Comparison Of 5 CP-690,550 Doses Vs. Placebo, For The Treatment Of Rheumatoid Arthritis In Japan

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Confirm Dose Responsiveness Following 12 Weeks Of The Administration Of CP-690,550 (5 Doses) Or Placebo In Subjects With Active Rheumatoid Arthritis Inadequately Responding To At Least 1 DMARD

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00687193

Enrollment

318

Registered

2008-05-30

Start date

2009-03-31

Completion date

2010-07-31

Last updated

2013-03-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arthritis, Rheumatoid

Keywords

Phase 2 monotherapy in Japan

Brief summary

To evaluate the dose-response relationship of 5 dose of CP-690,550, compared to placebo for the treatment of signs and symptoms in patients with active RA who failed an adequate trial of therapy with at least 1 DMARD in a 12-week therapy.

Interventions

DRUGPlacebo

Placebo BID, 3 blinded tablets administered BID for 12 weeks

DRUGCP-690,550

10mg BID, 3 blinded tablets administered BID for 12 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

20 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Subjects must have failed an adequate trial of therapy with at least 1 DMARD due to lack of efficacy or toxicity.

Exclusion criteria

* Current therapy with any DMARD

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	Week 12	ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in painful and 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
Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response	Week 2, 4, 8 and 12	ACR50 response: greater than or equal to (\>=) 50 percent (%) improvement in painful and 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) at each visit.
Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response	Week 2, 4, 8 and 12	ACR70 response: greater than or equal to (\>=) 70 percent (%) improvement in painful and 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) at each visit.
Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response	Week 2, 4, 8 and 12	ACR90 response: greater than or equal to (\>=) 90 percent (%) improvement in painful and tender joint count; \>= 90% improvement in swollen joint count; and \>= 90% 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) at each visit.
Change From Baseline in Disease Activity Score Based on 28-Joints Count Using C-reactive Protein [DAS28-3(CRP)]	Baseline, Week 2, 4, 8 and 12	The DAS28-3 (CRP) score is a measure of the perticipant's disease activity. It is based on the painful and tender joint count (28 joints), swollen joint count (28 joints) and CRP. DAS28-3 (CRP) scores range from 0 - 10; higher scores indicated greater affectation due to disease activity. Change = value at observation minus value at baseline
Change From Baseline in Disease Activity Score Based on 28-Joints Count Using Erythrocyte Sedimentation Rate [DAS28-4(ESR)]	Baseline, Week 2, 4, 8 and 12	The DAS28-4 (ESR) score is a measure of the participant's disease activity. It is based on the painful and tender joint count (28 joints), swollen joint count (28 joints), participant's global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10; higher scores indicated greater affectation due to disease activity. Change = score at observation minus score at baseline.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)	Baseline, Week 2, 4, 8 and 12	HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Change = score at observation minus score at baseline.
Change From Baseline in Painful and Tender Joint Counts	Baseline, Weeks 2, 4, 8 and 12	Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from baseline indicates an improvement. Change = value at observation minus value at baseline.
Change From Baseline in Swollen Joint Count (SJC)	Baseline, Week 2, 4, 8 and 12	Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from baseline indicates an improvement. Change = value at observation minus value at baseline.
Change From Baseline in Patient's Assessment of Pain	Baseline, Week 2, 4, 8 and 12	Change from Baseline in Patient's Assessment of Arthritis Pain -VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) was computed as Week 2, 4, 8 or 12 values minus baseline value. A negative value in change from baseline indicates an improvement. Change = value at observation minus value at baseline.
Change From Baseline in Patient's Global Assessment of Arthritis	Baseline, Week 2, 4, 8 and 12	Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 mm Visual Analog Scale where 0 = very well and 100 = very poorly. Change = score at observation minus score at baseline.
Change From Baseline in Physician's Global Assessment of Arthritis	Baseline, Week 2, 4, 8 and 12	Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity; very good and 100 mm = worst disease activity; very poor. Change = score at observation minus score at baseline.
Change From Baseline in C- Reactive Protein (CRP) (mg/L)	Baseline, Week 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. Change = value at observation minus value at baseline.
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4 and 8	Week 2, 4, and 8	ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in painful and 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)at each visit.
Change From Baseline in Euro Quality of Life (EQ-5D)	Baseline, Week 12	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Physical Functioning Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Role-Physical Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Bodily Pain Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -General Health Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Vitality Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change =score at Week 12 minus score at baseline
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Social Functioning Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Role-Emotional Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Mental Health Domain	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Physical Component Summary (PCS)	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Mental Component Summary (MCS)	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.
Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	Baseline, Week 12	ACR-N = calculated for each participant by taking lowest percentage improvement in (1) swollen joint count or (2) tender joint count or (3) the median of remaining 5 components of ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening. The AUC for ACR-N is measure of the area under the curve of the mean change from baseline in ACR-N. The trapezoidal rule was used to compute AUC.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
CP-690,550 1 mg Participants were administered 1 milligram (mg) of CP-690,550 orally twice daily for 12 weeks.	53
CP-690,550 3 mg Participants were administered 3 mg of CP-690,550 orally twice daily for 12 weeks.	53
CP-690,550 5 mg Participants were administered 5 mg of CP-690,550 orally twice daily for 12 weeks.	52
CP-690,550 10 mg Participants were administered 10 mg of CP-690,550 orally twice daily for 12 weeks.	53
CP-690,550 15 mg Participants were administered 15 mg of CP-690,550 orally twice daily for 12 weeks.	54
Placebo Participants were administered placebo tablet matched to CP-690,550 orally twice daily for 12 weeks.	52
Total	317

