A Phase 1, Double-Blind, Placebo-Controlled, Sponsor-Open, Randomized, Multiple Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PF-03654746 in Mild to Moderate Alzheimer's Disease Patients on Stable Donepezil Therapy

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10

时间窗: Day 10

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15

时间窗: Day 15

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Number of Participants With Clinically Significant Change From Baseline in Physical Examination

时间窗: Baseline up to 7 to 10 days after last dose

Physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any potential changes in physical status, as determined by the investigator. Any untoward findings identified on physical exams conducted after the administration of the first dose of study medication was captured as an adverse event.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25

时间窗: Day 25

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30

时间窗: Day 30

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Number of Participants With Clinically Significant Vital Sign Abnormalities

时间窗: Baseline up to 7 to 10 days after last dose

Criteria for potential clinical concern in vital signs: supine and standing systolic blood pressure (SBP) less than (\<) 90 millimeter of mercury (mmHg), supine and standing diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm, standing pulse rate \<40 bpm or \>140 bpm. Maximum increase or decrease from baseline in supine (Su) and standing (St) SBP \>=30 mmHg and maximum increase or decrease from baseline in supine and standing DBP \>=20 mmHg.

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

时间窗: Baseline up to 7 to 10 days after last dose

Criteria for potential clinical concern in ECG parameters: maximum PR interval of \>=300 milliseconds (msec), maximum QRS interval \>=200 msec, maximum fridericia's corrected QT (QTcF) interval \>=500 msec, PR interval or QRS interval increase from baseline \>=25 percent (%) or 50 percent (%), QTCF interval increase from baseline 30 to 60 msec or \>=60 msec.

Number of Participants With Clinically Significant Laboratory Test Abnormalities

时间窗: Baseline up to 7 to 10 days after last dose

Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (\< 0.8\*lower limit of normal\[LLN\]); leucocytes (\<0.6/\>1.5\*upper limit of normal \[ULN\]); platelets (\<0.5\*LLN/\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\*LLN/\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (\>3\*ULN), total protein, albumin (\<0.8\*LLN/\>1.2\*ULN); creatinine, urea (\>1.3\*ULN); glucose (\<0.6\*LLN/\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN/\>1.1\*ULN); urine red blood cells (RBCs), urine white blood cells (WBCs), urine epithelial cells (\>=6 high-powered field), urine bacteria \>20 high-powered field; qualitative urine glucose, ketones, protein values \>=1 in urine dipstick test. Total number of participants with any laboratory abnormalities was reported.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5

时间窗: Day 5

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20

时间窗: Day 20

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline

时间窗: Baseline

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 5

时间窗: Baseline, Day 5

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 25

时间窗: Baseline, Day 25

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Follow-up

时间窗: Baseline, Follow-up (7 to 10 days after last dose)

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 10

时间窗: Baseline, Day 10

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 25

时间窗: Baseline, Day 25

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 30

时间窗: Baseline, Day 30

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Follow-up

时间窗: Baseline, Follow-up (7 to 10 days after last dose)

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 15

时间窗: Baseline, Day 15

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 30

时间窗: Baseline, Day 30

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 5

时间窗: Baseline, Day 5

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 20

时间窗: Baseline, Day 20

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.

Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up

时间窗: Follow-up (7 to 10 days after last dose)

Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 10

时间窗: Baseline, Day 10

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 20

时间窗: Baseline, Day 20

NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 15

时间窗: Baseline, Day 15

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.