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

Phase 2
Completed
Conditions
Excessive Daytime Sleepiness
Narcolepsy
Interventions
Drug: Placebo
Registration Number
NCT01006122
Lead Sponsor
Pfizer
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 Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
95
Inclusion Criteria
  • ISDC diagnosis of narcolepsy
  • Excessive Daytime Sleepiness in association with a diagnosis of narcolepsy
  • An MWT (Maintenance of Wakefulness Test) average sleep latency of under 15 minutes at Baseline
Exclusion Criteria
  • No other diagnosed sleep disorders (e.g., sleep apnea)
  • Major medical disorders
  • Major psychiatric disorders

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
PF-03654746PF-03654746At the end of the second arm of the study, the patient will have completed the study and have a 7-10 day follow-up visit.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Maintenance of Wakefulness Test (MWT) Score at Day 21 of Stable Dosing PhaseBaseline, 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.

Secondary Outcome Measures
NameTimeMethod
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 PhaseBaseline, 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 PhaseBaseline, 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 PhaseBaseline, 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 PhaseBaseline, 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 ScoreDay 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)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 SpeedBaseline, 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 SpeedBaseline, 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 LearningBaseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase

One card learning: a cognitive test which assessed visual learning. Participants were to remember which cards were previously shown in a task. The outcome measure was accuracy of performance; arcsine transformation of the square root of the proportion of correct responses. Score ranges from 0 (worse) to 1.57 (best). Higher scores meant a better performance.

Computer Based Objective Cognition Testing (CogState) Continuous Paired Associate Learning (CPAL)Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase

CPAL: a cognitive test which assessed visual episodic learning. Participant was to learn and remember picture locations on the screen and was to tap the target on the central location to begin. As each picture was revealed, the participant was to remember where the picture was located and tap that location. The outcome measure was the number of errors made in correctly placing each of the 4 patterns in their location 4 times. Score ranges from 0 to infinity. Lower scores meant a better performance.

Computer Based Objective Cognition Testing (CogState ) Composite ScoreBaseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase

CogState had 5 outcome measures that measured the cognitive constructs. GMLT, detection, identification, one card learning and CPAL. GMLT score range: 0 (best) to infinity (worst), detection and identification score range: 2 (best) to 3.3 (worst); One card learning score range: 0 (worse) to 1.57 (best) and CPAL score range: 0 (best) to infinity (worst). The individual score was standardized at each assessment and was then averaged to yield a composite score; total possible score: minus infinity to plus infinity. Positive composite score=improved performance.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

Houston, Texas, United States

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