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.

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.

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.

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.

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.

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.

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.

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.

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.

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?").

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.