An Evaluation of Potential Next-day Residual Effects of Eszopiclone in Healthy Volunteers.

Study Overview
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Brief Summary
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This study will explore potential next-day residual effects of a single evening dose of 3mg of the hypnotic, eszopiclone, 7.5mg of zopiclone, and placebo, in healthy adult subjects.

Official Title
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A Randomised, Double-blind, Double-dummy, Placebo-controlled, 3-way Crossover Study to Evaluate Potential Next-day Residual Effects of a Single Evening Dose of 3mg Eszopiclone and 7.5mg Zopiclone in Healthy Adult Subjects.

Conditions
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Healthy Subjects, Sleep Initiation and Maintenance Disorders

Intervention / Treatment
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* Drug: GSK1755165; placebo; zopiclone


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Healthy male and female subjects providing written informed consent. EXCLUSION CRITERIA: Significant medical disorders; Sleeping difficulties; alcohol and/or substance abuse; Recent use of psychotropic medications, or need to use them during study; Very high BMI or very low BMI or bodyweight; Known hypersensitivity to the study medications or their excipients; Unwilling or unable to meet certain lifestyle or dietary restrictions during the study.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crossover<br>All subjects received all three treatments in a randomised order | Drug: GSK1755165; placebo; zopiclone<br>* Subjects receive either 3mg GSK1755165, matching placebo or 7.5mg zopiclone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Tracking Error Assessed During the Continuous Tracking Test (CTT) | Analysis was performed on the mean of the five assessments conducted 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind) The CTT is a task (duration of 8 minutes) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the mean tracking error - the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking. | 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Tracking Error (MTE) Assessed During the CTT | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) . The CTT is a task (8 minute duration) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the MTE, the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| CTT Mean Reaction Time | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) A further outcome derived from the CTT is a peripheral awareness task where the participant responds to a stimulus presented in the periphery of vision, while simultaneously attending to the tracking test. The mean reaction time, in milliseconds, to these stimuli over the trial period is taken as the response measure for this component of the divided attention task. A lower mean reaction time is indicative of better peripheral awareness. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Critical Flicker Fusion Test-Ascending Threshold | Critical Flicker Fusion (CFF) is a validated cognitive assessment task that provides an index of central nervous system (CNS) activity and attention modulated motion detection. Participants are required to discriminate flicker from fusion, and vice versa, in a set of four light-emitting diodes arranged in a one-centimetre square. These diodes are held in foveal fixation when viewed at a distance of one metre. Individual thresholds are determined on four ascending and four descending scales. The mean of the four ascending presentations give the ascending threshold frequency in hertz. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Critical Flicker Fusion Test -Descending Threshold | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four descending presentations from the CFF give the descending threshold frequency in hertz. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Critical Flicker Fusion Test-Overall Threshold | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four ascending and four descending presentations of the CFF give the overall threshold frequency in hertz. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| 1-Back Percentage of Correct Responses | The N-Back task requires the participant to indicate, using the mouse, whether the current stimulus presented on the screen and the one immediately before it visually match (i.e., one-back). In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 minutes. The percentage of correct responses is the percentage of correct responses given in 2 minutes. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| 3-Back Percentage of Correct Responses | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). In 3-back tasks, a comparison is made between the current stimulus and the two before the immediately preceding stimulus. In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 min. The percentage of correct responses is the percentage of correct responses given in 2 min. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| 1-Back Reaction Time | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| 3-Back Reaction Time | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Sedation Score, as Assessed by the Linear Analogue Rating Scales | The Linear Analogue Rating Scale (LARS) is used as a measure of the subjective effects of psychoactive drugs. Participants mark a series of 10 cm (100 unit line) analogue scales (1-100, 100 = most impaired) relating to dizzy, clumsy, anxious, relaxed, tired, drowsy, alert, energetic, sad, and depressed, indicating their present feeling with regard to a mid-point, representing their usual state of mind before treatment began. The higher the score, the more impaired the participant feels. The Tiredness, Alertness, Energy, and Drowsiness scores are averaged to derive an overall Sedation score. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Mood Score, as Assessed by the Linear Analogue Rating Scales | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Anxiety, Depression, Relaxed, and Sadness scores are averaged to derive an overall Mood score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 
| Coordination Score, as Assessed by the Linear Analogue Rating Scales | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Dizziness and Clumsiness scores are averaged to derive an overall Coordination score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired. | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zopiclone, Hypnotic, Residual effects, Eszopiclone