Trial Outcomes & Findings for Open Label, Dose-Regimen Study Evaluating Etanercept 50 mg Once-Weekly In Japanese Subjects With RA (NCT NCT00418717)
NCT ID: NCT00418717
Last Updated: 2012-03-02
Results Overview
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).
COMPLETED
PHASE3
42 participants
weeks 4 and 12
2012-03-02
Participant Flow
Subjects were recruited in Japan from January 2007 to September 2007.
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.
Participant milestones
| Measure |
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)
|
|---|---|
|
Treatment Period A - Weeks 1-4
STARTED
|
42
|
|
Treatment Period A - Weeks 1-4
COMPLETED
|
41
|
|
Treatment Period A - Weeks 1-4
NOT COMPLETED
|
1
|
|
Treatment Period B - Weeks 5-12
STARTED
|
41
|
|
Treatment Period B - Weeks 5-12
COMPLETED
|
39
|
|
Treatment Period B - Weeks 5-12
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
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)
|
|---|---|
|
Treatment Period A - Weeks 1-4
Protocol Violation
|
1
|
|
Treatment Period B - Weeks 5-12
Adverse Event
|
2
|
Baseline Characteristics
Open Label, Dose-Regimen Study Evaluating Etanercept 50 mg Once-Weekly In Japanese Subjects With RA
Baseline characteristics by cohort
| Measure |
Etanercept (ETN)
n=42 Participants
Weeks 1-4 (Treatment period A): Etanercept 25 mg bi-weekly (BW)
Weeks 5-12 (Treatment period B): Etanercept 50mg once weekly (QW)
|
|---|---|
|
Age Continuous
|
53.14 years
STANDARD_DEVIATION 13.21 • n=39 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: weeks 4 and 12Population: 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).
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).
Outcome measures
| Measure |
Etanercept (ETN)
n=39 Participants
Weeks 1-4 (Treatment period A): Etanercept 25 mg bi-weekly (BW)
Weeks 5-12 (Treatment period B): Etanercept 50mg once weekly (QW)
|
|---|---|
|
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
|
|
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
|
SECONDARY outcome
Timeframe: 7 days after week 4 and 7 days after week 12Population: 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).
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.
Outcome measures
| Measure |
Etanercept (ETN)
n=17 Participants
Weeks 1-4 (Treatment period A): Etanercept 25 mg bi-weekly (BW)
Weeks 5-12 (Treatment period B): Etanercept 50mg once weekly (QW)
|
|---|---|
|
Area Under the Concentration-Time Curve (AUC)
Treatment Period A: ETN 25mg BW (week 4)
|
19.67 ug*Day/mL
Standard Deviation 5.7
|
|
Area Under the Concentration-Time Curve (AUC)
Treatment Period B: ETN 50mg QW (week 12)
|
17.92 ug*Day/mL
Standard Deviation 6.09
|
Adverse Events
Etanercept (ETN)
Serious adverse events
| Measure |
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)
|
|---|---|
|
Renal and urinary disorders
Calculus Ureteric / Pyelonephritis
|
2.4%
1/41
|
Other adverse events
| Measure |
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)
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.4%
1/42
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.4%
1/42
|
|
Infections and infestations
Infections and Infestations
|
28.6%
12/42
|
|
Gastrointestinal disorders
Dry mouth
|
2.4%
1/42
|
|
Gastrointestinal disorders
Gastric ulcer
|
2.4%
1/42
|
|
Gastrointestinal disorders
Gingivitis
|
2.4%
1/42
|
|
Gastrointestinal disorders
Parotid gland enlargement
|
2.4%
1/42
|
|
Gastrointestinal disorders
Stomatitis
|
4.8%
2/42
|
|
Gastrointestinal disorders
Tongue ulceration
|
2.4%
1/42
|
|
Gastrointestinal disorders
Toothache
|
2.4%
1/42
|
|
Gastrointestinal disorders
Vomiting
|
2.4%
1/42
|
|
General disorders
Chest pain
|
2.4%
1/42
|
|
General disorders
Odema peripheral
|
2.4%
1/42
|
|
Investigations
White blood cell count increase
|
2.4%
1/42
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.4%
1/42
|
|
Nervous system disorders
Dizziness
|
7.1%
3/42
|
|
Nervous system disorders
Headache
|
4.8%
2/42
|
|
Renal and urinary disorders
Calculus ureteric
|
2.4%
1/42
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
4.8%
2/42
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
2.4%
1/42
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
2.4%
1/42
|
|
Skin and subcutaneous tissue disorders
Photodermatosis
|
2.4%
1/42
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.4%
1/42
|
|
Vascular disorders
Hypertension
|
4.8%
2/42
|
|
General disorders
Pyrexia
|
2.4%
1/42
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER