Phase I Methodology Study to Validate the Cantharidin Blister Model in Healthy Volunteers

NCT01762787 | Completed Phase 1

• 1 other identifier: 114416
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to refine the cantharidin-induced blister assay in healthy volunteers as a model of inflammatory disease. The study is an experimental trial in healthy volunteers in two parts; Part 1 to optimise the model and Part 2 to validate using two anti-inflammatory treatments with different modes of action.

Conditions

Inflammation

Outcome Measures

Primary Outcomes (3)

• Blister volume of fluid

  Volume of fluid extracted from blisters induced by cantharidin application

  48 hours

• Cell population in blister fluid

  Flow cytometry performed on cells from blister fluid including measurement of some or all of the following parameters: CD45, CD16, CD14, cell viability, CD206, CD64 or CD84, apoptosis, total blister leukocytes (CD45+), monocytes (CD14+), neutrophils (CD16 high), monocyte/macrophage like cells (CD64+ or CD84+); subsets of these cells that are undergoing apoptosis; subsets of monocyte/macrophages

  48 hours

• Inflammatory mediators in blister fluid

  Inflammatory mediators in blister fluid, measured by immunoassay as primary endpoints may include (but will not be limited to): MPO, IL-10, IL-8, IL-6, IL-1β, TNF-α, LTB4.

  48 hours

Secondary Outcomes (5)

• Blister volume of fluid

  72 hours

• Cell population in blister fluid

  72 hours

• Inflammatory mediators in blister fluid

  72 hours

• Numbers and types of leukocytes in blood, and inflammatory mediators in plasma

  72 hours

• Blister healing/skin appearance at 6 week follow up

  6 weeks

Study Arms (3)

Effect of Aspirin

ACTIVE COMPARATOR

Positive control as previously used in the cantharidin blister experimental model of inflammation

Drug: Cantharidin solution; Drug: Aspirin; Drug: Placebo to aspirin

Effect of steroid - Prednisolone

EXPERIMENTAL

Prednisolone selected as steroids should provide the most robust positive control anti-inflammatory therapy

Drug: Cantharidin solution; Drug: Prednisolone; Drug: Placebo to prednisolone

Cantharidin exposure to optimise blister formation

EXPERIMENTAL

Cantharidin exposure to optimise blister formation

Drug: Cantharidin solution

Interventions

Cantharidin solution DRUG

5 microlitres of 0.025 to 0.5% topically on Day 1, 2 and 3

Cantharidin exposure to optimise blister formation; Effect of Aspirin; Effect of steroid - Prednisolone

Aspirin DRUG

300mg three times daily orally over a course of 4 days (starting Day -3) Part 2 only

Effect of Aspirin

Prednisolone DRUG

30mg orally once a day over a course of 4 days (starting Day -3) Part 2 only

Effect of steroid - Prednisolone

Placebo to aspirin DRUG

0mg three times daily orally over a course of 4 days (starting Day -3) Part 2 only

Effect of Aspirin

Placebo to prednisolone DRUG

0mg orally once a day over a course of 4 days (starting Day -3) Part 2 only

Effect of steroid - Prednisolone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, complete blood count and clinical chemistry. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
• Male between 18 and 55 years of age inclusive, at the time of signing the informed consent
• 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 or very dark 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 7 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 2 only
• History of previous peptic ulcers, gastritis, GI bleed or history of bleeding problems, e.g. haemorrhoids or spontaneous nose bleeds
• Subjects with a history of asthma
• For aspirin only: History of sensitivity to aspirin or non steroidal anti-inflammatory drugs or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor contraindicates their participation
• For prednisolone only: Subjects with systemic infections, hypersensitivity to any formulation ingredient, or ocular herpes simplex will be excluded. Those with, or a previous history of, tuberculosis, hypertension, congestive heart failure, liver failure, renal insufficiency, diabetes mellitus or in those with a family history of diabetes, osteoporosis, glaucoma or in those with a family history or glaucoma, subjects with a history of severe affective disorders and particularly those with a previous history of steroid-induced psychoses (in themselves or first degree relatives), epilepsy, peptic ulceration or previous steroid myopathy will also be excluded
• For prednisolone only: if a subject has not had chicken pox previously
• For prednisolone only: no live vaccines to be administered within 3 months of last prednisolone dose

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Links

• Results for study 114416 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Inflammation

Interventions

Aspirin; Prednisolone

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: January 8, 2013
• Study Start: August 17, 2010
• Primary Completion: January 14, 2011
• Study Completion: January 14, 2011
• Last Updated: June 28, 2017

Record last verified: 2017-06

Locations

GB (1)