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TerminatedNCT01028911Updated Jun 4, 2014Results posted

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

A Phase 1 interventional study of PF-03654746 and Placebo in Alzheimer's Disease, sponsored by Pfizer. Terminated at 2 sites in United States. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2014-06-04.

Sponsored by Pfizer · Phase 1, Interventional, and Treatment

Why this study was terminated
This study terminated 27Apr2010 due to slow recruitment and the need to use the existing information to determine dosing for another study.
Phase
Phase 1
Study type
Interventional
Enrollment
9
Allocation
Randomized
Ages
55 Years to 85 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Alzheimer's Disease

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Keywords

  • Phase 1 Alzheimer's disease Safety Tolerability Pharmacokinetics
03

In context

Alzheimer Disease

3,765 studies on the registry are indexed under Alzheimer Disease; 881 are open to participants now.

This study's enrollment of 9 is below the median of 68 across 2,861 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Pfizer is the lead sponsor of 3,323 studies on the registry; 145 are open to participants now.

Of its 597 completed or terminated interventional studies of FDA-regulated products, 391 (65%) have results posted.

Browse Pfizer studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
55 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Probable Alzheimer's disease
  • Mini Mental State Examination score 18-26 inclusive
  • Aged 55-85

Exclusion criteria

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
9 participants (actual)

Study arms

  • Experimental
    PF-03654746

    Drug: PF-03654746

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugPF-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.

  • DrugPlacebo

    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.

06

What researchers measure

Primary outcomes

  1. Number of Participants With Clinically Significant Vital Sign Abnormalities

    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

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

    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

  3. Number of Participants With Clinically Significant Laboratory Test Abnormalities

    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

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

    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

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

    Time frame: Baseline

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

    Time frame: Day 5

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

    Time frame: Day 10

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

    Time frame: Day 15

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

    Time frame: Day 20

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

    Time frame: Day 25

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

    Time frame: Day 30

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

    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)

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

    Time frame: Baseline, Day 5

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

    Time frame: Baseline, Day 10

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

    Time frame: Baseline, Day 15

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

    Time frame: Baseline, Day 20

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

    Time frame: Baseline, Day 25

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

    Time frame: Baseline, Day 30

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

    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)

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

    Time frame: Baseline, Day 5

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

    Time frame: Baseline, Day 10

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

    Time frame: Baseline, Day 15

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

    Time frame: Baseline, Day 20

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

    Time frame: Baseline, Day 25

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

    Time frame: Baseline, Day 30

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

    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)

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

07

Results

Posted Jun 4, 2014
Limitations and caveats
The study was terminated early due to slow recruitment and the need to use the existing information to determine dosing for another study.

Participant flow

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.

Participant flow — Overall Study
MilestonePF-03654746 and DonepezilPlacebo and Donepezil
Started72
Completed72
Not completed00

Outcome measures

PrimaryNumber of Participants With Clinically Significant Vital Sign Abnormalities

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
Reported as:
Number · participants
Number of Participants With Clinically Significant Vital Sign Abnormalities
participantsPF-03654746 and DonepezilPlacebo and Donepezil
Supine SBP <90 mmHg00
Standing SBP <90 mmHg00
Supine DBP <50 mmHg00
Standing DBP <50 mmHg00
Supine pulse rate <40 bpm00
Supine pulse rate >120 bpm00
Standing pulse rate <40 bpm00
Standing pulse rate >140 bpm00
Su SBP: Maximum increase from baseline >=30 mmHg30
St SBP: Maximum increase from baseline >=30 mmHg10
Su DBP: Maximum increase from baseline >=20 mmHg20
St DBP: Maximum increase from baseline >=20 mmHg10
Su SBP: Maximum decrease from baseline >=30 mmHg01
St SBP: Maximum decrease from baseline >=30 mmHg00
Su DBP: Maximum decrease from baseline >=20 mmHg00
St DBP: Maximum decrease from baseline >=20 mmHg11
PrimaryNumber of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

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
Reported as:
Number · participants
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
participantsPF-03654746 and DonepezilPlacebo and Donepezil
Maximum PR interval >=300 msec00
Maximum QRS Complex >=200 msec00
Maximum QTCF interval >=500 msec10
PR interval increase from baseline >=25/50 %00
QRS complex increase from baseline >=25/50 %00
QTCF interval increase from baseline 30 to 60 msec20
QTCF interval increase from baseline >=60 msec10
PrimaryNumber of Participants With Clinically Significant Laboratory Test Abnormalities

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
Reported as:
Number · participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities
participantsPF-03654746 and DonepezilPlacebo and Donepezil
Number of Participants With Clinically Significant Laboratory Test Abnormalities70
PrimaryNumber of Participants With Clinically Significant Change From Baseline in Physical Examination

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
Reported as:
Number · participants
Number of Participants With Clinically Significant Change From Baseline in Physical Examination
participantsPF-03654746 and DonepezilPlacebo and Donepezil
Number of Participants With Clinically Significant Change From Baseline in Physical Examination00
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Baseline
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance23.76 ± 21.5715.65 ± 22.13
Somnolence30.49 ± 18.4016.70 ± 14.14
Sleep adequacy65.71 ± 32.0785.00 ± 21.21
Snore45.71 ± 37.8020.00 ± 28.28
Awaken short of breath or with headache8.57 ± 15.740.00 ± 0.00
Quantity of sleep7.86 ± 0.9010.50 ± 2.12
Optimal sleep0.71 ± 0.490.00 ± 0.00
Sleep problem index I23.81 ± 17.7010.00 ± 14.14
Sleep problem index II24.21 ± 15.8114.70 ± 17.68
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Day 5
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance25.01 ± 19.5615.65 ± 22.13
Somnolence28.57 ± 26.8716.70 ± 14.14
Sleep adequacy65.71 ± 22.2590.00 ± 14.14
Snore28.57 ± 30.2420.00 ± 28.28
Awaken short of breath or with headache8.57 ± 22.680.00 ± 0.00
Quantity of sleep7.57 ± 0.989.50 ± 0.71
Optimal sleep0.71 ± 0.490.00 ± 0.00
Sleep problem index I21.89 ± 14.258.35 ± 11.81
Sleep problem index II24.76 ± 14.6413.60 ± 16.12
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Day 10
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance27.69 ± 27.8613.15 ± 18.60
Somnolence29.53 ± 31.4616.70 ± 14.14
Sleep adequacy67.14 ± 29.2890.00 ± 14.14
Snore34.29 ± 35.9920.00 ± 28.28
Awaken short of breath or with headache14.29 ± 37.800.00 ± 0.00
Quantity of sleep7.43 ± 1.139.50 ± 0.71
Optimal sleep0.57 ± 0.530.00 ± 0.00
Sleep problem index I26.19 ± 20.148.35 ± 11.81
Sleep problem index II26.90 ± 19.4912.50 ± 14.57
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Day 15
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance28.76 ± 11.5813.15 ± 18.60
Somnolence28.57 ± 20.2716.70 ± 14.14
Sleep adequacy64.29 ± 31.0190.00 ± 14.14
Snore40.00 ± 41.6320.00 ± 28.28
Awaken short of breath or with headache5.71 ± 15.120.00 ± 0.00
Quantity of sleep7.29 ± 0.959.50 ± 0.71
Optimal sleep0.71 ± 0.490.00 ± 0.00
Sleep problem index I28.10 ± 16.558.35 ± 11.81
Sleep problem index II26.74 ± 15.2012.50 ± 14.57
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Day 20
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance23.57 ± 22.075.65 ± 7.99
Somnolence37.14 ± 30.7510.00 ± 14.14
Sleep adequacy61.43 ± 26.1095.00 ± 7.07
Snore42.86 ± 43.8610.00 ± 14.14
Awaken short of breath or with headache8.57 ± 15.740.00 ± 0.00
Quantity of sleep7.00 ± 1.419.50 ± 0.71
Optimal sleep0.43 ± 0.530.00 ± 0.00
Sleep problem index I26.19 ± 18.113.35 ± 4.74
Sleep problem index II26.67 ± 18.205.85 ± 8.27
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Day 25
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance23.76 ± 21.183.15 ± 4.45
Somnolence36.19 ± 28.246.65 ± 9.40
Sleep adequacy72.86 ± 22.1595.00 ± 7.07
Snore45.71 ± 47.2110.00 ± 14.14
Awaken short of breath or with headache5.71 ± 15.120.00 ± 0.00
Quantity of sleep7.71 ± 0.959.50 ± 0.71
Optimal sleep0.71 ± 0.490.00 ± 0.00
Sleep problem index I22.37 ± 16.861.65 ± 2.33
Sleep problem index II23.89 ± 16.043.60 ± 5.09
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at 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.

