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

Study Overview
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Brief Summary
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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
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Cold pain methodology development

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Diphenhydramine
* Drug: Morphine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cold pain methodology, Healthy male volunteers, gabapentin, Diphenhydramine, morphine