Clinical Trial: A Study Of A Novel Compound For Excessive Daytime Sleepiness Associated With Narcolepsy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Phase 2, Double Blind, Placebo-Controlled, Multi-Center Crossover Study Of PF-03654746 As A Daily Treatment For Excessive Daytime Sleepiness (EDS) Associated With Na

Brief Summary: Histaminergic agents are known to be involved with the sleep/wake cycle. This compound is a histaminergic agent which therefore may improve alertness and awakeness in patients with excessive daytime sleepiness (EDS) associated with narcolepsy. Significant improvement in EDS when treated with this compound compared to placebo in patients with narcolepsy is hypothesized.

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome: Change From Baseline in Maintenance of Wakefulness Test (MWT) Score at Day 21 of Stable Dosing Phase [ Time Frame: Baseline, Day 21 of stable dosing phase ]

MWT measured ability of participant to remain awake. Participants were instructed to try and remain awake during series of six 20-minute periods in a semi-recumbent position in dark room. Each period was terminated immediately after sleep onset or at end of 20 minutes if no sleep occurred. Poorest outcome was 0 minute the best was 20 minutes.


Original Primary Outcome:

  • Maintenance of Wakefulness Test [ Time Frame: baseline and end of each Stable Dosing Phase ]
  • Vital signs, safety labs [ Time Frame: screening, baseline, each study visit ]
  • ECG [ Time Frame: screening, baseline, end of each stable dosing phase ]
  • Sheehan Suicidality Tracking Scale [ Time Frame: screening, baseline and each study visit ]
  • Adverse Event logs [ Time Frame: baseline and each study visit ]


Current Secondary Outcome:

  • Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Day 5, 10, 15, 20 of Titration Phase and Day 7, 14, 21 of Stable Dosing Phase [ Time Frame: Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase ]
    ESS is a simple, self-administered questionnaire which provides a measurement of the participant's general level of daytime sleepiness. The participant rates the chance that he/she would fall asleep when in 8 different situations (e.g. sitting and reading, talking to someone, etc.) commonly encountered in daily life on a scale of 0 (no daytime sleep) to 3 (maximum daytime sleep). Total score was the sum of 8 situations ranges from 0 to 24 with a higher score indicating greater daytime sleepiness.
  • Change From Baseline in Brief Fatigue Inventory (BFI) Global Score at Day 5, 10, 15, 20 of Titration Phase and Day 7, 14, 21 of Stable Dosing Phase [ Time Frame: Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase ]
    BFI is a subjective-completed tool for the assessment of the impact of fatigue on daily functioning. There are 3 questions that pertain specifically to level of fatigue and 6 questions regarding general activity level, mood and quality of life, all are answered on an 11-point scale, with "0" being "No fatigue at all" to "10" being "As bad as you can imagine". The global score is calculated by taking the sum of all 9 rating scales for a minimum score of 0 and a maximum score of 90. Higher global scores are associated with more severe fatigue.
  • Change From Baseline in Cataplexy Episodes at Day 7, 14, 21 of Stable Dosing Phase [ Time Frame: Baseline, Day 7, 14, 21 of stable dosing phase ]
    Cataplexy is a medical condition in which a person suffers sudden physical collapse though remaining conscious. Cataplexy episodes is number of counts the participant had cataplexy.
  • Change From Baseline in 36-Item Short Form Health Survey (SF-36) at Day 21 of Stable Dosing Phase [ Time Frame: Baseline, Day 21 of stable dosing phase ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality, social functioning (SF), role emotional (RE) and mental health (MH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
  • Clinical Global Impression of Improvement (CGI-I) Scale Score [ Time Frame: Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase ]
    CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Clinician responded to a question: "Compared to your subject's condition at the beginning of treatment, how much has your subject changed?". Improvement was compared to baseline and was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
  • Computer Based Objective Cognition Testing (CogState) Groton Maze Learning Task (GMLT) [ Time Frame: Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase ]
    GMLT: a cognitive test which assessed executive function. Participant was shown a 10 multiplied by 10 grid of tiles on a computer touch screen. A 28-step pathway was hidden among 100 possible locations. The participant was instructed to move 1 step from the start location and then continue 1 tile at a time, toward the end to find the pathway. The outcome measure was total number of errors made in attempting to learn the same hidden pathway on 5 consecutive trials at a single session. Score ranges from 0 to infinity. Lower scores meant a better performance.
  • Computer Based Objective Cognition Testing (CogState) Detection Speed [ Time Frame: Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase ]
    Detection speed: a cognitive test which assessed psychomotor function. A playing card was presented face up in the center of the screen. As soon as this happened, the participant was to press the 'Yes' key. The outcome measure was speed of performance; mean of the log10 transformed reaction time for correct responses [measured in log10 milliseconds (msec)]. Scores ranges from 2 (best) to 3.3 (worst). Lower scores meant a better performance.
  • Computer Based Objective Cognition Testing (CogState) Identification Speed [ Time Frame: Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase ]
    Identification speed: a cognitive test which assessed visual attention. A playing card was presented face up in the center of the screen. As soon as this happened, the participant had to decide whether the card was red or not. The outcome measure was speed of performance; mean of the log10 transformed reaction time for correct responses (measured in log10 msec). Score ranges from 2 (best) to 3.3 (worst). Lower scores meant a better performance.
  • Computer Based Objective Cognition Testing (CogState) One Card Lea

    Original Secondary Outcome:

    • Epworth Sleepiness Scale [ Time Frame: screening, baseline and each study visit ]
    • MOS Sleep Scale [ Time Frame: baseline and each day of the study ]
    • SF-36 (Quality of LIfe scale) [ Time Frame: baseline and end of each stable dosing phase ]
    • Patient diaries (to capture cataplexy episodes) [ Time Frame: beginning at screening and each day of the study to end ]
    • CGI [ Time Frame: screening, baseline and each study visit ]
    • CogState computerized cognitive test battery [ Time Frame: baseline and each study visit ]


    Information By: Pfizer

    Dates:
    Date Received: October 29, 2009
    Date Started: November 2009
    Date Completion:
    Last Updated: April 8, 2014
    Last Verified: April 2014