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CompletedNCT00976599Updated Jan 9, 2013Results posted

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

A Phase 2 interventional study of CP-690,550 + methotrexate and Placebo + Methotrexate in Rheumatoid Arthritis, sponsored by Pfizer. Completed at 15 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-01-09.

Sponsored by Pfizer · Phase 2, Interventional, and Basic science

Phase
Phase 2
Study type
Interventional
Enrollment
29
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

To explore the effect of CP-690,550 on blood and synovial markers in subjects with rheumatoid arthritis. To evaluate the safety, tolerability and efficacy of CP-690,550.

02

Conditions studied

  • Rheumatoid Arthritis
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 29 is below the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Subject must have a diagnosis of rheumatoid arthritis based on the American College of Rheumatology Association

  • The subject has active disease at both Screening and Baseline, as defined:

    • ≥4 joints tender or painful on motion, AND
    • ≥4 joints swollen;
  • The subject must have at least one knee, one elbow, one wrist or two metacarpophalangeal joints with active synovitis suitable for biopsy by the shaver technique

Exclusion criteria

Exclusion Criteria:

  • No arthroscopy should have been performed in the past 3 months in the same joint that is to be biopsied in this study.
  • No intra-articular steroids should have been injected in the joint to be biopsied in this study in the previous 3 months.
  • Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels \< 9.0 gm/dL or hematocrit \< 30 % at screening visit or within the 3 months prior to baseline synovial biopsy.
  • An absolute white blood cell (WBC) count of \< 3.0 x 109/L (\<3000/mm3) or absolute neutrophil count of \<1.2 X 109/L (\<1200/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
  • Thrombocytopenia, as defined by a platelet count \<100 x 109/L (\< 100,000/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
  • Estimated GFR less than 40 ml/min based on Cockcroft Gault calculation .
05

Study design

Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
29 participants (actual)

Study arms

  • Experimental
    CP-690,550 + methotrexate

    Drug: CP-690,550 + methotrexate

  • Placebo comparator
    Placebo + methotrexate

    Drug: Placebo + Methotrexate

Interventions

  • DrugCP-690,550 + methotrexate

    CP-690,550 dose is 10 mg twice daily, oral tablets, for 4 weeks Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week

  • DrugPlacebo + Methotrexate

    Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28

    Synovial tissue biopsy were performed and assayed for mRNA gene expression by quantitative polymerized chain reaction (PCR) using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Interleukin-1beta (IL-1beta), IL-6, matrix metalloproteinase-3 (MMP3), cluster of differentiation 19 (CD19), cluster of differentiation 3 epsilon (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.

    Time frame: Day -7 (Baseline), Day 28

  2. 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

    Synovial tissue biopsy was to be performed and assayed for protein expression by quantitative PCR using standard curve method. Standard curve was to be generated by linear regression using log threshold cycle versus log (cell number). TNFalpha, IL-6, IL-17 and IL-10 data were to be presented as control normalized expression (relative expression) within synovial tissue.

    Time frame: Baseline (Day -7), Day 28

  3. Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28

    The intensity of CD3 and CD68 cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Surface marker CD68 macrophages and CD3 thymus cells (T cells) in the inflammatory cells of synovial tissue were detected by immunohistochemical staining.

    Time frame: Baseline (Day -7), Day 28

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

    Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3 epsilon (CD3E), STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.

    Time frame: Baseline (Day -7)

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

    Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3E, STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.

    Time frame: Day 28

  6. Blood Cytokine Level at Pre-dose on Day 1

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, active 70 kDa (p70) form of IL-12(IL-12p70), interferon gamma (IFNgamma) - induced protein 10 (IP-10), TNFalpha, granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein 1 alpha (MIP1a), monocyte chemotactic protein 1 (MCP1), soluble vascular endothelial growth factor (sVEGF), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), granulocyte colony-stimulating factor (G-CSF) was measured by immunoassay and the levels were expresses as picogram per milliliter (pg/mL).

