Insomnia
Conditions
Keywords
insomnia
Brief summary
A study in healthy volunteers of the next morning driving performance after middle-of-the-night dosing of 3.5 mg zolpidem tartrate sublingual tablet, a sleep aid. The next morning driving performance will be measured by taking a standardized driving test.
Interventions
DRUGzopiclone
7.5 mg tablet by mouth. Zopiclone is a commonly used hypnotic in Europe that is known to impair driving in the morning 9 hours after dosing.
3.5 mg zolpidem tartrate sublingual tablet taken either 3 or 4 hours prior to driving. Participants placed the study drug under the tongue and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.
DRUGPlacebo (sublingual tablet)
Placebo matching zolpidem tartrate sublingual tablet taken either 3 or 4 hours prior to driving. Participants placed the study drug under the tongue and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.
DRUGPlacebo
Placebo matching zopiclone
Sponsors
Transcept Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects between the ages of 21 and 64 inclusive. For female subjects only: Female subjects will be included if they are post-menopausal or sterilized, or if they are of childbearing potential, they are not breastfeeding, their pregnancy test is negative, they have no intention of becoming pregnant during the course of the study, and are using adequate contraceptive drugs or devices. Medically acceptable methods of contraception that may be used by the subject and/or her partner are: oral contraceptives, progestin injection or implants, condom with spermicide, diaphragm with spermicide, IUD, vaginal spermicidal suppository, surgical sterilization or abstinence. Females using oral contraception must have started using the medication at least 4 weeks prior to screening. Surgical sterilization must have occurred at least 6 weeks prior to screening. * Good health on the basis of pre-study history and physical examination, vital signs and the results of blood chemistry, hematology, and urinalysis * Good binocular visual acuity, corrected or uncorrected * Possession of valid driver's license for 3 years or more * Driving experience at least 3000 km/year * Signed informed consent
Exclusion criteria
* A history of drug addiction or drug or substance abuse, including alcohol abuse, within the past 12 months * Has a history of restless legs syndrome, sleep apnea, narcolepsy or other primary sleep disorder * A known hypersensitivity to zolpidem or zopiclone * Has undergone oral surgery, tooth extraction or piercing of the lip/tongue within 60 days prior to screening * Has used any medication to promote sleep, including herbal medications, within 14 days (or 5 half-lives of the drug, whichever is longer) prior to screening * Prescription medications for other health conditions are allowed as long as the subject has been on a stable dose at least 30 days prior to screening * Has taken any drugs known to induce hepatic drug metabolism (i.e., rifampin) within 30 days prior to screening * BMI \> 29 Kg/M\^2 * Current use of medication that affects driving performance * Smokes more than 10 cigarettes/day * Uses tobacco products during periods of nighttime awakening * Consumes more than 6 cups of coffee/day * Consumes more than 21 glasses of alcohol/week * Has received an investigational drug within 60 days or 5 half-lives (whichever is longer) prior to screening * Has any additional condition(s) that in the Investigator's opinion would: * Affect sleep/wake function * Prohibit the subject from completing the study * Not be in the best interest of the subject to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | 3-9 hours post dose | SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 2.5 cm threshold. A neutral driving performance shows a difference of SDLP \>= 2.5 cm and \<= -2.5 cm when compared to placebo. A worse performance is when the difference of SDLP \> 2.5 cm, and an improved performance is when the difference of SDLP \< -2.5 cm. |
| Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | 3-9 hours post dose | This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of \<.001 are listed in the data table as 0.000. A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Day 1 -6 weeks | Adverse Events were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness (summarized as 'unrelated' and 'related') to study treatment. Also included are counts of participants with serious AEs, AEs leading to discontinuation of study treatment, and deaths. |
| Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | 3-9 hours post dose | SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 2.0 cm threshold. A neutral driving performance shows a difference of SDLP \>= 2.0 cm and \<= -2.0 cm when compared to placebo. A worse performance is when the difference of SDLP \> 2.0 cm, and an improved performance is when the difference of SDLP \< -2.0 cm. |
| Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test | 3-9 hours post dose | Standard deviation of lateral position (SDLP) in a highway-driving lane is a surrogate measure for driving performance. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed. |
| Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | 3-9 hours post dose | SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 3.5 cm threshold. A neutral driving performance shows a difference of SDLP \>= 3.5 cm and \<= -3.5 cm when compared to placebo. A worse performance is when the difference of SDLP \> 3.5 cm, and an improved performance is when the difference of SDLP \< -3.5 cm. |
| Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | 3-9 hours post dose | This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of \<.001 are listed in the data table as 0.000. A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance. |
| Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | 3-9 hours post dose | This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of \<.001 are listed in the data table as 0.000. A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance. |
| Mean Standard Deviation of Speed (SDS) in the Highway Drive Test | 3-9 hours post dose | Mean standard deviation of speed (SDS) is a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed are recorded and analyzed. |
Countries
Netherlands
Participant flow
Pre-assignment details
Forty-four candidates were screened. Four screening failures: high blood pressure (2), positive drug test (1), personal reasons (1)
Participants by arm
| Arm | Count |
|---|---|
| Total Population All participants in this four-way cross-over study | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total Population |
|---|---|
| Age Continuous | 37 years STANDARD_DEVIATION 15 |
| Body Mass Index (BMI) | 23.2 kilograms/meter^2 STANDARD_DEVIATION 2.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 176 centimeters STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 39 participants |
| Region of Enrollment Netherlands | 40 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 20 Participants |
| Weight Female | 65 kilograms STANDARD_DEVIATION 8 |
| Weight Male | 79 kilograms STANDARD_DEVIATION 8 |
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 | 5 / 40 | 5 / 40 | 6 / 40 | 4 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 40 | 0 / 40 |
Outcome results
Primary
Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold
SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 2.5 cm threshold. A neutral driving performance shows a difference of SDLP \>= 2.5 cm and \<= -2.5 cm when compared to placebo. A worse performance is when the difference of SDLP \> 2.5 cm, and an improved performance is when the difference of SDLP \< -2.5 cm.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Neutral | 34 participants |
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Impaired | 5 participants |
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Improved | 1 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Neutral | 29 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Impaired | 10 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Improved | 1 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Impaired | 18 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Improved | 0 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold | Neutral | 22 participants |
Primary
Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy
This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of \<.001 are listed in the data table as 0.000. A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.025 proportion |
| Zolpidem 4 Hours Prior | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.125 proportion |
| Zolpidem 3 Hours Prior | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.025 proportion |
| Zolpidem 3 Hours Prior | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.250 proportion |
| Zopiclone | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.000 proportion |
| Zopiclone | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.450 proportion |
| Placebo | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | NA proportion |
| Placebo | Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | NA proportion |
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-2.5 cm in Standard Deviation of Lateral Position (SDLP) following administration of zolpidem tartrate sublingual tablet 4 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.2188McNemar
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-2.5 cm in Standard Deviation of Lateral Position (SDLP) following administration of zolpidem tartrate sublingual tablet 3 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.0117McNemar
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-2.5 cm in Standard Deviation of Lateral Position (SDLP) following administration of zopiclone 9 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: <0.0001McNemar
Secondary
Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test
Standard deviation of lateral position (SDLP) in a highway-driving lane is a surrogate measure for driving performance. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test | 16.7 centimeters | Standard Error 0.6 |
| Zolpidem 3 Hours Prior | Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test | 17.3 centimeters | Standard Error 0.6 |
| Zopiclone | Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test | 18.3 centimeters | Standard Error 0.6 |
| Placebo | Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test | 15.9 centimeters | Standard Error 0.6 |
Comparison: P-value is based on ANOVA model with fixed effects for sequence, period and treatment, a random effect for subject within sequence, and assuming compound symmetry covariance structure; the p-value is reported from LS Mean difference between Treatment Groups: LS mean of SDLP (Zolpidem 4 Hours) - LS mean of SDLP (Placebo).p-value: 0.017495% CI: [0.1, 1.5]ANOVA
Comparison: P-value is based on ANOVA model with fixed effects for sequence, period and treatment, a random effect for subject within sequence, and assuming compound symmetry covariance structure; the p-value is reported from LS Mean difference between Treatment Groups: LS mean of SDLP (Zolpidem 3 Hours) - LS mean of SDLP (Placebo).p-value: <0.000195% CI: [0.8, 2.1]ANOVA
Comparison: P-value is based on ANOVA model with fixed effects for sequence, period and treatment, a random effect for subject within sequence, and assuming compound symmetry covariance structure; the p-value is reported from LS Mean difference between Treatment Groups: LS mean of SDLP (Zopiclone) - LS mean of SDLP (Placebo).p-value: <0.000195% CI: [1.8, 3.1]ANOVA
Secondary
Mean Standard Deviation of Speed (SDS) in the Highway Drive Test
Mean standard deviation of speed (SDS) is a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed are recorded and analyzed.
Time frame: 3-9 hours post dose
Population: Intent to treat population. In one Zopiclone case, the velocity of the car was not recorded due to technical problems, and therefore SDS could not be calculated in this drive.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Mean Standard Deviation of Speed (SDS) in the Highway Drive Test | 1.98 kilometers/hour | Standard Error 0.08 |
| Zolpidem 3 Hours Prior | Mean Standard Deviation of Speed (SDS) in the Highway Drive Test | 1.91 kilometers/hour | Standard Error 0.08 |
| Zopiclone | Mean Standard Deviation of Speed (SDS) in the Highway Drive Test | 1.99 kilometers/hour | Standard Error 0.08 |
| Placebo | Mean Standard Deviation of Speed (SDS) in the Highway Drive Test | 1.83 kilometers/hour | Standard Error 0.08 |
Comparison: P-value is based on ANOVA model with fixed effects for sequence, period and treatment, a random effect for subject within sequence, and assuming compound symmetry covariance structure; the p-value is reported from LS Mean difference between Treatment Groups: LS mean of SDS (Zolpidem 4 hours prior) - LS mean of SDS (Placebo).p-value: 0.014595% CI: [0.03, 0.27]ANOVA
Comparison: P-value is based on ANOVA model with fixed effects for sequence, period and treatment, a random effect for subject within sequence, and assuming compound symmetry covariance structure; the p-value is reported from LS Mean difference between Treatment Groups: LS mean of SDS (Zolpidem 3 Hours) - LS mean of SDS (Placebo).p-value: 0.217995% CI: [-0.05, 0.2]ANOVA
Comparison: P-value is based on ANOVA model with fixed effects for sequence, period and treatment, a random effect for subject within sequence, and assuming compound symmetry covariance structure; the p-value is reported from LS Mean difference between Treatment Groups: LS mean of SDS (Zopiclone) - LS mean of SDS (Placebo).p-value: 0.009695% CI: [0.04, 0.29]ANOVA
Secondary
Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold
SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 2.0 cm threshold. A neutral driving performance shows a difference of SDLP \>= 2.0 cm and \<= -2.0 cm when compared to placebo. A worse performance is when the difference of SDLP \> 2.0 cm, and an improved performance is when the difference of SDLP \< -2.0 cm.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Neutral | 33 participants |
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Impaired | 6 participants |
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Improved | 1 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Neutral | 25 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Impaired | 13 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Improved | 2 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Impaired | 19 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Improved | 0 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold | Neutral | 21 participants |
Secondary
Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold
SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 3.5 cm threshold. A neutral driving performance shows a difference of SDLP \>= 3.5 cm and \<= -3.5 cm when compared to placebo. A worse performance is when the difference of SDLP \> 3.5 cm, and an improved performance is when the difference of SDLP \< -3.5 cm.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Improved | 0 participants |
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Neutral | 38 participants |
| Zolpidem 4 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Impaired | 2 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Improved | 0 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Impaired | 7 participants |
| Zolpidem 3 Hours Prior | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Neutral | 33 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Improved | 0 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Neutral | 26 participants |
| Zopiclone | Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold | Impaired | 14 participants |
Secondary
Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy
This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of \<.001 are listed in the data table as 0.000. A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.150 proportion |
| Zolpidem 4 Hours Prior | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.025 proportion |
| Zolpidem 3 Hours Prior | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.050 proportion |
| Zolpidem 3 Hours Prior | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.325 proportion |
| Zopiclone | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.475 proportion |
| Zopiclone | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.000 proportion |
| Placebo | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | NA proportion |
| Placebo | Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | NA proportion |
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-2.0 cm in Standard Deviation of Lateral Position (SDLP) following administration of zolpidem tartrate sublingual tablet 4 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.125McNemar
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-2.0 cm in Standard Deviation of Lateral Position (SDLP) following administration of zolpidem tartrate sublingual tablet 3 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.0074McNemar
