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

NCT01026064 | Completed Phase 1

• 1 other identifier: 112593
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammation

Keywords

Macrolides; Inflammation; Azithromycin; Cantharidin induced skin blister model

Outcome Measures

Primary Outcomes (2)

• 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)

  Study duration

• Total cell count, neutrophil count and monocyte/macrophage count in blister fluid.

  Part C: end of treatment and potentially 3 weeks later

Secondary Outcomes (6)

• Monocyte/macrophage phenotype in blister fluid.

  Part C: end of treatment and potentially 3 weeks later

• Inflammatory mediators in blister fluid.

  Part C: end of treatment and potentially 3 weeks later

• Markers of neutrophil activation.

  Part C: end of treatment and potentially 3 weeks later

• Inflammatory mediators in serum.

  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.

  Part C: end of treatment and potentially 3 weeks later

Study Arms (2)

Part C- Azithromycin

EXPERIMENTAL

2 x 250 mg once daily over 3 days

Other: Cantharidin; Drug: Azithromycin

Part C- Placebo

PLACEBO COMPARATOR

Once daily over 3 days

Other: Cantharidin; Drug: Placebo

Interventions

Cantharidin OTHER

Cantharone topical liquid containing 0.7% cantharidin (blistering agent) is applied as 25 µL of 0.1% cantharone solution in acetone

Part C- Azithromycin; Part C- Placebo

Azithromycin DRUG

Zithromax (250 mg oral capsule).

Part C- Azithromycin

Placebo DRUG

Matching placebo

Part C- Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Publications (1)

• Pene Dumitrescu T, Anic-Milic T, Oreskovic K, Padovan J, Brouwer KL, Zuo P, Schmith VD. Development of a population pharmacokinetic model to describe azithromycin whole-blood and plasma concentrations over time in healthy subjects. Antimicrob Agents Chemother. 2013 Jul;57(7):3194-201. doi: 10.1128/AAC.02430-12. Epub 2013 Apr 29.

  PMID: 23629714 DERIVED

Related Links

• Results for study 112593 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Inflammation

Interventions

Cantharidin; Azithromycin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2009
• First Posted: December 4, 2009
• Study Start: June 4, 2009
• Primary Completion: November 27, 2009
• Study Completion: November 27, 2009
• Last Updated: July 25, 2017

Record last verified: 2017-07

Locations

GB (1)