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TerminatedPhase 2Results posted

Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil

A Randomized, 18-week, Placebo-controlled, Double-blind, Parallel Group Study Of The Safety And Efficacy Of Pf-05212377 (Sam-760) In Subjects With Mild-to-moderate Alzheimer's Disease With Existing Neuropsychiatric Symptoms On A Stable Daily Dose Of Donepezil

Lead sponsor

Pfizer

Asset

PF-05212377

Listed sites

Recruiting sites

Enrollment

186

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•AD symptomatic therapy: stable

Primary endpoint

•ADAS-Cog

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

Eudract number2014-000830-42

Org study IDB2081011

NCT IDNCT01712074

Timeline

Milestones

Study first posted2012-10-23estimated

Study start2012-11 (month precision)

Primary completion2015-09actual (month precision)

Study completion2015-09actual (month precision)

Last update posted2017-03-20actual

Results first posted2017-03-20actual

Assets

Drug assets

PF-05212377

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Clinical diagnosis of probable AD with supportive brain imaging documentation

•Have existing neuropsychiatric symptoms as defined by a score equal or greater than 10 on the NPI at screening, arising from item scores equal or greater than 2 (frequency X severity) on at least 2 domains.

•Has been on donepezil (stable dose of 5 mg or 10 mg) for at least four months, with no intent to change such for the duration of the study

Exclusion criteria

•Demonstrate extreme agitation, physical aggression or violence to themselves, their caregiver, or others, and/or an inability to complete the ADAS-cog assessment at Screening.

•Have major structural brain disease other than Alzheimer's Disease

•Other severe acute or chronical medical or psychiatric condition or laboratory abnormality

Endpoints (48)

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

Other (unclassified)

Behavior / neuropsychiatric

Safety / tolerability / PK

Global cognition

Other clinical outcomes

Global cognition

2 endpoints

Primary/protocol endpoint

Change From Baseline in ADAS-cog13 Total Score at Week 16

Time frame:Baseline and Week 16

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline in ADAS-cog13 Total Score at Week 16

Time frame:Baseline and Week 16

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), scores on a scale	Standard error
PF-05212377 30 mgn=78 Participants	0.111	0.6290
Placebon=86 Participants	-0.584	0.5995

Mean Difference (Net)0.69580% CI-0.424 - 1.814p0.4256Mixed Models Analysis

Behavior / neuropsychiatric

4 endpoints

Secondary/protocol endpoint

Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5)

Time frame:Baseline and Week 16

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5)

Time frame:Baseline and Week 16

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), scores on a scale	Standard error
PF-05212377 30 mgn=78 Participants	-3.990	1.2441
Placebon=87 Participants	-6.184	1.1801

Mean Difference (Net)2.19480% CI-0.013 - 4.401p0.2027Mixed Models Analysis

Other/protocol endpoint

Participants in Each Category of C-CASA Mapped From the C-SSRS Responses

Time frame:From Screening to Week 18/Early Termination

event count, event

Other_pre_specified/registry result

Participants in Each Category of C-CASA Mapped From the C-SSRS Responses

Time frame:From Screening to Week 18/Early Termination

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
Placebo Run-inWeek 4 (Visit 2): <4>n=195 Participants	1	-
Week 6 (Visit 3): <4>n=195 Participants	0	-
Week 10 (Visit 4): : <4>n=195 Participants	0	-
Week 16/Early Termination (Visit 5): <4>n=195 Participants	0	-
Week 4 (Visit 2): <7>n=195 Participants	0	-
Week 6 (Visit 3): <7>n=195 Participants	0	-
PF-05212377 30 mgWeek 4 (Visit 2): <4>n=91 Participants	2	-
Week 6 (Visit 3): <4>n=91 Participants	0	-
Week 10 (Visit 4): : <4>n=91 Participants	2	-
Week 16/Early Termination (Visit 5): <4>n=91 Participants	1	-
Week 4 (Visit 2): <7>n=91 Participants	0	-
Week 6 (Visit 3): <7>n=91 Participants	1	-
PlaceboWeek 4 (Visit 2): <4>n=94 Participants	1	-
Week 6 (Visit 3): <4>n=94 Participants	1	-
Week 10 (Visit 4): : <4>n=94 Participants	0	-
Week 16/Early Termination (Visit 5): <4>n=94 Participants	0	-
Week 4 (Visit 2): <7>n=94 Participants	1	-
Week 6 (Visit 3): <7>n=94 Participants	0	-