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-2.0 cm in Standard Deviation of Lateral Position (SDLP) following administration of Zopiclone 9 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: <0.0001McNemar
Secondary
Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy
This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of \<.001 are listed in the data table as 0.000. A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance.
Time frame: 3-9 hours post dose
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.050 proportion |
| Zolpidem 4 Hours Prior | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.000 proportion |
| Zolpidem 3 Hours Prior | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.000 proportion |
| Zolpidem 3 Hours Prior | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.175 proportion |
| Zopiclone | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | 0.350 proportion |
| Zopiclone | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | 0.000 proportion |
| Placebo | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - impaired | NA proportion |
| Placebo | Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy | Probability - improved | NA proportion |
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-3.5 cm in Standard Deviation of Lateral Position (SDLP) following administration of zolpidem tartrate sublingual tablet 4 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.5McNemar
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-3.5 cm in Standard Deviation of Lateral Position (SDLP) following administration of zolpidem tartrate sublingual tablet 3 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.0156McNemar
Comparison: Symmetry analysis was performed for the probability of difference from placebo falling above and below the threshold of +/-3.5 cm in Standard Deviation of Lateral Position (SDLP) following administration of zopiclone 9 hours prior to driving. Statistically significant asymmetries indicate a decrement in driving performance. Lack of statistical significance indicates symmetry which shows a lack of treatment effect on driving performance.p-value: 0.0001McNemar
Secondary
Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs)
Adverse Events were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness (summarized as 'unrelated' and 'related') to study treatment. Also included are counts of participants with serious AEs, AEs leading to discontinuation of study treatment, and deaths.
Time frame: Day 1 -6 weeks
Population: Safety population (participants who were randomized and received at least one dose of study drug)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as moderate | 1 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Death | 0 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Unrelated | 3 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as severe | 0 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Discontinued study medication due to AE | 0 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as mild | 4 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one TEAE | 5 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Related | 2 participants |
| Zolpidem 4 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one serious AE | 0 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Unrelated | 2 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one TEAE | 5 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as mild | 5 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as moderate | 0 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as severe | 0 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Related | 3 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one serious AE | 0 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Discontinued study medication due to AE | 0 participants |
| Zolpidem 3 Hours Prior | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Death | 0 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one TEAE | 6 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Related | 2 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Death | 0 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Discontinued study medication due to AE | 0 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Unrelated | 4 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as mild | 6 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as severe | 0 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one serious AE | 0 participants |
| Zopiclone | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as moderate | 0 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one serious AE | 0 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Unrelated | 1 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Related | 3 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Death | 0 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as mild | 4 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | At least one TEAE | 4 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as moderate | 0 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | Discontinued study medication due to AE | 0 participants |
| Placebo | Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs) | TEAE graded as severe | 0 participants |