Driving Simulator Performance After Intake of Zopiclone Sleeping Pills

Study Overview
=================
Brief Summary
-----------------
Zopiclone, a widely used hypnotic drug, is frequently found in blood samples taken from drivers suspected of driving under the influence. In this study, the investigators aim to correlate zopiclone serum concentrations with degrees of driving impairment in healthy volunteers by use of a validated driving simulator. The investigators also aim to compare their results with the results from a previous study that investigated zopiclone impairment of cognitive and psychometric tests.

Official Title
-----------------
Driving Simulator Performance Related to Serum Concentrations of the Benzodiazepine-like Hypnotic Zopiclone

Conditions
-----------------
Automobile Driving

Intervention / Treatment
-----------------
* Drug: Zopiclone
* Drug: Ethanol
* Drug: Placebo pill
* Drug: Placebo drink


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male Caucasian ethnicity Age 25-35 years Possession of a driver's licence for at least five years Exclusion Criteria: Score ≥ 2 on the modified Apfel-scale to assess risk for motion sickness(*) History of driving under the influence of alcohol and/or illicit substances History or presence of alcohol or illicit drug abuse Former abnormal reaction to any hypnotic drug History of strong averse reactions to blood sampling procedures Regular (daily) intake of any prescribed drug, or intake of grapefruit juice or herbal remedies that can influence the metabolism of zopiclone (e.g. St John's wort) History of severe allergic reactions, or significant mental, cardiovascular, renal or hepatic disorder, or other significant disease as judged by the investigators Detection of any drugs of abuse on pre-session urine drug screening (*)Modified Apfel-criteria for prediction of postoperative nausea/vomiting: Smoker? yes 0, no 1 History of nausea and/or vomiting following surgery, dental treatment, injections or similar procedures? yes 0, no 1 History of car sickness after 10 years of age? yes 0, no 1 A score of two or more points excludes participation.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zopiclone 5 mg<br>Zopiclone 5 mg pill + placebo pill + placebo drink | Drug: Zopiclone<br>* Zopiclone pill 5 or 10 mg, given orally as a single dose.<br>* Other names: Zopiclon;Drug: Placebo pill<br>* Placebo pill identical to zopiclone pill, given orally as a single dose<br>Drug: Placebo drink<br>* Placebo drink, given orally as a single dose<br>|
| Experimental: Zopiclone 10 mg<br>2 x zopiclone 5 mg pills + placebo drink | Drug: Zopiclone<br>* Zopiclone pill 5 or 10 mg, given orally as a single dose.<br>* Other names: Zopiclon;Drug: Placebo drink<br>* Placebo drink, given orally as a single dose<br>|
| Active Comparator: Ethanol 0.8 g/L<br>2 x placebo pills + ethanol 50 g/70 kg | Drug: Ethanol<br>* 50 mg per 70 kg body weight, given orally as a single dose<br>* Other names: Ethyl alcohol;Drug: Placebo pill<br>* Placebo pill identical to zopiclone pill, given orally as a single dose<br>|
| Placebo Comparator: Placebo<br>2 x placebo pills + placebo drink | Drug: Placebo pill<br>* Placebo pill identical to zopiclone pill, given orally as a single dose<br>Drug: Placebo drink<br>* Placebo drink, given orally as a single dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standard deviation of lateral position (SDLP) on road | SDLP is a measure that quantifies the extent of car weaving while driving. It has been shown to correlate well with blood alcohol concentrations, and traffic accident risk. | 1 h after intake of study medication (during a 30 min driving simulator test session) | 
| Standard deviation of lateral position (SDLP) on road | SDLP is a measure that quantifies the extent of car weaving while driving. It has been shown to correlate well with blood alcohol concentrations, and traffic accident risk | 3,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Standard deviation of lateral position (SDLP) on road | SDLP is a measure that quantifies the extent of car weaving while driving. It has been shown to correlate well with blood alcohol concentrations, and traffic accident risk | 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average speed |  | 1 h, 3,5 hrs and 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Standard deviation of speed |  | 1 h, 3,5 hrs and 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Frequency of brake pedal pressures |  | 1 h, 3,5 hrs and 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Frequency of accelerator pedal pressures |  | 1 h, 3,5 hrs and 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Steering wheel movement speed and reversal frequency |  | 1 h, 3,5 hrs and 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Driving behavior at incidents |  | 1 h, 3,5 hrs and 6,5 hrs after intake of study medication (during a 30 min driving simulator test session) | 
| Clinical test for impairment (CTI) | The Norwegian CTI is a 25-item clinical test that is administered by physicians on subjects suspected of driving under the influence of drugs. The test conclusion is either impaired or not impaired. | 1,5 hrs, 4 hrs and 7 hrs after intake of study medication (after driving simulator test sessions) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Automobile driving, Zopiclone, Drug safety, Traffic accidents