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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01119222
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arms: 4
• Duration (Months): 3
• Patients Per Site Per Month: 6.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Gabapentin; Drug: Diphenhydramine; Drug: Morphine; Drug: Placebo	Phase 1

Detailed Description

Cold pain methodology development

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: 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
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

6. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bruxelles		Belgium	1070

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01119222
• Other Study ID Numbers: A9001388
• First Posted: May 7, 2010
• Last Update Posted: Mar 7, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Cold pain methodology; Healthy male volunteers; gabapentin; Diphenhydramine; morphine
• Additional relevant MeSH terms: Diphenhydramine; Promethazine; Morphine; Gabapentin

Study Results

Participant Flow

Pre-assignment Detail	Prior to entering the treatment phases of the study, participants were required to successfully pass cold pain screening tests. Twenty participants were randomized and 19 participants received treatment consisting of a crossover sequence of 4 study drugs administered in sequence I, II, III or IV.

Arm/Group Title	Placebo, Morphine, Diphenhydramine, Gabapentin	Morphine, Gabapentin, Placebo, Diphenhydramine	Gabapentin, Diphenhydramine, Morphine, Placebo	Diphenhydramine, Placebo, Gabapentin, Morphine
Arm/Group Description	Placebo (capsules, tablet and intravenous (IV) first, then morphine 10 mg IV, then diphenhydramine 50 mg tablet, then gabapentin 1200 mg capsule.	Morphine 10 mg intravenous (IV) first, then gabapentin 1200 mg capsule, placebo (capsules, tablet and IV), then diphenhydramine 50 mg tablet.	Gabapentin 1200 mg capsule first, then diphenhydramine 50 mg tablet, then morphine 10 mg intravenous (IV), then placebo (capsules, tablet and IV).	Diphenhydramine 50 mg tablet first, then placebo (capsules, tablet and intravenous (IV), then gabapentin 1200 mg capsule, then morphine 10 mg IV.
Period Title: Overall Study
STARTED	5	5	5	4
COMPLETED	5	5	5	4
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Includes all participants who initiated in any treatment sequence
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	19 100%

Outcome Measures

1. Primary Outcome

Title	Average Pain (0-120 Seconds): Cold Pain Test Visual Analog Scale (VAS)
Description	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.
Time Frame	Pre-dose, 1, 1.5, 2, 4, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

Participants for analysis = participants who completed all of the four treatment periods.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	19	19	19	19
Pre-dose	45.2 (16.15)	45.5 (16.10)	45.0 (16.66)	44.9 (15.16)
1 hour	41.9 (16.95)	28.6 (16.88)	45.1 (17.29)	38.4 (15.69)
1.5 hours	39.4 (16.21)	26.1 (18.28)	42.3 (16.67)	40.2 (17.75)
2 hours	40.4 (17.71)	25.6 (18.44)	40.5 (17.22)	39.5 (16.86)
4 hours	41.9 (16.37)	34.7 (18.29)	44.2 (17.35)	44.3 (16.70)
8 hours	44.7 (15.06)	36.7 (17.14)	43.8 (15.08)	44.2 (14.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	Pre-dose; mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual. Sample sizing calculated based on results from previous methodology studies performed using the same cold pain test; primary criteria was ability to detect a significant gabapentin effect over placebo.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 90%; -3.82 to 4.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.45
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments	Pre-dose; mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 90%; -3.53 to 4.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.45
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments	Pre-dose; mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 90%; -3.99 to 4.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.45
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	1 hour post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 90%; -1.15 to 5.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.97
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments	1 hour post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.18
	Confidence Interval	(2-Sided) 90%; -14.48 to -7.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.97
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments	1 hour post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.49
	Confidence Interval	(2-Sided) 90%; 2.20 to 8.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.96
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	1.5 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 90%; -5.53 to 4.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.87
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments	1.5 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-13.93
	Confidence Interval	(2-Sided) 90%; -18.74 to -9.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.87
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments	1.5 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.88
	Confidence Interval	(2-Sided) 90%; -2.01 to 7.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.92
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	2 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 90%; -5.32 to 6.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.66
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments	2 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-13.12
	Confidence Interval	(2-Sided) 90%; -19.14 to -7.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.59
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments	2 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 90%; -4.45 to 7.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.59
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	4 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.53
	Confidence Interval	(2-Sided) 90%; -7.39 to 2.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.90
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments	4 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.59
	Confidence Interval	(2-Sided) 90%; -14.44 to -4.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.90
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments	4 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -4.85 to 4.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.90
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	8 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 90%; -3.23 to 4.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.22
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments	8 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.47
	Confidence Interval	(2-Sided) 90%; -11.19 to -3.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.22
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments	8 hours post-dose: mixed effect model with random subject effect, fixed period and treatment effects and random subject-by-visit effect as residual.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 90%; -3.99 to 3.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.22
	Estimation Comments

2. Primary Outcome

Title	Interpolated Average Pain (0-8 Hours)
Description	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.
Time Frame	Pre-dose to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

Participants for analysis = participants who completed all of the four treatment periods.

Arm/Group Title	Gabpentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin 1200 mg	Morphine 10 mg	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	19	19	19	19
Least Squares Mean (Standard Error) [hours]	42.2 (3.67)	33.4 (3.67)	43.6 (3.67)	42.8 (3.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 90%; -4.24 to 3.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.17
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Morphine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.43
	Confidence Interval	(2-Sided) 90%; -13.07 to -5.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.17
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Diphenhydramine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 90%; -2.80 to 4.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.17
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Clinically Significant Findings in Vital Signs
Description	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.
Time Frame	Predose, Day 1, Day 2 each treatment period, follow-up visit (at least 7 days after last dosing)

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication. Although individual listing data for vital signs were collected, summary statistics were not generated for this outcome measure.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormal Findings on Physical Examination
Description	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.
Time Frame	Pre-dose and follow-up visit (at least 7 days after last dosing)

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication. Although individual subject data were collected, results were not captured for inclusion in the study database.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Number of Participants With Abnormal Findings on Electrocardiogram (ECG)
Description	Standard 12-lead ECG performed after subject had rested quietly for at least 10 minutes in a supine position.
Time Frame	Pre-dose and follow-up visit (at least 7 days after last dosing)

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication. Although individual subject data were collected and monitored, summary statistics were not generated for this outcome measure.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	0	0	0	0

6. Secondary Outcome

Title	Number of Participants With Abnormal Haematology, Clinical Chemistry, Urinalysis Results
Description	Standard haematology, clinical chemistry, and urinalysis safety laboratory tests.
Time Frame	Pre-dose, follow-up visit (at least 7 days after last dosing)

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication. Although individual subject data were collected and monitored, summary statistics were not generated for this outcome measure.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin 1200 mg	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	0	0	0	0

7. Secondary Outcome

Title	Number of Participants With Abnormal Cardiac Monitoring Results
Description	Continuous cardiac monitoring during intervenous (IV) infusion dosing (morphine or placebo).
Time Frame	Pre-dose through duration of IV infusion dosing

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication. Although continuous cardiac monitoring was performed throughout IV dosing, results were not captured for inclusion in the study database.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	0	0	0	0

8. Secondary Outcome

Title	Number of Participants With Abnormal Pulse Oxymetry Results
Description	Pulse oxymetry to monitor percentage of hemoglobin saturated with oxygen during intervenous (IV) infusion dosing (morphine or placebo).
Time Frame	Predose through duration of IV infusion dosing

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication. Although pulse oxymetry was performed throughout IV dosing, results were not captured for inclusion in the study database.

Arm/Group Title	Gabapentin	Morphine	Diphenhydramine	Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose	Morphine single IV 10 mg dose	Diphenhydramine single oral 50 mg dose	Oral and IV doses to match active treatments
Measure Participants	0	0	0	0

Adverse Events

Adverse Event Reporting Description	Safety population: all subjects who received at least 1 dose of study medication. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Arm/Group Title	Gabapentin		Morphine		Diphenhydramine		Placebo
Arm/Group Description	Gabapentin single oral 1200 mg dose		Morphine single IV 10 mg dose		Diphenhydramine single oral 50 mg dose		Oral and IV doses to match active treatments
All Cause Mortality
	Gabapentin		Morphine		Diphenhydramine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Gabapentin		Morphine		Diphenhydramine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)		0/19 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Gabapentin		Morphine		Diphenhydramine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/19 (47.4%)		18/19 (94.7%)		5/19 (26.3%)		3/19 (15.8%)
Eye disorders
Vision blurred	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Gastrointestinal disorders
Dry mouth	0/19 (0%)		3/19 (15.8%)		0/19 (0%)		0/19 (0%)
Nausea	0/19 (0%)		7/19 (36.8%)		0/19 (0%)		0/19 (0%)
Vomiting	0/19 (0%)		2/19 (10.5%)		0/19 (0%)		0/19 (0%)
General disorders
Asthenia	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Chest pain	0/19 (0%)		3/19 (15.8%)		0/19 (0%)		0/19 (0%)
Fatigue	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		2/19 (10.5%)
Feeling abnormal	2/19 (10.5%)		7/19 (36.8%)		0/19 (0%)		0/19 (0%)
Feeling drunk	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Infections and infestations
Oral herpes	1/19 (5.3%)		1/19 (5.3%)		0/19 (0%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Neck pain	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Nervous system disorders
Dizziness	1/19 (5.3%)		4/19 (21.1%)		0/19 (0%)		0/19 (0%)
Head discomfort	0/19 (0%)		2/19 (10.5%)		0/19 (0%)		0/19 (0%)
Headache	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Paraesthesia	0/19 (0%)		4/19 (21.1%)		0/19 (0%)		0/19 (0%)
Somnolence	6/19 (31.6%)		7/19 (36.8%)		5/19 (26.3%)		1/19 (5.3%)
Speech disorder	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Psychiatric disorders
Stress	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Pruritus	0/19 (0%)		1/19 (5.3%)		0/19 (0%)		0/19 (0%)
Vascular disorders
Hot flush	0/19 (0%)		4/19 (21.1%)		0/19 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.