Arthritis, Rheumatoid
Conditions
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.
Interventions
DRUGCP-195,543
CP-195543 is a potent and specific antagonist of the leukotriene B4 (LTB4) receptor.
DRUGcelecoxib
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.
DRUGMethotrexate
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.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | 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 C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | 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 | 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 | 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 | Baseline up to Week 12 | — |
| Time to Withdrawal Due to Lack of Efficacy | Baseline up to Week 12 | — |
| Number of Participants With Clinical Laboratory Abnormalities | 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 \[urine mucus and leucocytes\]). |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | 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 | 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 | 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 | 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 | 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 Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | 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 | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | 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 | Baseline, Day 7, 14, 21, 28, 42, 56, 84, 91 | — |
| Number of Participants With Abnormal Electrocardiogram (ECG) | 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 | 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. |
| Number of Adverse Events by Severity | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo and Celecoxib Placebo matched to CP-195543 capsule orally twice daily along with celecoxib capsule 200 milligram (mg) orally twice daily for 12 weeks. A stable dose of methotrexate greater than or equal to (\>=) 10 milligram per week (mg/week) and less than or equal to (\<=) 25 mg/week via oral or parenteral route was continued as background therapy. | 35 |
| CP-195543 and Celecoxib CP-195543 capsule 400 mg orally twice daily along with celecoxib capsule 200 mg orally twice daily for 12 weeks. A stable dose of methotrexate \>=10 mg/week and \<=25 mg/week via oral or parenteral route was continued as background therapy. | 34 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 10 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Other | 0 | 2 |
| Overall Study | Randomized but not Treated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo and Celecoxib | CP-195543 and Celecoxib | Total |
|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 11.6 | 57.7 years STANDARD_DEVIATION 12.7 | 55.9 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 33 Participants | 27 Participants | 60 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 35 | 31 / 34 |
| serious Total, serious adverse events | 1 / 35 | 2 / 34 |
Outcome results
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).
Time frame: Week 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Missing values were imputed using last observation carried forward (LOCF) method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | 31.43 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | 35.29 percentage of participants |
p-value: 0.733Chi-squared
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.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Baseline (n=34, 34) | 0.93 milligram per deciliter (mg/dL) | Standard Deviation 0.69 |
| Placebo and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=32, 31) | -0.06 milligram per deciliter (mg/dL) | Standard Deviation 0.75 |
| Placebo and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=32, 31) | 0.08 milligram per deciliter (mg/dL) | Standard Deviation 0.66 |
| Placebo and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=29, 25) | 0.67 milligram per deciliter (mg/dL) | Standard Deviation 3.78 |
| Placebo and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=32, 24) | 0.15 milligram per deciliter (mg/dL) | Standard Deviation 0.75 |
| Placebo and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=29, 21) | 0.60 milligram per deciliter (mg/dL) | Standard Deviation 3.47 |
| CP-195543 and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=32, 24) | 0.41 milligram per deciliter (mg/dL) | Standard Deviation 1.29 |
| CP-195543 and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Baseline (n=34, 34) | 1.36 milligram per deciliter (mg/dL) | Standard Deviation 1.35 |
| CP-195543 and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=29, 25) | 0.16 milligram per deciliter (mg/dL) | Standard Deviation 1.35 |
| CP-195543 and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=32, 31) | 0.15 milligram per deciliter (mg/dL) | Standard Deviation 1.33 |
| CP-195543 and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=29, 21) | 0.03 milligram per deciliter (mg/dL) | Standard Deviation 0.78 |
| CP-195543 and Celecoxib | Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=32, 31) | 0.61 milligram per deciliter (mg/dL) | Standard Deviation 2.05 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.052ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.108ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.573ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.342ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.501ANCOVA
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.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | 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 | Baseline (n=34, 34) | 4.78 units on a scale | Standard Deviation 0.56 |
| Placebo and Celecoxib | 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 | Change at Week 1 (n=32, 31) | -0.65 units on a scale | Standard Deviation 0.66 |
| Placebo and Celecoxib | 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 | Change at Week 2 (n=32, 31) | -0.56 units on a scale | Standard Deviation 0.87 |
| Placebo and Celecoxib | 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 | Change at Week 4 (n=29, 25) | -0.82 units on a scale | Standard Deviation 1.04 |
| Placebo and Celecoxib | 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 | Change at Week 8 (n=32, 24) | -0.84 units on a scale | Standard Deviation 0.96 |
| Placebo and Celecoxib | 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 | Change at Week 12 (n=29, 21) | -0.98 units on a scale | Standard Deviation 1.07 |
