We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Effects of GW679769 on Sleep and Cognitive Function in Subjects With Primary Insomnia

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00650871
First Posted: April 2, 2008
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
A study to investigate the effects of GW679769 on sleep and cognition. Potential subjects participate in a clinical screening visit and a two-night PSG recording session in the sleep laboratory. Eligible subjects then participate in three separate two-night PSG sessions in which they are randomized to receive placebo or one of two doses of GW679769 60 minutes prior to bedtime, one treatment for each session in a balanced order. Each treatment session is separated by a two-week drug-free period and occur on the same day of the week. A safety follow-up visit occurs 2 weeks after the last treatment session.

Condition Intervention Phase
Sleep Initiation and Maintenance Disorders Drug: GW679769 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Primary Purpose: Diagnostic
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effects of GW679769 (30mg and 90mg) on Sleep Continuity, PSG Sleep Recordings, Subjective Sleep Assessment, and Daytime Cognitive Function in Subjects With Primary Insomnia

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Wake time after sleep onset (WASO) derived from PSG recording [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 Days) ]
    WASO was measured from persistent sleep onset to lights on. It was calculated as number of wake epochs from persistent sleep onset to lights on divided by 2. WASO measures was analyzed using a mixed effect model with session and treatment as fixed effect and participants as random effect.


Secondary Outcome Measures:
  • Mean total sleep time (TST) as objective PSG measures of sleep continuity [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    TST was defined as duration of Rapid Eye Movement (REM) plus non-REM (NREM)(Stage 1, Stage 2, Stages 3/4) sleep from lights off to lights on. It was calculated as number of REM plus NREM (Stage 1, Stage 2, Stages 3/4) epochs from lights off to lights on divided by 2.

  • Mean latency to persistent sleep (LPS) as objective PSG measures of sleep continuity [ Time Frame: Night 1 and 2 of each treatment period (approximately 31 days) ]
    LPS was measured from lights off to the first epoch of 20 consecutive non-wake epochs (sleep onset).It was calculated as number of epochs from lights off to the first of 20 consecutive non-wake epochs (sleep onset) divided by 2.

  • Mean wake during sleep (WDS) as objective PSG measures of sleep continuity [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    WDS was the duration, in min, of wakefulness from persistent sleep onset to final epoch of sleep (stage 1, 2, 3/4, or REM), and corresponds to WDS. WDS was defined as duration of wakefulness from persistent sleep onset to final epoch of sleep (stage 1, 2, 3/4 or REM) (min). An awakening was defined as a PSG recording of at least one wake epoch, bracketed by an epoch of stage 1, 2, or stage 3/4 of NREM sleep or REM sleep. The score was derived by a central PSG reader and was analyzed as the mean of the PSG WDS recordings obtained on two consecutive nights.

  • Mean wake after sleep (WAS) as objective PSG measures of sleep continuity [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    WAS defined as the duration of wakefulness, in min, from final epoch of sleep to lights on The score was derived by a central PSG reader and was analyzed as the mean of the PSG WAS recordings obtained on two consecutive nights. If only one assessment was present for a particular PSG session, the score from that one assessment was used. The overall WAS for night 1 and 2 was reported.

  • Mean number of 1 minute awakenings during sleep as objective PSG measures of sleep continuity [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    Number of periods of awakening from persistent sleep onset to lights on were recorded. Number of times after persistent sleep onset that there was a wake entry on the PSG recording of at least 1 minute duration (at least 2 consecutive wake epochs). Pairs of awakenings were separated an epoch of NREM sleep or REM sleep. Two wake entries of at least one minute separated by stage 1 sleep was considered as a single awakening.

  • Total Time in NREM Stage 1 and stage 2 as objective PSG measures of sleep structure [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    NREM sleep time was defined as the duration (in min) of NREM sleep during time in bed. The scores were derived by a central PSG reader and was analyzed as the mean of the PSG NREM recordings obtained on two consecutive nights.Total Time in NREM Stage 1 and stage 2 as objective PSG measures of sleep structure were recorded on night 1 and 2 and mean over the two nights was reported.

  • Total Time in Slow Wave Sleep (SWS) as objective PSG measures of sleep structure [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    SWS was defined as the duration, in min, of stage 3 or 4 duration during time in bed. Total time in SWS as objective PSG measures of sleep structure was recorded on night 1 and 2 and mean over the two nights was reported.

