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Study Evaluating the Efficacy and Safety of Etanercept and Methotrexate in Japanese Subjects With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00445770
First received: March 8, 2007
Last updated: August 10, 2011
Last verified: August 2011
History of Changes
Results First Received: July 12, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Arthritis, Rheumatoid
Interventions: Drug: Etanercept
Drug: Methotrexate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Methotrexate Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly
Etanercept 10 mg Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks
Etanercept 25 mg Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks

Participant Flow:   Overall Study
    Methotrexate     Etanercept 10 mg     Etanercept 25 mg  
STARTED     176     192     182  
COMPLETED     123     157     151  
NOT COMPLETED     53     35     31  
Adverse Event                 9                 15                 19  
Lack of Efficacy                 38                 13                 6  
Lost to Follow-up                 0                 2                 0  
Not specified                 6                 5                 6  



  Baseline Characteristics
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Reporting Groups
  Description
Methotrexate Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly
Etanercept 10 mg Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks
Etanercept 25 mg Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Total Total of all reporting groups

Baseline Measures
    Methotrexate     Etanercept 10 mg     Etanercept 25 mg     Total  
Number of Participants  
[units: participants]
 		  176     192     182     550  
Age  
[units: years]
Mean ± Standard Deviation 		  50.40  ± 11.91     51.46  ± 12.21     51.81  ± 11.07     51.24  ± 11.74  
Gender  
[units: participants]
 		       
Female     140     154     145     439  
Male     36     38     37     111  
modified Total Sharp Score (mTSS) [1]
[units: scores on a scale]
Mean ± Standard Deviation 		  43.01  ± 46.78     45.17  ± 38.75     41.98  ± 41.51     43.42  ± 42.28  
Erosion Score [2]
[units: scores on a scale]
Mean ± Standard Deviation 		  25.09  ± 26.30     26.66  ± 22.1     25.23  ± 23.88     25.69  ± 24.05  
Joint Space Narrowing (JSN) Score [3]
[units: scores on a scale]
Mean ± Standard Deviation 		  17.92  ± 21.93     18.50  ± 19.14     16.75  ± 19.11     17.73  ± 20.03  
[1] mTSS=sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). Total mTSS scores possible ranged from 0 (normal) to 448 (worst possible total score).
[2] Joint erosion score: erosion severity in 44 joints (16 per hand and 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, total erosion score possible ranged from 0 (no erosion) to 280 (worst possible total score).
[3] JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Total JSN scores possible ranged from 0 (no/normal JSN) to 168 (worst possible total score).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52   [ Time Frame: Week 52 ]
  Show Outcome Measure 1

2.  Secondary:   Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24   [ Time Frame: Week 24 ]
  Show Outcome Measure 2

3.  Secondary:   Change From Baseline in Erosion Score at Weeks 24 and 52   [ Time Frame: Baseline, Week 24, and Week 52 ]
  Show Outcome Measure 3

4.  Secondary:   Change From Baseline in Joint Space Narrowing (JSN) Score at Weeks 24 and 52   [ Time Frame: Baseline, Week 24, and Week 52 ]
  Show Outcome Measure 4

5.  Secondary:   Percentage of Participants With no Progression of Joint Destruction at Week 52   [ Time Frame: Baseline and Week 52 ]
  Show Outcome Measure 5

6.  Secondary:   Change From Baseline in Swollen Joint Count at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 6

7.  Secondary:   Change From Baseline in Number of Painful Joints on Pressure or on Motion at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 7

8.  Secondary:   Change From Baseline in Physician's Global Assessment of Symptoms at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 8

9.  Secondary:   Change From Baseline in Patient's Global Assessment at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 9

10.  Secondary:   Change From Baseline in Mean Duration of Morning Stiffness at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 10

11.  Secondary:   Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 11

12.  Secondary:   Change From Baseline in VAS for Participant General Health at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 12

13.  Secondary:   Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 13

14.  Secondary:   Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 14

15.  Secondary:   Percentage of Participants With an ACR50 Response   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 15

16.  Secondary:   Percentage of Participants With an ACR70 Response   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 16

17.  Secondary:   Change From Baseline in Disease Activity Score (DAS) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 17

18.  Secondary:   Change From Baseline in Disease Activity Score in 28 Joints (DAS28) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 18

19.  Secondary:   Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 19

20.  Secondary:   Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 ]
  Show Outcome Measure 20

21.  Other Pre-specified:   Comparison of Etanercept Serum Concentrations Between the 10 mg and 25 mg Etanercept Doses   [ Time Frame: Weeks 12, 24, 52 ]
  Show Outcome Measure 21


  Serious Adverse Events
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  Other Adverse Events
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Time Frame No text entered.
Additional Description The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   2%  

Reporting Groups
  Description
Methotrexate Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly
Etanercept 10 mg Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks
Etanercept 25 mg Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks

Other Adverse Events
    Methotrexate     Etanercept 10 mg     Etanercept 25 mg  
Total, other (not including serious) adverse events        
# participants affected / at risk     92/176     106/192     102/182  
Cardiac disorders        
Palpitations † 1      
# participants affected / at risk     4/176 (2.27%)     0/192 (0.00%)     2/182 (1.10%)  
Ear and labyrinth disorders        
Vertigo † 1      
# participants affected / at risk     0/176 (0.00%)     5/192 (2.60%)     1/182 (0.55%)  
Eye disorders        
Conjunctivitis allergic † 1      
# participants affected / at risk     2/176 (1.14%)     0/192 (0.00%)     4/182 (2.20%)  
Gastrointestinal disorders        
Abdominal discomfort † 1      
# participants affected / at risk     4/176 (2.27%)     6/192 (3.13%)     0/182 (0.00%)  
Abdominal pain upper † 1      
# participants affected / at risk     5/176 (2.84%)     3/192 (1.56%)     3/182 (1.65%)  
Constipation † 1      
# participants affected / at risk     9/176 (5.11%)     6/192 (3.13%)     7/182 (3.85%)  
Diarrhoea † 1      
# participants affected / at risk     5/176 (2.84%)     5/192 (2.60%)     10/182 (5.49%)  
Gastritis † 1      
# participants affected / at risk     6/176 (3.41%)     3/192 (1.56%)     1/182 (0.55%)  
Nausea † 1      
# participants affected / at risk     7/176 (3.98%)     4/192 (2.08%)     1/182 (0.55%)  
Stomatitis † 1      
# participants affected / at risk     8/176 (4.55%)     8/192 (4.17%)     3/182 (1.65%)  
Vomiting † 1      
# participants affected / at risk     1/176 (0.57%)     3/192 (1.56%)     4/182 (2.20%)  
Dental caries † 1      
# participants affected / at risk     3/176 (1.70%)     4/192 (2.08%)     8/182 (4.40%)  
Periodontitis † 1      
# participants affected / at risk     0/176 (0.00%)     1/192 (0.52%)     5/182 (2.75%)  
General disorders        
Pyrexia † 1      
# participants affected / at risk     6/176 (3.41%)     2/192 (1.04%)     8/182 (4.40%)  
Hepatobiliary disorders        
Hepatic function abnormal † 1      
# participants affected / at risk     6/176 (3.41%)     5/192 (2.60%)     3/182 (1.65%)  
Infections and infestations        
Bronchitis † 1      
# participants affected / at risk     5/176 (2.84%)     5/192 (2.60%)     6/182 (3.30%)  
Cystitis † 1      
# participants affected / at risk     6/176 (3.41%)     4/192 (2.08%)     9/182 (4.95%)  
Gastroenteritis † 1      
# participants affected / at risk     5/176 (2.84%)     1/192 (0.52%)     1/182 (0.55%)  
Hordeolum † 1      
# participants affected / at risk     1/176 (0.57%)     2/192 (1.04%)     4/182 (2.20%)  
Influenza † 1      
# participants affected / at risk     6/176 (3.41%)     4/192 (2.08%)     1/182 (0.55%)  
Nasopharyngitis † 1      
# participants affected / at risk     43/176 (24.43%)     45/192 (23.44%)     37/182 (20.33%)  
Oral herpes † 1      
# participants affected / at risk     2/176 (1.14%)     6/192 (3.13%)     2/182 (1.10%)  
Otitis media † 1      
