Experimental Biomarker Study for Pain Thresholds

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: V116517 aqueous suspension; Drug: Placebo; Drug: Capsaicin; Drug: Celecoxib capsules

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • CCBR A/S

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria include:

1. Signed informed consent obtained.
2. Males aged 18 to 45, inclusive.
3. Body weight ranging from 50 to 100 kg and BMI ranging from 18 to 32 (kg/m2), inclusive.
4. Healthy and free of significant abnormal findings as determined by medical history, physical examination, clinical laboratory values, vital signs, and ECG.

Exclusion Criteria include:

1. Current or recent (within 5 years) history of drug or alcohol abuse.
2. History or any current conditions that might interfere with drug absorption, distribution, metabolism or excretion.
3. Any history of frequent nausea or emesis regardless of etiology.
4. 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.
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: February 24, 2016
• First Posted (Estimate): March 1, 2016

Study Record Updates

• Last Update Posted (Estimate): March 1, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

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; Dermatologic Agents; Cyclooxygenase 2 Inhibitors; Antipruritics; Celecoxib; Capsaicin
• Other Study ID Numbers: VND1004; 2011-002399-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO