Study To Assess The Effect Of Gabapentin, Diphenhydramine And Morphine On Cold Pain In Healthy Male Volunteers

A Randomised, Double-Blind, Double-Dummy, Placebo And Active Controlled, 4-Way Crossover Methodology Study To Assess The Effect Of Gabapentin, Diphenhydramine And Morphine On Cold Pain In Healthy Male Volunteers

Human experimental pain models are useful in understanding the mechanisms underlying clinical pain conditions and can be used to test the analgesic efficacy of drugs used in the management of pain. Once established these models can be used as mechanism biomarkers in early development clinical studies to establish proof of mechanism for novel compounds. The cold pain model is a mechanistic pain biomarker with potential application in proof of mechanism studies. In this study we aim to set up this cold pain model at a Clinical Research Unit and demonstrate we can effectively screen subjects for this model and examine the effect of morphine, diphenhydramine, and gabapentin in the cold pain model.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Gabapentin; Drug: Diphenhydramine; Drug: Morphine; Drug: Placebo

Detailed Description

Cold pain methodology development

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers having given consent to participate in the study who have no clinically significant anomalies and whose vital signs are within normal range.
• Subject having performed the cold pain test reproducibly ie, if the area under the pain-time curve (AUC) must be within 20% during successive tests within one cold pain test screening visit and within 30% between the two cold pain test screening visits.

Exclusion Criteria:

• Subject who have had a serious adverse reaction or significant hypersensitivity to any of the study drugs.
• Subjects with a history of or evidence of any neurological condition which could affect pain sensation.
• Subjects with an AUCcpt 0-120 sec in the cold pain test of <1000 in any of the screening tests (excluding familiarization).

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gabapentin 1200mg	Drug: Gabapentin; Capsule, single 1200mg dose
Active Comparator: Diphenhydramine 50 mg	Drug: Diphenhydramine; Tablet, single 50mg dose
Active Comparator: Morphine 10 mg	Drug: Morphine; IV, single 10mg dose
Placebo Comparator: Placebo formulations	Drug: Placebo; Placebo formulations (Capsule, tablet, IV to match the active treatments and to be administered in a double-dummy fashion).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Pain (0-120 Seconds): Cold Pain Test Visual Analog Scale (VAS)	Area under the cold pain test Visual Analog Scale (VAS) time curve (AUCcpt 0 to 120 seconds [sec]) averaged over the 120 sec for each time point assessed. Participant adjusted 100 millimeter (mm) electronic VAS with range of "no pain" (0) to "maximum pain" (100) at the anchor endpoints of the scale and "moderate pain" at the midpoint. Pain reported while non-dominant hand was placed in thermostatically controlled water bath at 2±1°C for a maximum of 120 sec.	Pre-dose, 1, 1.5, 2, 4, and 8 hours post-dose
Interpolated Average Pain (0-8 Hours)	Interpolated average pain (0 to 8 hours): area under the curve (AUC) of average pain (0 to 120 seconds) recorded at each of the time points taken over 8 hour time period divided by 8.	Pre-dose to 8 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Findings in Vital Signs	Supine blood pressure measured to nearest millimeter of mercury (mmHg), pulse rate measured with automated device or manually in the brachial/radial artery for at least 30 seconds.	Predose, Day 1, Day 2 each treatment period, follow-up visit (at least 7 days after last dosing)
Number of Participants With Clinically Significant Abnormal Findings on Physical Examination	Full physical examination consisting of an examination of the abdomen, cardiovascular systems, lungs, lymph nodes, mouth, musculoskeletal and neurological systems, skin, extremities, head, ears, eyes, nose, throat and thyroid gland.	Pre-dose and follow-up visit (at least 7 days after last dosing)
Number of Participants With Abnormal Findings on Electrocardiogram (ECG)	Standard 12-lead ECG performed after subject had rested quietly for at least 10 minutes in a supine position.	Pre-dose and follow-up visit (at least 7 days after last dosing)
Number of Participants With Abnormal Haematology, Clinical Chemistry, Urinalysis Results	Standard haematology, clinical chemistry, and urinalysis safety laboratory tests.	Pre-dose, follow-up visit (at least 7 days after last dosing)
Number of Participants With Abnormal Cardiac Monitoring Results	Continuous cardiac monitoring during intervenous (IV) infusion dosing (morphine or placebo).	Pre-dose through duration of IV infusion dosing
Number of Participants With Abnormal Pulse Oxymetry Results	Pulse oxymetry to monitor percentage of hemoglobin saturated with oxygen during intervenous (IV) infusion dosing (morphine or placebo).	Predose through duration of IV infusion dosing

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: July 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: May 5, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 7, 2010

Study Record Updates

• Last Update Posted (Estimate): March 7, 2011
• Last Update Submitted That Met QC Criteria: February 10, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: morphine; Healthy male volunteers; gabapentin; Diphenhydramine; Cold pain methodology
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; Anticonvulsants; Anesthetics, Local; Antimanic Agents; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Gabapentin; Diphenhydramine; Promethazine; Morphine
• Other Study ID Numbers: A9001388