Simulated Driving Study in Restless Legs Syndrome

A Randomized, Double Blind, Active- and Placebo-Controlled, Parallel Group Safety Study Assessing Simulated Driving Performance in XP13512-(GSK1838262) Treated Patients With Restless Legs Syndrome

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01332318

Acronym

XP083

Enrollment

130

Registered

2011-04-11

Start date

2007-04-30

Completion date

2007-11-30

Last updated

2013-07-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Restless Legs Syndrome

Brief summary

This study was a multi center, randomized, double blind, active and placebo controlled, parallel group study to assess simulated driving performance in XP13512 treated subjects with Restless Legs Syndrome (RLS). Eligible subjects were randomized to receive a once daily dose of placebo (2 groups), XP13512 1200 mg, or XP13512 1800 mg for 16 days. On Day 16, one of the placebo groups also received one 50 mg dose of diphenhydramine (DPH) to assess the effects of an agent known to have sedative properties, while the other 3 groups received a DPH placebo.

Detailed description

This study was a multicenter, randomized, double blind, active and placebo controlled, parallel group study. Eligible subjects were randomized in a 1:1:1:1 ratio to 1 of the following 4 treatment groups: A) XP13512 Placebo + Diphenhydramine Placebo (Pbo) B) XP13512 1200 mg/day + Diphenhydramine Placebo (1200 mg) C) XP13512 1800 mg/day + Diphenhydramine Placebo (1800 mg) D) XP13512 Placebo + 50 mg Diphenhydramine (Pbo/DPH)

Interventions

DRUGXP13512

XP13512 once daily for 16 days

DRUGDiphenhydramine

one 50 mg dose of diphenhydramine (DPH) on day 16

DRUGPlacebo

XP13512 placebo once daily for 16 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Men or women who were 21 through 65 years of age and fluent in English; * Subjects with RLS, based on the IRLSSG Diagnostic Criteria; * Currently a licensed and experienced driver who has driven an average of 3 or more times/week for the past 3 years; * Able to successfully complete the 5 minute practice simulated driving test at Screening; * History of RLS symptoms at least 15 nights in the prior month or, if on treatment, this frequency of symptoms before treatment was started; * Total RLS severity score of 15 or greater on the IRLS Rating Scale; * Documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights Discontinuation of treatments for RLS (e.g., opioids, benzodiazepines, dopamine agonists and/or gabapentin) at least 2 weeks prior to Screening; - * Body Mass Index of 34 or below; * Estimated creatinine clearance of at least 60 mL/min; * Agreed to maintain abstinence from alcohol and smoking throughout the entire study period; * Agreed to maintain abstinence from caffeine from midnight of the day prior to and until the end of each Visit (Visits 2 to 4).

Exclusion criteria

* A sleep disorder (e.g., sleep apnea) other than RLS that may significantly affect the assessment of RLS; * Current use of a sleeping medication or sedating medication; * Current use of CNS stimulants; * Neurologic disease or movement disorder; * Other medical conditions which could affect RLS assessments; * Significant medical history that may impair psychomotor coordination; * Subjects who had clinically significant or unstable medical conditions; * Serum ferritin level below 20 ng/mL; * Subjects currently suffering from moderate or severe depression using the Diagnostic and Statistical Manual of Mental Disorders and Treatment IV (DSM IV TR); * Subjects with a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to enrollment; * Shift workers or subjects who were not on normal day/night sleep cycles; * Subjects who had smoked an average of greater than one half pack of cigarettes (or nicotine equivalent) per day within 30 days of the Screening Visit; * Subjects who had consumed an average of \>5 cups (i.e., 40 ounces) of caffeinated beverages per day within 20 days of the Screening Visit; * Subjects with a history of allergy to gabapentin, diphenhydramine, or XP13512 excipients

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)	Baseline (Day -1) and Day 16	Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 16 mean LPV over the 1-hour drive minus the Baseline mean LPV over the 1-hour drive. The Day 16 measurement is at the time of maximum concentration (Tmax) for both GEn and DPH.

Secondary

Measure	Time frame	Description
Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Baseline (Days -1 and 1) and Days 14 and 15	Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 14 (in the evening) or Day 15 (in the morning after GEn dosed at 5 PM) mean LPV over the 1-hour drive minus the Baseline (Day -1 or Day 1) mean LPV over the 1-hour drive.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Baseline (Days -1 and 1) and Days 14, 15, and 16	Lane position was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall average lane position was calculated as the Day 14 (in the evening), 15 (in the morning after GEn dosed at 5 PM), or 16 (assessment at Tmax of GEn and DPH) mean lane position over the 1-hour drive minus the Baseline (Days -1 and 1) mean lane position over the 1-hour drive.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Baseline (Day -1) and Days 14 and 16; baseline (Day 1) and Day 15	Speed variability was defined as the standard deviation of the speed (measured in miles per hour). Participants were instructed to maintain a speed of 55 miles per hour during the test drive. Change from baseline in overall speed variability was calculated as the Day 14 (in the evening), 15 (in the morning), or 16 (at Tmax of GEn and DPH) mean speed variability over the 1-hour drive minus the Baseline (Days -1 and 1) mean speed variability over the 1-hour drive.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Baseline (Days -1 and 1) and Days 14, 15, and 16	Participants were instructed to maintain a speed of 55 miles per hour during the driving assessment. Change from baseline in overall average speed was calculated as the Day 14 (in the evening), 15 (in the morning), or 16 (at Tmax of GEn and DPH) mean speed over the 1-hour drive minus the Baseline (Days -1 and 1) mean speed over the 1-hour drive.
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Days 14, 15, and 16	A simulated crash was defined as a collision with an oncoming car or obstacle (e.g., tree) or when the distance to the center line was greater than 18 feet on either side of the road.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Baseline (Days -1 and 1) and Days 14, 15, and 16	Brake reaction time was assessed as the time it took for each participant to move their foot off the accelerator and onto the brake pedal after the appearance of a stop sign on the simulation screen. Change from baseline was calculated as the Day 14, 15, or 16 mean reaction time minus the Baseline (Days -1 and 1) mean reaction time.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Baseline (Days -1 and 1) and Days 14, 15, and 16	Alertness VAS was completed immediately before and after each simulated driving assessment. Participants indicated their alertness by marking a vertical line on a horizontal scale anchored by responses extremely sleepy and extremely alert. VAS score was determined by measuring the distance in millimeters (mm) from the left hand end of the line to the point the participant marked. Scores ranged from 0-100 mm, with higher scores indicating more alertness and lower scores indicating more sleepiness. Change score was calculated as the Day 14, 15, or 16 VAS score minus the Baseline VAS score.
Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score	Baseline (Day -1) and Day 14	The Epworth Sleepiness Scale (ESS) is a questionnaire designed to evaluate daytime sleepiness. Participants were asked to rate how likely they were to doze or fall asleep during 8 activities on a scale of 0 (would never do) to 3 (high chance of dozing). The total score ranges from 0-24, with a score greater than 10 representing excessive daytime sleepiness (an increased chance of dozing). Change from baseline was calculated as the Day 14 total score minus the Baseline total score.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Baseline (Days -1 and 1) and Days 14, 15, and 16	The BAC was designed as a comprehensive measure of cognitive function, including 6 individual tests: Verbal Memory Recall, Digit Sequencing, Token Motor Task, Verbal Fluency, Symbol Coding, and Tower of London. The composite/total BAC score is calculated by scoring each individual test, comparing each score to a healthy control sample (matched for sex and age category) to create z-scores, summing the z-scores, and rescaling the sum. The composite score range is -2127.8 to 1878.8, with higher scores indicating better cognition.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Baseline (Days -1and 1) and Days 14, 15, and 16	Participants were presented with 15 words and asked to recall as many as possible; the procedure was repeated 5 times. The total number of words recalled correctly across the 5 administrations of the list was the participant's Verbal Memory Recall score (range: 0-75). The scaled test score was calculated as ((BAC component raw test score - healthy control sample test mean)/healthy control sample test standard deviation); a healthy control sample was matched to the participant's sex and age category. The scaled test score range is -7.37 to 4.86; higher scaled scores indicate better cognition.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Baseline (Days -1and 1) and Days 14, 15, and 16	Participants (par.) were presented with sets of numbers of increasing length and asked to tell the experimenter the numbers in order from lowest to highest. The task has 7 levels; the first level had 2 digits in the set (e.g., 5, 2); the second level had 3 digits in the set, etc. The number of times the par. correctly arranged the numbers was recorded as the score for each level. The DSS is the sum of the 7 level scores (range: 0-28). The scaled test score was calculated as indicated for the Verbal Memory Test and ranges from -6.68 to 2.73; higher scaled scores indicate better cognition.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Baseline (Days -1and 1) and Days 14, 15, and 16	Participants were given 100 plastic tokens and asked to place them in a container, 2 at a time, as quickly as possible for 60 seconds. The number of tokens correctly placed in the container was the Token Motor Task score (range: 0-100). The BAC was conducted prior to each simulated driving test. The Token Motor Task scaled test score was calculated as indicated for the Verbal Memory Test. Change from baseline was calculated as the Day composite score minus the Baseline composite score. The scaled test score range is -6.95 to 3.35, with higher scaled scores indicating better cognition.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Baseline (Days -1 and 1) and Days 14, 15, and 16	Verbal Fluency included one semantic fluency and two letter fluency tasks. Participants were given 60 seconds to name as many words as possible within a given semantic category (supermarket items), and in two separate trials, participants were given 60 seconds to generate as many words as possible that began with a given letter. The total number of words from all of the 3 trials was the Verbal Fluency score (range: 0-150). The scaled test score was calculated as indicated for the Verbal Memory Test. The scaled test score range is -5 to 10.83; higher scaled scores indicate better cognition.
Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14	Day 14	The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-min increments beginning at 8AM on the day prior to the visit.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Baseline (Days -1and 1) and Days 14, 15, and 16	Participants (par.) were asked to look at 2 pictures simultaneously; each picture showed 3 different colored balls arranged on 3 pegs. Par. were to estimate the number of times the balls in 1 picture would have to be moved to make the arrangement of balls identical to that of the second picture. Par. were allowed 20 seconds to respond to each pair of pictures. The number of correct items was the TOL Score (range: 0-22). The TOL scaled test score was calculated as indicated for the Verbal Memory Test. The scaled test score range is -7.53 to 2.76; higher scaled scores indicate better cognition.
Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score	Baseline (Day -1) and Day 14	The IRLS Rating scale is a measure of RLS disease severity and reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total score ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement.
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Day 14	The CGI scale is a widely used tool designed to allow clinicians to rate the severity of illness and the change of the disease severity over time based on a seven-point rating scale, with a score of 1 being very much improved and a score of 7 being very much worse compared to baseline.
Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14	Day 14	The investigator-rated CGI-I is a clinician-rated assessment designed to allow clinicians to rate the change of their participant's disease severity over time based on a seven-point scale, with a score of 1 being very much improved, and a score of 7 being very much worse compared to baseline. For this endpoint, response was defined as a rating of very much improved or much improved (score of 1 or 2 on the scale) compared to baseline.
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Day 14	The participant-rated CGI-I scale is a self-rated assessment designed to allow participants to rate the change of their disease severity over time based on a seven-point scale, with a score of 1 being very much improved and a score of 7 being very much worse.
Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14	Day 14	The participant-rated CGI-I is a self-rated assessment designed to allow participants to rate the change of their disease severity over time based on a seven-point scale, with a score of 1 being very much improved, and a score of 7 being very much worse. Response was defined as a rating of very much improved or much improved (score of 1 or 2 on the scale).
Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14	Day 14	The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-min increments beginning at 8AM on the day prior to the visit. For Arms 2 and 3, upper limits of the confidence intervals are not available, as they are beyond the 24-hour time frame.
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	Day 14	The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-minute increments. The period was divided into 7 four-hour intervals (8 AM to 12 PM, 12 PM to 4 PM, 4 PM to 8 PM, 6 PM to 10 PM, 8 PM to 12 Midnight, Midnight to 4 AM, and 4 AM to 8 AM).
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Day 14	The PSQ is designed to evaluate sleep quality, ability to function, and the degree to which RLS symptoms interfere with sleep.
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Baseline (Days -1and 1) and Days 14, 15, and 16	The PghSD assessed participant's previous night's sleep. Change from baseline was calculated as the Day 14 (in the evening), 15 (in the morning), and 16 (at Tmax of GEn and DPH) value minus the Baseline (Days -1 and 1) value. Latency to sleep onset (time to fall asleep) and wake time after sleep onset are expressed in minutes.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Baseline (Days -1 and 1) and Days 14, 15, and 16	The PghSD assessed a participant's previous night's sleep. Change from baseline was calculated as the Day 14 (in the evening), 15 (in the morning after dose), and 16 (at Tmax)value minus the Baseline (Days -1 and 1) value. Total sleep time is expressed in hours.
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Baseline (Day -1and 1) and Days 14, 15, and 16	The PghSD assessed a participant's previous night's sleep. Sleep quality was assessed using a Visual Analogue Scale (VAS). Participants indicated their sleep quality by marking a vertical line on a horizontal scale anchored by responses very bad and very good. VAS score was determined by measuring the distance in millimeters (mm) from the left hand end of the line to the point that the participant marked. Scores ranged from 0 to 100 mm with higher scores indicating better sleep quality and lower scores indicating worse sleep quality.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Baseline (Days -1and 1) and Days 14, 15, and 16	Participants were given a list of numbers (numerals 1-9) that were each associated with a unique symbol. Participants decoded a list of 110 symbols as quickly as possible in 90 seconds. The total number of symbols correctly decoded was the Symbol Coding Score (range: 0-110). The Symbol Coding scaled test score was calculated as indicated for the Verbal Memory Test. Change from baseline was calculated as the Day composite score minus the Baseline composite score. The scaled test score range is -7 to 10.08, with higher scaled scores indicating better cognition.

