Study of CE-224,535 A Twice Daily Pill To Control Rheumatoid Arthritis In Patients Who Have Not Totally Improved With Methotrexate

ACR20 response: compared to baseline, greater than or equal to (\>=) 20 percent (%) improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Time frame: Week 12

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of the randomized study medication. Last observation carried forward (LOCF) was used to impute missing ACR components before computing ACR20 response.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (milligram per liter \[mg/L\]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (\<=) 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0= least difficulty and 3= extreme difficulty.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

Number of participants who withrew due to lack of efficacy were reported.

Time frame: Week 2, 4, 8, 12, 14

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

Number of tender/painful joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'number analyzed' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

Participants measured their pain at the time of assessment on a 0 to 100 mm VAS, with 0 mm= no pain and 100 mm= most severe pain.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'N' (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 given time points for each group, respectively.

Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 to 100 mm VAS, with 0 mm= very well and 100 mm= very poorly.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'number analyzed' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

ACR20 response: compared to baseline, \>=20% improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Time frame: Week 2, 4, 8

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. LOCF was used to impute missing ACR components before computing ACR20 response.

ACR50 response: compared to baseline, \>=50% improvement in tender joint count; \>= 50% improvement in swollen joint count; and \>= 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Time frame: Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. LOCF was used to impute missing ACR components before computing ACR50 response.

ACR70 response: compared to baseline, \>=70% improvement in tender joint count; \>= 70% improvement in swollen joint count; and \>= 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Time frame: Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. LOCF was used to impute missing ACR components before computing ACR70 response.

Physician global assessment of arthritis was measured on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), with 0 mm= very good and 100 mm= very poor. This was an evaluation based on the participant's disease signs, functional capacity and physical examination.

Time frame: Baseline, Week 2, 4, 8, 12

Population: FAS included all randomized participants who received at least 1 dose of the randomized study medication. Here, 'number analyzed' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

Time frame: Baseline up to Week 14

Population: Results are not reported because median time could not be estimated as very few participants discontinued study due to lack of efficacy.

Nominal times were used for summarizing the pharmacokinetic results (0 hours at randomization \[Day 1\] and Week 4 \[pre-dose\]; 1 hour at Week 2 \[post-dose\]; 2 hours at randomization \[post-dose on Day 1\]; and 3 hours at Week 2 \[post-dose\] and Week 4 \[post-dose\]).

Time frame: 0 hour (pre-dose), 2 hours post-dose at Day 1; 1, 3 hours post-dose at Week 2; 0 hour (pre-dose), 3 hours post-dose at Week 4

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