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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| PF-03654746 | Active Comparator | At 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Patients receiving placebo will undergo the same procedures as those receiving active treatment. Each patient will receive matching placebo tablets in a fixed dose escalation schedule beginning at 0.25 mg QD for 5 days; then up to 0.50 mg QD for another 5 days; and up to 1.0 mg QD for an additional 5 days. At the end of this fixed titration schedule, the patient will either stay at 1.0 mg; decrease to 0.5 mg or increase to 2.0 mg based upon the clinicians judgment regarding efficacy and side effects at the 1.0 dose level. The patient will then remain at the determined dose for a 3 week stable dosing period, with a 7 (-2/+ 9) day wash out and then crossover to repeat the same sequence for the second arm of the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Maintenance of Wakefulness Test (MWT) Score at 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. | Baseline, Day 21 of stable dosing phase |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Vital Signs Data | Criteria for potential clinical concern in vital signs: supine and standing systolic blood pressure (BP) less than (<) 90 millimeter of mercury (mmHg), supine and standing diastolic BP <50 mmHg, supine and standing heart rate <40 beats per minute (bpm) or >140 bpm. Number of participants who met the criteria for potential clinical concern was reported. | Baseline up to 7-10 days after Day 21 (stable dosing phase) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Phoenix | Arizona | 85006 | United States | ||
| Pfizer Investigational Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-03654746 First, Then Placebo | PF-03654746 at a starting dose of 0.25 milligram (mg) to maximum dose of 2 mg, depending upon the safety and tolerability, given orally once daily as powder in a capsule (PIC) in the titration phase (TP) at 5 days interval up to 15 to 25 days, depending on dose toleration followed by a 3-week stable dose phase (SP) at fixed dose stabilized in the TP in the first double-blind (DB) intervention period then placebo matched to PF-03654746 orally once daily as PIC in the second DB intervention period. A washout period of at least 7 days was maintained between each treatment period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Double-blind Intervention Period |
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| PF-03654746 | Drug | Each patient will receive PF-03654746 tablets in a fixed dose titration schedule beginning at 0.25 mg QD for 5 days; then up to 0.50 mg QD for another 5 days; and up to 1.0 mg QD for an additional 5 days. At the end of this fixed titration schedule, the patient will either stay at the 1.0 mg dose; decrease to 0.50 mg or increase to 2.0 mg based upon the clinician's judgement regarding efficacy and side effects at the 1.0 mg dose. The patient will remain at the determined dose for a 3 week stable dosing period. |
|
| Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
| 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 | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
| Change From Baseline in Cataplexy Episodes at 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. | Baseline, Day 7, 14, 21 of stable dosing phase |
| Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 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). | Baseline, Day 21 of stable dosing phase |
| Clinical Global Impression of Improvement (CGI-I) Scale Score | 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. | Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
| Computer Based Objective Cognition Testing (CogState) Groton Maze Learning Task (GMLT) | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
| Computer Based Objective Cognition Testing (CogState) Detection Speed | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
| Computer Based Objective Cognition Testing (CogState) Identification Speed | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
| Computer Based Objective Cognition Testing (CogState) One Card Learning | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
| Computer Based Objective Cognition Testing (CogState) Continuous Paired Associate Learning (CPAL) | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
| Computer Based Objective Cognition Testing (CogState ) Composite Score | 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. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
| Number of Participants With Laboratory Abnormalities | Laboratory parameters included hematology (hemoglobin, hematocrit, red blood cell count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid, sodium, potassium, chloride, bicarbonate, calcium); urinalysis (protein, blood), and clinical chemistry (glucose). Total number of participants with laboratory abnormalities was reported. | Baseline up to Day 21 of stable dosing phase |
| Number of Participants With Electrocardiogram (ECG) Findings | Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (>=) 300 milliseconds (msec), maximum QRS interval >=200 msec, maximum Fridericia's correction of QT (QTcF) interval of 450 to <480 msec, 480 to <500 msec and >=500 msec. Number of participants who met the criteria for potential clinical concern in ECG findings were reported. | Baseline up to Day 21 of stable dosing phase |
