Next-Day Residual Effects of Gabapentin, Diphenhydramine and Triazolam on Simulated Driving Performance in Normal Volunteers

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01888497
• Collaborator: (none)
• Enrollment: 59
• Locations: 4
• Arms: 4
• Actual Duration (Months): 4.5
• Patients Per Site: 14.8
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

This study will examine the next-day residual effects of a nighttime dose of gabapentin 250 mg, diphenhydramine citrate 76 mg and triazolam 0.5 mg compared to placebo and each other on simulated driving performance in normal volunteer subjects. It will also examine other measures of next-day performance and next-day sleepiness.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Gabapentin; Drug: Diphenhydramine citrate; Drug: Triazolam; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, CROSS-OVER, PLACEBO-CONTROLLED, SINGLE DOSE, CLINICAL TRIAL TO ASSESS THE NEXT-DAY RESIDUAL EFFECTS OF GABAPENTIN, DIPHENHYDRAMINE AND TRIAZOLAM ON SIMULATED DRIVING PERFORMANCE IN NORMAL VOLUNTEERS
• Actual Study Start Date: Jul 29, 2013
• Actual Primary Completion Date: Dec 14, 2013
• Actual Study Completion Date: Dec 14, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A	Drug: Gabapentin; 250 mg, oral, prior to bedtime on the night before performance testing
Experimental: Arm B	Drug: Diphenhydramine citrate; 76 mg, oral, prior to bedtime on the night before performance testing
Active Comparator: Arm C	Drug: Triazolam; 0.5 mg, oral, prior to bedtime on the night before performance testing
Placebo Comparator: Arm D	Drug: Placebo; Oral, prior to bedtime on the night before performance testing

Outcome Measures

Primary Outcome Measures

1. Standard Deviation of Lateral Position (SDLP) [7.25 hours post-dose]

   Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). SDLP was used to assess driver's ability to track their lane and was the standard deviation of lane positions through the entire drive.

Secondary Outcome Measures

1. Speed Deviation [7.25 hours post dose]

   Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Standard deviation of speed was reported in the outcome measure.

2. Lane Exceedance [7.25 hours post-dose]

   Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Mean lanes excursed/exceeded was reported in the outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males and females of non-childbearing potential, 25-55 years of age

• Valid driver's license

Exclusion Criteria:

• Psychiatric disorder

• Recent history of clinically significant neurological disorder, such as seizures, stroke, multiple sclerosis, or head trauma

• Recent histroy or current treatment for sleep disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baptist Sleep Centers, LLP	South Miami	Florida	United States	33143
2	Miami Research Associates	South Miami	Florida	United States	33143
3	NeuroTrials Research Sleep Lab	Atlanta	Georgia	United States	30342
4	NeuroTrials Research, Inc.	Atlanta	Georgia	United States	30342

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01888497
• Other Study ID Numbers: A9451178
• First Posted: Jun 27, 2013
• Last Update Posted: Feb 21, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Sleeplessness
• Additional relevant MeSH terms: Diphenhydramine; Promethazine; Triazolam; Gabapentin

Study Results

Participant Flow

Pre-assignment Detail	Prior to randomization, all participants were screened for simulator sickness and underwent standardized training on the driving simulator to ensure that participants fully understood how to perform the tests, were comfortable, and attained a stable level of performance on the various performance-based measures.