    Time frame: Pre-dose on Day 1

  7. Blood Cytokine Level at 1 Hour Post-dose on Day 1

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: 1 hour post-dose on Day 1

  8. Blood Cytokine Level at 4 Hours Post-dose on Day 1

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: 4 hours post-dose on Day 1

  9. Blood Cytokine Level at Pre-dose on Day 10

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: Pre-dose on Day 10

  10. Blood Cytokine Level at Pre-dose on Day 28

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: Pre-dose on Day 28

  11. Blood Cytokine Level at 1 Hour Post-dose on Day 28

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: 1 Hour Post-dose on Day 28

  12. Blood Cytokine Level at 4 Hours Post-dose on Day 28

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: 4 Hours Post-dose on Day 28

  13. Blood Cytokine Level at 8 Hours Post-dose on Day 28

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: 8 Hours Post-dose on Day 28

  14. Blood Cytokine Level at 24 Hours Post-dose on Day 28

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: 24 Hours Post-dose on Day 28

  15. Blood Cytokine Level at Pre-dose on Day 35 or Early Termination

    Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

    Time frame: Pre-dose on Day 35 or Early Termination

  16. Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1

    Blood samples were collected for fluorescence-activated cell sorting \[FACS\] analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, Bone-marrow cells (B cells) and natural killer (NK) cells were analyzed using fluorescent-labeled antibodies against clusters of differentiation (CD) markers.

    Time frame: Pre-dose on Day 1

  17. Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: 1 Hour Post-dose on Day 1

  18. Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: 4 Hours Post-dose on Day 1

  19. Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: Pre-dose on Day 10

  20. Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: Pre-dose on Day 28

  21. Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: 1 Hour Post-dose on Day 28

  22. Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: 4 Hours Post-dose on Day 28

  23. Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: 8 Hours Post-dose on Day 28

  24. Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: 24 Hours Post-dose on Day 28

  25. Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination

    Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

    Time frame: Pre-dose on Day 35 or Early Termination

  26. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific Enzyme-Linked Immunosorbent Assay \[ELISA\] method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples).

    Time frame: Pre-dose on Day 1

  27. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: 1 Hour Post-dose on Day 1

  28. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: 4 Hours Post-dose on Day 1

  29. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: Pre-dose on Day 10

  30. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: Pre-dose on Day 28

  31. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: 1 Hour Post-dose on Day 28

  32. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: 4 Hours Post-dose on Day 28

  33. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: 8 Hours Post-dose on Day 28

  34. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: 24 Hours Post-dose on Day 28

  35. Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination

    Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

    Time frame: Pre-dose on Day 35 or Early Termination

  36. Parathyroid Hormone (PTH) Level at Pre-dose on Day 1

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: Pre-dose on Day 1

  37. Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: 1 Hour Post-dose on Day 1

  38. Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: 4 Hours Post-dose on Day 1

  39. Parathyroid Hormone (PTH) Level at Pre-dose on Day 10

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: Pre-dose on Day 10

  40. Parathyroid Hormone (PTH) Level at Pre-dose on Day 28

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: Pre-dose on Day 28

  41. Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: 1 Hour Post-dose on Day 28

  42. Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: 4 Hours Post-dose on Day 28

  43. Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: 8 Hours Post-dose on Day 28

  44. Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: 24 Hours Post-dose on Day 28

  45. Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination

    Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

    Time frame: Pre-dose on Day 35 or Early Termination

  46. Osteoprotegerin (OPG) Level at Pre-dose on Day 1

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 1

  47. Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 1 Hour Post-dose on Day 1

  48. Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 4 Hours Post-dose on Day 1

  49. Osteoprotegerin (OPG) Level at Pre-dose on Day 10

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 10

  50. Osteoprotegerin (OPG) Level at Pre-dose on Day 28

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 28

  51. Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 1 Hour Post-dose on Day 28

  52. Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 4 Hours Post-dose on Day 28

  53. Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 8 Hours Post-dose on Day 28

  54. Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 24 Hours Post-dose on Day 28

  55. Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination

    Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 35 or Early Termination

  56. 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. 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. Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1

    Serum samples were analyzed for SAA concentrations using meso scale discovery (MSD) single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific Electro ChemiLuminescent ImmunoAssay (ECLIA).

    Time frame: Pre-dose on Day 1

  59. Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: 1 Hour Post-dose on Day 1

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

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: 4 Hours Post-dose on Day 1

  61. Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: Pre-dose on Day 10

  62. Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: Pre-dose on Day 28

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

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: 1 Hour Post-dose on Day 28

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

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: 4 Hours Post-dose on Day 28

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

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: 8 Hours Post-dose on Day 28

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

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: 24 Hours Post-dose on Day 28

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

    Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

    Time frame: Pre-dose on Day 35 or Early Termination

  68. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 1

  69. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 1 Hour Post-dose on Day 1

  70. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 4 Hours Post-dose on Day 1

  71. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 10

  72. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 28

  73. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 1 Hour Post-dose on Day 28

  74. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 4 Hours Post-dose on Day 28

  75. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 8 Hours Post-dose on Day 28

  76. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: 24 Hours Post-dose on Day 28

  77. Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination

    Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

    Time frame: Pre-dose on Day 35 or Early Termination

  78. Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1

    Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as nanogram per millimoles of creatinine (ng/mmol Cr).

