensitivity to azithromycin, macrolide/ketolide antibiotics or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026064

Locations

United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01026064 History of Changes
Other Study ID Numbers:	112593
Study First Received:	December 3, 2009
Last Updated:	January 4, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:

Macrolides
Inflammation
Azithromycin
Cantharidin induced skin blister model

Additional relevant MeSH terms:

Blister
Inflammation
Skin Diseases, Vesiculobullous
Skin Diseases
Pathological Conditions, Anatomical
Pathologic Processes
Anti-Inflammatory Agents
Cantharidin

Azithromycin
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 16, 2013