TerminatedPhase 1Results 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, 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

Lead sponsor

Pfizer

Asset

PF-03654746

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 18-26

Primary endpoints

•Clinically Significant Vital Sign Abnormalities•Clinically Significant Electrocardiogram (ECG) Abnormalities•Clinically Significant Laboratory Test Abnormalities

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDA8801016

NCT IDNCT01028911

Timeline

Milestones

Study start2009-12 (month precision)

Study first posted2009-12-09estimated

Primary completion2010-05actual (month precision)

Study completion2010-05actual (month precision)

Last update posted2014-06-04estimated

Results first posted2014-06-04estimated

Assets

Drug assets

PF-03654746

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (64)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Global cognition

Safety / tolerability / PK

Other (unclassified)

Global cognition

14 endpoints

Primary/protocol endpoint

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

Time frame:Baseline, Day 5

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Day 10

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Day 15

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline, Day 20

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 5

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilBaselinen=7 Participants	24.6	1.51
Change at Day 5n=7 Participants	-0.7	2.29
Placebo and DonepezilBaselinen=2 Participants	24.0	0.00
Change at Day 5n=2 Participants	3.0	0.00

Primary/protocol endpoint

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

Time frame:Baseline, Day 25

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 10

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	0.1	2.34
Placebo and Donepeziln=2 Participants	3.0	0.00

Primary/protocol endpoint

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

Time frame:Baseline, Day 30

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 15

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	1.3	1.80
Placebo and Donepeziln=2 Participants	2.5	0.71

Primary/protocol endpoint

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

Time frame:Baseline, Follow-up (7 to 10 days after last dose)

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 20

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	0.4	2.94
Placebo and Donepeziln=2 Participants	4.0	0.00

Primary/registry result

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

Time frame:Baseline, Day 25

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	1.0	2.08
Placebo and Donepeziln=2 Participants	3.5	0.71

Primary/registry result

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

Time frame:Baseline, Day 30

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	0.6	2.37
Placebo and Donepeziln=2 Participants	3.0	2.83

Primary/registry result

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

Time frame:Baseline, Follow-up (7 to 10 days after last dose)

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	0.7	1.60
Placebo and Donepeziln=2 Participants	3.0	4.24

Behavior / neuropsychiatric

30 endpoints

Primary/protocol endpoint

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

Time frame:Baseline

descriptive

Primary/protocol endpoint

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

Time frame:Day 5

descriptive

Primary/protocol endpoint

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

Time frame:Day 10

descriptive

Primary/protocol endpoint

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

Time frame:Day 15

descriptive

Primary/registry result

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

Time frame:Baseline

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	23.76	21.57
Somnolencen=7 Participants	30.49	18.40
Sleep adequacyn=7 Participants	65.71	32.07
Snoren=7 Participants	45.71	37.80
Awaken short of breath or with headachen=7 Participants	8.57	15.74
Quantity of sleepn=7 Participants	7.86	0.90
Optimal sleepn=7 Participants	0.71	0.49
Sleep problem index In=7 Participants	23.81	17.70
Sleep problem index IIn=7 Participants	24.21	15.81
Placebo and DonepezilSleep disturbancen=2 Participants	15.65	22.13
Somnolencen=2 Participants	16.70	14.14
Sleep adequacyn=2 Participants	85.00	21.21
Snoren=2 Participants	20.00	28.28
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	10.50	2.12
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	10.00	14.14
Sleep problem index IIn=2 Participants	14.70	17.68