    Time frame: Pre-dose on Day 1

  79. Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10

    Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

    Time frame: Pre-dose on Day 10

  80. Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28

    Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

    Time frame: Pre-dose on Day 28

  81. Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28

    Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

    Time frame: 24 Hours Post-dose on Day 28

  82. Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination

    Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

    Time frame: Pre-dose on Day 35 or Early Termination

Secondary outcomes

  1. Percentage of Participants Achieving American College of Rheumatology 20% Response

    ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

    Time frame: Day 28, 35 or Early Termination

  2. Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response

    ACR50 response: \>=50% improvement in TJC; \>= 50% improvement in SJC; and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

    Time frame: Day 28, 35 or Early Termination

  3. Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response

    ACR70 response: \>=70% improvement in TJC; \>= 70% improvement in SJC; and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

    Time frame: Day 28, 35 or Early Termination

  4. Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])

    DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP) (milligram per liter \[mg/L\]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (\<=) 3.2 implied low disease activity, greater than (\>) 3.2 to 5.1 implied moderate to high disease activity and less than (\<) 2.6 implied remission.

    Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination

  5. 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

    DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

    Time frame: Day 1 (Baseline), 28, 35 or Early Termination

  6. 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

    DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

    Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination

  7. Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])

    DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity, \> 3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

    Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination

  8. 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

    DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR \[mm/hour\] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity, \> 3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

    Time frame: Day 1 (Baseline), 28, 35 or Early Termination

  9. 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

    DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR \[mm/hour\] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity, \> 3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

    Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination

07

Results

Posted Jan 9, 2013

Participant flow

Participant flow — Overall Study
MilestoneCP-690,550Placebo
Started1514
Completed1514
Not completed00

Outcome measures

PrimaryChange From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28

Synovial tissue biopsy were performed and assayed for mRNA gene expression by quantitative polymerized chain reaction (PCR) using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Interleukin-1beta (IL-1beta), IL-6, matrix metalloproteinase-3 (MMP3), cluster of differentiation 19 (CD19), cluster of differentiation 3 epsilon (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.

Time frame:
Day -7 (Baseline), Day 28
Reported as:
Mean · relative expression unit (REU)
Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28
relative expression unit (REU)CP-690,550Placebo
Baseline: IL-1beta mRNA-2.73 ± 0.77-2.83 ± 0.80
Baseline: IL-6 mRNA-3.72 ± 0.67-3.96 ± 0.55
Baseline: MMP3 mRNA-2.01 ± 1.39-2.52 ± 1.64
Baseline: CD19 mRNA-2.98 ± 1.25-3.46 ± 1.34
Baseline: CD3E mRNA-1.58 ± 0.71-1.75 ± 0.58
Baseline: JAK1 mRNA0.30 ± 0.240.31 ± 0.29
Baseline: JAK2 mRNA0.17 ± 0.260.15 ± 0.25
Baseline: JAK3 mRNA-0.77 ± 0.40-0.88 ± 0.52
Baseline: STAT1 mRNA-0.43 ± 0.29-0.46 ± 0.33
Baseline: ISG15 mRNA-1.26 ± 0.23-1.33 ± 0.27
Baseline: CXCL10 mRNA-1.21 ± 0.85-1.24 ± 0.81
Baseline: CCL2 mRNA-1.70 ± 0.29-1.73 ± 0.39
Baseline: pSTAT1 protein0.18 ± 0.330.27 ± 0.39
Baseline: pSTAT3 protein0.77 ± 0.290.79 ± 0.30
Change at Day 28: IL-1beta mRNA-0.01 ± 0.880.09 ± 0.43
Change at Day 28: IL-6 mRNA-0.25 ± 0.86-0.08 ± 0.45
Change at Day 28: MMP3 mRNA-0.80 ± 0.92-0.03 ± 1.23
Change at Day 28: CD19 mRNA0.06 ± 0.85-0.31 ± 0.72
Change at Day 28: CD3E mRNA-0.07 ± 0.53-0.12 ± 0.44
Change at Day 28: JAK1 mRNA0.04 ± 0.36-0.10 ± 0.36
Change at Day 28: JAK2 mRNA-0.07 ± 0.40-0.10 ± 0.29
Change at Day 28: JAK3 mRNA-0.05 ± 0.35-0.13 ± 0.52
Change at Day 28: STAT1 mRNA-0.15 ± 0.460.01 ± 0.35
Change at Day 28: ISG15 mRNA-0.16 ± 0.400.11 ± 0.34
Change at Day 28: CXCL10 mRNA-0.49 ± 0.750.15 ± 0.61
Change at Day 28: CCL2 mRNA-0.20 ± 0.30-0.02 ± 0.28
Change at Day 28: pSTAT1 protein-0.20 ± 0.44-0.10 ± 0.36
Change at Day 28: pSTAT3 protein-0.10 ± 0.42-0.10 ± 0.18
PrimaryChange 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

