A Study to Evaluate the Safety, Tolerability, and Blood Levels of PF-03654746 in Subjects With Mild to Moderate Alzheimer's Disease

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01028911
• Collaborator: (none)
• Enrollment: 9
• Locations: 2
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a study to evaluate the safety, tolerability and blood levels of PF-03654746 in subjects will mild to moderate Alzheimer's disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: PF-03654746; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-03654746	Drug: PF-03654746; PF-03654746 capsule of 0.25 mg, 0.5 mg, and 1.0 mg strength. Drug is dosed orally once a day. Forced titration dosing for the first 15 days of the study being at 0.25 mg for 5 days, then 0.5 mg for days 6-10, then 1.0 mg for days 11-15. Flexible dosing for the next 15 days depending on tolerability and safety assessments done by the investigator.
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo capsules to PF-03654746 with strengths of 0.25 mg, 0.5 mg, and 1.0 mg. Drug is dosed orally once a day. Forced titration dosing for the first 15 days of the study being at 0.25 mg for 5 days, then 0.5 mg for days 6-10, then 1.0 mg for days 11-15. Flexible dosing for the next 15 days depending on tolerability and safety assessments done by the investigator.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Vital Sign Abnormalities [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.

2. Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [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.

3. Number of Participants With Clinically Significant Laboratory Test Abnormalities [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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary Outcome Measures

1. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-03654746 [0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30]

2. Maximum Serum Concentration (Cmax) for PF-03654746 [0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30]

3. Time to Reach Maximum Observed Serum Concentration (Tmax) for PF-03654746 [0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30]

4. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Donepezil [0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30]

5. Maximum Plasma Concentration (Cmax) for Donepezil [0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30]

6. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Donepezil [0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Probable Alzheimer's disease

• Mini Mental State Examination score 18-26 inclusive

• Aged 55-85

Exclusion Criteria:

• Dementia other than Alzheimer's disease

• Clinically significant cardiovascular disease in the past 6 months prior to screening

• Creatinine clearance <30 mL/min

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Wichita	Kansas	United States	67207
2	Pfizer Investigational Site	Wichita	Kansas	United States	67211

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01028911
• Other Study ID Numbers: A8801016
• First Posted: Dec 9, 2009
• Last Update Posted: Jun 4, 2014
• Last Verified: May 1, 2014

• Keywords provided by Pfizer: Phase 1 Alzheimer's disease Safety Tolerability Pharmacokinetics
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	Participants who were on a stable dose of donepezil (Aricept) 10 milligram (mg) once daily for at least 30 days before screening and on stable morning dosing at least 14 days before Day 0 were enrolled in this study.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Period Title: Overall Study
STARTED	7	2
COMPLETED	7	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil	Total
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Total of all reporting groups
Overall Participants	7	2	9
Age, Customized (participants) [Number]
45 to 64 years	1 14.3%	0 0%	1 11.1%
Greater than or equal to (>=) 65 years	6 85.7%	2 100%	8 88.9%
Sex: Female, Male (Count of Participants)
Female	1 14.3%	0 0%	1 11.1%
Male	6 85.7%	2 100%	8 88.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Vital Sign Abnormalities
Description	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.
Time Frame	Baseline up to 7 to 10 days after last dose

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Supine SBP <90 mmHg	0 0%	0 0%
Standing SBP <90 mmHg	0 0%	0 0%
Supine DBP <50 mmHg	0 0%	0 0%
Standing DBP <50 mmHg	0 0%	0 0%
Supine pulse rate <40 bpm	0 0%	0 0%
Supine pulse rate >120 bpm	0 0%	0 0%
Standing pulse rate <40 bpm	0 0%	0 0%
Standing pulse rate >140 bpm	0 0%	0 0%
Su SBP: Maximum increase from baseline >=30 mmHg	3 42.9%	0 0%
St SBP: Maximum increase from baseline >=30 mmHg	1 14.3%	0 0%
Su DBP: Maximum increase from baseline >=20 mmHg	2 28.6%	0 0%
St DBP: Maximum increase from baseline >=20 mmHg	1 14.3%	0 0%
Su SBP: Maximum decrease from baseline >=30 mmHg	0 0%	1 50%
St SBP: Maximum decrease from baseline >=30 mmHg	0 0%	0 0%
Su DBP: Maximum decrease from baseline >=20 mmHg	0 0%	0 0%
St DBP: Maximum decrease from baseline >=20 mmHg	1 14.3%	1 50%