Primary/protocol endpoint

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

Time frame:Day 20

descriptive

Primary/registry result

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

Time frame:Day 5

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	25.01	19.56
Somnolencen=7 Participants	28.57	26.87
Sleep adequacyn=7 Participants	65.71	22.25
Snoren=7 Participants	28.57	30.24
Awaken short of breath or with headachen=7 Participants	8.57	22.68
Quantity of sleepn=7 Participants	7.57	0.98
Optimal sleepn=7 Participants	0.71	0.49
Sleep problem index In=7 Participants	21.89	14.25
Sleep problem index IIn=7 Participants	24.76	14.64
Placebo and DonepezilSleep disturbancen=2 Participants	15.65	22.13
Somnolencen=2 Participants	16.70	14.14
Sleep adequacyn=2 Participants	90.00	14.14
Snoren=2 Participants	20.00	28.28
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	8.35	11.81
Sleep problem index IIn=2 Participants	13.60	16.12

Primary/protocol endpoint

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

Time frame:Day 25

descriptive

Primary/registry result

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

Time frame:Day 10

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	27.69	27.86
Somnolencen=7 Participants	29.53	31.46
Sleep adequacyn=7 Participants	67.14	29.28
Snoren=7 Participants	34.29	35.99
Awaken short of breath or with headachen=7 Participants	14.29	37.80
Quantity of sleepn=7 Participants	7.43	1.13
Optimal sleepn=7 Participants	0.57	0.53
Sleep problem index In=7 Participants	26.19	20.14
Sleep problem index IIn=7 Participants	26.90	19.49
Placebo and DonepezilSleep disturbancen=2 Participants	13.15	18.60
Somnolencen=2 Participants	16.70	14.14
Sleep adequacyn=2 Participants	90.00	14.14
Snoren=2 Participants	20.00	28.28
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	8.35	11.81
Sleep problem index IIn=2 Participants	12.50	14.57

Primary/protocol endpoint

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

Time frame:Day 30

descriptive

Primary/registry result

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

Time frame:Day 15

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	28.76	11.58
Somnolencen=7 Participants	28.57	20.27
Sleep adequacyn=7 Participants	64.29	31.01
Snoren=7 Participants	40.00	41.63
Awaken short of breath or with headachen=7 Participants	5.71	15.12
Quantity of sleepn=7 Participants	7.29	0.95
Optimal sleepn=7 Participants	0.71	0.49
Sleep problem index In=7 Participants	28.10	16.55
Sleep problem index IIn=7 Participants	26.74	15.20
Placebo and DonepezilSleep disturbancen=2 Participants	13.15	18.60
Somnolencen=2 Participants	16.70	14.14
Sleep adequacyn=2 Participants	90.00	14.14
Snoren=2 Participants	20.00	28.28
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	8.35	11.81
Sleep problem index IIn=2 Participants	12.50	14.57

Primary/protocol endpoint

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

Time frame:Follow-up (7 to 10 days after last dose)

descriptive

Primary/registry result

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

Time frame:Day 20

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	23.57	22.07
Somnolencen=7 Participants	37.14	30.75
Sleep adequacyn=7 Participants	61.43	26.10
Snoren=7 Participants	42.86	43.86
Awaken short of breath or with headachen=7 Participants	8.57	15.74
Quantity of sleepn=7 Participants	7.00	1.41
Optimal sleepn=7 Participants	0.43	0.53
Sleep problem index In=7 Participants	26.19	18.11
Sleep problem index IIn=7 Participants	26.67	18.20
Placebo and DonepezilSleep disturbancen=2 Participants	5.65	7.99
Somnolencen=2 Participants	10.00	14.14
Sleep adequacyn=2 Participants	95.00	7.07
Snoren=2 Participants	10.00	14.14
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	3.35	4.74
Sleep problem index IIn=2 Participants	5.85	8.27

Primary/protocol endpoint

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

Time frame:Baseline, Day 5

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Day 25

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	23.76	21.18
Somnolencen=7 Participants	36.19	28.24
Sleep adequacyn=7 Participants	72.86	22.15
Snoren=7 Participants	45.71	47.21
Awaken short of breath or with headachen=7 Participants	5.71	15.12
Quantity of sleepn=7 Participants	7.71	0.95
Optimal sleepn=7 Participants	0.71	0.49
Sleep problem index In=7 Participants	22.37	16.86
Sleep problem index IIn=7 Participants	23.89	16.04
Placebo and DonepezilSleep disturbancen=2 Participants	3.15	4.45
Somnolencen=2 Participants	6.65	9.40
Sleep adequacyn=2 Participants	95.00	7.07
Snoren=2 Participants	10.00	14.14
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	1.65	2.33
Sleep problem index IIn=2 Participants	3.60	5.09

Primary/protocol endpoint

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

Time frame:Baseline, Day 10

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Day 30

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	23.04	21.99
Somnolencen=7 Participants	37.16	24.62
Sleep adequacyn=7 Participants	72.86	22.15
Snoren=7 Participants	42.86	43.86
Awaken short of breath or with headachen=7 Participants	5.71	15.12
Quantity of sleepn=7 Participants	7.86	1.07
Optimal sleepn=7 Participants	0.57	0.53
Sleep problem index In=7 Participants	21.90	17.52
Sleep problem index IIn=7 Participants	23.26	16.21
Placebo and DonepezilSleep disturbancen=2 Participants	3.15	4.45
Somnolencen=2 Participants	6.65	9.40
Sleep adequacyn=2 Participants	95.00	7.07
Snoren=2 Participants	10.00	14.14
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	1.65	2.33
Sleep problem index IIn=2 Participants	3.60	5.09

Primary/protocol endpoint

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

Time frame:Baseline, Day 15

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Follow-up (7 to 10 days after last dose)

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilSleep disturbancen=7 Participants	16.44	17.07
Somnolencen=7 Participants	32.39	27.62
Sleep adequacyn=7 Participants	72.86	23.60
Snoren=7 Participants	42.86	43.86
Awaken short of breath or with headachen=7 Participants	5.71	15.12
Quantity of sleepn=7 Participants	8.14	0.69
Optimal sleepn=7 Participants	0.71	0.49
Sleep problem index In=7 Participants	17.61	15.25
Sleep problem index IIn=7 Participants	19.67	14.12
Placebo and DonepezilSleep disturbancen=2 Participants	3.15	4.45
Somnolencen=2 Participants	6.65	9.40
Sleep adequacyn=2 Participants	95.00	7.07
Snoren=2 Participants	10.00	14.14
Awaken short of breath or with headachen=2 Participants	0.00	0.00
Quantity of sleepn=2 Participants	9.50	0.71
Optimal sleepn=2 Participants	0.00	0.00
Sleep problem index In=2 Participants	1.65	2.33
Sleep problem index IIn=2 Participants	3.60	5.09

Primary/protocol endpoint

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

Time frame:Baseline, Day 20

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 5

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and DonepezilBaselinen=7 Participants	4.1	6.09
Change at Day 5n=7 Participants	-1.9	5.64
Placebo and DonepezilBaselinen=2 Participants	3.0	4.24
Change at Day 5n=2 Participants	-1.0	1.41

Primary/protocol endpoint

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

Time frame:Baseline, Day 25

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 10

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	-1.7	4.75
Placebo and Donepeziln=2 Participants	-1.0	1.41

Primary/protocol endpoint

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

Time frame:Baseline, Day 30

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 15

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	-2.6	4.39
Placebo and Donepeziln=2 Participants	-1.0	1.41

Primary/protocol endpoint

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

Time frame:Baseline, Follow-up (7 to 10 days after last dose)

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline, Day 20

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	-2.7	5.71
Placebo and Donepeziln=2 Participants	0.0	0.00

Primary/registry result

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

Time frame:Baseline, Day 25

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	-2.6	4.39
Placebo and Donepeziln=2 Participants	0.0	0.00

Primary/registry result

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

Time frame:Baseline, Day 30

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	-1.4	5.22
Placebo and Donepeziln=2 Participants	0.0	0.00

Primary/registry result

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

Time frame:Baseline, Follow-up (7 to 10 days after last dose)

