Experimental Biomarker Study for Pain Thresholds

Study Overview
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Brief Summary
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The purpose of this study is to characterize the heat pain tolerance threshold (HPTolTr) in primary hyperalgesic skin after topical capsaicin application, and to assess heat pain and mechanical thresholds (eg, pressure pain, stimulus-response) following skin sensitization by UVB (ultraviolet B) irradiation and topical capsaicin.

Official Title
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Randomized, Double Blind, Positive- Controlled, Three-way Cross-over Human Experimental Biomarker Study of V116517 in Healthy Male Subjects

Conditions
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Pain

Intervention / Treatment
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* Drug: V116517 aqueous suspension
* Drug: Celecoxib capsules
* Drug: Placebo
* Drug: Capsaicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Signed informed consent obtained. Males aged 18 to 45, inclusive. Body weight ranging from 50 to 100 kg and BMI ranging from 18 to 32 (kg/m2), inclusive. Healthy and free of significant abnormal findings as determined by medical history, physical examination, clinical laboratory values, vital signs, and ECG. Exclusion Criteria include: Current or recent (within 5 years) history of drug or alcohol abuse. History or any current conditions that might interfere with drug absorption, distribution, metabolism or excretion. Any history of frequent nausea or emesis regardless of etiology. Any history of allergic-type reactions to sulfonamides, or any experience of asthma, urticarial, or other allergic-type reactions after taking aspirin or other NSAIDS. Subjects who do not develop erythema at the maximum dose of the UVB source (MED determination for UVB model) will be excluded from the study. Other protocol-specific inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V116517<br>V116517 aqueous suspension; 300 mg | Drug: V116517 aqueous suspension<br>* 300 mg (approximately 100 mL) aqueous suspension taken orally x 1 dose<br>Drug: Placebo<br>* Placebo for V116517 aqueous suspension taken orally x 1 dose and/or placebo for celecoxib, 2 capsules taken orally x 1 dose<br>Drug: Capsaicin<br>* 1% administered topically<br>|
| Active Comparator: Celecoxib<br>Celecoxib capsules; 400 mg (2 capsules of 200 mg each) | Drug: Celecoxib capsules<br>* 400 mg (2 capsules of 200 mg each) taken orally x 1 dose<br>* Other names: Celebra®;Drug: Placebo<br>* Placebo for V116517 aqueous suspension taken orally x 1 dose and/or placebo for celecoxib, 2 capsules taken orally x 1 dose<br>Drug: Capsaicin<br>* 1% administered topically<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo for V116517 aqueous suspension taken orally x 1 dose and/or placebo for celecoxib, 2 capsules taken orally x 1 dose<br>Drug: Capsaicin<br>* 1% administered topically<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat pain tolerance threshold (HPTolTr) in primary hyperalgesic skin after topical capsaicin application | Mean temperature in degrees Celsius (°C) based on the difference (post-dose and pre-dose) of the differences between the capsaicin at the control arm and the treated arm | 3.5 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat Pain Threshold (HPTr) | Mean temperature in degrees Celsius (°C) | 3.5 hours post-dose | 
| Heat Pain tolerance threshold (HPTolTr) | Mean temperature in degrees Celsius (°C) | Pre-dose and 3.5 hours post-dose | 
| Pressure Pain Threshold (PPTr) | Mean pressure kPA | 3.5 hours post-dose | 
| Pressure Pain tolerance threshold (PPTolTr) | Mean pressure kPA | 3.5 hours post-dose | 
| Peripheral nociceptor activation using Laser Doppler flowmetry | Peripheral nociceptor activation will be assessed by monitoring cutaneous blood flow using Laser Doppler imaging | 3.5 hours post-dose | 
| Erythema at the treated area using Erythema index | Erythema at the treated area will be assessed using colorimetry | 3.5 hours post-dose | 
| Stimulus-response function to graded von Frey hair stimulation | The mean pain intensity of the stimulations on a '0-10' visual analog scale (VAS), where '0' indicates ''no pain and '10' indicates '' the most intense pain imaginable'' | 3.5 hours post-dose | 
| Secondary pin-prick hyperalgesic area | The area will be assessed using a 60 g weighted von Frey hair, and subjects are asked to report when the sensation changes to a different sensation, unpleasant or burning pain sensation | 3.5 hours post-dose | 
| Evaluation of change in body temperature | Oral temperature in degrees Celsius (˚C) | Pre-dose and up to 72 hours post-dose |