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

Primary Purpose

Insomnia

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

zopiclone

zolpidem tartrate sublingual tablet

Placebo (sublingual tablet)

Placebo

About this trial

This is an interventional treatment trial for Insomnia focused on measuring insomnia

Eligibility Criteria

21 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Maastricht University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Placebo Comparator

Arm Label

zopiclone

zolpidem 3 hours prior

zolpidem 4 hours prior

Placebo

Arm Description

Zopiclone is taken at bedtime 9 hours before driving. The middle-of-the-night medication is a placebo matching 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.

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.

A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is a placebo matching zolpidem tartrate sublingual tablet.

Outcomes

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

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

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

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

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)

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

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

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.

Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

Full Information

NCT ID

NCT01106859

First Posted

April 16, 2010

Last Updated

February 10, 2012

Sponsor

Transcept Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01106859

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2012

Overall Recruitment Status

Completed

Study Start Date

June 2010 (undefined)

Primary Completion Date

September 2010 (Actual)

Study Completion Date

September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Transcept Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Insomnia

Keywords

insomnia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

zopiclone

Arm Type

Active Comparator

Arm Description

Zopiclone is taken at bedtime 9 hours before driving. The middle-of-the-night medication is a placebo matching zolpidem tartrate sublingual tablet.

Arm Title

zolpidem 3 hours prior

Arm Type

Experimental

Arm Description

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.

Arm Title

zolpidem 4 hours prior

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

A placebo matching zopiclone is taken at bedtime. The middle-of-the-night treatment is a placebo matching zolpidem tartrate sublingual tablet.

Intervention Type

Drug

Intervention Name(s)

zopiclone

Other Intervention Name(s)

non-benzodiazepine hypnotic agent, Zimovane, Imovane

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

zolpidem tartrate sublingual tablet

Other Intervention Name(s)

Intermezzo®

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo (sublingual tablet)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo matching zopiclone

Primary Outcome Measure Information:

Title

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

Description

Time Frame

3-9 hours post dose

Title

Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

Description

Time Frame

3-9 hours post dose

Secondary Outcome Measure Information:

Title

Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test

Description

Time Frame

3-9 hours post dose

Title

Mean Standard Deviation of Speed (SDS) in the Highway Drive Test

Description

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

Title

Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs)

Description

Time Frame

Day 1 -6 weeks

Title

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

Description

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

Title

Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

Description

Time Frame

3-9 hours post dose

Title

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

Description

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

Title

Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

Description

Time Frame

3-9 hours post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Annemiek Vermeeren, PhD

Organizational Affiliation

Maastricht University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maastricht University

City

Maastricht

ZIP/Postal Code

6229 ER

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

24587571

Citation

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.

Results Reference

derived

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

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