Countries

United States

Participant flow

Participants by arm

Arm	Count
GEn Placebo and DPH Placebo Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	34
GEn 1200 mg and DPH Placebo Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	31
GEn 1800 mg and DPH Placebo Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	34
GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	30
Total	129

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	3	0	0
Overall Study	Protocol Violation	1	0	1	1
Overall Study	Withdrawal by Subject	1	1	0	1

Baseline characteristics

Characteristic	GEn Placebo and DPH Placebo	GEn 1200 mg and DPH Placebo	GEn 1800 mg and DPH Placebo	GEn Placebo and DPH 50 mg on Day 16	Total
Age Continuous	49.6 Years STANDARD_DEVIATION 11.4	46.8 Years STANDARD_DEVIATION 11.31	49.3 Years STANDARD_DEVIATION 10.27	40.6 Years STANDARD_DEVIATION 11.8	46.8 Years STANDARD_DEVIATION 11.62
Race/Ethnicity, Customized Other, Unknown	0 participants	0 participants	1 participants	0 participants	1 participants
Race/Ethnicity, Customized White or Caucasian	34 participants	31 participants	33 participants	30 participants	128 participants
Sex: Female, Male Female	20 Participants	21 Participants	17 Participants	19 Participants	77 Participants
Sex: Female, Male Male	14 Participants	10 Participants	17 Participants	11 Participants	52 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	10 / 34	16 / 31	21 / 34	11 / 30
serious Total, serious adverse events	0 / 34	0 / 31	0 / 34	0 / 30

Outcome results

Primary

Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)

Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 16 mean LPV over the 1-hour drive minus the Baseline mean LPV over the 1-hour drive. The Day 16 measurement is at the time of maximum concentration (Tmax) for both GEn and DPH.

Time frame: Baseline (Day -1) and Day 16

Population: Modified Intent-to-Treat (MITT) Population: all participants in the Safety Population who completed at least one Baseline and one End of Study (Days 14-16) simulated driving assessment. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)	-0.10 feet	Standard Error 0.06
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)	0.15 feet	Standard Error 0.06
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)	0.15 feet	Standard Error 0.06
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)	0.16 feet	Standard Error 0.06

95% CI: [0.08, 0.42]

95% CI: [0.09, 0.41]

95% CI: [0.09, 0.42]

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)

Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 14 (in the evening) or Day 15 (in the morning after GEn dosed at 5 PM) mean LPV over the 1-hour drive minus the Baseline (Day -1 or Day 1) mean LPV over the 1-hour drive.

Time frame: Baseline (Days -1 and 1) and Days 14 and 15

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 14, n=33, 28, 33, 28	-0.06 feet	Standard Deviation 0.17
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 15, n=32, 28, 31, 27	-0.01 feet	Standard Deviation 0.14
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 15, n=32, 28, 31, 27	0.13 feet	Standard Deviation 0.4
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 14, n=33, 28, 33, 28	0.17 feet	Standard Deviation 0.43
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 14, n=33, 28, 33, 28	-0.01 feet	Standard Deviation 0.28
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 15, n=32, 28, 31, 27	0.02 feet	Standard Deviation 0.32
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 14, n=33, 28, 33, 28	-0.08 feet	Standard Deviation 0.15
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)	Day 15, n=32, 28, 31, 27	-0.10 feet	Standard Deviation 0.19

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time

Brake reaction time was assessed as the time it took for each participant to move their foot off the accelerator and onto the brake pedal after the appearance of a stop sign on the simulation screen. Change from baseline was calculated as the Day 14, 15, or 16 mean reaction time minus the Baseline (Days -1 and 1) mean reaction time.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 14, n=33, 25, 32, 27	-0.04 seconds	Standard Deviation 0.08
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 16, n=30, 28, 33, 27	-0.04 seconds	Standard Deviation 0.1
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 15, n=32, 25, 30, 25	-0.00 seconds	Standard Deviation 0.07
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 14, n=33, 25, 32, 27	-0.07 seconds	Standard Deviation 0.09
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 16, n=30, 28, 33, 27	-0.05 seconds	Standard Deviation 0.15
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 15, n=32, 25, 30, 25	-0.03 seconds	Standard Deviation 0.08
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 15, n=32, 25, 30, 25	-0.01 seconds	Standard Deviation 0.15
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 14, n=33, 25, 32, 27	-0.03 seconds	Standard Deviation 0.12
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 16, n=30, 28, 33, 27	-0.03 seconds	Standard Deviation 0.1
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 14, n=33, 25, 32, 27	-0.04 seconds	Standard Deviation 0.12
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 16, n=30, 28, 33, 27	-0.03 seconds	Standard Deviation 0.16
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time	Day 15, n=32, 25, 30, 25	-0.05 seconds	Standard Deviation 0.1

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position

Lane position was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall average lane position was calculated as the Day 14 (in the evening), 15 (in the morning after GEn dosed at 5 PM), or 16 (assessment at Tmax of GEn and DPH) mean lane position over the 1-hour drive minus the Baseline (Days -1 and 1) mean lane position over the 1-hour drive.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 14, n=33, 28, 33, 28	0.05 feet	Standard Deviation 0.35
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 15, n=32, 28, 31, 27	0.01 feet	Standard Deviation 0.35
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 16, n=30, 28, 33, 28	0.17 feet	Standard Deviation 0.44
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 15, n=32, 28, 31, 27	0.12 feet	Standard Deviation 0.39
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 14, n=33, 28, 33, 28	-0.02 feet	Standard Deviation 0.64
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 16, n=30, 28, 33, 28	0.13 feet	Standard Deviation 0.48
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 14, n=33, 28, 33, 28	0.03 feet	Standard Deviation 0.32
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 15, n=32, 28, 31, 27	0.04 feet	Standard Deviation 0.34
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 16, n=30, 28, 33, 28	0.14 feet	Standard Deviation 0.32
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 15, n=32, 28, 31, 27	0.04 feet	Standard Deviation 0.28
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 16, n=30, 28, 33, 28	0.08 feet	Standard Deviation 0.31
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position	Day 14, n=33, 28, 33, 28	0.08 feet	Standard Deviation 0.29