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
PF-03654746 and Donepeziln=7 Participants	-2.6	4.39
Placebo and Donepeziln=2 Participants	1.5	2.12

Safety / tolerability / PK

14 endpoints

Primary/protocol endpoint

Number of Participants With Clinically Significant Vital Sign Abnormalities

Time frame:Baseline up to 7 to 10 days after last dose

event count, event

Primary/protocol endpoint

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

Time frame:Baseline up to 7 to 10 days after last dose

event count, event

Primary/protocol endpoint

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

Time frame:Baseline up to 7 to 10 days after last dose

change from baseline, event

Primary/registry result

Number of Participants With Clinically Significant Vital Sign Abnormalities

Time frame:Baseline up to 7 to 10 days after last dose

event count, event

Posted result

Group	Value (number), participants	Reported bounds
PF-03654746 and DonepezilSupine SBP <90 mmHgn=7 Participants	0	-
Standing SBP <90 mmHgn=7 Participants	0	-
Supine DBP <50 mmHgn=7 Participants	0	-
Standing DBP <50 mmHgn=7 Participants	0	-
Supine pulse rate <40 bpmn=7 Participants	0	-
Supine pulse rate >120 bpmn=7 Participants	0	-
Standing pulse rate <40 bpmn=7 Participants	0	-
Standing pulse rate >140 bpmn=7 Participants	0	-
Su SBP: Maximum increase from baseline >=30 mmHgn=7 Participants	3	-
St SBP: Maximum increase from baseline >=30 mmHgn=7 Participants	1	-
Su DBP: Maximum increase from baseline >=20 mmHgn=7 Participants	2	-
St DBP: Maximum increase from baseline >=20 mmHgn=7 Participants	1	-
Su SBP: Maximum decrease from baseline >=30 mmHgn=7 Participants	0	-
St SBP: Maximum decrease from baseline >=30 mmHgn=7 Participants	0	-
Su DBP: Maximum decrease from baseline >=20 mmHgn=7 Participants	0	-
St DBP: Maximum decrease from baseline >=20 mmHgn=7 Participants	1	-
Placebo and DonepezilSupine SBP <90 mmHgn=2 Participants	0	-
Standing SBP <90 mmHgn=2 Participants	0	-
Supine DBP <50 mmHgn=2 Participants	0	-
Standing DBP <50 mmHgn=2 Participants	0	-
Supine pulse rate <40 bpmn=2 Participants	0	-
Supine pulse rate >120 bpmn=2 Participants	0	-
Standing pulse rate <40 bpmn=2 Participants	0	-
Standing pulse rate >140 bpmn=2 Participants	0	-
Su SBP: Maximum increase from baseline >=30 mmHgn=2 Participants	0	-
St SBP: Maximum increase from baseline >=30 mmHgn=2 Participants	0	-
Su DBP: Maximum increase from baseline >=20 mmHgn=2 Participants	0	-
St DBP: Maximum increase from baseline >=20 mmHgn=2 Participants	0	-
Su SBP: Maximum decrease from baseline >=30 mmHgn=2 Participants	1	-
St SBP: Maximum decrease from baseline >=30 mmHgn=2 Participants	0	-
Su DBP: Maximum decrease from baseline >=20 mmHgn=2 Participants	0	-
St DBP: Maximum decrease from baseline >=20 mmHgn=2 Participants	1	-

