Trial Outcomes & Findings for Next-Day Residual Effects of Gabapentin, Diphenhydramine and Triazolam on Simulated Driving Performance in Normal Volunteers (NCT NCT01888497)

Last Updated: 2021-02-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

59 participants

Primary outcome timeframe

7.25 hours post-dose

Results posted on

2021-02-21

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Diphenhydramine Citrate, Gabapentin, Placebo, Triazolam 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.	Gabapentin, Triazolam, Diphenhydramine Citrate, Placebo 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.	Triazolam, Placebo, Gabapentin, Diphenhydramine Citrate 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.	Placebo, Diphenhydramine Citrate, Triazolam, Gabapentin 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.
First Intervention Period STARTED	13	14	15	17
First Intervention Period COMPLETED	13	14	15	17
First Intervention Period NOT COMPLETED	0	0	0	0
Washout Period 1 STARTED	13	14	15	17
Washout Period 1 COMPLETED	13	14	14	16
Washout Period 1 NOT COMPLETED	0	0	1	1
Second Intervention Period STARTED	13	14	14	16
Second Intervention Period COMPLETED	13	14	14	16
Second Intervention Period NOT COMPLETED	0	0	0	0
Washout Period 2 STARTED	13	14	14	16
Washout Period 2 COMPLETED	13	14	14	14
Washout Period 2 NOT COMPLETED	0	0	0	2
Third Intervention Period STARTED	13	14	14	14
Third Intervention Period COMPLETED	13	14	14	14
Third Intervention Period NOT COMPLETED	0	0	0	0
Washout Period 3 STARTED	13	14	14	14
Washout Period 3 COMPLETED	13	14	14	14
Washout Period 3 NOT COMPLETED	0	0	0	0
Fourth Intervention Period STARTED	13	14	14	14
Fourth Intervention Period COMPLETED	13	14	14	14
Fourth Intervention Period NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Triazolam, Placebo, Gabapentin, Diphenhydramine Citrate 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.	Placebo, Diphenhydramine Citrate, Triazolam, Gabapentin 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.
Washout Period 1 Withdrawal by Subject	1	1
Washout Period 2 Adverse Event	0	1
Washout Period 2 Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=59 Participants All participants randomized to receive diphenhydramine citrate first, gabapentin first, triazolam first or placebo first.
Age, Continuous	41.1 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants

PRIMARY outcome

Timeframe: 7.25 hours post-dose

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

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	Gabapentin n=55 Participants A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Diphenhydramine Citrate n=57 Participants A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Triazolam n=56 Participants 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.
Standard Deviation of Lateral Position (SDLP)	33.2 centimeter (cm) Standard Deviation 8.0	34.2 centimeter (cm) Standard Deviation 10.0	35.4 centimeter (cm) Standard Deviation 8.9	47.4 centimeter (cm) Standard Deviation 12.0

SECONDARY outcome

Timeframe: 7.25 hours post dose

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	Gabapentin n=55 Participants A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Diphenhydramine Citrate n=57 Participants A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Triazolam n=56 Participants 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.
Speed Deviation	0.9 meters per second (m/sec) Standard Deviation 0.3	0.9 meters per second (m/sec) Standard Deviation 0.3	1.0 meters per second (m/sec) Standard Deviation 0.3	1.3 meters per second (m/sec) Standard Deviation 0.6

SECONDARY outcome

Timeframe: 7.25 hours post-dose

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	Gabapentin n=55 Participants A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Diphenhydramine Citrate n=57 Participants A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Triazolam n=56 Participants 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.
Lane Exceedance	37.8 lanes exceeded Standard Deviation 45.9	46.7 lanes exceeded Standard Deviation 58.5	52.4 lanes exceeded Standard Deviation 62.0	147.7 lanes exceeded Standard Deviation 113.6

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Gabapentin

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Diphenhydramine Citrate

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Triazolam

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=58 participants at risk A single dose of 1 placebo capsule and 2 placebo tablets orally in one of the four intervention periods.	Gabapentin n=55 participants at risk A single dose of 1 gabapentin 250 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Diphenhydramine Citrate n=57 participants at risk A single dose of 1 diphenhydramine citrate 76 mg capsule and 2 placebo tablets orally in one of the four intervention periods.	Triazolam n=56 participants at risk 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.
Eye disorders Vision blurred	1.7% 1/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	0.00% 0/56 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.
Gastrointestinal disorders Abdominal pain upper	1.7% 1/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	0.00% 0/56 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.
Gastrointestinal disorders Dry mouth	1.7% 1/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	0.00% 0/56 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.
Gastrointestinal disorders Nausea	0.00% 0/58 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.	3.6% 2/55 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.	1.8% 1/57 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.	3.6% 2/56 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.
General disorders Sensation of foreign body	0.00% 0/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	1.8% 1/56 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.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/58 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.	0.00% 0/55 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.	1.8% 1/57 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.	0.00% 0/56 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.
Nervous system disorders Dizziness	0.00% 0/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	1.8% 1/56 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.
Nervous system disorders Headache	0.00% 0/58 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.	0.00% 0/55 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.	1.8% 1/57 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.	1.8% 1/56 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.
Nervous system disorders Hypoaesthesia	1.7% 1/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	0.00% 0/56 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.
Nervous system disorders Lethargy	0.00% 0/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	5.4% 3/56 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.
Nervous system disorders Paraesthesia	1.7% 1/58 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.	0.00% 0/55 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.	0.00% 0/57 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.	0.00% 0/56 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.
Nervous system disorders Somnolence	0.00% 0/58 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.	0.00% 0/55 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.	1.8% 1/57 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.	10.7% 6/56 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.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
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Restriction type: OTHER