  • Total Time in REM as objective PSG measures of sleep structure [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    REM sleep time was also known as stage REM duration. It was defined as the number of minutes of stage REM during time in bed. Time in REM as objective PSG measures of sleep structure was recorded on night 1 and 2 and mean over the two nights was reported.

  • Latency to REM as objective PSG measures of sleep structure [ Time Frame: Night 1 and 2 of each treatment period (Approximately up to 31 days) ]
    Latency to REM as objective PSG measures of sleep structure was recorded on night 1 and 2 and mean over the two nights was reported.

  • Total sleep time (TST) as parameter of subjective post-sleep questionnaire [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    TST was the duration in min of REM plus NREM (Stage 1, Stage 2, Stages 3/4) sleep from lights off to lights on obtained on two consecutive nights of each PSG session. It was calculated as the number of REM plus NREM (Stage 1, Stage 2, Stages 3/4) epochs from lights off to lights on that is during Time in Bed (TIB). TST as parameter of subjective post-sleep questionnaire was recorded in response to the question, How long (total hours and minutes) do you think you slept last night? The questionnaire was reported by the participants on the next day of the PSG nights 1 and 2 and mean over the two nights was reported.

  • WASO as parameter of subjective post-sleep questionnaire [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    WASO was defined as the amount of time awake after persistent sleep onset to lights on. An awakening was defined as a PSG recording of at least one wake epoch, bracketed by an epoch of stage 1, 2, or stage 3/4 of NREM sleep or REM sleep. WASO was calculated as summation of number of WAS and number of WDS. WASO as parameter of subjective post-sleep questionnaire was assessed from response of the question Did you wake up during the night? The questionnaire was reported by the participants on the next day of the PSG nights 1 and 2 and mean over the two nights was reported.

  • Sleep onset latency (SOL) as parameter of subjective post-sleep questionnaire [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    SOL is the time required to fall asleep. SOL as parameter of subjective post-sleep questionnaire was recorded in response to the question, How long do you think it took you to fall asleep last night? The questionnaire was reported by the participants on the next day of the PSG nights 1 and 2 and mean over the two nights was reported.

  • Number of awakenings as parameter of subjective post-sleep questionnaire [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    Number of awakenings was subjective (participant-rated) measurement of number of awakening after sleep onset. Number of awakenings as parameter of subjective post-sleep questionnaire was recorded in response to the question, How many times do you think you woke up? The questionnaire was reported by the participants on the next day of the PSG nights 1 and 2 and mean over the two nights was reported.

  • Sleep quality (SQ) as parameter of subjective post-sleep questionnaire [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    SQ as parameter of subjective post-sleep questionnaire was recorded in response to the question, How would you describe the quality of your sleep last night? The responses from participants were recorded as very poor = 1, poor = 2, average= 3,good= 4, very good= 5 indicating the SQ. The questionnaire was reported by the participants on the next day of the PSG nights 1 and 2 and mean over the two nights was reported.

  • Digit symbol substitution test (DSST) as a measure of daytime cognitive function [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    DSST was a widely used measure of performance impairment. It is a typical test of association involved in substituting symbols for digits over a period of time. The number of correct signs substituted was taken as the score. Participants marked a geometric pattern associated with one of the digits displayed on a computer screen. Participants had 90 seconds to match as many geometric patterns as possible. The dependent measure were the number of patterns the participant were able to mark correctly (i.e., number of trials correct). Minimum possible score is 0= impaired cognitive function, there was no upper limit of the score. Higher the score indicated betterment in the daytime cognitive function. Mean DSST was calculated from the observations recorded on days followed by first and second PSG nights and mean over the two nights was reported.

  • Mean Hopkins Verbal Learning Test-Revised (HVLT-R) score including total recall and delayed recall as a measure of Daytime Cognitive Function [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    HVLT-R assesses verbal learning and memory. It comprised of four subscales including total recall, delayed recall, retention score, and recognition discrimination index. The total recall score was the number of correctly reported words in each of the 3 learning trials and the score ranged from 0 to 36. The delayed recall score was the number of correctly reported words in the delayed recall test and the score ranged from 0 to 12. The retention score represented the score on the delayed recall test divided by the higher of the recall scores from learning trials 2 and 3, multiplied by 100. It was practically ranged from 0 to 100. Higher score indicated betterment in the daytime cognitive function. The recognition discrimination index (RDI) was calculated by subtracting the total false positives score (semantically-related plus semantically un-related) from the total true-positives score obtained in the delayed recognition test).

