Arthritis, Rheumatoid
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety and efficacy of a once-weekly dose of etanercept for rheumatoid arthritis. Currently, patients in Japan can only use 25 mg etanercept two times a week. If a once-a-week regimen of 50 mg is approved, this would be more convenient for most patients. This once-weekly regimen is used in countries outside of Japan.
Interventions
DRUGetanercept
Period A: Weeks 1-4: Etanercept 25mg (25mg vial)bi-weekly (BW); Period B: Weeks 5-12: Etanercept 50mg (50mg vial) weekly (QW)
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Subjects of Japanese ancestry and living in Japan. * Subjects who are receiving the approved dose of 25 mg etanercept BIW for at least 6 months and have stable disease activity, as determined by investigator's judgment for 3 months before test articles administration. * Subjects who have mildly active rheumatoid arthritis as demonstrated by 5 swollen joints and 5 tender/painful joints. Main
Exclusion criteria
* Prior treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs) and/or methotrexate (MTX) within 6 months of the baseline visit. * Subjects considered being in disease remission, per investigator's judgment. * Received other biological drugs, rituximab, anti-CD-4 agents, or diphtheria interleukin-2 fusion protein (DAB-IL-2) within 6 months prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score Using 28-joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4ESR) by Treatment Period. | weeks 4 and 12 | DAS28-4ESR is a clinical index of rheumatoid arthritis disease activity based on information from swollen joints, tender joints, acute phase response (Erythrocyte Sedimentation Rate) and general health. DAS28-4ESR scores range from 0 - 10, where a score of less than or equal to 3.2 implies well controlled disease and greater than or equal to 5.1 implies active disease. In this analysis, the DAS28-4ESR is compared for 2 different treatment regimens (used sequentially by the same patient population): Treatment Period A: ETN 25 mg BW (at week 4) vs Treatment Period B: ETN 50 mg QW (at week 12). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 7 days after week 4 and 7 days after week 12 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. In this analysis, the AUC is compared for 2 different treatment regimens (used sequentially by the same patient population): Treatment Period A: ETN 25 mg BW (at week 4) vs Treatment Period B: ETN 50 mg QW (at week 12). Blood samples were taken on day 0 of PK analysis and collected every day after for 7 days for weeks 4 and 12. |
Countries
Japan
Participant flow
Recruitment details
Subjects were recruited in Japan from January 2007 to September 2007.
Pre-assignment details
Subjects were screened up to 4 weeks and received 25 mg etanercept (as test article) BW for 4 weeks during treatment period A. At the end of the period A, the same cohort of subjects entered period B and received etanercept 50 mg (as test article) QW for 8 weeks to assess the efficacy and safety of a QW regimen.
Participants by arm
| Arm | Count |
|---|---|
| Etanercept (ETN) Weeks 1-4 (Treatment period A): Etanercept 25 mg bi-weekly (BW)
Weeks 5-12 (Treatment period B): Etanercept 50mg once weekly (QW) | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period A - Weeks 1-4 | Protocol Violation | 1 |
| Treatment Period B - Weeks 5-12 | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Etanercept (ETN) |
|---|---|
| Age Continuous | 53.14 years STANDARD_DEVIATION 13.21 |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / — |
| serious Total, serious adverse events | 1 / — |
Outcome results
Primary
Disease Activity Score Using 28-joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4ESR) by Treatment Period.
DAS28-4ESR is a clinical index of rheumatoid arthritis disease activity based on information from swollen joints, tender joints, acute phase response (Erythrocyte Sedimentation Rate) and general health. DAS28-4ESR scores range from 0 - 10, where a score of less than or equal to 3.2 implies well controlled disease and greater than or equal to 5.1 implies active disease. In this analysis, the DAS28-4ESR is compared for 2 different treatment regimens (used sequentially by the same patient population): Treatment Period A: ETN 25 mg BW (at week 4) vs Treatment Period B: ETN 50 mg QW (at week 12).
Time frame: weeks 4 and 12
Population: The analysis population was modified intent to treat (mITT), which included all patients who completed the 25 mg BW dose treatment period and received at least 1 dose of 50 mg OW. Data on observed cases: 41 patients from ENT 25 mg BW (week 4) and 39 patients from ETN 50 mg OW (week 12).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etanercept (ETN) | Disease Activity Score Using 28-joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4ESR) by Treatment Period. | Treatment Period A: ETN 25mg BW (week 4) | 3.26 units on scale | Standard Deviation 0.66 |
| Etanercept (ETN) | Disease Activity Score Using 28-joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4ESR) by Treatment Period. | Treatment Period B: ETN 50mg QW (week 12) | 3.13 units on scale | Standard Deviation 0.65 |
95% CI: [-0.25, 0.06]
Secondary
Area Under the Concentration-Time Curve (AUC)
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. In this analysis, the AUC is compared for 2 different treatment regimens (used sequentially by the same patient population): Treatment Period A: ETN 25 mg BW (at week 4) vs Treatment Period B: ETN 50 mg QW (at week 12). Blood samples were taken on day 0 of PK analysis and collected every day after for 7 days for weeks 4 and 12.
Time frame: 7 days after week 4 and 7 days after week 12
Population: The analysis population was the Pharmacokinetic (PK) subset, which included all patients who completed the 25 mg BW dose treatment period, received at least 1 dose of 50 mg QW and elected to participate in the PK assessment. Data on observed cases: 18 patients from ETN 25 mg BW (week 4) and 17 patients from ETN 50 mg QW (week 12).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etanercept (ETN) | Area Under the Concentration-Time Curve (AUC) | Treatment Period B: ETN 50mg QW (week 12) | 17.92 ug*Day/mL | Standard Deviation 6.09 |
| Etanercept (ETN) | Area Under the Concentration-Time Curve (AUC) | Treatment Period A: ETN 25mg BW (week 4) | 19.67 ug*Day/mL | Standard Deviation 5.7 |