A Study Of CP-195543 And Celecoxib Dual Therapy In Subjects With Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00424294
• Recruitment Status: Terminated
• First Posted: January 19, 2007
• Results First Posted: September 25, 2014
• Last Update Posted: September 25, 2014
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 18, 2007
• First Posted Date: January 19, 2007
• Results First Submitted Date: September 10, 2014
• Results First Posted Date: September 25, 2014
• Last Update Posted Date: September 25, 2014
• Study Start Date: June 2006
• Actual Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2014)

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: 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).

• Original Primary Outcome Measures (submitted: January 18, 2007): ACR 20 response rate after 12 weeks of treatment

Current Secondary Outcome Measures (submitted: September 10, 2014)

• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 [ Time Frame: Week 1, 2, 4, 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).
• Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 1, 2, 4, 8, 12 ]
  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).
• Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 1, 2, 4, 8, 12 ]
  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).
• Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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.
• Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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.
• Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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.
• Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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).
• Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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).
• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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.
• Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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.
• 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 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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.
• Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 [ Time Frame: Baseline, Week 1, 2, 4, 8, 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).
• 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 [ Time Frame: Baseline up to Week 13 ]
  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]).

• Original Secondary Outcome Measures (submitted: January 18, 2007): Safety and tolerability Evaluate health and functional status

Current Other Pre-specified Outcome Measures (submitted: September 10, 2014)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose ]
  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
• Number of Adverse Events by Severity [ Time Frame: Baseline up to 28 days after last dose ]
  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.
• Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 [ Time Frame: Baseline, Day 7, 14, 21, 28, 42, 56, 84, 91 ]
  Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated in sitting position.
• Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 [ Time Frame: Baseline, Day 7, 14, 21, 28, 42, 56, 84, 91 ]
• Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: Baseline up to Week 12 ]
  Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec), Maximum QTcB interval (Bazett's Correction) (msec) in range of 450 to less than 480 msec, Maximum QTcF interval (Fridericia's Correction) in range of 450 to less than 480 msec, maximum QTc interval increase from baseline in range of 30 to less than 60 msec and >=60 msec.
• Number of Participants With Categorical Vital Signs Data [ Time Frame: Baseline, Week 12 ]
  Number of participants with maximum increase from Baseline in sitting SBP and DBP of greater than or equal to 30 mmHg at Week 12 was reported.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Of CP-195543 And Celecoxib Dual Therapy In Subjects With Rheumatoid Arthritis
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Of CP-195543 And Celecoxib Dual Therapy In The Treatment Of The Signs And Symptoms Of Rheumatoid Arthritis In Subjects Who Are Inadequately Controlled On Methotrexate
• Brief Summary: To evaluate the efficacy, safety and tolerability of CP-195543 and celecoxib dual therapy in subjects with rheumatoid arthritis
• Detailed Description: 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid

Intervention

• Drug: CP-195,543
  CP-195543 is a potent and specific antagonist of the leukotriene B4 (LTB4) receptor.
• Drug: celecoxib
  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.
• Drug: Methotrexate
  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.

Study Arms

• Active Comparator: Celecoxib
  Celecoxib with placebo therapy.
  Intervention: Drug: celecoxib
• Methotrexate
  Background Methotrexate taken in both CP-195,543/Celecoxib and Celecoxib only arms.
  Intervention: Drug: Methotrexate
• Experimental: CP-195,543
  CP-195,543 and Celecoxib dual therapy.
  Intervention: Drug: CP-195,543

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 24, 2011): 70
• Original Enrollment (submitted: January 18, 2007): 120
• Actual Study Completion Date: February 2008
• Actual Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• A diagnosis of RA based upon the American college of Rheumatology 1987 revised criteria
• Active disease at Screening
• Stable dose of methotrexate between 10-25 mg/week oral or parenteral

Exclusion Criteria:

• A diagnosis of any other inflammatory or secondary, noninflammatory arthritis that, in the opinion of the Investigator, would interfere with disease activity assessments
• A history of hypersensitivity or allergic type reactions to cyclooxygenase inhibitors, opiates, aspirin or sulfonamides

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00424294
• Other Study ID Numbers: A7701005
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: September 2014