InflammationPhase 1NCT01026064
Cantharidin-induced Skin Blister for Testing Anti-inflammatory Effects of Macrolides
A Phase 1 study testing Cantharidin and Azithromycin in people with Inflammation, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Inflammation
- What is being tested?
- Cantharidin and Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 4 Jun 2009to 27 Nov 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: Utility of the Cantharidin-induced Skin Blister Assay for Evaluation of Anti-inflammatory Effects of Macrolides in Healthy Volunteers
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.
Read the 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.
- Conditions
- Inflammation
- Being tested
- Cantharidin, Azithromycin, Placebo
- Keywords
- Macrolides, Inflammation, Azithromycin, Cantharidin induced skin blister model
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CantharidinOther
Cantharone topical liquid containing 0.7% cantharidin (blistering agent) is applied as 25 µL of 0.1% cantharone solution in acetone
AzithromycinDrug
Zithromax (250 mg oral capsule).
PlaceboDrug
Matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Part C- Azithromycin | Experimental | 2 x 250 mg once daily over 3 days Receives: Other: Cantharidin; Drug: Azithromycin |
| Part C- Placebo | Placebo comparator | Once daily over 3 days Receives: Other: Cantharidin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Study duration
Total cell count, neutrophil count and monocyte/macrophage count in blister fluid.
Measured: Part C: end of treatment and potentially 3 weeks later
Secondary outcomes (6)
Monocyte/macrophage phenotype in blister fluid.
Measured: Part C: end of treatment and potentially 3 weeks later
Inflammatory mediators in blister fluid.
Measured: Part C: end of treatment and potentially 3 weeks later
Markers of neutrophil activation.
Measured: Part C: end of treatment and potentially 3 weeks later
Inflammatory mediators in serum.
Measured: 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.
Measured: Part C: end of treatment and potentially 3 weeks later
Exploratory Outcome: Additional inflammatory mediators of interest may be determined.
Measured: Part C: end of treatment and potentially 3 weeks later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2009 (estimated)
- Study start4 Jun 2009
- Primary completion27 Nov 2009
- Study completion27 Nov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01026064
- Sponsor's protocol ID
- 112593
- Status last verified
- Jul 2017
- First submitted
- 3 Dec 2009
- Last updated
- 25 Jul 2017
- Results posted
- No
Publications
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.
PubMed 23629714
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Utility of the Cantharidin-induced Skin Blister Assay for Evaluation of Anti-inflammatory Effects of Macrolides in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01026064
- Acronym / sponsor ID
- 112593
- Conditions
- Inflammation
- Keywords
- Macrolides, Inflammation, Azithromycin, Cantharidin induced skin blister model
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 4 Jun 2009 (actual)
- Primary completion
- 27 Nov 2009 (actual)
- Study completion
- 27 Nov 2009 (actual)
- First posted
- 4 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part C- Azithromycin | Experimental | Other: Cantharidin, Drug: Azithromycin2 x 250 mg once daily over 3 days |
| Part C- Placebo | Placebo comparator | Other: Cantharidin, Drug: PlaceboOnce daily over 3 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CantharidinCantharone topical liquid containing 0.7% cantharidin (blistering agent) is applied as 25 µL of 0.1% cantharone solution in acetone | Other | Part C- Azithromycin, Part C- Placebo |
| AzithromycinZithromax (250 mg oral capsule). | Drug | Part C- Azithromycin |
| PlaceboMatching placebo | Drug | Part C- Placebo |
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
6 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2017.
- Derived from this study: PubMed 23629714Pene 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.
- Results for study 112593 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cantharidin and Azithromycin in people with Inflammation, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01026064, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2017.