Acute Response Capsaicin Flare Study

Study Overview
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Brief Summary
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Prior to administering PF-04427429 to patients we wish to increase the understanding of functional effects associated with calcitonin gene related peptide (CGRP) pathways. This study will examine whether it is possible for a single dose of PF-04427429 to acutely attenuate a capsaicin induced flare response.

Detailed Description
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Proof of mechanism in healthy volunteers

Official Title
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A Double Blind, Randomized, Placebo-Controlled, Third-Party Open, Modified Cross-Over Study To Examine The Acute Effect Of PF-04427429 On Capsaicin Flare Response In Healthy Volunteers Using EMLA Cream As Positive Control

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-04427429
* Other: Capsaicin challenge
* Drug: Placebo
* Other: Capsaicin challenge
* Other: EMLA positive control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between the ages of 18 and 50 years inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. Skintype I-III with a distance from base of scaphoid to antecubital fossa >26cm on their forearms. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, genitourinary, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, symptomatic, seasonal allergies at time of dosing). Use of biologics including any live vaccines within 3 months prior to screening or prior treatment with an antibody in a previous clinical trial or treatment with an immunoglobulin in the past 6 months. 12-lead ECG demonstrating QTcF >450 msec at screening. Subjects with scars or tattoos on the forearms, or with evidence of sunburn, or excessive hairy volar forearms.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04427429<br> | Drug: PF-04427429<br>* Single dose IV infusion up to 300mg<br>Other: Capsaicin challenge<br>* Capsaicin challenge: 110 mg (0.075% capsaicin) to be applied at pre-dose and at 2h, 5h, 8h and 24h post-dose as well as 1 week and 4 weeks post final treatment period<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo IV infusion (saline) to be administered during two of the three treatment periods<br>Other: Capsaicin challenge<br>* Capsaicin challenge: 110 mg (0.075% capsaicin) to be applied at pre-dose and at 2h, 5h, 8h and 24h post-dose as well as 1 week and 4 weeks post final treatment period<br>|
| Active Comparator: EMLA<br> | Other: EMLA positive control<br>* 2g EMLA cream to be applied ONCE during study period 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean blood perfusion induced by capsaicin challenge, between 30 and 60 minutes post each administration of capsaicin |  | 7 weeks post first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events including dose site reactions, blood pressure, pulse rate, ECG, ADA and laboratory safety |  | 12 weeks post final dose | 
| Plasma concentrations of free PF-04427429 |  | 6 weekly following week 15 | 
| Plasma concentrations of free and total CGRP |  | 6 weekly following week 15 | 
| Mean blood perfusion induced by capsaicin challenge, between 40 and 60 minutes post each administration of capsaicin. |  | 7 weeks post first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy male volunteers, capsaicin challenge, safety, toleration