| CP-195543 and Celecoxib | 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 | Change at Week 8 (n=32, 24) | -1.04 units on a scale | Standard Deviation 1.05 |
| CP-195543 and Celecoxib | 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 | Baseline (n=34, 34) | 4.68 units on a scale | Standard Deviation 0.84 |
| CP-195543 and Celecoxib | 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 | Change at Week 4 (n=29, 25) | -0.83 units on a scale | Standard Deviation 0.77 |
| CP-195543 and Celecoxib | 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 | Change at Week 1 (n=32, 31) | -0.71 units on a scale | Standard Deviation 0.81 |
| CP-195543 and Celecoxib | 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 | Change at Week 12 (n=29, 21) | -1.19 units on a scale | Standard Deviation 1.4 |
| CP-195543 and Celecoxib | 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 | Change at Week 2 (n=32, 31) | -0.86 units on a scale | Standard Deviation 0.72 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.701ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.167ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.948ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.834ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.977ANCOVA
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).
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 2.83 hour | Standard Deviation 3.68 |
| Placebo and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -0.11 hour | Standard Deviation 1.83 |
| Placebo and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | 0.03 hour | Standard Deviation 2.16 |
| Placebo and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -0.76 hour | Standard Deviation 1.65 |
| Placebo and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | 0.34 hour | Standard Deviation 4.16 |
| Placebo and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | 1.05 hour | Standard Deviation 7.61 |
| CP-195543 and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -1.03 hour | Standard Deviation 5.09 |
| CP-195543 and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 3.22 hour | Standard Deviation 4.34 |
| CP-195543 and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -1.51 hour | Standard Deviation 4.53 |
| CP-195543 and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -0.61 hour | Standard Deviation 1.5 |
| CP-195543 and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -1.65 hour | Standard Deviation 5.01 |
| CP-195543 and Celecoxib | Change From Baseline in Duration of Morning Stiffness at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -1.34 hour | Standard Deviation 4.21 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.291ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.08ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.466ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.267ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.1ANCOVA
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.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Baseline (n=34, 34) | 1.65 units on a scale | Standard Deviation 0.54 |
| Placebo and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=32, 30) | 0.34 units on a scale | Standard Deviation 0.43 |
| Placebo and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=31, 29) | -0.18 units on a scale | Standard Deviation 0.54 |
| Placebo and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=30, 25) | -0.34 units on a scale | Standard Deviation 0.56 |
| Placebo and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=32, 24) | -0.38 units on a scale | Standard Deviation 0.67 |
| Placebo and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=29, 20) | -0.38 units on a scale | Standard Deviation 0.59 |
| CP-195543 and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=32, 24) | -0.30 units on a scale | Standard Deviation 0.61 |
| CP-195543 and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Baseline (n=34, 34) | 1.65 units on a scale | Standard Deviation 0.65 |
| CP-195543 and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=30, 25) | -0.29 units on a scale | Standard Deviation 0.46 |
| CP-195543 and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=32, 30) | -0.18 units on a scale | Standard Deviation 0.34 |
| CP-195543 and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=29, 20) | -0.44 units on a scale | Standard Deviation 0.78 |
| CP-195543 and Celecoxib | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=31, 29) | -0.24 units on a scale | Standard Deviation 0.38 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.369ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.666ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.53ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.632ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.801ANCOVA
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.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 50.94 mm | Standard Deviation 23.36 |
| Placebo and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 30) | -13.27 mm | Standard Deviation 20.21 |
| Placebo and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 32) | -9.53 mm | Standard Deviation 23.98 |
| Placebo and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -8.16 mm | Standard Deviation 23.62 |
| Placebo and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -14.06 mm | Standard Deviation 24.82 |
| Placebo and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -11.50 mm | Standard Deviation 22.9 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -12.04 mm | Standard Deviation 29.37 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 54.74 mm | Standard Deviation 22.25 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -14.12 mm | Standard Deviation 24.97 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 30) | -11.33 mm | Standard Deviation 15.97 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -21.43 mm | Standard Deviation 35.24 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 32) | -9.50 mm | Standard Deviation 23.65 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.507ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.743ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.914ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.715ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.558ANCOVA
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).
