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

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.

• Drug: ICA-105665
  Subjects randomized to receive ICA -105665 will receive 200 mg BID
• Drug: Ibuprofen
  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.
  Other Name: Cuprofen
• Drug: Placebo

  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.

  Other Name: orange Syrup BP

• Experimental: ICA-105665
  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.
  Intervention: Drug: ICA-105665
• Active Comparator: Ibuprofen
  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.
  Intervention: Drug: Ibuprofen
• Placebo Comparator: Placebo
  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.
  Intervention: Drug: Placebo

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.