A Study Of PF-04171327 In The Treatment Of The Signs And Symptoms Of Rheumatoid Arthritis

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Day 7 and 14

HAQ-DI assessed the ability of participants to perform task in 8 domains of daily living activities: dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities. Each item was scored on a 4-point scale ranging from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do, higher scores indicate more difficulty. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible HAQ-DI score range: 0 (no difficulty) to 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.

Time frame: Baseline, Day 7, 14

Change From Baseline in Participant Assessment of Arthritis Pain at Day 7 and 14

Participant assessment of arthritis pain included assessment of severity of arthritis pain using a 100 millimeter (mm) visual analog scale (VAS). Participants placed a mark on the VAS between 0 mm (no pain) and 100 mm (most severe pain), which corresponded to the magnitude of their pain, higher scores indicate more pain.

Time frame: Baseline, Day 7, 14

Change From Baseline in Participant Global Assessment (PGA) of Arthritis at Day 7 and 14

PGA was a questionnaire where participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participants' response were recorded using a 100 mm visual analog scale placing a mark on the scale, between 0 mm (very well condition) to 100 mm (very poor condition). Higher scores indicate higher degree of arthritis.

Time frame: Baseline, Day 7, 14

Change From Baseline in Physician Global Assessment (PhGA) of Arthritis at Day 7 and 14

PhGA included assessment of severity of arthritis pain where physicians were asked to rate the severity of the participant's overall arthritis. The physician's response was recorded using a visual analog scale between 0 mm (very good condition) to 100 mm (very poor condition). Higher scores indicate higher degree of arthritis.

Time frame: Baseline, Day 7, 14

Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) at Day 14

SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. Score for each of the 8 aspects are scaled from 0 (worst condition) to 100 (best condition), where higher scores indicate better health status. These 8 domains were also reported as two summary scores: physical component scores and mental component scores. Score range for each of the 2 summary scores = 0 (worst condition) to 100 (best condition), where higher scores represent better health status.

Time frame: Baseline, Day 14 (D14)

Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 7, 14 and 42

DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (normal range of CRP is \<10 mg/L, decrease in the level of CRP indicates reduction in inflammation). Total DAS28-3 (CRP) score range: 0 (least severe) to 9.4 (most severe), higher scores indicate more disease activity.

Time frame: Baseline, Day 7, 14, 42

Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Day 7

DAS28-4 (CRP) examines progression or improvement of RA. It was assessed from SJC and TJC using the 28 joints count, CRP (normal range of CRP is \<10 mg/L, decrease in the level of CRP indicates reduction in inflammation) and PGA of disease activity (participant global assessment of diseases condition scores ranging from 0 \[very well condition\] to 100 \[very poor condition\], higher scores indicated greater affectation due to disease activity). Total DAS28-4 (CRP) transformed score range: 0 (least severe) to 10 (most severe), higher scores indicate more severe disease activity. DAS28-4 (CRP) scores: \<=3.2 implied low disease activity; \>3.2 to 5.1 implied moderate to high disease activity.

Time frame: Baseline, Day 7

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Day 7 and 14

ACR20 responder: participants who achieved at =20% improvement in tender and swollen 28-joints count, and \>=20% improvement in at least 3 of the following 5 measures: 1) participant's assessment of arthritis pain (participant's self-assessed severity of arthritis pain, score range from 0\[no pain\] to 100\[most severe pain\], higher scores=more pain), 2) PGA of arthritis (participant's assessed overall arthritis activity, score range from 0\[no arthritis\] to 100\[extreme arthritis\], higher scores=higher degree of arthritis), 3) PhGA of arthritis (physician rated severity of participants overall arthritis activity, score range from 0\[no arthritis\] to 100\[extreme arthritis\], higher scores=higher degree of arthritis), 4) HAQ-DI (assessment of functional disability, score range from 0\[no difficulty\] to 3\[extreme difficulty\], higher scores=more functional limitation) and 5) CRP (assessment of inflammation, normal range of CRP is \<10 mg/L, decrease in the level of CRP=reduction in inflammation).

Time frame: Day 7, 14

Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 7 and 14

ACR50 responder: participants who achieved at =50% improvement in tender and swollen 28-joints count, and \>=50% improvement in at least 3 of the following 5 measures: 1) participant's assessment of arthritis pain (participant's self-assessed severity of arthritis pain, score range from 0\[no pain\] to 100\[most severe pain\], higher scores=more pain), 2) PGA of arthritis (participant's assessed overall arthritis activity, score range from 0\[no arthritis\] to 100\[extreme arthritis\], higher scores=higher degree of arthritis), 3) PhGA of arthritis (physician rated severity of participants overall arthritis activity, score range from 0\[no arthritis\] to 100\[extreme arthritis\], higher scores=higher degree of arthritis), 4) HAQ-DI (assessment of functional disability, score range from 0\[no difficulty\] to 3\[extreme difficulty\], higher scores=more functional limitation) and 5) CRP (assessment of inflammation, normal range of CRP is \<10 mg/L, decrease in the level of CRP=reduction in inflammation).

