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Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis (OPTIMA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00420927
First received: January 9, 2007
Last updated: April 16, 2012
Last verified: April 2012
History of Changes
Results First Received: July 1, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Biological: adalimumab
Drug: methotrexate
Biological: placebo

  Participant Flow
  Hide Participant Flow

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
ADA+MTX Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1
PBO+MTX Methotrexate (MTX) monotherapy plus blinded placebo during Period 1
ADA+MTX/PBO+MTX (Arm 1) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2
ADA+MTX/ADA+MTX (Arm 2) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2
ADA+MTX/OL ADA+MTX (Arm 3) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2
PBO+MTX/PBO+MTX (Arm 4) Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2
PBO+MTX/OL ADA+MTX (Arm 5) Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2

Participant Flow for 2 periods

 Period 1:   Period 1
    ADA+MTX     PBO+MTX     ADA+MTX/PBO+MTX (Arm 1)     ADA+MTX/ADA+MTX (Arm 2)     ADA+MTX/OL ADA+MTX (Arm 3)     PBO+MTX/PBO+MTX (Arm 4)     PBO+MTX/OL ADA+MTX (Arm 5)  
STARTED     515     517     0 [1]   0 [1]   0 [1]   0 [1]   0 [1]
COMPLETED     466     460     0     0     0     0     0  
NOT COMPLETED     49     57     0     0     0     0     0  
Adverse Event                 19                 15                 0                 0                 0                 0                 0  
Withdrawal by Subject                 7                 12                 0                 0                 0                 0                 0  
Lost to Follow-up                 8                 6                 0                 0                 0                 0                 0  
Lack of efficacy/Loss of efficacy                 1                 6                 0                 0                 0                 0                 0  
Death                 2                 0                 0                 0                 0                 0                 0  
Subject moved/relocated                 0                 2                 0                 0                 0                 0                 0  
Noncompliant with study drug                 1                 1                 0                 0                 0                 0                 0  
Randomization error                 1                 0                 0                 0                 0                 0                 0  
Suspected tuberculosis/positive test                 1                 1                 0                 0                 0                 0                 0  
Study site closure                 0                 1                 0                 0                 0                 0                 0  
Subject received new diagnosis                 0                 2                 0                 0                 0                 0                 0  
Received wrong treatment/incorrect dose                 0                 1                 0                 0                 0                 0                 0  
Failed to meet entry criteria                 8                 7                 0                 0                 0                 0                 0  
Took prohibited medication                 1                 3                 0                 0                 0                 0                 0  
[1] This treatment group is not relevant to Period 1.

Period 2:   Period 2
    ADA+MTX     PBO+MTX     ADA+MTX/PBO+MTX (Arm 1)     ADA+MTX/ADA+MTX (Arm 2)     ADA+MTX/OL ADA+MTX (Arm 3)     PBO+MTX/PBO+MTX (Arm 4)     PBO+MTX/OL ADA+MTX (Arm 5)  
STARTED     0 [1]   0 [1]   102     105     259     112     348  
COMPLETED     0     0     89     95     216     97     295  
NOT COMPLETED     0     0     13     10     43     15     53  
Adverse Event                 0                 0                 7                 3                 17                 6                 20  
Withdrawal by Subject                 0                 0                 1                 3                 11                 2                 12  
Lost to Follow-up                 0                 0                 2                 2                 6                 3                 9  
Lack of efficacy/Loss of efficacy                 0                 0                 2                 1                 6                 2                 6  
Received wrong treatment/incorrect dose                 0                 0                 0                 0                 0                 0                 1  
Subject unable to find transportation                 0                 0                 0                 0                 0                 0                 1  
Physician Decision                 0                 0                 0                 0                 1                 1                 0  
Sponsor decision                 0                 0                 1                 0                 0                 0                 1  
Randomization error                 0                 0                 0                 0                 1                 1                 0  
Noncompliant with study drug                 0                 0                 0                 1                 0                 0                 2  
Methotrexate intolerance                 0                 0                 0                 0                 0                 0                 1  
Took prohibited medication                 0                 0                 0                 0                 1                 0                 0  
[1] This treatment group is not relevant to Period 2.



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
ADA+MTX Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1
PBO+MTX Methotrexate (MTX) monotherapy plus blinded placebo(PBO) during Period 1
ADA+MTX/PBO+MTX (Arm 1) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2
ADA+MTX/ADA+MTX (Arm 2) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2
ADA+MTX/OL ADA+MTX (Arm 3) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2
PBO+MTX/PBO+MTX (Arm 4) Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2
PBO+MTX/OL ADA+MTX (Arm 5) Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Total Total of all reporting groups

Baseline Measures
    ADA+MTX     PBO+MTX     ADA+MTX/PBO+MTX (Arm 1)     ADA+MTX/ADA+MTX (Arm 2)     ADA+MTX/OL ADA+MTX (Arm 3)     PBO+MTX/PBO+MTX (Arm 4)     PBO+MTX/OL ADA+MTX (Arm 5)     Total  
Number of Participants  
[units: participants]
 		  515     517     0     0     0     0     0     1032  
Age  
[units: participants]
 		               
<=18 years     0     0                         0  
Between 18 and 65 years     418     431                         849  
>=65 years     97     86                         183  
Age  
[units: years]
Mean ± Standard Deviation 		  50.7  ± 14.48     50.4  ± 13.62                         50.6  ± 14.05  
Gender  
[units: participants]
 		               
Female     380     382                         762  
Male     135     135                         270  
Region of Enrollment  
[units: participants]
 		               
Argentina     32     29                         61  
Australia     5     8                         13  
Austria     11     12                         23  
Belgium     41     40                         81  
Canada     57     58                         115  
Czech Republic     22     19                         41  
France     4     8                         12  
Germany     43     41                         84  
Hungary     8     10                         18  
Mexico     26     27                         53  
Netherlands     0     3                         3  
New Zealand     3     3                         6  
Norway     4     5                         9  
Poland     12     9                         21  
Slovakia     6     3                         9  
South Africa     31     32                         63  
Spain     25     30                         55  
Sweden     10     11                         21  
United Kingdom     26     17                         43  
United States     149     152                         301  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4   [ Time Frame: Week 78 ]
  Show Outcome Measure 1

2.  Secondary:   Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1   [ Time Frame: Week 78 ]
  Show Outcome Measure 2

3.  Secondary:   Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 3

4.  Secondary:   Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 4

5.  Secondary:   Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 5

6.  Secondary:   Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 6

7.  Secondary:   Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 7

8.  Secondary:   Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 8

9.  Secondary:   Change From Baseline in DAS28 Score at Week 78   [ Time Frame: Baseline to Week 78 ]
  Show Outcome Measure 9

10.  Secondary:   Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 10

11.  Secondary:   Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 11

12.  Secondary:   Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 12

13.  Secondary:   Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 13

14.  Secondary:   Change From Baseline in CDAI Score at Week 78   [ Time Frame: Baseline to Week 78 ]
  Show Outcome Measure 14

15.  Secondary:   Change From Baseline in SDAI Score at Week 78   [ Time Frame: Baseline to Week 78 ]
  Show Outcome Measure 15

16.  Secondary:   Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78   [ Time Frame: Baseline to Week 78 ]
  Show Outcome Measure 16

17.  Secondary:   Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 17

18.  Secondary:   Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 18

19.  Secondary:   Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78   [ Time Frame: Week 78 ]
  Show Outcome Measure 19


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Show Other Adverse Events


  More Information
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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
No text entered.  


Results Point of Contact:  
Name/Title: Global Medical Services
Organization: Abbott
phone: 1-800-633-9110


No publications provided


Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00420927     History of Changes
Other Study ID Numbers: M06-810, 2006-004139-31
Study First Received: January 9, 2007
Results First Received: July 1, 2011
Last Updated: April 16, 2012
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria : Federal Ministry for Labour, Health, and Social Affairs
Belgium: Directorate general for the protection of Public health: Medicines
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: Ministry of Health, Welfare and Sport
New Zealand: Health Research Council
New Zealand: Ministry of Health
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Institutional Review Board