Safety / tolerability / PK

4 endpoints

Other/protocol endpoint

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation

Time frame:Week 4 to Week 18

threshold achievement, event

Other/protocol endpoint

Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

change from baseline, event

Other_pre_specified/registry result

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation

Time frame:Week 4 to Week 18

threshold achievement, event

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
PF-05212377 30 mgn=91 Participants	3.3	-
Placebon=94 Participants	0	-

Other_pre_specified/registry result

Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

change from baseline, event

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
PF-05212377 30 mgAbsolute Supine Systolic BP<90 mmHgn=91 Participants	0	-
Absolute Standing Systolic BP<90 mmHgn=91 Participants	0	-
Absolute Supine Diastolic BP<50 mmHgn=91 Participants	0	-
Absolute Standing Diastolic BP <50 mmHgn=91 Participants	0	-
Absolute Supine Pulse Rate <40 bpmn=91 Participants	0	-
Absolute Supine Pulse Rate >120 bpmn=91 Participants	0	-
Absolute Standing Pulse Rate <40 bpmn=91 Participants	0	-
Absolute Standing Pulse Rate >140 bpmn=91 Participants	0	-
Increase in Supine Systolic BP>=30 mmHgn=91 Participants	0	-
Increase in Standing Systolic BP>=30 mmHgn=91 Participants	2.2	-
Increase in Supine Diastolic BP >=20 mmHgn=91 Participants	4.4	-
Increase in Standing Diastolic BP >=20 mmHgn=91 Participants	3.3	-
Decrease in Supine Systolic BP>=30 mmHgn=91 Participants	5.5	-
Decrease in Standing Systolic BP>=30 mmHgn=91 Participants	5.5	-
Decrease in Supine Diastolic BP >=20 mmHgn=91 Participants	8.8	-
Decrease in Standing Diastolic BP >=20 mmHgn=91 Participants	4.4	-
PlaceboAbsolute Supine Systolic BP<90 mmHgn=94 Participants	1.1	-
Absolute Standing Systolic BP<90 mmHgn=94 Participants	1.1	-
Absolute Supine Diastolic BP<50 mmHgn=94 Participants	2.1	-
Absolute Standing Diastolic BP <50 mmHgn=94 Participants	0	-
Absolute Supine Pulse Rate <40 bpmn=94 Participants	0	-
Absolute Supine Pulse Rate >120 bpmn=94 Participants	0	-
Absolute Standing Pulse Rate <40 bpmn=94 Participants	0	-
Absolute Standing Pulse Rate >140 bpmn=94 Participants	0	-
Increase in Supine Systolic BP>=30 mmHgn=94 Participants	5.3	-
Increase in Standing Systolic BP>=30 mmHgn=94 Participants	3.2	-
Increase in Supine Diastolic BP >=20 mmHgn=94 Participants	4.3	-
Increase in Standing Diastolic BP >=20 mmHgn=94 Participants	5.3	-
Decrease in Supine Systolic BP>=30 mmHgn=94 Participants	5.3	-
Decrease in Standing Systolic BP>=30 mmHgn=94 Participants	5.3	-
Decrease in Supine Diastolic BP >=20 mmHgn=94 Participants	5.3	-
Decrease in Standing Diastolic BP >=20 mmHgn=94 Participants	6.4	-

Other clinical outcomes

2 endpoints

Other/protocol endpoint

Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3)

Time frame:Baseline and Week 6

descriptive

Other_pre_specified/registry result

Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3)

Time frame:Baseline and Week 6

descriptive

Posted result

Group	Value (mean), millimeters of mercury (mm Hg)	Reported bounds
PF-05212377 30 mgSupine Systolic BPn=89 Participants	-3.6	--38 - 19
Standing Systolic BPn=89 Participants	-4.1	--49 - 20
Supine Diastolic BPn=89 Participants	-2.2	--37 - 26
Standing Diastolic BPn=89 Participants	-1.1	--23 - 17
PlaceboSupine Systolic BPn=93 Participants	-3.9	--52 - 30
Standing Systolic BPn=93 Participants	-3.0	--38 - 22
Supine Diastolic BPn=93 Participants	-1.8	--33 - 20
Standing Diastolic BPn=93 Participants	-1.0	--23 - 21