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 3.14 units on a scale | Standard Deviation 0.88 |
| Placebo and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -0.58 units on a scale | Standard Deviation 0.83 |
| Placebo and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -0.38 units on a scale | Standard Deviation 0.92 |
| Placebo and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -0.39 units on a scale | Standard Deviation 0.95 |
| Placebo and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -0.58 units on a scale | Standard Deviation 0.9 |
| Placebo and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -0.40 units on a scale | Standard Deviation 1.22 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -0.46 units on a scale | Standard Deviation 1.02 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 3.24 units on a scale | Standard Deviation 0.89 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -0.68 units on a scale | Standard Deviation 0.95 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -0.48 units on a scale | Standard Deviation 0.89 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -0.57 units on a scale | Standard Deviation 1.33 |
| CP-195543 and Celecoxib | Change From Baseline in Patient's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -0.61 units on a scale | Standard Deviation 0.95 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.172ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.738ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.948ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.428ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.861ANCOVA
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).
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 3.37 units on a scale | Standard Deviation 0.49 |
| Placebo and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -0.76 units on a scale | Standard Deviation 0.61 |
| Placebo and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -0.74 units on a scale | Standard Deviation 0.83 |
| Placebo and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -0.71 units on a scale | Standard Deviation 0.94 |
| Placebo and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -0.67 units on a scale | Standard Deviation 1.05 |
| Placebo and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -0.67 units on a scale | Standard Deviation 0.99 |
| CP-195543 and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -0.71 units on a scale | Standard Deviation 0.69 |
| CP-195543 and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 3.32 units on a scale | Standard Deviation 0.59 |
| CP-195543 and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -0.60 units on a scale | Standard Deviation 0.71 |
| CP-195543 and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -0.58 units on a scale | Standard Deviation 0.67 |
| CP-195543 and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -0.67 units on a scale | Standard Deviation 1.2 |
| CP-195543 and Celecoxib | Change From Baseline in Physician's Global Assessment of Arthritis at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -0.58 units on a scale | Standard Deviation 0.76 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.325ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.386ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.532ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.909ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.994ANCOVA
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.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 11.49 swollen joints | Standard Deviation 4.85 |
| Placebo and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -3.18 swollen joints | Standard Deviation 4.23 |
| Placebo and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -2.74 swollen joints | Standard Deviation 5.59 |
| Placebo and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -3.45 swollen joints | Standard Deviation 6.2 |
| Placebo and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -2.79 swollen joints | Standard Deviation 6.38 |
| Placebo and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -3.80 swollen joints | Standard Deviation 6.7 |
| CP-195543 and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -6.71 swollen joints | Standard Deviation 5.44 |
| CP-195543 and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 12.00 swollen joints | Standard Deviation 5.75 |
| CP-195543 and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -6.32 swollen joints | Standard Deviation 4.71 |
| CP-195543 and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -4.35 swollen joints | Standard Deviation 4.41 |
| CP-195543 and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -6.38 swollen joints | Standard Deviation 6.1 |
| CP-195543 and Celecoxib | Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -5.97 swollen joints | Standard Deviation 5.27 |
Comparison: Week 1: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.252ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.032ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.031ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.018ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.17ANCOVA
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.
