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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ICA-105665; Drug: Ibuprofen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• • • Pfizer Investigational Site
• United Kingdom
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9QZ
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: ICA-105665; Subjects randomized to receive ICA -105665 will receive 200 mg BID
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.	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 Names: Cuprofen
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.	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 Names: orange Syrup BP

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: August 19, 2009
• First Submitted That Met QC Criteria: August 19, 2009
• First Posted (Estimate): August 20, 2009

Study Record Updates

• Last Update Posted (Estimate): September 28, 2012
• Last Update Submitted That Met QC Criteria: September 27, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: ICA-105665-05; B5311006