Other (unclassified)

36 endpoints

Other/protocol endpoint/low confidence

Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period

Time frame:Week 4 to Week 16

threshold achievement, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3)

Time frame:Baseline and Week 6

change from baseline, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4)

Time frame:Baseline and Week 10

change from baseline, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

change from baseline, improvement

Other/protocol endpoint/low confidence

Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

threshold achievement, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3)

Time frame:Baseline and Week 6

change from baseline, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4)

Time frame:Baseline and Week 10

change from baseline, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

change from baseline, improvement

Other/protocol endpoint/low confidence

Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

threshold achievement, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3)

Time frame:Baseline and Week 6

change from baseline, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4)

Time frame:Baseline and Week 10

change from baseline, improvement

Other/protocol endpoint/low confidence

Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

change from baseline, improvement

Other/protocol endpoint/low confidence

Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

threshold achievement, improvement

Other/protocol endpoint/low confidence

Pulse Rate Changes From Baseline - Week 6 (Visit 3)

Time frame:Baseline and Week 6

descriptive

Other/protocol endpoint/low confidence

BP Changes From Baseline - Week 10 (Visit 4)

Time frame:Baseline and Week 10

descriptive

Other/protocol endpoint/low confidence

Pulse Rate Changes From Baseline - Week 10 (Visit 4)

Time frame:Baseline and Week 10

descriptive

Other/protocol endpoint/low confidence

BP Changes From Baseline - Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

descriptive

Other/protocol endpoint/low confidence

Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

descriptive

Other_pre_specified/registry result/low confidence

Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period

Time frame:Week 4 to Week 16

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
PF-05212377 30 mgn=91 Participants	36.0	-
Placebon=94 Participants	52.0	-

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3)

Time frame:Baseline and Week 6

change from baseline, improvement

Posted result

Group	Value (mean), milliseconds (msec)	Reported bounds
PF-05212377 30 mgn=85 Participants	-2.8	--52 - 24
Placebon=89 Participants	-3.6	--82 - 35

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4)

Time frame:Baseline and Week 10

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=79 Participants	-0.1	--42 - 23
Placebon=87 Participants	-1.3	--61 - 61

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=82 Participants	-2.5	--69 - 24
Placebon=85 Participants	-1.6	--49 - 33

Other_pre_specified/registry result/low confidence

Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
PF-05212377 30 mgPost-Baseline Maximum Absolute Value >=300 msecn=86 Participants	0	-
Post-Baseline Maximum Increase >=25/50%n=86 Participants	0	-
PlaceboPost-Baseline Maximum Absolute Value >=300 msecn=90 Participants	4.4	-
Post-Baseline Maximum Increase >=25/50%n=90 Participants	0	-

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3)

Time frame:Baseline and Week 6

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=88 Participants	-0.3	--22 - 43
Placebon=92 Participants	-0.8	--14 - 10

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4)

Time frame:Baseline and Week 10

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=81 Participants	-0.1	--13 - 45
Placebon=90 Participants	0.1	--15 - 22

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=85 Participants	0.1	--14 - 18
Placebon=89 Participants	-0.3	--21 - 14

Other_pre_specified/registry result/low confidence

Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	Reported bounds
PF-05212377 30 mgPost-Baseline Maximum Absolute Value >=200 msecn=91 Participants	0	-
Post-Baseline Maximum Increase >=25/50%n=91 Participants	0	-
PlaceboPost-Baseline Maximum Absolute Value >=200 msecn=93 Participants	0	-
Post-Baseline Maximum Increase >=25/50%n=93 Participants	0	-

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3)

Time frame:Baseline and Week 6

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=88 Participants	-3.0	--31 - 37
Placebon=92 Participants	-4.9	--35 - 35

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4)

Time frame:Baseline and Week 10

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=81 Participants	-0.2	--38 - 47
Placebon=90 Participants	-5.5	--40 - 48

Other_pre_specified/registry result/low confidence

Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

change from baseline, improvement

Posted result

Group	Value (mean), msec	Reported bounds
PF-05212377 30 mgn=85 Participants	0.8	--31 - 34
Placebon=89 Participants	-2.2	--62 - 30