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed

Participants were instructed to maintain a speed of 55 miles per hour during the driving assessment. Change from baseline in overall average speed was calculated as the Day 14 (in the evening), 15 (in the morning), or 16 (at Tmax of GEn and DPH) mean speed over the 1-hour drive minus the Baseline (Days -1 and 1) mean speed over the 1-hour drive.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 15, n=32, 28, 31, 27	0.75 miles per hour	Standard Deviation 1.75
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 14, n=33, 28, 33, 28	1.24 miles per hour	Standard Deviation 1.49
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 16, n=30, 28, 33, 28	1.70 miles per hour	Standard Deviation 1.92
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 15, n=32, 28, 31, 27	0.33 miles per hour	Standard Deviation 0.97
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 14, n=33, 28, 33, 28	0.66 miles per hour	Standard Deviation 1.34
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 16, n=30, 28, 33, 28	0.90 miles per hour	Standard Deviation 1.58
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 14, n=33, 28, 33, 28	0.42 miles per hour	Standard Deviation 1.43
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 15, n=32, 28, 31, 27	0.30 miles per hour	Standard Deviation 1.12
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 16, n=30, 28, 33, 28	0.92 miles per hour	Standard Deviation 1.64
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 15, n=32, 28, 31, 27	0.37 miles per hour	Standard Deviation 1.04
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 16, n=30, 28, 33, 28	0.84 miles per hour	Standard Deviation 1.64
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed	Day 14, n=33, 28, 33, 28	0.12 miles per hour	Standard Deviation 1.51

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability

Speed variability was defined as the standard deviation of the speed (measured in miles per hour). Participants were instructed to maintain a speed of 55 miles per hour during the test drive. Change from baseline in overall speed variability was calculated as the Day 14 (in the evening), 15 (in the morning), or 16 (at Tmax of GEn and DPH) mean speed variability over the 1-hour drive minus the Baseline (Days -1 and 1) mean speed variability over the 1-hour drive.

Time frame: Baseline (Day -1) and Days 14 and 16; baseline (Day 1) and Day 15

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 16, n=30, 28, 33, 28	-0.54 miles per hour	Standard Deviation 0.55
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 15, n=32, 28, 31, 27	-0.26 miles per hour	Standard Deviation 0.48
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 14, n=33, 28, 33, 28	-0.22 miles per hour	Standard Deviation 0.63
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 16, n=30, 28, 33, 28	-0.12 miles per hour	Standard Deviation 2.02
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 14, n=33, 28, 33, 28	-0.19 miles per hour	Standard Deviation 1.42
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 15, n=32, 28, 31, 27	0.43 miles per hour	Standard Deviation 2.22
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 14, n=33, 28, 33, 28	-0.32 miles per hour	Standard Deviation 1.17
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 15, n=32, 28, 31, 27	-0.07 miles per hour	Standard Deviation 0.69
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 16, n=30, 28, 33, 28	0.23 miles per hour	Standard Deviation 1.95
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 16, n=30, 28, 33, 28	-0.08 miles per hour	Standard Deviation 1.11
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 15, n=32, 28, 31, 27	-0.33 miles per hour	Standard Deviation 0.43
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability	Day 14, n=33, 28, 33, 28	-0.47 miles per hour	Standard Deviation 0.96

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score

Alertness VAS was completed immediately before and after each simulated driving assessment. Participants indicated their alertness by marking a vertical line on a horizontal scale anchored by responses extremely sleepy and extremely alert. VAS score was determined by measuring the distance in millimeters (mm) from the left hand end of the line to the point the participant marked. Scores ranged from 0-100 mm, with higher scores indicating more alertness and lower scores indicating more sleepiness. Change score was calculated as the Day 14, 15, or 16 VAS score minus the Baseline VAS score.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. Varying numbers of participants did not complete either the pre- or post-drive VAS at either Baseline or the day of assessment; as such, the number of participants analyzed varies by day.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Pre-Drive, n=32, 28, 33, 28	6.3 millimeters	Standard Deviation 23.44
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Pre Drive Difference, n=33,27,32,27	-4.7 millimeters	Standard Deviation 22.22
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Pre Drive Difference, n=31,28,33,28	7.7 millimeters	Standard Deviation 22.38
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Pre-Drive, n=33, 27, 33, 28	1.5 millimeters	Standard Deviation 15.56
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Pre Drive Difference, n=33,28,32,28	3.1 millimeters	Standard Deviation 26.04
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Drive, n=33, 28, 32, 28	7.7 millimeters	Standard Deviation 21.72
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Drive, n=31, 28, 33, 28	14.3 millimeters	Standard Deviation 22.23
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Drive, n=33, 27, 32, 27	-3.2 millimeters	Standard Deviation 18.92
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Pre-Drive, n=33, 28, 32, 28	4.5 millimeters	Standard Deviation 22.98
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Drive, n=33, 27, 32, 27	-6.1 millimeters	Standard Deviation 28.44
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Pre-Drive, n=32, 28, 33, 28	0.8 millimeters	Standard Deviation 32.79
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Pre Drive Difference, n=33,27,32,27	-6.3 millimeters	Standard Deviation 24.55
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Drive, n=33, 28, 32, 28	3.2 millimeters	Standard Deviation 21.76
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Pre-Drive, n=33, 28, 32, 28	-2.6 millimeters	Standard Deviation 25.43
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Pre Drive Difference, n=33,28,32,28	5.9 millimeters	Standard Deviation 20.69
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Pre Drive Difference, n=31,28,33,28	-4.5 millimeters	Standard Deviation 36.14
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Drive, n=31, 28, 33, 28	-3.6 millimeters	Standard Deviation 32.01
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Pre-Drive, n=33, 27, 33, 28	0.2 millimeters	Standard Deviation 26.98
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Drive, n=33, 27, 32, 27	4.8 millimeters	Standard Deviation 21.08
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Pre-Drive, n=33, 28, 32, 28	-3.5 millimeters	Standard Deviation 29.39
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Drive, n=33, 28, 32, 28	3.3 millimeters	Standard Deviation 21.48
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Pre Drive Difference, n=33,28,32,28	4.9 millimeters	Standard Deviation 25.09
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Pre-Drive, n=33, 27, 33, 28	7.2 millimeters	Standard Deviation 21.53
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Pre Drive Difference, n=33,27,32,27	-2.2 millimeters	Standard Deviation 27.45
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Pre-Drive, n=32, 28, 33, 28	-8.8 millimeters	Standard Deviation 27.61
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Drive, n=31, 28, 33, 28	-7.5 millimeters	Standard Deviation 26.17
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Pre Drive Difference, n=31,28,33,28	1.3 millimeters	Standard Deviation 34.13
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Pre-Drive, n=32, 28, 33, 28	-11.8 millimeters	Standard Deviation 24
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Pre-Drive, n=33, 27, 33, 28	0.4 millimeters	Standard Deviation 22.1
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Pre Drive Difference, n=33,28,32,28	0.1 millimeters	Standard Deviation 24.66
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Pre Drive Difference, n=31,28,33,28	-2.3 millimeters	Standard Deviation 23.91
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 16; Post-Drive, n=31, 28, 33, 28	-14.0 millimeters	Standard Deviation 29.25
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Post-Drive, n=33, 28, 32, 28	-3.0 millimeters	Standard Deviation 22.62
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Pre Drive Difference, n=33,27,32,27	-3.7 millimeters	Standard Deviation 33.84
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 15; Post-Drive, n=33, 27, 32, 27	-3.1 millimeters	Standard Deviation 22.97
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score	Day 14; Pre-Drive, n=33, 28, 32, 28	-3.1 millimeters	Standard Deviation 20.99

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item

The PghSD assessed a participant's previous night's sleep. Change from baseline was calculated as the Day 14 (in the evening), 15 (in the morning after dose), and 16 (at Tmax)value minus the Baseline (Days -1 and 1) value. Total sleep time is expressed in hours.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. Participants in the GEn placebo and DPH placebo and the GEn placebo and DPH 50 mg on Day 16 arms have been combined into the GEn placebo and DPH group. The number of participants assessed for each PghSD question at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 15, n=60, 28, 33	-0.2 hours	Standard Deviation 2.1
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 14, n=59, 26, 33	0.3 hours	Standard Deviation 1.6
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 16, n=59, 26, 33	0.5 hours	Standard Deviation 1.82
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 15, n=60, 28, 33	0.2 hours	Standard Deviation 1.24
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 14, n=59, 26, 33	0.2 hours	Standard Deviation 1.82
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 16, n=59, 26, 33	0.3 hours	Standard Deviation 1.32
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 14, n=59, 26, 33	1.0 hours	Standard Deviation 2.39
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 16, n=59, 26, 33	0.4 hours	Standard Deviation 1.91
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item	Day 15, n=60, 28, 33	0.3 hours	Standard Deviation 1.54

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score

The BAC was designed as a comprehensive measure of cognitive function, including 6 individual tests: Verbal Memory Recall, Digit Sequencing, Token Motor Task, Verbal Fluency, Symbol Coding, and Tower of London. The composite/total BAC score is calculated by scoring each individual test, comparing each score to a healthy control sample (matched for sex and age category) to create z-scores, summing the z-scores, and rescaling the sum. The composite score range is -2127.8 to 1878.8, with higher scores indicating better cognition.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 16, n=32, 28, 33, 28	7.2 scores on a scale	Standard Deviation 7.24
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 14, n=33, 28, 33, 28	4.6 scores on a scale	Standard Deviation 5.64
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 15, n=33, 28, 33, 28	4.8 scores on a scale	Standard Deviation 5.39
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 14, n=33, 28, 33, 28	5.3 scores on a scale	Standard Deviation 7.01
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 16, n=32, 28, 33, 28	9.1 scores on a scale	Standard Deviation 8.98
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 15, n=33, 28, 33, 28	3.4 scores on a scale	Standard Deviation 4.59
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 15, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 6.61
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 14, n=33, 28, 33, 28	5.3 scores on a scale	Standard Deviation 6.88
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 16, n=32, 28, 33, 28	7.1 scores on a scale	Standard Deviation 8.34
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 14, n=33, 28, 33, 28	7.0 scores on a scale	Standard Deviation 6.25
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 16, n=32, 28, 33, 28	10.7 scores on a scale	Standard Deviation 6.05
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score	Day 15, n=33, 28, 33, 28	4.8 scores on a scale	Standard Deviation 4.66

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)

Participants (par.) were presented with sets of numbers of increasing length and asked to tell the experimenter the numbers in order from lowest to highest. The task has 7 levels; the first level had 2 digits in the set (e.g., 5, 2); the second level had 3 digits in the set, etc. The number of times the par. correctly arranged the numbers was recorded as the score for each level. The DSS is the sum of the 7 level scores (range: 0-28). The scaled test score was calculated as indicated for the Verbal Memory Test and ranges from -6.68 to 2.73; higher scaled scores indicate better cognition.

Time frame: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 14, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.84
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 16, n=32, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.79
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 15, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.83
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 14, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.9
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 16, n=32, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.66
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 15, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.86
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 14, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.75
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 15, n=33, 28, 33, 28	-0.2 scores on a scale	Standard Deviation 0.72
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 16, n=32, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.73
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 14, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.8
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 16, n=32, 28, 33, 28	0.7 scores on a scale	Standard Deviation 0.75
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)	Day 15, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.69

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score

Participants were given 100 plastic tokens and asked to place them in a container, 2 at a time, as quickly as possible for 60 seconds. The number of tokens correctly placed in the container was the Token Motor Task score (range: 0-100). The BAC was conducted prior to each simulated driving test. The Token Motor Task scaled test score was calculated as indicated for the Verbal Memory Test. Change from baseline was calculated as the Day composite score minus the Baseline composite score. The scaled test score range is -6.95 to 3.35, with higher scaled scores indicating better cognition.

Time frame: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 14, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 1.03
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 16, n=32, 28, 33, 28	0.4 scores on a scale	Standard Deviation 1.08
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 15, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 1.12
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 14, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 1.06
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 16, n=32, 28, 33, 28	0.4 scores on a scale	Standard Deviation 1.04
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 15, n=33, 28, 33, 28	-0.0 scores on a scale	Standard Deviation 0.93
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 15, n=33, 28, 33, 28	-0.2 scores on a scale	Standard Deviation 0.86
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 14, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 1.29
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 16, n=32, 28, 33, 28	0.1 scores on a scale	Standard Deviation 1.34
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 14, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.89
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 16, n=32, 28, 33, 28	0.4 scores on a scale	Standard Deviation 1.09
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score	Day 15, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.67

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score

Verbal Fluency included one semantic fluency and two letter fluency tasks. Participants were given 60 seconds to name as many words as possible within a given semantic category (supermarket items), and in two separate trials, participants were given 60 seconds to generate as many words as possible that began with a given letter. The total number of words from all of the 3 trials was the Verbal Fluency score (range: 0-150). The scaled test score was calculated as indicated for the Verbal Memory Test. The scaled test score range is -5 to 10.83; higher scaled scores indicate better cognition.

