To evaluate the efficacy, safety and tolerability of CP-195543 and celecoxib dual therapy in subjects with rheumatoid arthritis
Trial enrollment was prematurely discontinued on December 3, 2007. The results of an interim efficacy and safety analysis demonstrated an overall poor tolerability profile and high discontinuation rate when dual therapy with CP-195543 and Celecoxib was administered. The decision to discontinue further enrollment in the trial was not based on any efficacy or serious safety concerns. Previously enrolled study participants continued in the study and the trial completed on February 27, 2008.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
70
CP-195543 is a potent and specific antagonist of the leukotriene B4 (LTB4) receptor.
Celecoxib is a nonsteroidal anit-inflammatory drug (NSAID) marketed worldwide (in the United States \[US\] as Celeberex) and approved for the relief of signs and symptoms of osteoarthritis.
Methotrexate is a folate analogue that, based on it efficacy and safety in RA, is commonly used as frontline DMARD treatment in patients with moderate to severe disease who do not respond to NSAIDs alone.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
ACR20 response: 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
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8
ACR20 response: \>=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 1, 2, 4, 8
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 response: \>=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 1, 2, 4, 8, 12
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 response: \>=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).
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Pfizer Investigational Site
Huntsville, Alabama, United States
Pfizer Investigational Site
Scottsdale, Arizona, United States
Pfizer Investigational Site
Upland, California, United States
Pfizer Investigational Site
Boca Raton, Florida, United States
Pfizer Investigational Site
Clearwater, Florida, United States
Pfizer Investigational Site
Dunedin, Florida, United States
Pfizer Investigational Site
Fort Lauderdale, Florida, United States
Pfizer Investigational Site
Lake Mary, Florida, United States
Pfizer Investigational Site
Miramar, Florida, United States
Pfizer Investigational Site
New Port Richey, Florida, United States
...and 29 more locations
Time frame: Week 1, 2, 4, 8, 12
Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12
Participants were assessed for tender/painful joints using a 28-joint count comprised of left and right shoulders, elbows, wrists, proximal interphalangeal joints, metacarpophalangeal joints and knees. Artificial joints were not assessed.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12
Participants were assessed for swollen joints using a 28-joint count comprised of left and right shoulders, elbows, wrists, proximal interphalangeal joints, metacarpophalangeal joints and knees. Artificial joints were not assessed.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12
Patient's assessment of arthritis pain was assessed using a 100 millimeter (mm) visual analogue scale (VAS) with range: 0 = no pain to 100 = worst possible pain.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12
Patient's global assessment of arthritic condition assessed all the ways participants' illness and health conditions affect them at the time of assessment. The response was scored on a 5-point scale: 1 = Very Good (Asymptomatic and no limitation of normal activities), 2 = Good (Mild symptoms and no limitation of normal activities), 3 = Fair (Moderate symptoms and limitation of some normal activities), 4 = Poor (Severe symptoms and inability to carry out most normal activities) and 5 = Very Poor (Very severe symptoms which are intolerable and inability to carry out all normal activities).
Time frame: Baseline, Week 1, 2, 4, 8, 12
Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12
Investigator assessed overall appearance of arthritis at the time of the visit. The response was scored on a 5-point scale: 1 = Very Good (Asymptomatic and no limitation of normal activities), 2 = Good (Mild symptoms and no limitation of normal activities), 3 = Fair (Moderate symptoms and limitation of some normal activities), 4 = Poor (Severe symptoms and inability to carry out most normal activities) and 5 = Very Poor (Very severe symptoms which are intolerable and inability to carry out all normal activities).
Time frame: Baseline, Week 1, 2, 4, 8, 12
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12
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 1, 2, 4, 8, 12
Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12
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 1, 2, 4, 8, 12
Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 1, 2, 4, 8 and 12
DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP. It was calculated as DAS28-3 (CRP) = 1.15 + 1.10 \* (\[0.56 \* square root of TJC\] + \[0.28 \* square root of SJC\] + \[0.36 \* natural logarithm of {CRP+1}\]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 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 1, 2, 4, 8, 12
Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12
Duration of morning stiffness was defined as the time elapsed between the time participant woke up and was able to resume normal activities without stiffness in hours (duration was recorded in hours to the nearest quarter. For those participants with unrelenting stiffness, duration was recorded as 24 hours).
Time frame: Baseline, Week 1, 2, 4, 8, 12
Number of Participants Who Withdrew From Study Due to Lack of Efficacy
Time frame: Baseline up to Week 12
Time to Withdrawal Due to Lack of Efficacy
Time frame: Baseline up to Week 12
Number of Participants With Clinical Laboratory Abnormalities
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick \[urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin\], microscopy \[urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous \[urine mucus and leucocytes\]).
Time frame: Baseline up to Week 13