Time frame: Baseline, Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.Here,n signifies those participants who were evaluable at specified time point for each arm,respectively. For descriptive data,observed cases were reported and for statistical data,LOCF imputation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 15.54 tender/painful joints | Standard Deviation 5.55 |
| Placebo and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -4.45 tender/painful joints | Standard Deviation 5.15 |
| Placebo and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -3.82 tender/painful joints | Standard Deviation 6.24 |
| Placebo and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -5.68 tender/painful joints | Standard Deviation 6.48 |
| Placebo and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -5.15 tender/painful joints | Standard Deviation 6.46 |
| Placebo and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -5.67 tender/painful joints | Standard Deviation 5.86 |
| CP-195543 and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 8 (n=33, 24) | -6.00 tender/painful joints | Standard Deviation 7.68 |
| CP-195543 and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Baseline (n=35, 34) | 13.74 tender/painful joints | Standard Deviation 7.15 |
| CP-195543 and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 4 (n=31, 25) | -5.04 tender/painful joints | Standard Deviation 6.09 |
| CP-195543 and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 1 (n=33, 31) | -4.68 tender/painful joints | Standard Deviation 6.29 |
| CP-195543 and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 12 (n=30, 21) | -5.95 tender/painful joints | Standard Deviation 9.45 |
| CP-195543 and Celecoxib | Change From Baseline in Tender/Painful Joint Count (TJC) at Week 1, 2, 4, 8 and 12 | Change at Week 2 (n=34, 31) | -6.13 tender/painful joints | Standard Deviation 6.15 |
Comparison: Week 1: Analysis of covariance (ANCOVA) with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.635ANCOVA
Comparison: Week 2: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.044ANCOVA
Comparison: Week 4: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.957ANCOVA
Comparison: Week 8: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.597ANCOVA
Comparison: Week 12: ANCOVA with treatment and site as independent variables and baseline as the covariate was used for the analysis.p-value: 0.96ANCOVA
Secondary
Number of Participants Who Withdrew From Study Due to Lack of Efficacy
Time frame: Baseline up to Week 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo and Celecoxib | Number of Participants Who Withdrew From Study Due to Lack of Efficacy | 2 participants |
| CP-195543 and Celecoxib | Number of Participants Who Withdrew From Study Due to Lack of Efficacy | 1 participants |
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 \[urine mucus and leucocytes\]).
Time frame: Baseline up to Week 13
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo and Celecoxib | Number of Participants With Clinical Laboratory Abnormalities | 15 participants |
| CP-195543 and Celecoxib | Number of Participants With Clinical Laboratory Abnormalities | 14 participants |
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).
Time frame: Week 1, 2, 4, 8
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Missing values were imputed using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 1 | 31.43 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 2 | 28.57 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 4 | 28.57 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 8 | 25.71 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 8 | 38.24 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 1 | 23.53 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 4 | 41.18 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 1, 2, 4 and 8 | Week 2 | 35.29 percentage of participants |
Comparison: Week 1: p-value was calculated by Chi-square test.p-value: 0.463Chi-squared
Comparison: Week 2: p-value was calculated by Chi-square test.p-value: 0.549Chi-squared
Comparison: Week 4: p-value was calculated by Chi-square test.p-value: 0.272Chi-squared
Comparison: Week 8: p-value was calculated by Chi-square test.p-value: 0.265Chi-squared
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).
Time frame: Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Missing values were imputed using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 2 | 0.0 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 8 | 5.71 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 4 | 8.57 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 8.57 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 1 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 12 | 14.71 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 1 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 2 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 4 | 2.94 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Week 8 | 11.76 percentage of participants |
Comparison: Week 4: p-value was calculated by Fisher exact test.p-value: 0.939Fisher Exact
Comparison: Week 8: p-value was calculated by Fisher exact test.p-value: 0.323Fisher Exact
Comparison: Week 12: p-value was calculated by Fisher exact test.p-value: 0.338Fisher Exact
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).
Time frame: Week 1, 2, 4, 8, 12
Population: FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Missing values were imputed using LOCF method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 2 | 0.0 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 8 | 0.0 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 4 | 0.0 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 2.86 percentage of participants |
| Placebo and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 1 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 2.94 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 1 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 2 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 4 | 0.0 percentage of participants |
| CP-195543 and Celecoxib | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 8 | 0.0 percentage of participants |
Comparison: Week 12: p-value was calculated by Fisher exact test.p-value: 0.746Fisher Exact
Secondary
Time to Withdrawal Due to Lack of Efficacy
Time frame: Baseline up to Week 12
Population: Median time and corresponding confidence interval (CI) were not estimable because only less than half of the participants withdrew from study due to lack of efficacy and hence, were insufficient for the analysis.
