Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet

Phase 1

Completed

Conditions: Insomnia

Interventions: Drug: zolpidem tartrate sublingual tablet
Drug: zopiclone
Drug: Placebo (sublingual tablet)
Drug: Placebo

Registration Number: NCT01106859

Lead Sponsor: Transcept Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
zopiclone	Placebo (sublingual tablet)	Zopiclone is taken at bedtime 9 hours before driving. The middle-of-the-night medication is a placebo matching zolpidem tartrate sublingual tablet.
zolpidem 3 hours prior	zolpidem tartrate sublingual tablet	A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is zolpidem tartrate sublingual tablet taken 3 hours prior to driving.
zolpidem 3 hours prior	Placebo	A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is zolpidem tartrate sublingual tablet taken 3 hours prior to driving.
zolpidem 4 hours prior	zolpidem tartrate sublingual tablet	A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is zolpidem tartrate sublingual tablet taken 4 hours prior to driving.
zolpidem 4 hours prior	Placebo	A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is zolpidem tartrate sublingual tablet taken 4 hours prior to driving.
Placebo	Placebo (sublingual tablet)	A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is a placebo matching zolpidem tartrate sublingual tablet.
Placebo	Placebo	A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is a placebo matching zolpidem tartrate sublingual tablet.
zopiclone	zopiclone	Zopiclone is taken at bedtime 9 hours before driving. The middle-of-the-night medication is a placebo matching zolpidem tartrate sublingual tablet.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.