  • HVLT-R (Retention %) as a measure of daytime Cognitive Function [ Time Frame: Night 1, Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    The HVLT-R offers a brief assessment of verbal learning and memory (recognition and recall) and its use had been validated with brain-disordered populations. Eight distinct forms of the HVLT-R were available, eliminating practice effects on repeated administrations. Each form consists of a list of 12 nouns (targets) with four words drawn from each of three semantic categories. The semantic categories differ across the eight forms, but the forms were very similar in their psychometric properties. The HVLT-R tasks included three learning trials, a delayed recall trial (20-25 minute delay), and a yes/no delayed recognition trial. This latter trial consists of a randomized list that includes the 12 target words and 12 non-target words, 6 of which are drawn from the same semantic categories as the targets. Mean percent retention of the target words was measured as a daytime cognitive function and mean over the three measures recorded at Night 1, Day 1 and 2 are reported.

  • HVLT-R (Recognition Discrimination Index [RDI]) as a measure of daytime Cognitive Function [ Time Frame: Night 1, Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    The HVLT-R offers a brief assessment of verbal learning and memory (recognition and recall) and its use had been validated with brain-disordered populations. Eight distinct forms of the HVLT-R were available, eliminating practice effects on repeated administrations. Each form consists of a list of 12 nouns (targets) with four words drawn from each of three semantic categories. The semantic categories differ across the eight forms, but the forms were very similar in their psychometric properties. The HVLT-R tasks included three learning trials, a delayed recall trial (20-25 minute delay), and a yes/no delayed recognition trial. This latter trial consists of a randomized list that includes the 12 target words and 12 non-target words, 6 of which are drawn from the same semantic categories as the targets. Recognition Discrimination Index of the target words was measured as a daytime cognitive function and mean over the three measures recorded at Night 1, Day 1 and 2 are reported.

  • Leeds Sleep Evaluation Questionnaire as scales for sleepiness/alertness [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    LSEQ had been used to monitor subjectively perceived changes in sleep during psychopharmacological investigation involving a variety of psychoactive agents. The questionnaire contains ten self-rating 100-mm-line analogue questions pertaining to four consecutive aspects of sleep: getting to sleep (GTS), QOS, awakening from sleep (AFS) and behaviour following wakefulness (BFW). Scores on the four LSEQ subscales vary between 100 (the largest possible positive change experienced after drug administration) and 0 (the largest possible negative change experienced after drug administration).

  • Stanford Sleepiness Scale as scales for sleepiness/alertness [ Time Frame: Day 1 and 2 post PSG of each treatment period (Approximately up to 31 days) ]
    Stanford Sleepiness Scale was assessed using the sleep evaluation questionnaire on Day 1 and 7 prior to dosing and at approximately 1 hour intervals after dosing until discharge from the clinic. It was rated on a seven point scale (1-7), where lower score indicates active and higher score indicates sleep onset soon; 1: feeling active, vital, alert, or wide awake, 2: functioning at high levels, but not at peak; able to concentrate, 3: awake, but relaxed; responsive but not fully alert, 4: somewhat foggy, let down, 5: foggy; losing interest in remaining awake; slowed down, 6: sleepy, woozy, fighting sleep; prefer to lie down, 7: no longer fighting sleep, sleep onset soon; having dream-like thoughts and X: asleep. The mean over Day 1 and Day 2 post PSG nights are reported.


Enrollment: 48
Actual Study Start Date: July 30, 2004
Study Completion Date: August 30, 2005
Primary Completion Date: August 30, 2005 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GW679769 Drug: Placebo
    Other Name: GW679769
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Healthy male and female subjects with primary insomnia with normal EG may be eligible for inclusion.

Exclusion Criteria:

  • clinically significant physical or psychiatric illness or abnormal sleep patterns.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00650871


Locations
United States, California
GSK Investigational Site
San Diego, California, United States, 92123
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30342
United States, New York
GSK Investigational Site
New York, New York, United States, 10025
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27705
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45246
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00650871     History of Changes
Other Study ID Numbers: GW679769/903
First Submitted: March 31, 2008
First Posted: April 2, 2008
Last Update Posted: October 12, 2017
Last Verified: August 2017

Keywords provided by GlaxoSmithKline:
sleep,
polysomnography.
GW679769,
primary insomnia,
cognitive function,

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders
Casopitant
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action