Primary/registry result

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

Time frame:Baseline up to 7 to 10 days after last dose

event count, event

Posted result

Group	Value (number), participants	Reported bounds
PF-03654746 and DonepezilMaximum PR interval >=300 msecn=7 Participants	0	-
Maximum QRS Complex >=200 msecn=7 Participants	0	-
Maximum QTCF interval >=500 msecn=7 Participants	1	-
PR interval increase from baseline >=25/50 %n=7 Participants	0	-
QRS complex increase from baseline >=25/50 %n=7 Participants	0	-
QTCF interval increase from baseline 30 to 60 msecn=7 Participants	2	-
QTCF interval increase from baseline >=60 msecn=7 Participants	1	-
Placebo and DonepezilMaximum PR interval >=300 msecn=2 Participants	0	-
Maximum QRS Complex >=200 msecn=2 Participants	0	-
Maximum QTCF interval >=500 msecn=2 Participants	0	-
PR interval increase from baseline >=25/50 %n=2 Participants	0	-
QRS complex increase from baseline >=25/50 %n=2 Participants	0	-
QTCF interval increase from baseline 30 to 60 msecn=2 Participants	0	-
QTCF interval increase from baseline >=60 msecn=2 Participants	0	-

Primary/registry result

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

Time frame:Baseline up to 7 to 10 days after last dose

change from baseline, event

Posted result

Group	Value (number), participants	Reported bounds
PF-03654746 and Donepeziln=7 Participants	0	-
Placebo and Donepeziln=2 Participants	0	-

Secondary/protocol endpoint

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

concentration, descriptive

Secondary/protocol endpoint

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

time to event, event

Secondary/protocol endpoint

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

concentration, descriptive

Secondary/protocol endpoint

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

time to event, event

Secondary/registry result

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

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanogran per millileter (ng/mL)	Standard deviation
PF-03654746 and Donepeziln=7 Participants	9.430	2.7317

Secondary/registry result

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

time to event, event

Posted result

Group	Value (median), hours	Reported bounds
PF-03654746 and Donepeziln=7 Participants	3.00	-1.00 - 3.00

Secondary/registry result

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

concentration, descriptive

Posted result

Group	Value (geometric_mean), ng/mL	Standard deviation
PF-03654746 and DonepezilDay 0n=7 Participants	45.47	12.847
Day 30n=7 Participants	50.28	14.864
Placebo and DonepezilDay 0n=2 Participants	53.89	10.465
Day 30n=2 Participants	49.73	1.7678

Adjusted Geometric Means Ratio119.8290% CI75.90 - 189.16

Secondary/registry result

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

time to event, event

Posted result

Group	Value (median), hours	Reported bounds
PF-03654746 and DonepezilDay 0n=7 Participants	2.98	-0.967 - 3.00
Day 30n=7 Participants	3.00	-2.98 - 12.0
Placebo and DonepezilDay 0n=2 Participants	2.99	-2.98 - 3.00
Day 30n=2 Participants	2.98	-2.98 - 2.98

Other (unclassified)

6 endpoints

Primary/protocol endpoint/low confidence

Number of Participants With Clinically Significant Laboratory Test Abnormalities

Time frame:Baseline up to 7 to 10 days after last dose

event count, event

Primary/registry result/low confidence

Number of Participants With Clinically Significant Laboratory Test Abnormalities

Time frame:Baseline up to 7 to 10 days after last dose

event count, event

Posted result

Group	Value (number), participants	Reported bounds
PF-03654746 and Donepeziln=7 Participants	7	-
Placebo and Donepeziln=2 Participants	0	-

Secondary/protocol endpoint/low confidence

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

descriptive

Secondary/protocol endpoint/low confidence

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

descriptive

Secondary/registry result/low confidence

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

descriptive

Posted result

Group	Value (geometric_mean), nanogram hour per milliliter (ng*hr/mL)	Standard deviation
PF-03654746 and Donepeziln=7 Participants	118.6	35.687

Secondary/registry result/low confidence

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

descriptive

Posted result

Group	Value (geometric_mean), ng*hr/mL	Standard deviation
PF-03654746 and DonepezilDay 0n=7 Participants	881.6	282.03
Day 30n=7 Participants	1035	364.62
Placebo and DonepezilDay 0n=2 Participants	1109	176.07
Day 30n=2 Participants	1013	91.217

Adjusted Geometric Means Ratio128.4090% CI75.90 - 217.21

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.