Time frame: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 14, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.91
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 15, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.65
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 16, n=32, 28, 33, 28	0.7 scores on a scale	Standard Deviation 1.04
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 14, n=33, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.84
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 16, n=32, 28, 33, 28	0.7 scores on a scale	Standard Deviation 0.83
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 15, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.65
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 15, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.68
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 16, n=32, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.97
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 14, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.76
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 15, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.87
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 14, n=33, 28, 33, 28	0.6 scores on a scale	Standard Deviation 0.68
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score	Day 16, n=32, 28, 33, 28	0.9 scores on a scale	Standard Deviation 0.98

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score

Participants were presented with 15 words and asked to recall as many as possible; the procedure was repeated 5 times. The total number of words recalled correctly across the 5 administrations of the list was the participant's Verbal Memory Recall score (range: 0-75). The scaled test score was calculated as ((BAC component raw test score - healthy control sample test mean)/healthy control sample test standard deviation); a healthy control sample was matched to the participant's sex and age category. The scaled test score range is -7.37 to 4.86; higher scaled scores indicate better cognition.

Time frame: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 14, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.77
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 16, n=32, 28, 33, 28	-0.2 scores on a scale	Standard Deviation 0.78
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 15, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.63
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 14, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.83
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 16, n=32, 28, 33, 28	-0.1 scores on a scale	Standard Deviation 0.88
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 15, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.75
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 15, n=33, 28, 33, 28	-0.0 scores on a scale	Standard Deviation 0.93
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 14, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.82
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 16, n=32, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.97
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 14, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.94
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 16, n=32, 28, 33, 28	0.0 scores on a scale	Standard Deviation 0.92
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score	Day 15, n=33, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.8

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score

Participants were given a list of numbers (numerals 1-9) that were each associated with a unique symbol. Participants decoded a list of 110 symbols as quickly as possible in 90 seconds. The total number of symbols correctly decoded was the Symbol Coding Score (range: 0-110). The Symbol Coding scaled test score was calculated as indicated for the Verbal Memory Test. Change from baseline was calculated as the Day composite score minus the Baseline composite score. The scaled test score range is -7 to 10.08, with higher scaled scores indicating better cognition.

Time frame: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 16, n=32, 28, 33, 28	1.3 scores on a scale	Standard Deviation 0.92
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 14, n=33, 28, 33, 28	0.6 scores on a scale	Standard Deviation 0.57
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 15, n=33, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.85
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 14, n=33, 28, 33, 28	0.6 scores on a scale	Standard Deviation 0.87
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 16, n=32, 28, 33, 28	1.4 scores on a scale	Standard Deviation 1.28
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 15, n=33, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.78
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 15, n=33, 28, 33, 28	-0.0 scores on a scale	Standard Deviation 1.04
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 14, n=33, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.72
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 16, n=32, 28, 33, 28	1.0 scores on a scale	Standard Deviation 0.95
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 14, n=33, 28, 33, 28	0.6 scores on a scale	Standard Deviation 0.85
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 16, n=32, 28, 33, 28	1.3 scores on a scale	Standard Deviation 0.81
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score	Day 15, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.78

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score

Participants (par.) were asked to look at 2 pictures simultaneously; each picture showed 3 different colored balls arranged on 3 pegs. Par. were to estimate the number of times the balls in 1 picture would have to be moved to make the arrangement of balls identical to that of the second picture. Par. were allowed 20 seconds to respond to each pair of pictures. The number of correct items was the TOL Score (range: 0-22). The TOL scaled test score was calculated as indicated for the Verbal Memory Test. The scaled test score range is -7.53 to 2.76; higher scaled scores indicate better cognition.

Time frame: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 14, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.59
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 16, n=32, 28, 33, 28	0.1 scores on a scale	Standard Deviation 0.73
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 15, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 0.65
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 14, n=33, 28, 33, 28	0.2 scores on a scale	Standard Deviation 1.03
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 16, n=32, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.91
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 15, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 0.9
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 15, n=33, 28, 33, 28	0.4 scores on a scale	Standard Deviation 0.89
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 14, n=33, 28, 33, 28	0.3 scores on a scale	Standard Deviation 1.17
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 16, n=32, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.96
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 14, n=33, 28, 33, 28	0.5 scores on a scale	Standard Deviation 0.95
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 16, n=32, 28, 33, 28	0.6 scores on a scale	Standard Deviation 0.92
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score	Day 15, n=33, 28, 33, 28	0.5 scores on a scale	Standard Deviation 1.3

Secondary

Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score

The Epworth Sleepiness Scale (ESS) is a questionnaire designed to evaluate daytime sleepiness. Participants were asked to rate how likely they were to doze or fall asleep during 8 activities on a scale of 0 (would never do) to 3 (high chance of dozing). The total score ranges from 0-24, with a score greater than 10 representing excessive daytime sleepiness (an increased chance of dozing). Change from baseline was calculated as the Day 14 total score minus the Baseline total score.

Time frame: Baseline (Day -1) and Day 14

Population: Modified Intent-to-Treat (MITT) Population

Arm	Measure	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score	-2.6 scores on a scale	Standard Deviation 3.22
GEn 1200 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score	-2.3 scores on a scale	Standard Deviation 5.61
GEn 1800 mg and DPH Placebo	Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score	-2.4 scores on a scale	Standard Deviation 5.04
GEn Placebo and DPH 50 mg on Day 16	Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score	-2.4 scores on a scale	Standard Deviation 4.88

Secondary

Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score

The IRLS Rating scale is a measure of RLS disease severity and reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total score ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement.

Time frame: Baseline (Day -1) and Day 14

Arm	Measure	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score	-7.6 scores on a scale	Standard Deviation 7.63
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score	-12.4 scores on a scale	Standard Deviation 9.93
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score	-13.1 scores on a scale	Standard Deviation 8.09

Secondary

Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality

The PghSD assessed a participant's previous night's sleep. Sleep quality was assessed using a Visual Analogue Scale (VAS). Participants indicated their sleep quality by marking a vertical line on a horizontal scale anchored by responses very bad and very good. VAS score was determined by measuring the distance in millimeters (mm) from the left hand end of the line to the point that the participant marked. Scores ranged from 0 to 100 mm with higher scores indicating better sleep quality and lower scores indicating worse sleep quality.

Time frame: Baseline (Day -1and 1) and Days 14, 15, and 16

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 15, n=61, 28, 33	11.8 millimeters	Standard Deviation 27.3
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 14, n=61, 28, 33	21.2 millimeters	Standard Deviation 29.47
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 16, n=59, 28, 33	20.7 millimeters	Standard Deviation 25.01
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 15, n=61, 28, 33	24.6 millimeters	Standard Deviation 29.15
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 14, n=61, 28, 33	29.9 millimeters	Standard Deviation 30.76
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 16, n=59, 28, 33	27.4 millimeters	Standard Deviation 24.11
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 14, n=61, 28, 33	35.1 millimeters	Standard Deviation 28.84
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 16, n=59, 28, 33	16.7 millimeters	Standard Deviation 28.86
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality	Day 15, n=61, 28, 33	18.0 millimeters	Standard Deviation 24.82

Secondary

Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items

The PghSD assessed participant's previous night's sleep. Change from baseline was calculated as the Day 14 (in the evening), 15 (in the morning), and 16 (at Tmax of GEn and DPH) value minus the Baseline (Days -1 and 1) value. Latency to sleep onset (time to fall asleep) and wake time after sleep onset are expressed in minutes.

