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

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ClinicalTrials.gov Identifier: NCT01106859
Recruitment Status : Completed
First Posted : April 20, 2010
Results First Posted : January 20, 2012
Last Update Posted : February 14, 2012
Sponsor:
Information provided by (Responsible Party):
Transcept Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE April 16, 2010
First Posted Date  ICMJE April 20, 2010
Results First Submitted Date  ICMJE December 15, 2011
Results First Posted Date  ICMJE January 20, 2012
Last Update Posted Date February 14, 2012
Study Start Date  ICMJE June 2010
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2012)
  • 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 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 19, 2010)
Assessment of impaired driving as determined by the number of subjects whose Standard Deviation of Lateral Position (a common measure of onroad weaving) on active drug exceeds 2.5 cm versus placebo [ Time Frame: 12 weeks ]
Change History Complete list of historical versions of study NCT01106859 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2012)
  • Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2010)
  • Assessment of impaired driving as determined by the number of subjects whose Standard Deviation of Lateral Position (a common measure of onroad weaving) on active drug exceeds 2.0 cm versus placebo [ Time Frame: 12 weeks ]
  • Assessment of impaired driving as determined by the number of subjects whose Standard Deviation of Lateral Position (a common measure of onroad weaving) on active drug exceeds 3.5 cm versus placebo [ Time Frame: 12 weeks ]
  • Active versus placebo (mean ±) standard deviation of Standard Deviation of Lateral Position (a common measure of on-road weaving) [ Time Frame: 12 weeks ]
  • Active versus placebo (mean ±) standard deviation of Standard of Deviation of Speed (a common measure of the ability to maintain a constant driving speed) [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet
Official Title  ICMJE Assessment of Next-Morning Driving Performance After Middle of the Night Administration of Zolpidem Tartrate Sublingual Tablet 3.5 mg in Healthy Adult Volunteers: Single-center, Double-blind, Randomized, Placebo-controlled, Four-way Crossover Study
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Insomnia
Intervention  ICMJE
  • Drug: zopiclone
    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.
    Other Names:
    • non-benzodiazepine hypnotic agent
    • Zimovane
    • Imovane
  • Drug: zolpidem tartrate sublingual tablet
    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.
    Other Name: Intermezzo®
  • Drug: Placebo (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.
  • Drug: Placebo
    Placebo matching zopiclone
Study Arms  ICMJE
  • Active Comparator: zopiclone
    Zopiclone is taken at bedtime 9 hours before driving. The middle-of-the-night medication is a placebo matching zolpidem tartrate sublingual tablet.
    Interventions:
    • Drug: zopiclone
    • Drug: Placebo (sublingual tablet)
  • Experimental: zolpidem 3 hours prior
    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.
    Interventions:
    • Drug: zolpidem tartrate sublingual tablet
    • Drug: Placebo
  • Experimental: zolpidem 4 hours prior
    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.
    Interventions:
    • Drug: zolpidem tartrate sublingual tablet
    • Drug: Placebo
  • Placebo Comparator: Placebo
    A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is a placebo matching zolpidem tartrate sublingual tablet.
    Interventions:
    • Drug: Placebo (sublingual tablet)
    • Drug: Placebo
Publications * Vermeeren A, Vuurman EF, Leufkens TR, Van Leeuwen CJ, Van Oers AC, Laska E, Rico S, Steinberg F, Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. Sleep. 2014 Mar 1;37(3):489-96. doi: 10.5665/sleep.3482.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 19, 2010)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2010
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01106859
Other Study ID Numbers  ICMJE ZI-18
2010-019959-22 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Transcept Pharmaceuticals
Study Sponsor  ICMJE Transcept Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Annemiek Vermeeren, PhD Maastricht University
PRS Account Transcept Pharmaceuticals
Verification Date February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP