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

NCT01106859 | Completed Phase 1 Results

• 2 other identifiers: ZI-182010-019959-22
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Insomnia

Keywords

insomnia

Outcome Measures

Primary Outcomes (2)

• 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.

  3-9 hours post dose

• 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.

  3-9 hours post dose

Secondary Outcomes (7)

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

  3-9 hours post dose

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

  3-9 hours post dose

• Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs)

  Day 1 -6 weeks

• 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

• 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

Study Arms (4)

zopiclone

ACTIVE COMPARATOR

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; Drug: Placebo (sublingual tablet)

zolpidem 3 hours prior

EXPERIMENTAL

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; Drug: Placebo

zolpidem 4 hours prior

EXPERIMENTAL

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; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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); Drug: Placebo

Interventions

zopiclone DRUG

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.

Also known as: non-benzodiazepine hypnotic agent, Zimovane, Imovane

zopiclone

zolpidem tartrate sublingual tablet DRUG

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.

Also known as: Intermezzo®

zolpidem 3 hours prior; zolpidem 4 hours prior

Placebo (sublingual tablet) DRUG

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.

Placebo; zopiclone

Placebo DRUG

Placebo matching zopiclone

Placebo; zolpidem 3 hours prior; zolpidem 4 hours prior

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Transcept Pharmaceuticals: lead

Study Sites (1)

Maastricht University

Maastricht, 6229 ER, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 24587571 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

zopiclone; Zolpidem; Administration, Sublingual

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Administration, Oral; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

No studies directly connect SDLP thresholds with an increased risk of an accident for an individual. Nor has a SDLP threshold been adopted by a regulatory body. Based on published literature, an SDLP change of 2.5 cm was used in the primary outcome.

Results Point of Contact

• Title: Clinical Leader
• Organization: Purdue Pharma LP

800-733-1333

Study Officials

• Annemiek Vermeeren, PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2010
• First Posted: April 20, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: February 14, 2012
• Results First Posted: January 20, 2012

Record last verified: 2012-02

Locations

NL (1)