Synovial tissue biopsy was to be performed and assayed for protein expression by quantitative PCR using standard curve method. Standard curve was to be generated by linear regression using log threshold cycle versus log (cell number). TNFalpha, IL-6, IL-17 and IL-10 data were to be presented as control normalized expression (relative expression) within synovial tissue.

Time frame:
Baseline (Day -7), Day 28

No measurements were reported for this outcome.

PrimaryChange From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28

The intensity of CD3 and CD68 cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Surface marker CD68 macrophages and CD3 thymus cells (T cells) in the inflammatory cells of synovial tissue were detected by immunohistochemical staining.

Time frame:
Baseline (Day -7), Day 28
Reported as:
Mean · percentage area stained
Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28
percentage area stainedCP-690,550Placebo
Baseline: CD3+ Cells (n=12, 12)7.33 ± 6.127.92 ± 7.49
Baseline: CD68+ Cells (n=12, 13)31.83 ± 20.5932.85 ± 26.05
Change at Day 28: CD3+ Cells (n=10, 8)1.50 ± 3.950.13 ± 7.38
Change at Day 28: CD68+ Cells (n=12, 11)1.67 ± 19.860.82 ± 18.37
PrimaryBlood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)

Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3 epsilon (CD3E), STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.

Time frame:
Baseline (Day -7)
Reported as:
Mean · REU
Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)
REUCP-690,550Placebo
CD19 mRNA0.11 ± 0.280.29 ± 0.25
CD3E mRNA0.41 ± 0.440.40 ± 0.38
STAT1 mRNA0.06 ± 0.250.02 ± 0.13
STAT3 mRNA0.61 ± 0.130.64 ± 0.08
ISG15 mRNA-0.65 ± 0.45-0.56 ± 0.47
CXCL10 mRNA-1.58 ± 0.33-1.65 ± 0.19
PrimaryBlood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28

Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3E, STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.

Time frame:
Day 28
Reported as:
Mean · REU
Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28
REUCP-690,550Placebo
CD19 mRNA0.35 ± 0.240.30 ± 0.25
CD3E mRNA0.49 ± 0.340.40 ± 0.32
STAT1 mRNA-0.01 ± 0.280.04 ± 0.21
STAT3 mRNA0.60 ± 0.130.59 ± 0.13
ISG15 mRNA-0.93 ± 0.20-0.48 ± 0.51
CXCL10 mRNA-1.64 ± 0.22-1.59 ± 0.28
PrimaryBlood Cytokine Level at Pre-dose on Day 1

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, active 70 kDa (p70) form of IL-12(IL-12p70), interferon gamma (IFNgamma) - induced protein 10 (IP-10), TNFalpha, granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein 1 alpha (MIP1a), monocyte chemotactic protein 1 (MCP1), soluble vascular endothelial growth factor (sVEGF), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), granulocyte colony-stimulating factor (G-CSF) was measured by immunoassay and the levels were expresses as picogram per milliliter (pg/mL).

Time frame:
Pre-dose on Day 1
Reported as:
Mean · pg/mL
Blood Cytokine Level at Pre-dose on Day 1
pg/mLCP-690,550Placebo
IL-1alpha0.75 ± 0.680.67 ± 0.68
IL-1beta0.42 ± 0.390.41 ± 0.41
IL-40.29 ± 0.290.17 ± 0.16
IL-60.97 ± 0.670.77 ± 0.45
IL-70.89 ± 0.320.74 ± 0.23
IL-81.17 ± 0.241.19 ± 0.27
IL-100.25 ± 0.240.33 ± 0.37
IL-12p700.31 ± 0.290.35 ± 0.44
IL-17A0.49 ± 0.480.44 ± 0.37
IL-211.56 ± 1.101.47 ± 1.04
IP-102.22 ± 0.232.23 ± 0.30
TNFalpha0.45 ± 0.430.44 ± 0.51
IFNgamma0.15 ± 0.160.11 ± 0.07
G-CSF0.57 ± 0.470.60 ± 0.34
GM-CSF0.48 ± 0.480.36 ± 0.46
MCP12.14 ± 0.262.09 ± 0.32
MIP1a0.85 ± 0.450.90 ± 0.32
sVEGF1.96 ± 0.441.87 ± 0.28
sVCAM-14.95 ± 0.175.07 ± 0.17
sICAM-14.65 ± 0.124.76 ± 0.17
PrimaryBlood Cytokine Level at 1 Hour Post-dose on Day 1