| Medical Outcomes Study (MOS) Sleep Scale Score | Participant-rated questionnaire to assess sleep quality and quantity. Consists of 12-item questionnaires answered on a range of 1 to 6 for questions (Q) 3 to 12, 1 to 5 for Q1(some questions are reversed so that high score reflects more of the attributes); and Q2 answered on 0 to 24. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range:0 to 100; higher score = greater intensity of attribute. The items contribute to each scale and are averaged to create 7 scale scores and 2 sleep scale index. Scales with at least one item answered was used to generate a scale score. Scales include; sleep disturbance (SD), sleep quantity, snoring, awaken short of breath (ASoB), somnolence, sleep adequacy and optimal sleep; and a 9-item overall sleep problems index(SPI) I and II Subscales range from 0-100 except for sleep quantity (SQ) ranging from0 to 24. Except for sleep quantity, higher scores=greater impairment. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
| Number of Participants With Response to Sheehan Suicidality Tracking Scale (STS) | Sheehan-STS is an 8-item clinician/participant administered prospective rating scale and an indicator of trigger assessment that tracks both treatment-emergent suicidal ideation and behaviors). Items 1a, 2-6, 8 scored on 5-point Likert scale (0=not at all, 1=a little, 2=moderately, 3=very, and 4=extremely). Items 1, 1b, 7, an indicator of trigger assessment (TA) require yes/no response. Items included 1= Ever suffer any accident, 1a= Extent plan/intend to hurt yourself, 1b= Intend to die, 2= Wish dead, 3= Want to harm yourself, 4= Think about suicide, 5= Plan for a suicide, 6= Prepare for suicide (PS) with intent to die (ITD), 7= Injure yourself on purpose, 8= Attempt suicide. Result for item 1 indicates if any of the participant ever suffered any accident, 1b indicates if any of the participant intended to die, 7 indicates if any of the participant injured themselves purposely and trigger assessment indicates if any of the participant evoked trigger assessment. | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
| Phoenix |
| Arizona |
| 85051 |
| United States |
| Pfizer Investigational Site | Tucson | Arizona | 85712 | United States |
| Pfizer Investigational Site | Los Angeles | California | 90048 | United States |
| Pfizer Investigational Site | Orange | California | 92868 | United States |
| Pfizer Investigational Site | Brandon | Florida | 33511 | United States |
| Pfizer Investigational Site | St. Petersburg | Florida | 33707 | United States |
| Pfizer Investigational Site | Atlanta | Georgia | 30342 | United States |
| Pfizer Investigational Site | Macon | Georgia | 31201 | United States |
| Pfizer Investigational Site | Vernon Hills | Illinois | 60061 | United States |
| Pfizer Investigational Site | Crestview Hills | Kentucky | 41017 | United States |
| Pfizer Investigational Site | Louisville | Kentucky | 40217 | United States |
| Pfizer Investigational Site | Hattiesburg | Mississippi | 39401 | United States |
| Pfizer Investigational Site | Hattiesburg | Mississippi | 39402 | United States |
| Pfizer Investigational Site | Durham | North Carolina | 27710 | United States |
| Pfizer Investigational Site | Dublin | Ohio | 43017 | United States |
| Pfizer Investigational Site | Philadelphia | Pennsylvania | 19114 | United States |
| Pfizer Investigational Site | Philadelphia | Pennsylvania | 19139 | United States |
| Pfizer Investigational Site | Columbia | South Carolina | 29201 | United States |
| Pfizer Investigational Site | Austin | Texas | 78731 | United States |
| Pfizer Investigational Site | Houston | Texas | 77063 | United States |
| FG001 | Placebo First Then, PF-03654746 | Placebo matched to PF-03654746 orally once daily as PIC in the first DB intervention period then PF-03654746 at a starting dose of 0.25 mg to maximum dose of 2 mg, depending upon the safety and tolerability, given orally once daily as PIC in the TP at 5 days interval up to 15 to 25 days, depending on dose toleration followed by a 3-week SP at fixed dose stabilized in the TP in the second DB intervention. A washout period of at least 7 days was maintained between each treatment period. |
| COMPLETED |
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| NOT COMPLETED |
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| Wash-out Period (at Least 7 Days) |
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| Second Double-blind Intervention Period |
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Full analysis set (FAS) consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study | Included all participants randomized to receive PF-03654746 first and placebo first. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline in Maintenance of Wakefulness Test (MWT) Score at 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. | Full analysis set (FAS) consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "N"(number of participants analyzed) signifies participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specified time points for each arm. | Posted | Mean | Standard Deviation | minutes | Baseline, Day 21 of stable dosing phase |
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| Secondary | 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 | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
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| Secondary | 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 | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
