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

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.

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.

Study Overview

• Status: Completed
• Conditions: Sleep Initiation and Maintenance Disorders; Healthy Subjects
• Intervention / Treatment: Drug: GSK1755165; placebo; zopiclone

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XP
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: June 17, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (Estimate): June 18, 2008

Study Record Updates

• Last Update Posted (Estimate): June 5, 2012
• Last Update Submitted That Met QC Criteria: May 31, 2012
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Hypnotic; Eszopiclone; Zopiclone; Residual effects
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Zopiclone
• Other Study ID Numbers: ESZ111503