2. Primary Outcome

Title	Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Description	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.
Time Frame	Baseline up to 7 to 10 days after last dose

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Maximum PR interval >=300 msec	0 0%	0 0%
Maximum QRS Complex >=200 msec	0 0%	0 0%
Maximum QTCF interval >=500 msec	1 14.3%	0 0%
PR interval increase from baseline >=25/50 %	0 0%	0 0%
QRS complex increase from baseline >=25/50 %	0 0%	0 0%
QTCF interval increase from baseline 30 to 60 msec	2 28.6%	0 0%
QTCF interval increase from baseline >=60 msec	1 14.3%	0 0%

3. Primary Outcome

Title	Number of Participants With Clinically Significant Laboratory Test Abnormalities
Description	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.
Time Frame	Baseline up to 7 to 10 days after last dose

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Number [participants]	7 100%	0 0%

4. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Physical Examination
Description	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.
Time Frame	Baseline up to 7 to 10 days after last dose

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Number [participants]	0 0%	0 0%

5. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	23.76 (21.57)	15.65 (22.13)
Somnolence	30.49 (18.40)	16.70 (14.14)
Sleep adequacy	65.71 (32.07)	85.00 (21.21)
Snore	45.71 (37.80)	20.00 (28.28)
Awaken short of breath or with headache	8.57 (15.74)	0.00 (0.00)
Quantity of sleep	7.86 (0.90)	10.50 (2.12)
Optimal sleep	0.71 (0.49)	0.00 (0.00)
Sleep problem index I	23.81 (17.70)	10.00 (14.14)
Sleep problem index II	24.21 (15.81)	14.70 (17.68)

6. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Description	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.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	25.01 (19.56)	15.65 (22.13)
Somnolence	28.57 (26.87)	16.70 (14.14)
Sleep adequacy	65.71 (22.25)	90.00 (14.14)
Snore	28.57 (30.24)	20.00 (28.28)
Awaken short of breath or with headache	8.57 (22.68)	0.00 (0.00)
Quantity of sleep	7.57 (0.98)	9.50 (0.71)
Optimal sleep	0.71 (0.49)	0.00 (0.00)
Sleep problem index I	21.89 (14.25)	8.35 (11.81)
Sleep problem index II	24.76 (14.64)	13.60 (16.12)

7. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Description	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.
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	27.69 (27.86)	13.15 (18.60)
Somnolence	29.53 (31.46)	16.70 (14.14)
Sleep adequacy	67.14 (29.28)	90.00 (14.14)
Snore	34.29 (35.99)	20.00 (28.28)
Awaken short of breath or with headache	14.29 (37.80)	0.00 (0.00)
Quantity of sleep	7.43 (1.13)	9.50 (0.71)
Optimal sleep	0.57 (0.53)	0.00 (0.00)
Sleep problem index I	26.19 (20.14)	8.35 (11.81)
Sleep problem index II	26.90 (19.49)	12.50 (14.57)

8. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Description	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.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	28.76 (11.58)	13.15 (18.60)
Somnolence	28.57 (20.27)	16.70 (14.14)
Sleep adequacy	64.29 (31.01)	90.00 (14.14)
Snore	40.00 (41.63)	20.00 (28.28)
Awaken short of breath or with headache	5.71 (15.12)	0.00 (0.00)
Quantity of sleep	7.29 (0.95)	9.50 (0.71)
Optimal sleep	0.71 (0.49)	0.00 (0.00)
Sleep problem index I	28.10 (16.55)	8.35 (11.81)
Sleep problem index II	26.74 (15.20)	12.50 (14.57)

9. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Description	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.
Time Frame	Day 20

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	23.57 (22.07)	5.65 (7.99)
Somnolence	37.14 (30.75)	10.00 (14.14)
Sleep adequacy	61.43 (26.10)	95.00 (7.07)
Snore	42.86 (43.86)	10.00 (14.14)
Awaken short of breath or with headache	8.57 (15.74)	0.00 (0.00)
Quantity of sleep	7.00 (1.41)	9.50 (0.71)
Optimal sleep	0.43 (0.53)	0.00 (0.00)
Sleep problem index I	26.19 (18.11)	3.35 (4.74)
Sleep problem index II	26.67 (18.20)	5.85 (8.27)

10. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Description	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.
Time Frame	Day 25

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	23.76 (21.18)	3.15 (4.45)
Somnolence	36.19 (28.24)	6.65 (9.40)
Sleep adequacy	72.86 (22.15)	95.00 (7.07)
Snore	45.71 (47.21)	10.00 (14.14)
Awaken short of breath or with headache	5.71 (15.12)	0.00 (0.00)
Quantity of sleep	7.71 (0.95)	9.50 (0.71)
Optimal sleep	0.71 (0.49)	0.00 (0.00)
Sleep problem index I	22.37 (16.86)	1.65 (2.33)
Sleep problem index II	23.89 (16.04)	3.60 (5.09)

11. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Description	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.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	23.04 (21.99)	3.15 (4.45)
Somnolence	37.16 (24.62)	6.65 (9.40)
Sleep adequacy	72.86 (22.15)	95.00 (7.07)
Snore	42.86 (43.86)	10.00 (14.14)
Awaken short of breath or with headache	5.71 (15.12)	0.00 (0.00)
Quantity of sleep	7.86 (1.07)	9.50 (0.71)
Optimal sleep	0.57 (0.53)	0.00 (0.00)
Sleep problem index I	21.90 (17.52)	1.65 (2.33)
Sleep problem index II	23.26 (16.21)	3.60 (5.09)

12. Primary Outcome

Title	Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Description	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.
Time Frame	Follow-up (7 to 10 days after last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Sleep disturbance	16.44 (17.07)	3.15 (4.45)
Somnolence	32.39 (27.62)	6.65 (9.40)
Sleep adequacy	72.86 (23.60)	95.00 (7.07)
Snore	42.86 (43.86)	10.00 (14.14)
Awaken short of breath or with headache	5.71 (15.12)	0.00 (0.00)
Quantity of sleep	8.14 (0.69)	9.50 (0.71)
Optimal sleep	0.71 (0.49)	0.00 (0.00)
Sleep problem index I	17.61 (15.25)	1.65 (2.33)
Sleep problem index II	19.67 (14.12)	3.60 (5.09)

13. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 5
Description	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.
Time Frame	Baseline, Day 5

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Baseline	4.1 (6.09)	3.0 (4.24)
Change at Day 5	-1.9 (5.64)	-1.0 (1.41)

14. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 10
Description	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.
Time Frame	Baseline, Day 10

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	-1.7 (4.75)	-1.0 (1.41)

15. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 15
Description	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.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	-2.6 (4.39)	-1.0 (1.41)

16. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 20
Description	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.
Time Frame	Baseline, Day 20

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	-2.7 (5.71)	0.0 (0.00)

17. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 25
Description	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.
Time Frame	Baseline, Day 25

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	-2.6 (4.39)	0.0 (0.00)

18. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 30
Description	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.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	-1.4 (5.22)	0.0 (0.00)

19. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Follow-up
Description	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.
Time Frame	Baseline, Follow-up (7 to 10 days after last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	-2.6 (4.39)	1.5 (2.12)

20. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 5
Description	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.
Time Frame	Baseline, Day 5

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Baseline	24.6 (1.51)	24.0 (0.00)
Change at Day 5	-0.7 (2.29)	3.0 (0.00)

21. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 10
Description	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.
Time Frame	Baseline, Day 10

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	0.1 (2.34)	3.0 (0.00)

22. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 15
Description	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.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	1.3 (1.80)	2.5 (0.71)

23. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 20
Description	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.
Time Frame	Baseline, Day 20

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	0.4 (2.94)	4.0 (0.00)

24. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 25
Description	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.
Time Frame	Baseline, Day 25

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	1.0 (2.08)	3.5 (0.71)

25. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 30
Description	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.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	0.6 (2.37)	3.0 (2.83)

26. Primary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Follow-up
Description	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.
Time Frame	Baseline, Follow-up (7 to 10 days after last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who took at least 1 dose of study drug.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Mean (Standard Deviation) [units on a scale]	0.7 (1.60)	3.0 (4.24)

27. Secondary Outcome

Title	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-03654746
Time Frame	0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.

Arm/Group Title	PF-03654746 and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7
Geometric Mean (Standard Deviation) [nanogram hour per milliliter (ng*hr/mL)]	118.6 (35.687)

28. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) for PF-03654746
Time Frame	0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.

Arm/Group Title	PF-03654746 and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7
Geometric Mean (Standard Deviation) [nanogran per millileter (ng/mL)]	9.430 (2.7317)

29. Secondary Outcome

Title	Time to Reach Maximum Observed Serum Concentration (Tmax) for PF-03654746
Time Frame	0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.

Arm/Group Title	PF-03654746 and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7
Median (Full Range) [hours]	3.00

30. Secondary Outcome

Title	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Donepezil
Time Frame	0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Day 0	881.6 (282.03)	1109 (176.07)
Day 30	1035 (364.62)	1013 (91.217)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 and Donepezil, Placebo and Donepezil
	Comments	Day 30: Natural log transformed AUCtau of donepezil was analyzed using a mixed effect model with sequence, day and treatment as fixed effects and participant within sequence as a random effect.The adjusted mean differences and 90% confidence intervals for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% confidence intervals for the ratios. Values were back-transformed from the log scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Means Ratio
	Estimated Value	128.40
	Confidence Interval	(2-Sided) 90%; 75.90 to 217.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) for Donepezil
Time Frame	0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Day 0	45.47 (12.847)	53.89 (10.465)
Day 30	50.28 (14.864)	49.73 (1.7678)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-03654746 and Donepezil, Placebo and Donepezil
	Comments	Day 30: Natural log transformed AUCtau of donepezil was analyzed using a mixed effect model with sequence, day and treatment as fixed effects and participant within sequence as a random effect.The adjusted mean differences and 90% confidence intervals for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% confidence intervals for the ratios. Values were back-transformed from the log scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Means Ratio
	Estimated Value	119.82
	Confidence Interval	(2-Sided) 90%; 75.90 to 189.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for Donepezil
Time Frame	0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.

Arm/Group Title	PF-03654746 and Donepezil	Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.	Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
Measure Participants	7	2
Day 0	2.98	2.99
Day 30	3.00	2.98

Adverse Events

Arm/Group Title	PF-03654746 and Donepezil		Placebo and Donepezil
Arm/Group Description	PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.		Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
All Cause Mortality
	PF-03654746 and Donepezil		Placebo and Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PF-03654746 and Donepezil		Placebo and Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	PF-03654746 and Donepezil		Placebo and Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		0/2 (0%)
Nervous system disorders
Headache	1/7 (14.3%)		0/2 (0%)
Psychiatric disorders
Abnormal dreams	1/7 (14.3%)		0/2 (0%)
Euphoric mood	1/7 (14.3%)		0/2 (0%)
Hypnagogic hallucination	1/7 (14.3%)		0/2 (0%)
Illusion	1/7 (14.3%)		0/2 (0%)
Reproductive system and breast disorders
Erectile dysfunction	1/7 (14.3%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)		0/2 (0%)
Epistaxis	1/7 (14.3%)		0/2 (0%)
Nasal congestion	1/7 (14.3%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Urticaria	1/7 (14.3%)		0/2 (0%)

Limitations/Caveats

The study was terminated early due to slow recruitment and the need to use the existing information to determine dosing for another study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.