Time frame:
Day 30
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance23.04 ± 21.993.15 ± 4.45
Somnolence37.16 ± 24.626.65 ± 9.40
Sleep adequacy72.86 ± 22.1595.00 ± 7.07
Snore42.86 ± 43.8610.00 ± 14.14
Awaken short of breath or with headache5.71 ± 15.120.00 ± 0.00
Quantity of sleep7.86 ± 1.079.50 ± 0.71
Optimal sleep0.57 ± 0.530.00 ± 0.00
Sleep problem index I21.90 ± 17.521.65 ± 2.33
Sleep problem index II23.26 ± 16.213.60 ± 5.09
PrimaryMedical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up

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)
Reported as:
Mean · units on a scale
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Sleep disturbance16.44 ± 17.073.15 ± 4.45
Somnolence32.39 ± 27.626.65 ± 9.40
Sleep adequacy72.86 ± 23.6095.00 ± 7.07
Snore42.86 ± 43.8610.00 ± 14.14
Awaken short of breath or with headache5.71 ± 15.120.00 ± 0.00
Quantity of sleep8.14 ± 0.699.50 ± 0.71
Optimal sleep0.71 ± 0.490.00 ± 0.00
Sleep problem index I17.61 ± 15.251.65 ± 2.33
Sleep problem index II19.67 ± 14.123.60 ± 5.09
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at 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.

Time frame:
Baseline, Day 5
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 5
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Baseline4.1 ± 6.093.0 ± 4.24
Change at Day 5-1.9 ± 5.64-1.0 ± 1.41
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at 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.

Time frame:
Baseline, Day 10
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 10
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 10-1.7 ± 4.75-1.0 ± 1.41
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at 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.

Time frame:
Baseline, Day 15
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 15
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 15-2.6 ± 4.39-1.0 ± 1.41
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at 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.

Time frame:
Baseline, Day 20
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 20
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 20-2.7 ± 5.710.0 ± 0.00
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at 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.

Time frame:
Baseline, Day 25
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 25
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 25-2.6 ± 4.390.0 ± 0.00
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at 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.

Time frame:
Baseline, Day 30
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 30
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 30-1.4 ± 5.220.0 ± 0.00
PrimaryChange From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Follow-up

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)
Reported as:
Mean · units on a scale
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Follow-up
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Follow-up-2.6 ± 4.391.5 ± 2.12
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at 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.

Time frame:
Baseline, Day 5
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 5
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Baseline24.6 ± 1.5124.0 ± 0.00
Change at Day 5-0.7 ± 2.293.0 ± 0.00
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at 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.

Time frame:
Baseline, Day 10
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 10
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 100.1 ± 2.343.0 ± 0.00
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at 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.

Time frame:
Baseline, Day 15
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 15
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 151.3 ± 1.802.5 ± 0.71
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at 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.

Time frame:
Baseline, Day 20
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 20
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 200.4 ± 2.944.0 ± 0.00
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at 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.

Time frame:
Baseline, Day 25
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 25
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 251.0 ± 2.083.5 ± 0.71
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at 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.

Time frame:
Baseline, Day 30
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 30
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 300.6 ± 2.373.0 ± 2.83
PrimaryChange From Baseline in Mini Mental State Examination (MMSE) Total Score at Follow-up

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)
Reported as:
Mean · units on a scale
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Follow-up
units on a scalePF-03654746 and DonepezilPlacebo and Donepezil
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Follow-up0.7 ± 1.603.0 ± 4.24
SecondaryArea 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
Reported as:
Geometric mean · nanogram hour per milliliter (ng*hr/mL)
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-03654746
nanogram hour per milliliter (ng*hr/mL)PF-03654746 and Donepezil
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-03654746118.6 ± 35.687
SecondaryMaximum 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
Reported as:
Geometric mean · nanogran per millileter (ng/mL)
Maximum Serum Concentration (Cmax) for PF-03654746
nanogran per millileter (ng/mL)PF-03654746 and Donepezil
Maximum Serum Concentration (Cmax) for PF-036547469.430 ± 2.7317
SecondaryTime 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
Reported as:
Median · hours
Time to Reach Maximum Observed Serum Concentration (Tmax) for PF-03654746
hoursPF-03654746 and Donepezil
Time to Reach Maximum Observed Serum Concentration (Tmax) for PF-036547463.00 (1.00 to 3.00)
SecondaryArea 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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Donepezil
ng*hr/mLPF-03654746 and DonepezilPlacebo and Donepezil
Day 0881.6 ± 282.031109 ± 176.07
Day 301035 ± 364.621013 ± 91.217
Statistical analysis
  • PF-03654746 and Donepezil vs Placebo and Donepezil · Adjusted geometric means ratio: 128.40 · 90% CI 75.90 to 217.21
SecondaryMaximum 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
Reported as:
Geometric mean · ng/mL
Maximum Plasma Concentration (Cmax) for Donepezil
ng/mLPF-03654746 and DonepezilPlacebo and Donepezil
Day 045.47 ± 12.84753.89 ± 10.465
Day 3050.28 ± 14.86449.73 ± 1.7678
Statistical analysis
  • PF-03654746 and Donepezil vs Placebo and Donepezil · Adjusted geometric means ratio: 119.82 · 90% CI 75.90 to 189.16
SecondaryTime 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
Reported as:
Median · hours
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Donepezil
hoursPF-03654746 and DonepezilPlacebo and Donepezil
Day 02.98 (0.967 to 3.00)2.99 (2.98 to 3.00)
Day 303.00 (2.98 to 12.0)2.98 (2.98 to 2.98)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PF-03654746 and Donepezil—0/7 (0%)5/7 (71.4%)
Placebo and Donepezil—0/2 (0%)0/2 (0%)
Most frequent other events
Most frequent other events
EventPF-03654746 and DonepezilPlacebo and Donepezil
HeadacheNervous system disorders1/70/2
Abnormal dreamsPsychiatric disorders1/70/2
Euphoric moodPsychiatric disorders1/70/2
Hypnagogic hallucinationPsychiatric disorders1/70/2
IllusionPsychiatric disorders1/70/2
Erectile dysfunctionReproductive system and breast disorders1/70/2
CoughRespiratory, thoracic and mediastinal disorders1/70/2
EpistaxisRespiratory, thoracic and mediastinal disorders1/70/2
Nasal congestionRespiratory, thoracic and mediastinal disorders1/70/2
UrticariaSkin and subcutaneous tissue disorders1/70/2

Baseline characteristics

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

Age, Customized
Age, Customized(participants)PF-03654746 and DonepezilPlacebo and DonepezilTotal
45 to 64 years101
Greater than or equal to (>=) 65 years628
Sex: Female, Male
Sex: Female, Male(Participants)PF-03654746 and DonepezilPlacebo and DonepezilTotal
Female101
Male628
08

Study locations

2 sites
  • Pfizer Investigational Site
    Wichita, Kansas 67207, United States
  • Pfizer Investigational Site
    Wichita, Kansas 67211, United States
09

References and documents

10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Dec 2009, a primary completion of May 2010 and a completion of May 2010. It does not say whether these dates are actual or estimated.

Results were first posted in Jun 2014, 4 years 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 7, 2009
First posted
Dec 9, 2009
Start
Dec 2009
Primary completionActual
May 2010
CompletionActual
May 2010
Results first posted
Jun 4, 2014
Last update
Jun 4, 2014
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 4, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01028911
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Dec 9, 2009
Start date
Dec 2009
Primary completion
May 2010
Completion
May 2010
Results posted
Jun 4, 2014
Last update
Jun 4, 2014

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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