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
1 hour post-dose on Day 1
Reported as:
Mean · pg/mL
Blood Cytokine Level at 1 Hour Post-dose on Day 1
pg/mLCP-690,550Placebo
IL-1alpha0.76 ± 0.680.73 ± 0.68
IL-1beta0.43 ± 0.420.40 ± 0.43
IL-40.29 ± 0.280.15 ± 0.13
IL-60.90 ± 0.520.78 ± 0.43
IL-70.86 ± 0.360.72 ± 0.26
IL-81.12 ± 0.311.15 ± 0.23
IL-100.23 ± 0.220.31 ± 0.35
IL-12p700.36 ± 0.310.34 ± 0.43
IL-17A0.58 ± 0.460.42 ± 0.36
IL-211.45 ± 1.161.45 ± 1.07
IP-102.17 ± 0.252.22 ± 0.31
TNFalpha0.41 ± 0.460.44 ± 0.52
IFNgamma0.12 ± 0.070.10 ± 0.00
G-CSF0.56 ± 0.470.62 ± 0.36
GM-CSF0.49 ± 0.490.39 ± 0.49
MCP12.09 ± 0.262.03 ± 0.33
MIP1a0.83 ± 0.470.89 ± 0.33
sVEGF1.98 ± 0.421.87 ± 0.27
sVCAM-14.94 ± 0.155.06 ± 0.17
sICAM-14.64 ± 0.134.76 ± 0.18
PrimaryBlood Cytokine Level at 4 Hours Post-dose on Day 1

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
4 hours post-dose on Day 1
Reported as:
Mean · pg/mL
Blood Cytokine Level at 4 Hours Post-dose on Day 1
pg/mLCP-690,550Placebo
IL-1alpha0.77 ± 0.690.65 ± 0.70
IL-1beta0.43 ± 0.460.41 ± 0.42
IL-40.28 ± 0.280.18 ± 0.17
IL-60.74 ± 0.410.72 ± 0.39
IL-70.82 ± 0.390.73 ± 0.28
IL-81.18 ± 0.221.15 ± 0.25
IL-100.19 ± 0.200.30 ± 0.35
IL-12p700.35 ± 0.290.38 ± 0.43
IL-17A0.53 ± 0.470.39 ± 0.40
IL-211.60 ± 1.091.36 ± 1.07
IP-102.10 ± 0.222.20 ± 0.33
TNFalpha0.41 ± 0.470.45 ± 0.51
IFNgamma0.17 ± 0.130.12 ± 0.07
G-CSF0.55 ± 0.470.62 ± 0.41
GM-CSF0.50 ± 0.480.38 ± 0.48
MCP11.98 ± 0.292.07 ± 0.34
MIP1a0.81 ± 0.470.86 ± 0.33
sVEGF1.93 ± 0.421.85 ± 0.28
sVCAM-14.96 ± 0.155.03 ± 0.21
sICAM-14.66 ± 0.124.74 ± 0.20
PrimaryBlood Cytokine Level at Pre-dose on Day 10

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · pg/mL
Blood Cytokine Level at Pre-dose on Day 10
pg/mLCP-690,550Placebo
IL-1alpha0.74 ± 0.660.69 ± 0.68
IL-1beta0.36 ± 0.460.42 ± 0.43
IL-40.28 ± 0.280.19 ± 0.18
IL-60.68 ± 0.550.78 ± 0.45
IL-70.83 ± 0.310.61 ± 0.38
IL-81.15 ± 0.291.21 ± 0.29
IL-100.21 ± 0.230.32 ± 0.35
IL-12p700.34 ± 0.320.34 ± 0.43
IL-17A0.50 ± 0.480.41 ± 0.36
IL-211.62 ± 1.021.63 ± 0.86
IP-102.01 ± 0.252.18 ± 0.33
TNFalpha0.48 ± 0.490.48 ± 0.50
IFNgamma0.11 ± 0.050.11 ± 0.03
G-CSF0.60 ± 0.430.60 ± 0.31
GM-CSF0.48 ± 0.460.37 ± 0.48
MCP12.17 ± 0.342.09 ± 0.38
MIP1a0.83 ± 0.520.89 ± 0.35
sVEGF1.93 ± 0.441.90 ± 0.28
sVCAM-14.90 ± 0.165.03 ± 0.16
sICAM-14.63 ± 0.114.74 ± 0.20
PrimaryBlood Cytokine Level at Pre-dose on Day 28

