Effect Of PF-06305591 On Capsaicin And Capsaicin/Heat-Induced Neurogenic Flare

Study Overview
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Brief Summary
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The purpose of this study is to examine the effect of PF-06305591 on capsaicin and capsaicin/heat-induced neurogenic flare.

Official Title
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A Double Blind, Randomized, Placebo-Controlled, Third-Party Open, Cross-Over Study To Examine The Effect Of PF-06305591 On Capsaicin And Capsaicin/Heat-Induced Neurogenic Flare In Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06305591
* Other: Capsaicin challenge
* Drug: Placebo
* Other: Capsaicin challenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male Caucasian subjects with skin type I-III inclusive (Fitzpatrick Scale), between the ages of 18 and 55 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). An informed consent document signed and dated by the subject. Subjects must have a distance from base of scaphoid to antecubital fossa equal of greater to 26 cm on their forearms. Subjects who demonstrate a capsaicin -mediated neurogenic flare with a value >200 on the arbitrary Laser Doppler output at any of the time points 30, 40, 50 or 60 minutes following administration of capsaicin at Screening. Exclusion Criteria: Evidence or history of clinically significant hematological (ie, abnormalities due to prolonged exposure to altitude), renal), endocrine or dismetabolic, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or pain condition, dermatological or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Subjects with scars or tattoos on the forearms, or with evidence of sunburn, or excessively hairy volar forearms. History of febrile illness within 5 days prior to dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06305591<br> | Drug: PF-06305591<br>* 150 mg PF 06305591 will be administered to subjects as a 100 mL extemporaneous prepared oral solution once.<br>Other: Capsaicin challenge<br>* 110 mg capsaicin cream (Axsain®) will be applied topically at each visit.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo will be administered to subjects as a 100 mL extemporaneous prepared oral solution once.<br>Other: Capsaicin challenge<br>* 110 mg capsaicin cream (Axsain®) will be applied topically at each visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean blood perfusion (calculated as area under the effect curve [AUEC]) between 40 and 60 minutes post administration of capsaicin in the 3 cm x 3 cm area of capsaicin application. |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean blood perfusion (calculated as AUEC), between 40 and 60 minutes post administration of capsaicin in the 12 cm x 5 cm area of laser Doppler scanning. |  | 1 day | 
| Peak blood flow perfusion following the first use of the Peltier device between 0 and 30 minutes following termination of heat application in the 3 cm x 3 cm area of capsaicin application. |  | 1 day | 
| Peak blood flow perfusion following the first use of the Peltier device between 0 and 30 minutes following termination of heat application in the 12 cm x 5 cm area of laser Doppler scanning. |  | 1 day | 
| Peak blood flow perfusion following the second use of the Peltier device between 0 and 30 minutes following termination of heat application in the 3 cm x 3 cm area of capsaicin application. |  | 1 day | 
| Peak blood flow perfusion following the second use of the Peltier device between 0 and 30 minutes following termination of heat application in the 12 cm x 5 cm area of laser Doppler scanning. |  | 1 day | 
| Mean blood perfusion (calculated as AUEC) post first use of the Peltier device between 0 and 30 minutes following termination of heat application in the 3 cm x 3 cm area of capsaicin application. |  | 1 day | 
| Mean blood perfusion (calculated as AUEC) post first use of the Peltier device between 0 and 30 minutes following termination of heat application in the 12 cm x 5 cm area of capsaicin application. |  | 1 day | 
| Mean blood perfusion (calculated as AUEC) post second use of the Peltier device between 0 and 30 minutes following termination of heat application in the 3 cm x 3 cm area of capsaicin application. |  | 1 day | 
| Mean blood perfusion (calculated as AUEC) post second use of the Peltier device between 0 and 30 minutes following termination of heat application in the 12 cm x 5 cm area of capsaicin application. |  | 1 day | 
| Pain Intensity Scores as measured by an 11 point Numerical Rating Scale (NRS) 30-60 minutes post topical application of capsaicin cream. |  | 1 day | 
| Pain Intensity Scores as measured by an 11 point Numerical Rating Scale (NRS) immediately following the first and second application of the heat stimulus. |  | 1 day | 
| Plasma level of PF 06305591. |  | 2 days |