A Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00976599
First received: September 11, 2009
Last updated: December 4, 2012
Last verified: December 2012
Results First Received: December 4, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition: Rheumatoid Arthritis
Interventions: Drug: CP-690,550 + methotrexate
Drug: Placebo + 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
CP-690,550 CP-690,550 10 milligram (mg) tablet orally twice daily up to Day 27 followed by single oral dose on Day 28.
Placebo Placebo matched to CP-690,550 10 mg tablet orally twice daily up to Day 27 followed by single oral dose on Day 28.

Participant Flow:   Overall Study
    CP-690,550     Placebo  
STARTED     15     14  
COMPLETED     15     14  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
CP-690,550 CP-690,550 10 mg tablet orally twice daily up to Day 27 followed by single oral dose on Day 28.
Placebo Placebo matched to CP-690,550 10 mg tablet orally twice daily up to Day 27 followed by single oral dose on Day 28.
Total Total of all reporting groups

Baseline Measures
    CP-690,550     Placebo     Total  
Number of Participants  
[units: participants]
  15     14     29  
Age  
[units: years]
Mean ± Standard Deviation
  53.5  ± 9.2     53.1  ± 14.3     53.3  ± 11.7  
Gender  
[units: participants]
     
Female     14     12     26  
Male     1     2     3  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28   [ Time Frame: Day -7 (Baseline), Day 28 ]

2.  Primary:   Change From Baseline in Protein Expression of Tumor Necrosis Factor Alpha (TNFalpha), Interleukin-6 (IL-6), Interleukin-17a (IL-17a) and Interleukin-10 (IL-10) at Day 28   [ Time Frame: Baseline (Day -7), Day 28 ]

3.  Primary:   Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28   [ Time Frame: Baseline (Day -7), Day 28 ]

4.  Primary:   Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)   [ Time Frame: Baseline (Day -7) ]

5.  Primary:   Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28   [ Time Frame: Day 28 ]

6.  Primary:   Blood Cytokine Level at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

7.  Primary:   Blood Cytokine Level at 1 Hour Post-dose on Day 1   [ Time Frame: 1 hour post-dose on Day 1 ]

8.  Primary:   Blood Cytokine Level at 4 Hours Post-dose on Day 1   [ Time Frame: 4 hours post-dose on Day 1 ]

9.  Primary:   Blood Cytokine Level at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

10.  Primary:   Blood Cytokine Level at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

11.  Primary:   Blood Cytokine Level at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

12.  Primary:   Blood Cytokine Level at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

13.  Primary:   Blood Cytokine Level at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

14.  Primary:   Blood Cytokine Level at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

15.  Primary:   Blood Cytokine Level at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

16.  Primary:   Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

17.  Primary:   Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1   [ Time Frame: 1 Hour Post-dose on Day 1 ]

18.  Primary:   Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1   [ Time Frame: 4 Hours Post-dose on Day 1 ]

19.  Primary:   Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

20.  Primary:   Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

21.  Primary:   Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

22.  Primary:   Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

23.  Primary:   Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

24.  Primary:   Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

25.  Primary:   Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

26.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

27.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1   [ Time Frame: 1 Hour Post-dose on Day 1 ]

28.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1   [ Time Frame: 4 Hours Post-dose on Day 1 ]

29.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

30.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

31.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

32.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

33.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

34.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

35.  Primary:   Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

36.  Primary:   Parathyroid Hormone (PTH) Level at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

37.  Primary:   Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1   [ Time Frame: 1 Hour Post-dose on Day 1 ]

38.  Primary:   Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1   [ Time Frame: 4 Hours Post-dose on Day 1 ]

39.  Primary:   Parathyroid Hormone (PTH) Level at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

40.  Primary:   Parathyroid Hormone (PTH) Level at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

41.  Primary:   Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

42.  Primary:   Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

43.  Primary:   Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

44.  Primary:   Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

45.  Primary:   Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

46.  Primary:   Osteoprotegerin (OPG) Level at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

47.  Primary:   Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1   [ Time Frame: 1 Hour Post-dose on Day 1 ]

48.  Primary:   Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1   [ Time Frame: 4 Hours Post-dose on Day 1 ]

49.  Primary:   Osteoprotegerin (OPG) Level at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

50.  Primary:   Osteoprotegerin (OPG) Level at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

51.  Primary:   Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

52.  Primary:   Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

53.  Primary:   Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

54.  Primary:   Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

55.  Primary:   Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

56.  Primary:   Plasma Level of Matrix Metallopeptidase (MMP13)   [ Time Frame: Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28 ]

57.  Primary:   Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18)   [ Time Frame: Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28 ]

58.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

59.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1   [ Time Frame: 1 Hour Post-dose on Day 1 ]

60.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1   [ Time Frame: 4 Hours Post-dose on Day 1 ]

61.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

62.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

63.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

64.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

65.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

66.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

67.  Primary:   Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

68.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

69.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1   [ Time Frame: 1 Hour Post-dose on Day 1 ]

70.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1   [ Time Frame: 4 Hours Post-dose on Day 1 ]

71.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

72.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

73.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28   [ Time Frame: 1 Hour Post-dose on Day 28 ]

74.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28   [ Time Frame: 4 Hours Post-dose on Day 28 ]

75.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28   [ Time Frame: 8 Hours Post-dose on Day 28 ]

76.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

77.  Primary:   Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

78.  Primary:   Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1   [ Time Frame: Pre-dose on Day 1 ]

79.  Primary:   Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10   [ Time Frame: Pre-dose on Day 10 ]

80.  Primary:   Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28   [ Time Frame: Pre-dose on Day 28 ]

81.  Primary:   Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28   [ Time Frame: 24 Hours Post-dose on Day 28 ]

82.  Primary:   Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination   [ Time Frame: Pre-dose on Day 35 or Early Termination ]

83.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 20% Response   [ Time Frame: Day 28, 35 or Early Termination ]

84.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response   [ Time Frame: Day 28, 35 or Early Termination ]

85.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response   [ Time Frame: Day 28, 35 or Early Termination ]

86.  Secondary:   Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])   [ Time Frame: Day -7, 1 (Baseline), 28, 35 or Early Termination ]

87.  Secondary:   Change From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 28 and 35   [ Time Frame: Day 1 (Baseline), 28, 35 or Early Termination ]

88.  Secondary:   Percentage of Participants With Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) <=3.2 and <2.6   [ Time Frame: Day -7, 1 (Baseline), 28, 35 or Early Termination ]

89.  Secondary:   Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])   [ Time Frame: Day -7, 1 (Baseline), 28, 35 or Early Termination ]

90.  Secondary:   Change From Baseline in Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Day 28 and 35   [ Time Frame: Day 1 (Baseline), 28, 35 or Early Termination ]

91.  Secondary:   Percentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) <=3.2 and <2.6   [ Time Frame: Day -7, 1 (Baseline), 28, 35 or Early Termination ]


  Serious Adverse Events


  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: 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: Pfizer
ClinicalTrials.gov Identifier: NCT00976599     History of Changes
Other Study ID Numbers: A3921073
Study First Received: September 11, 2009
Results First Received: December 4, 2012
Last Updated: December 4, 2012
Health Authority: United States: Food and Drug Administration