Other Pre-specified
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
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Here, n signifies those participants who were evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 7 (n=33, 30) | -1.0 beats per minute | Standard Deviation 10 |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 28 (n=1, 2) | -2.0 beats per minute | — |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 14 (n=5, 1) | -3.0 beats per minute | — |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 42 (n=4, 2) | 3.3 beats per minute | Standard Deviation 7.37 |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 91 (n=3, 3) | 1.0 beats per minute | Standard Deviation 9.54 |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 56 (n=0, 3) | NA beats per minute | — |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 21 (n=0, 1) | NA beats per minute | — |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 84 (n=27, 17) | 0.8 beats per minute | Standard Deviation 9.41 |
| Placebo and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Baseline (n=35, 34) | 74.3 beats per minute | Standard Deviation 7.62 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 91 (n=3, 3) | -2.0 beats per minute | Standard Deviation 7.21 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 84 (n=27, 17) | 5.1 beats per minute | Standard Deviation 14.19 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Baseline (n=35, 34) | 74.5 beats per minute | Standard Deviation 10.62 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 7 (n=33, 30) | 2.2 beats per minute | Standard Deviation 9.7 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 14 (n=5, 1) | -6.4 beats per minute | Standard Deviation 2.19 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 21 (n=0, 1) | 2.0 beats per minute | — |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 28 (n=1, 2) | 2.0 beats per minute | Standard Deviation 8.49 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 42 (n=4, 2) | -3.0 beats per minute | Standard Deviation 4.24 |
| CP-195543 and Celecoxib | Change From Baseline in Heart Rate Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 56 (n=0, 3) | 7.7 beats per minute | Standard Deviation 3.21 |
Other Pre-specified
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.
Time frame: Baseline, Day 7, 14, 21, 28, 42, 56, 84, 91
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Here, n signifies those participants who were evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Baseline: SBP (n=35, 34) | 123.7 millimeter of mercury (mmHg) | Standard Deviation 12.33 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 7: SBP (n=33, 30) | -0.2 millimeter of mercury (mmHg) | Standard Deviation 12.46 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 14: SBP (n=1, 5) | 5.0 millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 21: SBP (n=0, 1) | NA millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 28: SBP (n=1, 2) | 18.0 millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 42: SBP (n=4, 2) | 3.3 millimeter of mercury (mmHg) | Standard Deviation 4.57 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 56: SBP (n=0, 3) | NA millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 84: SBP (n=27, 17) | 4.7 millimeter of mercury (mmHg) | Standard Deviation 13.44 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 91: SBP (n=3, 3) | 3.3 millimeter of mercury (mmHg) | Standard Deviation 13.65 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Baseline: DBP (n=35, 34) | 77.9 millimeter of mercury (mmHg) | Standard Deviation 8.03 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 7: DBP (n=33, 30) | -1.3 millimeter of mercury (mmHg) | Standard Deviation 8.32 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 14: DBP (n=1, 5) | -1.0 millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 21: DBP (n=0, 1) | NA millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 28: DBP (n=1, 2) | -4.0 millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 42: DBP (n=4, 2) | -1.8 millimeter of mercury (mmHg) | Standard Deviation 7.76 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 56: DBP (n=0, 3) | NA millimeter of mercury (mmHg) | — |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 84: DBP (n=27, 17) | 1.4 millimeter of mercury (mmHg) | Standard Deviation 7.77 |
| Placebo and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 91: DBP (n=3, 3) | 2.7 millimeter of mercury (mmHg) | Standard Deviation 6.43 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 28: DBP (n=1, 2) | 8.0 millimeter of mercury (mmHg) | Standard Deviation 16.97 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Baseline: SBP (n=35, 34) | 124.6 millimeter of mercury (mmHg) | Standard Deviation 14.97 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Baseline: DBP (n=35, 34) | 75.8 millimeter of mercury (mmHg) | Standard Deviation 10.81 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 7: SBP (n=33, 30) | 0.5 millimeter of mercury (mmHg) | Standard Deviation 12.91 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 91: DBP (n=3, 3) | -5.3 millimeter of mercury (mmHg) | Standard Deviation 4.62 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 14: SBP (n=1, 5) | 3.2 millimeter of mercury (mmHg) | Standard Deviation 4.15 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 7: DBP (n=33, 30) | 1.4 millimeter of mercury (mmHg) | Standard Deviation 10.57 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 21: SBP (n=0, 1) | 0.0 millimeter of mercury (mmHg) | — |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 42: DBP (n=4, 2) | -2.0 millimeter of mercury (mmHg) | Standard Deviation 11.31 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 28: SBP (n=1, 2) | 0.0 millimeter of mercury (mmHg) | Standard Deviation 0 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 14: DBP (n=1, 5) | 1.2 millimeter of mercury (mmHg) | Standard Deviation 7.16 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 42: SBP (n=4, 2) | 0.0 millimeter of mercury (mmHg) | Standard Deviation 28.28 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 84: DBP (n=27, 17) | -0.5 millimeter of mercury (mmHg) | Standard Deviation 12.21 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 56: SBP (n=0, 3) | -2.0 millimeter of mercury (mmHg) | Standard Deviation 8 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 21: DBP (n=0, 1) | 16.0 millimeter of mercury (mmHg) | — |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 84: SBP (n=27, 17) | 6.8 millimeter of mercury (mmHg) | Standard Deviation 15.58 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 56: DBP (n=0, 3) | -4.0 millimeter of mercury (mmHg) | Standard Deviation 7.21 |
| CP-195543 and Celecoxib | Change From Baseline in Systolic and Diastolic Blood Pressure at Day 7, 14, 21, 28, 42, 56, 84 and 91 | Change at Day 91: SBP (n=3, 3) | -15.7 millimeter of mercury (mmHg) | Standard Deviation 12.58 |
Other Pre-specified
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.
Time frame: Baseline up to 28 days after last dose
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Number of Adverse Events by Severity | Mild | 40 adverse events |
| Placebo and Celecoxib | Number of Adverse Events by Severity | Moderate | 26 adverse events |
| Placebo and Celecoxib | Number of Adverse Events by Severity | Severe | 0 adverse events |
| CP-195543 and Celecoxib | Number of Adverse Events by Severity | Mild | 41 adverse events |
| CP-195543 and Celecoxib | Number of Adverse Events by Severity | Moderate | 25 adverse events |
| CP-195543 and Celecoxib | Number of Adverse Events by Severity | Severe | 5 adverse events |
Other Pre-specified
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.
Time frame: Baseline up to Week 12
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | Maximum QTcB Interval (Bazett's Correction) | 3 participants |
| Placebo and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF interval 30 to <60 msec Increase | 1 participants |
| Placebo and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | Maximum QTcF Interval (Fridericia's Correction) | 0 participants |
| Placebo and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF interval >=60 msec Increase | 0 participants |
| Placebo and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | Maximum QTc Interval (msec) | 0 participants |
| CP-195543 and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF interval >=60 msec Increase | 0 participants |
| CP-195543 and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | Maximum QTc Interval (msec) | 7 participants |
| CP-195543 and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | Maximum QTcB Interval (Bazett's Correction) | 9 participants |
| CP-195543 and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | Maximum QTcF Interval (Fridericia's Correction) | 2 participants |
| CP-195543 and Celecoxib | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF interval 30 to <60 msec Increase | 2 participants |
Other Pre-specified
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.
Time frame: Baseline, Week 12
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug. Detailed categorical data was not estimated since summarized continuous data of the vital signs were considered sufficient for the analysis as per investigator's discretion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Number of Participants With Categorical Vital Signs Data | SBP: >=30 mmHg Increase | 1 participants |
| Placebo and Celecoxib | Number of Participants With Categorical Vital Signs Data | DBP: >=30 mmHg Increase | 1 participants |
| CP-195543 and Celecoxib | Number of Participants With Categorical Vital Signs Data | SBP: >=30 mmHg Increase | 1 participants |
| CP-195543 and Celecoxib | Number of Participants With Categorical Vital Signs Data | DBP: >=30 mmHg Increase | 3 participants |
Other Pre-specified
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.
Time frame: Baseline up to 28 days after last dose
Population: Safety analysis set is same as FAS. FAS was an intent-to-treat analysis set including all participants randomized to treatment who had taken at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo and Celecoxib | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 29 participants |
| Placebo and Celecoxib | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
| CP-195543 and Celecoxib | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 31 participants |
| CP-195543 and Celecoxib | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |