A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

Time frame: Baseline (Day 1)

Population: FAS included all participants who consumed at least 1 dose of randomized study medication.

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

Time frame: Baseline, Week 12

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

Time frame: Baseline, Week 3, 6, 9

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. Number analyzed signifies those participants who were evaluable for this measure at the specified time points for each arm, respectively.

NPI total score evaluates disturbances in 12 behavioral domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating and night time behavior. NPI total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater behavioral disturbances.

Time frame: Baseline, Week 3, 6, 9, 12

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. Number Analyzed signifies those participants who were evaluable for this measure at the specified time points for each arm, respectively.

CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.

Time frame: Week 3, 6, 9, 12

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. Number Analyzed signifies those participants who were evaluable for this measure at the specified time points for each arm, respectively.

NPI total score evaluates disturbances in 12 behavioral domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating and night time behavior. NPI total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater behavioral disturbances.

Time frame: Baseline

Population: FAS included all participants who consumed at least 1 dose of randomized study medication.

The complete physical and neurological examination included examination of abdomen, ears, extremities, eyes, general, head, heart, lungs, lymph nodes, mouth, musculoskeletal, neck, nose, ocular fundi, pulse, skin, throat, thyroid, and others. Abnormality was judged by investigator.

Time frame: Screening (28 days before Baseline), Week 12

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Here, Number Analyzed signifies those participants who were evaluable for specified rows for each arm, respectively.

C-SSRS assessed whether participant experienced the following: suicidal behavior which includes suicide attempt, interrupted attempt, aborted attempt, and preparatory acts towards imminent suicidal behavior (response of Yes on preparatory acts or behavior); suicidal ideation (response of Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent); self-injurious behavior (SIB), intent unknown (response of Yes on Has subject engaged in Non-suicidal Self-Injurious Behavior?).

Time frame: Screening, Baseline, Post-baseline (Week 1 up to 12)

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Here, Number Analyzed signifies those participants who were evaluable for specified rows for each arm, respectively.

Criteria for laboratory test abnormality: a) Hematology: white blood cells (WBC) \<0.6\*lower limit of normal (LLN)/\>1.5\*upper limit of normal (ULN), hemoglobin, hematocrit, red blood cells (RBC), lymphocytes \<0.8\*LLN, total neutrophils \<0.8\*LLN/ \>1.2\*ULN, basophils, eosinophils, monocytes \>1.2\*ULN; b) Liver Function: total bilirubin \>1.5\*ULN, aspartate aminotransferase (AT), alanine AT\[\>0.3\*ULN, total protein, albumin \<0.8\*LLN/ \>1.2\*ULN; c) Renal Function: creatinine \>1.3\*ULN, uric acid \>1.2\*ULN; d) Electrolytes: sodium \<0.95\*LLN/ \>1.05\*ULN, potassium, chloride, bicarbonate \<0.9\*LLN/ \>1.1\*ULN; e) Clinical Chemistry: glucose \<0.6\*LLN/ \>1.5\*ULN, glycosylated hemoglobin \>1.3\*ULN; f) Urinalysis: ketones, protein, blood/hemoglobin, urine glucose \>=1, RBC, WBC \>=6, hyaline casts \>1; g) Hormones: tetraiodothyronine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) \<0.8\*LLN/1.2\*ULN.

Time frame: Baseline up to Week 12

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure.

Criteria for ECG (12-lead) abnormalities were as follow: 1) PR interval: greater than and equal to (\>=) 300 milliseconds (msec), 2) PR interval: maximum increase from baseline \>=25 percent (%) (if baseline PR interval greater than \[\>\] 100 msec) or \>=50% (if baseline PR interval less than or equal to \[\<=\] 100 msec); 3) QRS complex: \>=200 msec, 4) QRS complex: maximum increase from baseline \>=25% or \>=50%; 5) QT interval \>=500 msec; 6) QT interval corrected using Bazett's formula (QTcB): 450 to less than (\<) 480 msec, 7) QTcB: 480 to \<500 msec, 8) QTcB: \>=500 msec, 10) QTcB: 30 to \<60 msec increase from baseline, 11) QTcB: \>=60 msec increase from baseline; 9) QT interval corrected using the Fridericia's formula (QTcF): 450 to \<480 msec, 10) QTcF: 480 to \< 500 msec, 11) QTcF: \>=500 msec, 12) QTcF: 30 to \<60 msec increase from baseline, 13) QTcF: change\>=60 msec increase from baseline.

Time frame: Baseline up to Week 12

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Here, Number Analyzed signifies those participants who were evaluable for specified rows for each arm, respectively.

Pre-defined criteria vital signs abnormalities included maximum increase or decrease of greater than or equal to (\>=) 30 millimeters of mercury (mmHg) from baseline for supine systolic blood pressure (SBP); maximum increase or decrease of \>=20 mmHg from baseline for supine diastolic BP (DBP); maximum increase or decrease of \>=30 mmHg from baseline for standing SBP; maximum increase or decrease of \>=20 mmHg from baseline for standing DBP. Orthostatic hypotension was defined as a drop of more than 10 mmHg in diastolic BP or a drop of more than 20 mmHg in systolic BP within 3 minutes of standing from the supine position.

Time frame: Baseline up to Week 12 for change in supine or standing blood pressure; Week 1, 3, 6, 9, 12 for orthostatic hypotension

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Number Analyzed signifies those participants who were evaluable for the specified rows for each arm, respectively.

Time frame: Pre-dose on Week 1; 0 to 3 hours following cognitive testing at Week 3, 6, 9, 12

Population: FAS included all the participants who consumed at least 1 dose of randomized study medication. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this measure and Number Analyzed signifies those participants who were evaluable for this measure at the specified time points.