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| Secondary | Change From Baseline in Cataplexy Episodes at 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | cataplexy episodes | Baseline, Day 7, 14, 21 of stable dosing phase |
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| Secondary | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 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). | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 21 of stable dosing phase |
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| Secondary | Clinical Global Impression of Improvement (CGI-I) Scale Score | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | units on a scale | Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
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| Other Pre-specified | Number of Participants With Vital Signs Data | Criteria for potential clinical concern in vital signs: supine and standing systolic blood pressure (BP) less than (<) 90 millimeter of mercury (mmHg), supine and standing diastolic BP <50 mmHg, supine and standing heart rate <40 beats per minute (bpm) or >140 bpm. Number of participants who met the criteria for potential clinical concern was reported. | Safety analysis set consisted of all participants who received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure. | Posted | Number | participants | Baseline up to 7-10 days after Day 21 (stable dosing phase) |
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| Other Pre-specified | Number of Participants With Laboratory Abnormalities | Laboratory parameters included hematology (hemoglobin, hematocrit, red blood cell count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid, sodium, potassium, chloride, bicarbonate, calcium); urinalysis (protein, blood), and clinical chemistry (glucose). Total number of participants with laboratory abnormalities was reported. | Safety analysis set consisted of all participants who received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure. | Posted | Number | participants | Baseline up to Day 21 of stable dosing phase |
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| Other Pre-specified | Number of Participants With Electrocardiogram (ECG) Findings | Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (>=) 300 milliseconds (msec), maximum QRS interval >=200 msec, maximum Fridericia's correction of QT (QTcF) interval of 450 to <480 msec, 480 to <500 msec and >=500 msec. Number of participants who met the criteria for potential clinical concern in ECG findings were reported. | Safety analysis set consisted of all participants who received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure. | Posted | Number | participants | Baseline up to Day 21 of stable dosing phase |
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| Other Pre-specified | Medical Outcomes Study (MOS) Sleep Scale Score | Participant-rated questionnaire to assess sleep quality and quantity. Consists of 12-item questionnaires answered on a range of 1 to 6 for questions (Q) 3 to 12, 1 to 5 for Q1(some questions are reversed so that high score reflects more of the attributes); and Q2 answered on 0 to 24. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range:0 to 100; higher score = greater intensity of attribute. The items contribute to each scale and are averaged to create 7 scale scores and 2 sleep scale index. Scales with at least one item answered was used to generate a scale score. Scales include; sleep disturbance (SD), sleep quantity, snoring, awaken short of breath (ASoB), somnolence, sleep adequacy and optimal sleep; and a 9-item overall sleep problems index(SPI) I and II Subscales range from 0-100 except for sleep quantity (SQ) ranging from0 to 24. Except for sleep quantity, higher scores=greater impairment. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
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| Other Pre-specified | Number of Participants With Response to Sheehan Suicidality Tracking Scale (STS) | Sheehan-STS is an 8-item clinician/participant administered prospective rating scale and an indicator of trigger assessment that tracks both treatment-emergent suicidal ideation and behaviors). Items 1a, 2-6, 8 scored on 5-point Likert scale (0=not at all, 1=a little, 2=moderately, 3=very, and 4=extremely). Items 1, 1b, 7, an indicator of trigger assessment (TA) require yes/no response. Items included 1= Ever suffer any accident, 1a= Extent plan/intend to hurt yourself, 1b= Intend to die, 2= Wish dead, 3= Want to harm yourself, 4= Think about suicide, 5= Plan for a suicide, 6= Prepare for suicide (PS) with intent to die (ITD), 7= Injure yourself on purpose, 8= Attempt suicide. Result for item 1 indicates if any of the participant ever suffered any accident, 1b indicates if any of the participant intended to die, 7 indicates if any of the participant injured themselves purposely and trigger assessment indicates if any of the participant evoked trigger assessment. | FAS. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. Results for a parameter are not reported at certain time points since none of the participants were evaluable for the parameter at those time points. | Posted | Number | participants | Baseline, Day 5, 10, 15, 20 of titration phase; Day 7, 14, 21 of stable dosing phase |
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| Secondary | Computer Based Objective Cognition Testing (CogState) Groton Maze Learning Task (GMLT) | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | errors | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
