CE-224,535 is known to block a chemical that acts as a gateway to some of your immune cells. Blocking this gateway prevents the cells from pushing out 2 chemicals called IL-1 and IL-18 that are known to cause some of the inflammation seen in rheumatoid arthritis. It is hoped that taking this drug will reduce the symptoms of rheumatoid arthritis

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

Arthritis, Rheumatoid

CE-224,535

Placebo

A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY OF CE-224,535, AN ANTAGONIST OF THE P2X7 RECEPTOR, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF RHEUMATOID ARTHRITIS IN SUBJECTS WHO ARE INADEQUATELY CONTROLLED ON 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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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

Arizona Arthritis & Rheumatology Associates, P.C.

Omega Research Consultants LLC

Florida Arthritis Center

Tampa Medical Group, PA

American Health Network

Best Clinical Trials, LLC (Administrative Only)

George Stanley Walker, MD

Majid Abdul Jawad, MD

The Arthritis and Osteoporosis Center of Maryland

University Physicians

University of Missouri-Columbia

Arthritis Center of Reno

New Horizons Clinical Research

Arthritis Northwest

Clínica Santa María, Sección Reumatología

Revmatologicka ambulance

Revmatologicky ustav

Investigadores Clinicos Asociados

Krakowskie Centrum Medyczne NZOZ

Zaklad Reumatologii i Immunologii Klinicznej

Oddzial Reumatologiczno-Rehabilitacyjny IIR Ortopedyczno-Rehabilitacyjny

Inha University Hospital, Medicine/Rheumatology

Pusan National University Hospital, Rheumatology, Internal Medicine

Hospital Nuestra Señora de La Esperanza

Complexo Hospitalario Universitario A Coruña

Hospital General Universitario Gregorio Marañon

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

CE-224,535 500 milligram (mg) tablet orally twice daily for 12 weeks.

Placebo tablet matched to CE-224,535 500 milligram (mg) tablet orally twice daily for 12 weeks.

Total

Age, Continuous

Sex: Female, Male

Pfizer ClinicalTrials.gov Call Center

Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the normal approximation method.

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).

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.

Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Week 12

Week 2: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the normal approximation method.

Week 4: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the normal approximation method.

Week 8: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the normal approximation method.

Week 2

Week 4

Week 8

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).

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.

Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Week 2, 4 and 8

Week 2: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the Barnard exact test.

Week 4: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the Barnard exact test.

Week 12: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the normal approximation method.

Week 12

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).

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.

Percentage of Participants With American College of Rheumatology 50% (ACR50) Response

Week 8: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the Barnard exact test.

Week 12: Treatment effect was estimated by the difference of percentages between the treatment groups, and tested using the Barnard exact test.

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).

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.

Percentage of Participants With American College of Rheumatology 70% (ACR70) Response

Baseline: Tender joints

Baseline: Swollen joints

Week 2: Tender joints

Week 2: Swollen joints

Week 4: Tender joints

Week 4: Swollen joints

Week 8: Tender joints

Week 8: Swollen joints

Week 12: Tender joints

Week 12: Swollen joints

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.

Number of Tender/Painful and Swollen Joints

Baseline

Physician Global Assessment (PGA) of Arthritis

Patient's Global Assessment of Arthritis

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.

Patient's Global Assessment of Arthritic Pain

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) Score

Baseline: (n= 53, 47)

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.

Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])

C-Reactive Protein (CRP)

Week 2: p-value was analyzed using Barnard Exact Test.

Week 4: p-value was analyzed using Barnard Exact Test.

Week 8: p-value was analyzed using Barnard Exact Test.

Week 12: p-value was analyzed using Barnard Exact Test.

Week 14: p-value was analyzed using Barnard Exact Test.

Week 14

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

Incidence of Withdrawal Due to Lack of Efficacy

CE-224,535 500 milligram (mg) tablet twice daily for 12 weeks.

Placebo matched to CE-224,535 500 milligram (mg) tablet twice daily for 12 weeks.

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

Time to Withdrawal Due to Lack of Efficacy

0 hour

1 hour

2 hours

3 hours

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 \[post-dose\]).

CE-224,535 Plasma Concentrations

Placebo tablet matched to CE-224,535 500 mg tablet orally twice daily for 12 weeks.

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

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?