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

Arthritis, Rheumatoid Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00424294
• Other study ID #: A7701005
• Status: Terminated
• Phase: Phase 2
• First received: January 18, 2007
• Last updated: September 10, 2014
• Start date: June 2006
• Est. completion date: February 2008

Study information

• Verified date: September 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy, safety and tolerability of CP-195543 and celecoxib dual therapy in subjects with rheumatoid arthritis

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: February 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

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

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Boca Raton	Florida
United States	Pfizer Investigational Site	Clearwater	Florida
United States	Pfizer Investigational Site	Covington	Louisiana
United States	Pfizer Investigational Site	Dunedin	Florida
United States	Pfizer Investigational Site	Fort Lauderdale	Florida
United States	Pfizer Investigational Site	Frederick	Maryland
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Huntsville	Alabama
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Kalamazoo	Michigan
United States	Pfizer Investigational Site	Killeen	Texas
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Lake Mary	Florida
United States	Pfizer Investigational Site	Lexington	Kentucky
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Miramar	Florida
United States	Pfizer Investigational Site	Moline	Illinois
United States	Pfizer Investigational Site	Munster	Indiana
United States	Pfizer Investigational Site	New Orleans	Louisiana
United States	Pfizer Investigational Site	New Port Richey	Florida
United States	Pfizer Investigational Site	Ogden	Utah
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Olean	New York
United States	Pfizer Investigational Site	Orange City	Florida
United States	Pfizer Investigational Site	Orlando	Florida
United States	Pfizer Investigational Site	Philladelphia	Pennsylvania
United States	Pfizer Investigational Site	Port Richey	Florida
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	Sarasota	Florida
United States	Pfizer Investigational Site	Sarasota	Florida
United States	Pfizer Investigational Site	Scottsdale	Arizona
United States	Pfizer Investigational Site	Springfield	Illinois
United States	Pfizer Investigational Site	Springfield	Missouri
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Tupelo	Mississippi
United States	Pfizer Investigational Site	Upland	California
United States	Pfizer Investigational Site	Venice	Florida
United States	Pfizer Investigational Site	Vero Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Baseline up to 28 days after last dose	Yes
Other	Number of Adverse Events by Severity	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.	Baseline up to 28 days after last dose	Yes
Other	Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated in sitting position.	Baseline, Day 7, 14, 21, 28, 42, 56, 84, 91	Yes
Other	Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91		Baseline, Day 7, 14, 21, 28, 42, 56, 84, 91	Yes
Other	Number of Participants With Abnormal Electrocardiogram (ECG)	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.	Baseline up to Week 12	Yes
Other	Number of Participants With Categorical Vital Signs Data	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.	Baseline, Week 12	Yes
Primary	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).	Week 12	No
Secondary	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).	Week 1, 2, 4, 8	No
Secondary	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).	Week 1, 2, 4, 8, 12	No
Secondary	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).	Week 1, 2, 4, 8, 12	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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).	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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).	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	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).	Baseline, Week 1, 2, 4, 8, 12	No
Secondary	Number of Participants Who Withdrew From Study Due to Lack of Efficacy		Baseline up to Week 12	No
Secondary	Time to Withdrawal Due to Lack of Efficacy		Baseline up to Week 12	No
Secondary	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]).	Baseline up to Week 13	Yes

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