Time frame: Baseline (Days -1and 1) and Days 14, 15, and 16

Arm	Measure	Group	Value (MEAN)	Dispersion
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 14; Latency to Sleep Onset, n=61, 28, 33	-8.1 minutes	Standard Deviation 54.74
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 14; Wake Time After Sleep Onset, n=59, 26, 33	-14.0 minutes	Standard Deviation 45.46
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 15; Latency to Sleep Onset n=61, 28, 33	-8.7 minutes	Standard Deviation 57.28
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 15; Wake Time After Sleep Onset, n=60, 28, 33	4.9 minutes	Standard Deviation 61.11
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 16; Latency to Sleep Onset, n=60, 28, 23	-17.3 minutes	Standard Deviation 46.6
GEn Placebo and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 16; Wake Time After Sleep Onset, n=59, 26, 33	-15.8 minutes	Standard Deviation 55.44
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 16; Wake Time After Sleep Onset, n=59, 26, 33	-26.3 minutes	Standard Deviation 29.5
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 14; Latency to Sleep Onset, n=61, 28, 33	-3.2 minutes	Standard Deviation 62.96
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 15; Wake Time After Sleep Onset, n=60, 28, 33	-30.8 minutes	Standard Deviation 51.97
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 16; Latency to Sleep Onset, n=60, 28, 23	-3.3 minutes	Standard Deviation 55.67
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 14; Wake Time After Sleep Onset, n=59, 26, 33	-23.3 minutes	Standard Deviation 41.11
GEn 1200 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 15; Latency to Sleep Onset n=61, 28, 33	-14.9 minutes	Standard Deviation 54.05
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 14; Wake Time After Sleep Onset, n=59, 26, 33	-26.9 minutes	Standard Deviation 45.18
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 15; Latency to Sleep Onset n=61, 28, 33	-35.8 minutes	Standard Deviation 59.02
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 16; Wake Time After Sleep Onset, n=59, 26, 33	-9.9 minutes	Standard Deviation 60.58
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 15; Wake Time After Sleep Onset, n=60, 28, 33	-14.8 minutes	Standard Deviation 64.07
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 14; Latency to Sleep Onset, n=61, 28, 33	-25.7 minutes	Standard Deviation 60.32
GEn 1800 mg and DPH Placebo	Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items	Day 16; Latency to Sleep Onset, n=60, 28, 23	-19.3 minutes	Standard Deviation 52.76

Secondary

Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14

The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-min increments beginning at 8AM on the day prior to the visit. For Arms 2 and 3, upper limits of the confidence intervals are not available, as they are beyond the 24-hour time frame.

Time frame: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the

Arm	Measure	Value (MEDIAN)
GEn Placebo and DPH Placebo	Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14	7.0 participants
GEn 1200 mg and DPH Placebo	Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14	14.3 participants
GEn 1800 mg and DPH Placebo	Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14	15.5 participants

Secondary

Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14

The CGI scale is a widely used tool designed to allow clinicians to rate the severity of illness and the change of the disease severity over time based on a seven-point rating scale, with a score of 1 being very much improved and a score of 7 being very much worse compared to baseline.

Time frame: Day 14

Arm	Measure	Group	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Improved, score of 2	15 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Worse, score of 5	4 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	No Change, score of 4	15 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Improved, score of 1	7 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Worse, score of 7	0 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Worse, score of 6	1 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Improved, score of 3	19 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	No Change, score of 4	4 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Improved, score of 1	10 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Improved, score of 2	7 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Improved, score of 3	7 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Worse, score of 5	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Worse, score of 6	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Worse, score of 7	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Worse, score of 5	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Improved, score of 2	8 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Worse, score of 7	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Worse, score of 6	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	No Change, score of 4	4 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Improved, score of 3	6 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Improved, score of 1	15 participants

Secondary

Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14

The participant-rated CGI-I scale is a self-rated assessment designed to allow participants to rate the change of their disease severity over time based on a seven-point scale, with a score of 1 being very much improved and a score of 7 being very much worse.

Time frame: Day 14

Arm	Measure	Group	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Improved, score of 2	16 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Worse, score of 5	5 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	No Change, score of 4	17 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Improved, score of 1	7 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Worse, score of 7	0 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Worse, score of 6	2 participants
GEn Placebo and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Improved, score of 3	14 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	No Change, score of 4	3 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Improved, score of 1	9 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Improved, score of 2	11 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Improved, score of 3	3 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Worse, score of 5	2 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Worse, score of 6	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Worse, score of 7	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Worse, score of 5	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Improved, score of 2	9 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Worse, score of 7	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Much Worse, score of 6	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	No Change, score of 4	4 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Minimally Improved, score of 3	6 participants
GEn 1800 mg and DPH Placebo	Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14	Very Much Improved, score of 1	14 participants

Secondary

Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14

The investigator-rated CGI-I is a clinician-rated assessment designed to allow clinicians to rate the change of their participant's disease severity over time based on a seven-point scale, with a score of 1 being very much improved, and a score of 7 being very much worse compared to baseline. For this endpoint, response was defined as a rating of very much improved or much improved (score of 1 or 2 on the scale) compared to baseline.

Time frame: Day 14

Arm	Measure	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14	22 participants
GEn 1200 mg and DPH Placebo	Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14	17 participants
GEn 1800 mg and DPH Placebo	Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14	23 participants

Secondary

Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14

The participant-rated CGI-I is a self-rated assessment designed to allow participants to rate the change of their disease severity over time based on a seven-point scale, with a score of 1 being very much improved, and a score of 7 being very much worse. Response was defined as a rating of very much improved or much improved (score of 1 or 2 on the scale).

Time frame: Day 14

Arm	Measure	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14	23 participants
GEn 1200 mg and DPH Placebo	Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14	20 participants
GEn 1800 mg and DPH Placebo	Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14	23 participants

Secondary

Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14

The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-minute increments. The period was divided into 7 four-hour intervals (8 AM to 12 PM, 12 PM to 4 PM, 4 PM to 8 PM, 6 PM to 10 PM, 8 PM to 12 Midnight, Midnight to 4 AM, and 4 AM to 8 AM).

