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

This study has been terminated.
(See Detailed Description field)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00424294
First received: January 18, 2007
Last updated: September 10, 2014
Last verified: September 2014

January 18, 2007
September 10, 2014
June 2006
December 2007   (final data collection date for primary outcome measure)
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
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).
ACR 20 response rate after 12 weeks of treatment
Complete list of historical versions of study NCT00424294 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Time to Withdrawal Due to Lack of Efficacy [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]
  • Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Baseline up to Week 13 ] [ Designated as safety issue: Yes ]
    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]).
Safety and tolerability Evaluate health and functional status
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.
Not Provided
 
A Study Of CP-195543 And Celecoxib Dual Therapy In Subjects With Rheumatoid Arthritis
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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Arthritis, Rheumatoid
  • 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.
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
70
February 2008
December 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00424294
A7701005
Yes
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP