Effects of ICA-105665 Using the Intradermal Capsaicin and Ultraviolet B (UV-B) Models in Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is; to determine the pharmacodynamic (PD) effects of ICA-105665 using the intradermal (ID) capsaicin model in healthy male subjects, and to investigate the effect of ICA-105665 on inflammatory hyperalgesia using the ultraviolet B (UV-B) model in healthy male subjects.

Official Title
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A Randomized, Placebo-Controlled, 3-way Crossover Study to Investigate the Pharmacodynamic Effects of ICA-105665 Using the Intradermal Capsaicin and UV-B Models in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: ICA-105665
* Drug: Ibuprofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males aged 18 to 55 years (inclusive). Body mass index (BMI) of 18 to 30 kg/m2. Non-smokers and smokers of up to 5 cigarettes or equivalent per day. Must be able to abstain from smoking during residential periods. Demonstration of positive hyperalgesia as defined by an area of hyperalgesia = 15 cm2 15 minutes after ID administration of 100 µg capsaicin. Demonstration of negative hyperalgesia as defined by an area of hyperalgesia < 5 cm2 15 minutes after ID administration of capsaicin vehicle. Subject with a skin type compatible with the measures, and without significant skin allergies, pigmentary disorders, or any active dermatological conditions that might interfere with the conduct of the study. Exclusion Criteria: Subject has had a clinically significant illness in the 4 weeks before screening. Use of prescribed medications and herbal supplements in the 7 days prior to dosing or over the counter preparations, including multivitamins and paracetamol, in the 48 h before dosing. Subject has a significant history of drug/solvent abuse (within 2 years prior to Day 1), or a positive drugs of abuse test at screening. Subject with a history of alcohol abuse or currently drinks in excess of 28 units per week (males), or has a positive breath alcohol test at the Screening visit or on Day 1. Subject has a Heat pain tolerance threshold (HPTT) of = 50°C at screening. Subjects who do not develop erythema at the highest intensity of UV-B light used to establish Minimum erythema dose (MED). Known allergy or intolerance to capsaicin or hot peppers. Subjects who have any skin trauma, scars or other skin disorder or tattoos on their forearms or on the front of their thighs. Subject with active chronic pain conditions or a history of chronic pain conditions. Any condition that might interfere with the absorption, distribution, metabolism, and/or excretion of drugs. Previous ingestion of ICA-105665. Considering or scheduled to undergo any surgical procedure during the duration of the study. Prolonged QT/QTc interval (repeatedly = 450 msec). Received any agent known to alter hepatic or renal clearance (e.g., erythromycin, cimetidine, barbiturates, phenothiazines, clarithromycin, troleandomycin, ketoconazole, miconazole, fluconazole, itraconazole, etc.) for a period of 30 days prior to Day 1. History of risk factors for Torsades de Pointes (family history of long QT syndrome, heart failure, hypokalemia). Subject is unable to tolerate being blindfolded. Subject has participated in a clinical study involving capsaicin within 1 year of the Screening visit. Subject has a history of skin cancer. Subject has a clinically significant history of anemia.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICA-105665<br>Three study drug treatments will be used: ICA-105665, ibuprofen, and placebo (for both ICA-105665 and Ibuprofen). The order of study drug treatment given to each subject during each specified treatment period is determined at randomization. | Drug: ICA-105665<br>* Subjects randomized to receive ICA -105665 will receive 200 mg BID<br>|
| Active Comparator: Ibuprofen<br>Three study drug treatments will be used: ICA-105665, ibuprofen, and placebo (for both ICA-105665 and Ibuprofen). The order of study drug treatment given to each subject during each specified treatment period is determined at randomization. | Drug: Ibuprofen<br>* Subjects randomized to receive Ibuprofen will receive placebo to ICA-105665 at all scheduled dosing times on Days 1 to 4 and a single dose of 800 mg Ibuprofen on the morning of Day 4.<br>* Other names: Cuprofen;|
| Placebo Comparator: Placebo<br>Three study drug treatments will be used: ICA-105665, ibuprofen, and placebo (for both ICA-105665 and Ibuprofen). The order of study drug treatment given to each subject during each specified treatment period is determined at randomization. | Drug: Placebo<br>* Subjects randomized to receive placebo will receive placebo to ICA -105665 at all scheduled dosing times on Days 1 to 4 and placebo to Ibuprofen on the morning of Day 4.<br>* Other names: orange Syrup BP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Capsaicin: Visual Analogue Scale, hyperalgesia, allodynia, laser Doppler blood flow. UV-B pain assessments: Heat pain detection threshold, Heat pain tolerance threshold (HPTT), Laser Doppler blood flow (intensity and area), Skin temperature. |  | Capsaicin - Time 0, to 2 hours after injection. UV-B Pain: 2 hours post | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UV-B: Heat pain,Laser Doppler Blood Flow |  | 24 hours after irradiation |