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	0	1	2	3	0	2
Overall Study	Lack of Efficacy	1	1	0	0	0	2
Overall Study	Protocol Violation	1	2	0	1	2	0

Baseline characteristics

Characteristic	CP-690,550 1 mg	CP-690,550 3 mg	CP-690,550 5 mg	CP-690,550 10 mg	CP-690,550 15 mg	Placebo	Total
Age, Customized < 18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Customized >= 65 years	6 Participants	9 Participants	8 Participants	12 Participants	12 Participants	9 Participants	56 Participants
Age, Customized Between 18 and 44 years	8 Participants	11 Participants	13 Participants	9 Participants	12 Participants	14 Participants	67 Participants
Age, Customized Between 45 and 64 years	39 Participants	33 Participants	31 Participants	32 Participants	30 Participants	29 Participants	194 Participants
Sex: Female, Male Female	42 Participants	47 Participants	44 Participants	44 Participants	44 Participants	43 Participants	264 Participants
Sex: Female, Male Male	11 Participants	6 Participants	8 Participants	9 Participants	10 Participants	9 Participants	53 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	14 / 53	16 / 53	19 / 52	22 / 53	22 / 54	16 / 52
serious Total, serious adverse events	0 / 53	3 / 53	2 / 52	2 / 53	1 / 54	1 / 52

Outcome results

Primary

Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in painful and 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: The full analysis set included all participants who were randomized to the study and received at least 1 dose of study medication. Missing values were handled using the Last Observation Carried Forward (LOCF) method.

Arm	Measure	Value (NUMBER)
CP-690,550 1 mg	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	20 participants
CP-690,550 3 mg	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	36 participants
CP-690,550 5 mg	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	38 participants
CP-690,550 10 mg	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	45 participants
CP-690,550 15 mg	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	49 participants
Placebo	Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	8 participants

Secondary

Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)

ACR-N = calculated for each participant by taking lowest percentage improvement in (1) swollen joint count or (2) tender joint count or (3) the median of remaining 5 components of ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening. The AUC for ACR-N is measure of the area under the curve of the mean change from baseline in ACR-N. The trapezoidal rule was used to compute AUC.

Time frame: Baseline, Week 12

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
CP-690,550 1 mg	Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	498.47 units on a scale	Standard Error 341.96
CP-690,550 3 mg	Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	1876.4 units on a scale	Standard Error 341.96
CP-690,550 5 mg	Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	2573.0 units on a scale	Standard Error 345.23
CP-690,550 10 mg	Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	3887.4 units on a scale	Standard Error 341.96
CP-690,550 15 mg	Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	3628.9 units on a scale	Standard Error 338.78
Placebo	Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N)	-2415 units on a scale	Standard Error 345.23

Secondary

Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Bodily Pain Domain

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline.

Time frame: Baseline, Week 12