Arm/Group Title	Diphenhydramine Citrate, Gabapentin, Placebo, Triazolam	Gabapentin, Triazolam, Diphenhydramine Citrate, Placebo	Triazolam, Placebo, Gabapentin, Diphenhydramine Citrate	Placebo, Diphenhydramine Citrate, Triazolam, Gabapentin
Arm/Group Description	A single dose of 1 diphenhydramine citrate 76 milligram (mg) capsule and 2 placebo tablets orally in first intervention period followed by a single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in second intervention period, then a single dose of 1 placebo capsule and 2 placebo tablets orally in third intervention period and then a single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in fourth intervention period. Each intervention period consisted of dosing day on which the study treatment was administered at night followed by testing day. A washout period of 7 to 14 days was maintained between each intervention period.	A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in first intervention period followed by a single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in second intervention period then a single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in third intervention period and then a single dose of 1 placebo capsule and 2 placebo tablets orally in fourth intervention period. Each intervention period consisted of dosing day on which the study treatment was administered at night followed by testing day. A washout period of 7 to 14 days was maintained between each intervention period.	A single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in first intervention period followed by 1 placebo capsule and 2 placebo tablets orally in second intervention period then a single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in third intervention period and then a single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in fourth intervention period. Each intervention period consisted of dosing day on which the study treatment was administered at night followed by testing day. A washout period of 7 to 14 days was maintained between each intervention period.	A single dose of 1 placebo capsule and 2 placebo tablets orally in first intervention period followed by a single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in second intervention period then a single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in third intervention period and then a single dose of gabapentin 250 mg capsule and 2 placebo tablets orally in fourth intervention period. Each intervention period consisted of dosing day on which the study treatment was administered at night followed by testing day. A washout period of 7 to 14 days was maintained between each intervention period.
Period Title: First Intervention Period
STARTED	13	14	15	17
COMPLETED	13	14	15	17
NOT COMPLETED	0	0	0	0
Period Title: First Intervention Period
STARTED	13	14	15	17
COMPLETED	13	14	14	16
NOT COMPLETED	0	0	1	1
Period Title: First Intervention Period
STARTED	13	14	14	16
COMPLETED	13	14	14	16
NOT COMPLETED	0	0	0	0
Period Title: First Intervention Period
STARTED	13	14	14	16
COMPLETED	13	14	14	14
NOT COMPLETED	0	0	0	2
Period Title: First Intervention Period
STARTED	13	14	14	14
COMPLETED	13	14	14	14
NOT COMPLETED	0	0	0	0
Period Title: First Intervention Period
STARTED	13	14	14	14
COMPLETED	13	14	14	14
NOT COMPLETED	0	0	0	0
Period Title: First Intervention Period
STARTED	13	14	14	14
COMPLETED	13	14	14	14
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	All participants randomized to receive diphenhydramine citrate first, gabapentin first, triazolam first or placebo first.
Overall Participants	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (9.0)
Sex: Female, Male (Count of Participants)
Female	13 22%
Male	46 78%

Outcome Measures

1. Primary Outcome

Title	Standard Deviation of Lateral Position (SDLP)
Description	Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). SDLP was used to assess driver's ability to track their lane and was the standard deviation of lane positions through the entire drive.
Time Frame	7.25 hours post-dose

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of investigational product and provided any data post-randomization.

Arm/Group Title	Placebo	Gabapentin	Diphenhydramine Citrate	Triazolam
Arm/Group Description	A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in one of the four intervention periods.
Measure Participants	58	55	57	56
Mean (Standard Deviation) [centimeter (cm)]	33.2 (8.0)	34.2 (10.0)	35.4 (8.9)	47.4 (12.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Triazolam
	Comments	For primary endpoint sequential order of testing: triazolam versus (vs) placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	13.82
	Confidence Interval	(2-Sided) 95%; 10.85 to 17.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gabapentin
	Comments	For primary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	For gabapentin versus placebo comparison, the non-inferiority margin for upper limit of 95 percent (%) confidence interval (CI) was 2.4 cm.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; -0.66 to 2.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Diphenhydramine Citrate
	Comments	For primary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; -0.39 to 2.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Diphenhydramine Citrate
	Comments	For primary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	2.37
	Confidence Interval	(2-Sided) 95%; 1.01 to 3.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

2. Secondary Outcome

Title	Speed Deviation
Description	Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Standard deviation of speed was reported in the outcome measure.
Time Frame	7.25 hours post dose

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of investigational product and provided any data post-randomization.

Arm/Group Title	Placebo	Gabapentin	Diphenhydramine Citrate	Triazolam
Arm/Group Description	A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in one of the four intervention periods.
Measure Participants	58	55	57	56
Mean (Standard Deviation) [meters per second (m/sec)]	0.9 (0.3)	0.9 (0.3)	1.0 (0.3)	1.3 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Triazolam
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gabapentin
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	For gabapentin versus placebo comparison, the non-inferiority margin for upper limit of 95% CI was 0.1 m/sec.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Diphenhydramine Citrate
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.02 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Diphenhydramine Citrate
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

3. Secondary Outcome

Title	Lane Exceedance
Description	Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Mean lanes excursed/exceeded was reported in the outcome measure.
Time Frame	7.25 hours post-dose

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of investigational product and provided any data post-randomization.

Arm/Group Title	Placebo	Gabapentin	Diphenhydramine Citrate	Triazolam
Arm/Group Description	A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	A single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in one of the four intervention periods.
Measure Participants	58	55	57	56
Mean (Standard Deviation) [lanes exceeded]	37.8 (45.9)	46.7 (58.5)	52.4 (62.0)	147.7 (113.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Triazolam
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	103.25
	Confidence Interval	(2-Sided) 95%; 72.00 to 130.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gabapentin
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	For gabapentin versus placebo comparison, the non-inferiority margin for upper limit of 95% CI was 8 lanes.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	5.00
	Confidence Interval	(2-Sided) 95%; -4.00 to 16.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Diphenhydramine Citrate
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.213
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	3.00
	Confidence Interval	(2-Sided) 95%; -3.00 to 9.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Diphenhydramine Citrate
	Comments	For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Statistical comparison was performed at a two-sided significance level of 0.05.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehman estimate
	Estimated Value	11.00
	Confidence Interval	(2-Sided) 95%; 4.00 to 20.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehman estimate of treatment difference was reported.

Adverse Events

Adverse Event Reporting Description	Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. Safety population was evaluated.
Arm/Group Title	Placebo		Gabapentin		Diphenhydramine Citrate		Triazolam
Arm/Group Description	A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.		A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.		A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.		A single dose of 2 triazolam 0.25 mg tablets (equivalent to triazolam 0.5 mg) and 1 placebo capsule orally in one of the four intervention periods.
All Cause Mortality
	Placebo		Gabapentin		Diphenhydramine Citrate		Triazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Gabapentin		Diphenhydramine Citrate		Triazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/55 (0%)		0/57 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Gabapentin		Diphenhydramine Citrate		Triazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/58 (5.2%)		2/55 (3.6%)		3/57 (5.3%)		10/56 (17.9%)
Eye disorders
Vision blurred	1/58 (1.7%)		0/55 (0%)		0/57 (0%)		0/56 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/58 (1.7%)		0/55 (0%)		0/57 (0%)		0/56 (0%)
Dry mouth	1/58 (1.7%)		0/55 (0%)		0/57 (0%)		0/56 (0%)
Nausea	0/58 (0%)		2/55 (3.6%)		1/57 (1.8%)		2/56 (3.6%)
General disorders
Sensation of foreign body	0/58 (0%)		0/55 (0%)		0/57 (0%)		1/56 (1.8%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/58 (0%)		0/55 (0%)		1/57 (1.8%)		0/56 (0%)
Nervous system disorders
Dizziness	0/58 (0%)		0/55 (0%)		0/57 (0%)		1/56 (1.8%)
Headache	0/58 (0%)		0/55 (0%)		1/57 (1.8%)		1/56 (1.8%)
Hypoaesthesia	1/58 (1.7%)		0/55 (0%)		0/57 (0%)		0/56 (0%)
Lethargy	0/58 (0%)		0/55 (0%)		0/57 (0%)		3/56 (5.4%)
Paraesthesia	1/58 (1.7%)		0/55 (0%)		0/57 (0%)		0/56 (0%)
Somnolence	0/58 (0%)		0/55 (0%)		1/57 (1.8%)		6/56 (10.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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.