Other_pre_specified/registry result/low confidence

Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern

Time frame:Week 4 to Week 16

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
PF-05212377 30 mgPost-Baseline Absolute Value of 450-<480 msecn=91 Participants	15.4	-
Post-Baseline Absolute Value of 480-<500 msecn=91 Participants	4.4	-
Change from Baseline of 30 -<60 msecn=91 Participants	6.6	-
Change from Baseline >=60 msecn=91 Participants	0	-
PlaceboPost-Baseline Absolute Value of 450-<480 msecn=93 Participants	14.0	-
Post-Baseline Absolute Value of 480-<500 msecn=93 Participants	1.1	-
Change from Baseline of 30 -<60 msecn=93 Participants	3.2	-
Change from Baseline >=60 msecn=93 Participants	0	-

Other_pre_specified/registry result/low confidence

Pulse Rate Changes From Baseline - Week 6 (Visit 3)

Time frame:Baseline and Week 6

descriptive

Posted result

Group	Value (mean), beats per minute (bpm)	Reported bounds
PF-05212377 30 mgSupine Pulse Raten=89 Participants	-1.4	--30 - 30
Standing Pulse Raten=89 Participants	-0.3	--20 - 30
PlaceboSupine Pulse Raten=93 Participants	1.4	--21 - 20
Standing Pulse Raten=93 Participants	1.3	--12 - 27

Other_pre_specified/registry result/low confidence

BP Changes From Baseline - Week 10 (Visit 4)

Time frame:Baseline and Week 10

descriptive

Posted result

Group	Value (mean), mmHg	Reported bounds
PF-05212377 30 mgSupine Systolic BPn=81 Participants	-3.4	--36 - 20
Standing Systolic BPn=81 Participants	-3.8	--33 - 32
Supine Diastolic BPn=81 Participants	-2.4	--32 - 20
Standing Diastolic BPn=81 Participants	-1.2	--20 - 20
PlaceboSupine Systolic BPn=91 Participants	-0.3	--68 - 34
Standing Systolic BPn=91 Participants	0.8	--49 - 49
Supine Diastolic BPn=91 Participants	-0.7	--39 - 25
Standing Diastolic BPn=91 Participants	0.3	--26 - 39

Other_pre_specified/registry result/low confidence

Pulse Rate Changes From Baseline - Week 10 (Visit 4)

Time frame:Baseline and Week 10

descriptive

Posted result

Group	Value (mean), bpm	Reported bounds
PF-05212377 30 mgSupine Pulse Raten=81 Participants	-0.4	--26 - 22
Standing Pulse Raten=81 Participants	-0.7	--20 - 24
PlaceboSupine Pulse Raten=91 Participants	0.5	--24 - 17
Standing Pulse Raten=91 Participants	1.8	--19 - 21

Other_pre_specified/registry result/low confidence

BP Changes From Baseline - Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

descriptive

Posted result

Group	Value (mean), mmHg	Reported bounds
PF-05212377 30 mgSupine Systolic BPn=85 Participants	-1.4	--30 - 27
Standing Systolic BPn=85 Participants	-1.0	--30 - 32
Supine Diastolic BPn=85 Participants	-2.1	--39 - 22
Standing Diastolic BPn=85 Participants	-0.8	--23 - 23
PlaceboSupine Systolic BPn=90 Participants	-1.1	--30 - 72
Standing Systolic BPn=90 Participants	-1.1	--26 - 66
Supine Diastolic BPn=90 Participants	-0.3	--18 - 35
Standing Diastolic BPn=90 Participants	0.0	--20 - 36

Other_pre_specified/registry result/low confidence

Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5)

Time frame:Baseline and Week 16/Early Termination

descriptive

Posted result

Group	Value (mean), bpm	Reported bounds
PF-05212377 30 mgSupine Pulse Raten=85 Participants	-0.8	--29 - 31
Standing Pulse Raten=85 Participants	-1.9	--24 - 29
PlaceboSupine Pulse Raten=90 Participants	0.6	--22 - 20
Standing Pulse Raten=90 Participants	0.8	--17 - 17

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Fullerton T, Binneman B, David W, Delnomdedieu M, Kupiec J, Lockwood P, Mancuso J, Miceli J, Bell J. A Phase 2 clinical trial of PF-05212377 (SAM-760) in subjects with mild to moderate Alzheimer's disease with existing neuropsychiatric symptoms on a stable daily dose of donepezil. Alzheimers Res Ther. 2018 Apr 5;10(1):38. doi: 10.1186/s13195-018-0368-9.
PMID29622037via DERIVED

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.