# participants affected / at risk     1/176 (0.57%)     4/192 (2.08%)     0/182 (0.00%)  
Pharyngitis † 1      
# participants affected / at risk     12/176 (6.82%)     18/192 (9.38%)     15/182 (8.24%)  
Pneumonia † 1      
# participants affected / at risk     0/176 (0.00%)     5/192 (2.60%)     2/182 (1.10%)  
Upper respiratory tract infection † 1      
# participants affected / at risk     20/176 (11.36%)     20/192 (10.42%)     21/182 (11.54%)  
Injury, poisoning and procedural complications        
Contusion † 1      
# participants affected / at risk     4/176 (2.27%)     4/192 (2.08%)     8/182 (4.40%)  
Investigations        
Alanine aminotransferase increased † 1      
# participants affected / at risk     22/176 (12.50%)     12/192 (6.25%)     10/182 (5.49%)  
Aspartate aminotransferase increased † 1      
# participants affected / at risk     18/176 (10.23%)     8/192 (4.17%)     8/182 (4.40%)  
Blood alkaline phosphatase increased † 1      
# participants affected / at risk     3/176 (1.70%)     2/192 (1.04%)     5/182 (2.75%)  
Blood pressure increased † 1      
# participants affected / at risk     3/176 (1.70%)     3/192 (1.56%)     4/182 (2.20%)  
Blood urine present † 1      
# participants affected / at risk     2/176 (1.14%)     5/192 (2.60%)     2/182 (1.10%)  
Transaminases increased † 1      
# participants affected / at risk     8/176 (4.55%)     5/192 (2.60%)     5/182 (2.75%)  
Musculoskeletal and connective tissue disorders        
Arthralgia † 1      
# participants affected / at risk     7/176 (3.98%)     2/192 (1.04%)     1/182 (0.55%)  
Nervous system disorders        
Dizziness † 1      
# participants affected / at risk     1/176 (0.57%)     6/192 (3.13%)     3/182 (1.65%)  
Headache † 1      
# participants affected / at risk     4/176 (2.27%)     5/192 (2.60%)     9/182 (4.95%)  
Psychiatric disorders        
Insomnia † 1      
# participants affected / at risk     9/176 (5.11%)     9/192 (4.69%)     2/182 (1.10%)  
Respiratory, thoracic and mediastinal disorders        
Cough † 1      
# participants affected / at risk     0/176 (0.00%)     4/192 (2.08%)     6/182 (3.30%)  
Rhinitis allergic † 1      
# participants affected / at risk     3/176 (1.70%)     6/192 (3.13%)     1/182 (0.55%)  
Skin and subcutaneous tissue disorders        
Dermatitis † 1      
# participants affected / at risk     0/176 (0.00%)     2/192 (1.04%)     4/182 (2.20%)  
Dermatitis contact † 1      
# participants affected / at risk     4/176 (2.27%)     3/192 (1.56%)     4/182 (2.20%)  
Eczema † 1      
# participants affected / at risk     8/176 (4.55%)     7/192 (3.65%)     8/182 (4.40%)  
Erythema † 1      
# participants affected / at risk     1/176 (0.57%)     4/192 (2.08%)     1/182 (0.55%)  
Pruritus † 1      
# participants affected / at risk     3/176 (1.70%)     12/192 (6.25%)     5/182 (2.75%)  
Rash † 1      
# participants affected / at risk     8/176 (4.55%)     10/192 (5.21%)     10/182 (5.49%)  
Urticaria † 1      
# participants affected / at risk     2/176 (1.14%)     4/192 (2.08%)     1/182 (0.55%)  
Vascular disorders        
Hypertension † 1      
# participants affected / at risk     2/176 (1.14%)     4/192 (2.08%)     4/182 (2.20%)  
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA version 13.0



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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Total Sharp Score and modified total Sharp Score were used interchangeably in the protocol and meant the same thing. In the statistical analysis plan and study results, mTSS was used consistently.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided


Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc
ClinicalTrials.gov Identifier: NCT00445770     History of Changes
Other Study ID Numbers: 0881A1-315, B1801002
Study First Received: March 8, 2007
Results First Received: July 12, 2011
Last Updated: August 10, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency