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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Transcept Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01106859
First received: April 16, 2010
Last updated: February 10, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Insomnia
Drug: zopiclone
Drug: zolpidem tartrate sublingual tablet
Drug: Placebo (sublingual tablet)
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Transcept Pharmaceuticals:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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:
  • Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test [ Time Frame: 3-9 hours post dose ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 40
Study Start Date: June 2010
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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.
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
Placebo matching zopiclone
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.
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
Placebo matching zopiclone
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.
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

  Eligibility

Ages Eligible for Study:   21 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01106859

Locations
Netherlands
Maastricht University
Maastricht, Netherlands, 6229 ER
Sponsors and Collaborators
Transcept Pharmaceuticals
Investigators
Principal Investigator: Annemiek Vermeeren, PhD Maastricht University
  More Information

No publications provided by Transcept Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Transcept Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01106859     History of Changes
Other Study ID Numbers: ZI-18, 2010-019959-22
Study First Received: April 16, 2010
Results First Received: December 15, 2011
Last Updated: February 10, 2012
Health Authority: United States: Institutional Review Board
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Transcept Pharmaceuticals:
insomnia

Additional relevant MeSH terms:
Zolpidem
Zopiclone
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
GABA-A Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014