Time frame: Day 14

Arm	Measure	Group	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	4 AM to 8 AM	39 participants
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	8 AM to 12 PM	37 participants
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	12 PM to 4 PM	35 participants
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	4 PM to 8 PM	36 participants
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	6 PM to 10 PM	27 participants
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	8 PM to 12 AM	18 participants
GEn Placebo and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	12 AM to 4 AM	24 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	12 AM to 4 AM	17 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	4 PM to 8 PM	19 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	6 PM to 10 PM	18 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	4 AM to 8 AM	23 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	8 PM to 12 AM	13 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	8 AM to 12 PM	21 participants
GEn 1200 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	12 PM to 4 PM	20 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	4 AM to 8 AM	26 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	8 PM to 12 AM	18 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	4 PM to 8 PM	26 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	12 AM to 4 AM	24 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	12 PM to 4 PM	23 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	6 PM to 10 PM	23 participants
GEn 1800 mg and DPH Placebo	Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14	8 AM to 12 PM	27 participants

Secondary

Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)

A simulated crash was defined as a collision with an oncoming car or obstacle (e.g., tree) or when the distance to the center line was greater than 18 feet on either side of the road.

Time frame: Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Arm	Measure	Group	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 5 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 2 Crashes, n=33, 28, 33, 28	2 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 3 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 4 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 1 Crash, n=33, 28, 33, 28	2 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 13 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 1 Crash, n=33, 28, 31, 28	1 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 2 Crashes, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 4 Crashes, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 13 Crashes, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 1 Crash, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 3 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 4 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 5 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 13 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 17 Crashes, n=30, 28, 33, 28	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 13 Crashes, n=33, 28, 33, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 4 Crashes, n=33, 28, 31, 28	2 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 17 Crashes, n=30, 28, 33, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 3 Crashes, n=30, 28, 33, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 13 Crashes, n=30, 28, 33, 28	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 13 Crashes, n=33, 28, 31, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 3 Crashes, n=33, 28, 33, 28	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 1 Crash, n=30, 28, 33, 28	5 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 5 Crashes, n=33, 28, 33, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 1 Crash, n=33, 28, 31, 28	4 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 4 Crashes, n=33, 28, 33, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 2 Crashes, n=33, 28, 33, 28	2 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 4 Crashes, n=30, 28, 33, 28	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 2 Crashes, n=33, 28, 31, 28	3 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 5 Crashes, n=30, 28, 33, 28	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 1 Crash, n=33, 28, 33, 28	1 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 13 Crashes, n=33, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 5 Crashes, n=33, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 5 Crashes, n=30, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 1 Crash, n=33, 28, 31, 28	1 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 2 Crashes, n=33, 28, 31, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 17 Crashes, n=30, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 4 Crashes, n=33, 28, 31, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 13 Crashes, n=33, 28, 31, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 13 Crashes, n=30, 28, 33, 28	1 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 1 Crash, n=30, 28, 33, 28	3 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 3 Crashes, n=30, 28, 33, 28	2 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 1 Crash, n=33, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 2 Crashes, n=33, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 4 Crashes, n=30, 28, 33, 28	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 3 Crashes, n=33, 28, 33, 28	1 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 4 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 17 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 2 Crashes, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 3 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 1 Crash, n=33, 28, 33, 28	1 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 5 Crashes, n=30, 28, 33, 28	1 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 1 Crash, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 4 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 2 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 5 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 13 Crashes, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 13 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 1 Crash, n=30, 28, 33, 28	2 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 13 Crashes, n=30, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 15; 4 Crashes, n=33, 28, 31, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 14; 4 Crashes, n=33, 28, 33, 28	0 participants
GEn Placebo and DPH 50 mg on Day 16	Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)	Day 16; 3 Crashes, n=30, 28, 33, 28	0 participants

Secondary

Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14

The PSQ is designed to evaluate sleep quality, ability to function, and the degree to which RLS symptoms interfere with sleep.

Time frame: Day 14

Arm	Measure	Group	Value (NUMBER)
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Nights with RLS Symptoms	8 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Excellent	9 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3-4 Awakenings/Night due to RLS	8 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-2 Nights with RLS Symptoms	12 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Excellent	8 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-2 Wakenings/Night due to RLS	41 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3-4 Nights with RLS Symptoms	17 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3+ Hours Awake/Night due to RLS	0 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Awakenings/Night due to RLS	10 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	5-6 Nights with RLS Symptoms	13 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-<2 Hours Awake/Night due to RLS	3 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	7 Nights with RLS Symptoms	11 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Good	32 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	2-<3 Hours Awake/Night due to RLS	2 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	<1 Hour Awake/Night due to RLS	3 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Moderate	20 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Poor	21 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Hours Awake/Night due to RLS	53 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Poor	1 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Reasonable	31 participants
GEn Placebo and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	5+ Awakenings/Night due to RLS	2 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-<2 Hours Awake/Night due to RLS	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Excellent	5 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Reasonable	18 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Poor	5 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Excellent	6 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Good	17 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Moderate	5 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Poor	0 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Nights with RLS Symptoms	8 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-2 Nights with RLS Symptoms	7 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3-4 Nights with RLS Symptoms	6 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	5-6 Nights with RLS Symptoms	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	7 Nights with RLS Symptoms	6 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Awakenings/Night due to RLS	7 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-2 Wakenings/Night due to RLS	18 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3-4 Awakenings/Night due to RLS	2 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	5+ Awakenings/Night due to RLS	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Hours Awake/Night due to RLS	23 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	<1 Hour Awake/Night due to RLS	4 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	2-<3 Hours Awake/Night due to RLS	1 participants
GEn 1200 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3+ Hours Awake/Night due to RLS	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Nights with RLS Symptoms	10 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Reasonable	17 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3-4 Awakenings/Night due to RLS	1 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Poor	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3+ Hours Awake/Night due to RLS	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	5+ Awakenings/Night due to RLS	1 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Moderate	4 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	2-<3 Hours Awake/Night due to RLS	2 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Hours Awake/Night due to RLS	31 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Good	18 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Excellent	14 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	<1 Hour Awake/Night due to RLS	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	5-6 Nights with RLS Symptoms	3 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Ability to Function: Excellent	11 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	7 Nights with RLS Symptoms	3 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	3-4 Nights with RLS Symptoms	8 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	Sleep Quality: Poor	2 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	0 Awakenings/Night due to RLS	8 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-2 Nights with RLS Symptoms	9 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-<2 Hours Awake/Night due to RLS	0 participants
GEn 1800 mg and DPH Placebo	Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14	1-2 Wakenings/Night due to RLS	23 participants

Secondary

Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14

Time frame: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the

Arm	Measure	Value (NUMBER)
GEn Placebo and DPH Placebo	Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14	9.84 percentage of participants
GEn 1200 mg and DPH Placebo	Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14	35.71 percentage of participants
GEn 1800 mg and DPH Placebo	Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14	42.42 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Simulated Driving Study in Restless Legs Syndrome

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)

Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score

Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score

Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score

Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score

Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality

Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items

Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14

Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14

Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14

Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14

Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14

Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14

Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)

Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14

Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14