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| Secondary | Computer Based Objective Cognition Testing (CogState) Detection Speed | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | log10 msec | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
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| Secondary | Computer Based Objective Cognition Testing (CogState) Identification Speed | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | log10 msec | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
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| Secondary | Computer Based Objective Cognition Testing (CogState) One Card Learning | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | arcsine (square root proportion correct) | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
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| Secondary | Computer Based Objective Cognition Testing (CogState) Continuous Paired Associate Learning (CPAL) | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | errors | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
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| Secondary | Computer Based Objective Cognition Testing (CogState ) Composite Score | 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. | FAS consisted of all participants who were randomized to a treatment sequence and received at least 1 dose of study drug. Here "N" (number of participants analyzed) signifies participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specified time points for each arm, respectively. | Posted | Mean | Standard Deviation | Units on a scale | Baseline, Day 5, 10, 15, 20 of titration phase; Day 21 of stable dosing phase |
|
Not provided
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-03654746 | PF-03654746 at a starting dose of 0.25 milligram (mg) to maximum dose of 2 mg, depending upon the safety and tolerability, given orally once daily as powder in a capsule (PIC) in the titration phase (TP) at 5 days interval up to 15 to 25 days, depending on dose toleration followed by a 3-week stable dose phase (SP) at fixed dose stabilized in the TP in first or second DB intervention periods. | 1 | 78 | 48 | 78 | ||
| EG001 | Placebo | Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods. | 1 | 79 | 43 | 79 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injury | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Drug exposure during pregnancy | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Eye irritation | Eye disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Eye swelling | Eye disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Chapped lips | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Tooth impacted | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Feeling jittery | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Irritability | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Swelling | General disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Otitis externa | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Joint sprain | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Post concussion syndrome | Injury, poisoning and procedural complications | MedDRA v13.1 | Non-systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Semen volume decreased | Investigations | MedDRA v13.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Burning sensation | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Abnormal dreams | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Initial insomnia | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Middle insomnia | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Mood altered | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Nervousness | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Nicotine dependence | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Nightmare | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Tension | Psychiatric disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Epididymitis | Reproductive system and breast disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Galactorrhoea | Reproductive system and breast disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA v13.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA v13.1 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| ID | Term |
|---|---|
| D006970 | Disorders of Excessive Somnolence |
| D009290 | Narcolepsy |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C569672 | N-ethyl-3-fluoro-3-(3-fluoro-4-(pyrrolidinylmethyl)phenyl)cyclobutanecarboxamide |
Not provided
Not provided
Not provided
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Death |
|
Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods.
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|
|
Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods.
|
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| Units | Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| OG001 | Placebo | Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods. |
|
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| OG001 | Placebo | Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods. |
|
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Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods.
|
|
Placebo matched to PF-03654746 orally once daily as PIC in the first or second DB intervention periods. |
|
|