Time frame: Day 7, 14

Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Day 7 and 14

ACR70 responder: participants who achieved at =70% improvement in tender and swollen 28-joints count, and \>=70% improvement in at least 3 of the following 5 measures: 1) participant's assessment of arthritis pain (participant's self-assessed severity of arthritis pain, score range from 0\[no pain\] to 100\[most severe pain\], higher scores=more pain), 2) PGA of arthritis (participant's assessed overall arthritis activity, score range from 0\[no arthritis\] to 100\[extreme arthritis\], higher scores=higher degree of arthritis), 3) PhGA of arthritis (physician rated severity of participants overall arthritis activity, score range from 0\[no arthritis\] to 100\[extreme arthritis\], higher scores=higher degree of arthritis), 4) HAQ-DI (assessment of functional disability, score range from 0\[no difficulty\] to 3\[extreme difficulty\], higher scores=more functional limitation) and 5) CRP (assessment of inflammation, normal range of CRP is \<10 mg/L, decrease in the level of CRP=reduction in inflammation).

Time frame: Day 7, 14

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 31 days after last dose (Day 45) that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Baseline up to Day 45

Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities

Criteria for laboratory abnormalities: Hematology (hemoglobin, hematocrit \<0.8\*baseline; platelet count \<75 or \>700\*10\^3 per mm\^3; leucocytes \<2.5 or \>17.5\*10\^3 per mm\^3); chemistry (total bilirubin \>1.5\*upper limit of reference range \[ULN\]; aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, \>3.0\*ULN; total protein, albumin \<0.8\*lower limit of reference range \[LLN\] or \>1.2\*ULN; blood urea nitrogen \[BUN\]/urea, creatinine \>1.3\*ULN; glucose \[fasting\] \<0.6\*LLN or \>1.5\*ULN; uric acid \>1.2\*ULN; sodium \<0.95\*LLN or \>1.05\*ULN; potassium, calcium \<0.9\*LLN or \>1.1\*ULN; albumin, total protein \<0.8\*LLN or \>1.2\*ULN; urinalysis (urine white blood cell (WBC) =\>6/ high power field (hpf); urine red blood cell (RBC) =\>6/hpf). Number of participants with clinically significant change from baseline in laboratory abnormalities identified by investigator were reported.

Time frame: Baseline up to Day 45

Change From Baseline in Body Weight at Day 7 and 14

Time frame: Baseline, Day 7, 14

Number of Participants With Clinically Significant Vital Signs Abnormalities

Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, heart rate and body temperature. Vital sign measurements were performed with the participant in the seated position. Clinical significance vital sign abnormality was determined by investigator.

Time frame: Baseline up to Day 45

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

Clinically significant ECG findings included PR interval \>=300 milliseconds (msec) or \>=25% increase from baseline (if baseline PR interval \>200 msec) or \>=50% increase (if baseline PR interval less than or equal to \[\<=\] 200 msec); QRS interval \>=200 msec or \>=25% increase from baseline (if baseline PR interval \>100 msec) or \>=50% increase (if baseline PR interval \<= 100 msec); QT interval \>=500 msec, corrected QT interval \>=500 msec.

Time frame: Baseline up to Day 45

Plasma Concentration of PF-00251802 Versus Time Summary on Day 7 and Day 14

Plasma concentration of PF-00251802 versus time summary, a metabolite of PF-04171327 was reported in this outcome measure.

Time frame: 0, 1, 2, 3 and 4 hours post-dose on Day 7, 14

Ratio of Apparent Oral Clearance on Day 1 to Day 14 of Methotrexate

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Methotrexate was used as a background therapy by participants.

Time frame: Pre-dose (0 hour), 1, 2, 3 and 4 hours post-dose

Change From Baseline in Lymphocyte Counts at Day 1, 7 and 14

Time frame: Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14

Change From Baseline in Neutrophil Counts at Day 1, 7 and 14

Time frame: Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14

Change From Baseline in Eosinophil Counts at Day 1, 7 and 14

Time frame: Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14

Change From Baseline in Osteocalcin Level at Day 1, 7 and 14

Time frame: Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14

Change From Baseline in Plasma Cortisol Level at Day 1, 7 and 14

Time frame: Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14

Change From Baseline in Ratio of Urinary N-terminal Telopeptide of Type 1 Collagen (uNTX-I) Level to Urinary Creatinine (uCr) Level at Day 7 and 14

Unit of ratio of urinary N-terminal telopeptide of type 1 collagen (uNTX-I) level to urinary creatinine (uCr) level was nanomoles bone collagen equivalents (nmol bce) per millimole creatinine (mmol cr).

Time frame: Baseline, Day 7 and 14

Change From Baseline in Adiponectin Level at Day 7 and 14

Time frame: Baseline, Day 7 and 14