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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Placebo
Drug: Gabapentin
Drug: Morphine
Drug: Diphenhydramine

Registration Number: NCT01119222

Lead Sponsor: Pfizer

Brief Summary: 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.

Detailed Description: Cold pain methodology development

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 19

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo formulations	Placebo	-
Gabapentin 1200mg	Gabapentin	-
Morphine 10 mg	Morphine	-
Diphenhydramine 50 mg	Diphenhydramine	-

Primary Outcome Measures

Name	Time	Method
Interpolated Average Pain (0-8 Hours)	Pre-dose to 8 hours post-dose	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.
Average Pain (0-120 Seconds): Cold Pain Test Visual Analog Scale (VAS)	Pre-dose, 1, 1.5, 2, 4, and 8 hours post-dose	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Abnormal Findings on Physical Examination	Pre-dose and follow-up visit (at least 7 days after last dosing)	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.
Number of Participants With Abnormal Pulse Oxymetry Results	Predose through duration of IV infusion dosing	Pulse oxymetry to monitor percentage of hemoglobin saturated with oxygen during intervenous (IV) infusion dosing (morphine or placebo).
Number of Participants With Clinically Significant Findings in Vital Signs	Predose, Day 1, Day 2 each treatment period, follow-up visit (at least 7 days after last dosing)	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.
Number of Participants With Abnormal Cardiac Monitoring Results	Pre-dose through duration of IV infusion dosing	Continuous cardiac monitoring during intervenous (IV) infusion dosing (morphine or placebo).
Number of Participants With Abnormal Findings on Electrocardiogram (ECG)	Pre-dose and follow-up visit (at least 7 days after last dosing)	Standard 12-lead ECG performed after subject had rested quietly for at least 10 minutes in a supine position.
Number of Participants With Abnormal Haematology, Clinical Chemistry, Urinalysis Results	Pre-dose, follow-up visit (at least 7 days after last dosing)	Standard haematology, clinical chemistry, and urinalysis safety laboratory tests.