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · pg/mL
Blood Cytokine Level at Pre-dose on Day 28
pg/mLCP-690,550Placebo
IL-1alpha0.69 ± 0.710.68 ± 0.68
IL-1beta0.41 ± 0.450.39 ± 0.39
IL-40.24 ± 0.250.15 ± 0.15
IL-60.64 ± 0.420.78 ± 0.32
IL-70.75 ± 0.340.53 ± 0.30
IL-81.19 ± 0.361.14 ± 0.32
IL-100.18 ± 0.170.32 ± 0.31
IL-12p700.27 ± 0.260.35 ± 0.43
IL-17A0.49 ± 0.470.37 ± 0.37
IL-211.47 ± 1.081.53 ± 0.99
IP-102.01 ± 0.192.24 ± 0.40
TNFalpha0.46 ± 0.490.43 ± 0.48
IFNgamma0.11 ± 0.030.10 ± 0.00
G-CSF0.65 ± 0.390.66 ± 0.34
GM-CSF0.48 ± 0.480.35 ± 0.45
MCP12.21 ± 0.352.09 ± 0.40
MIP1a0.84 ± 0.440.83 ± 0.34
sVEGF1.89 ± 0.411.83 ± 0.27
sVCAM-14.89 ± 0.145.01 ± 0.19
sICAM-14.61 ± 0.094.70 ± 0.21
PrimaryBlood Cytokine Level at 1 Hour Post-dose on Day 28

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · pg/mL
Blood Cytokine Level at 1 Hour Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1alpha0.69 ± 0.680.69 ± 0.67
IL-1beta0.40 ± 0.410.39 ± 0.38
IL-40.25 ± 0.250.15 ± 0.14
IL-60.67 ± 0.520.77 ± 0.39
IL-70.69 ± 0.380.61 ± 0.33
IL-81.10 ± 0.231.12 ± 0.33
IL-100.18 ± 0.160.33 ± 0.33
IL-12p700.33 ± 0.280.36 ± 0.44
IL-17A0.44 ± 0.450.36 ± 0.34
IL-211.46 ± 1.061.52 ± 0.99
IP-102.00 ± 0.212.23 ± 0.39
TNFalpha0.39 ± 0.460.43 ± 0.48
IFNgamma0.12 ± 0.060.11 ± 0.04
G-CSF0.63 ± 0.390.66 ± 0.29
GM-CSF0.47 ± 0.470.36 ± 0.45
MCP12.23 ± 0.302.06 ± 0.35
MIP1a0.81 ± 0.450.83 ± 0.33
sVEGF1.85 ± 0.381.81 ± 0.26
sVCAM-14.85 ± 0.155.04 ± 0.17
sICAM-14.58 ± 0.104.73 ± 0.23
PrimaryBlood Cytokine Level at 4 Hours Post-dose on Day 28

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Blood Cytokine Level at 4 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1alpha0.67 ± 0.690.75 ± 0.66
IL-1beta0.27 ± 0.320.33 ± 0.39
IL-40.22 ± 0.270.14 ± 0.11
IL-60.56 ± 0.300.69 ± 0.29
IL-70.66 ± 0.450.56 ± 0.36
IL-81.07 ± 0.211.07 ± 0.25
IL-100.16 ± 0.130.28 ± 0.32
IL-12p700.26 ± 0.270.31 ± 0.44
IL-17A0.37 ± 0.440.34 ± 0.37
IL-211.51 ± 1.051.68 ± 0.92
IP-101.89 ± 0.212.13 ± 0.36
TNFalpha0.38 ± 0.420.38 ± 0.49
IFNgamma0.12 ± 0.070.11 ± 0.04
G-CSF0.57 ± 0.430.72 ± 0.26
GM-CSF0.49 ± 0.470.38 ± 0.46
MCP12.09 ± 0.231.99 ± 0.38
MIP1a0.71 ± 0.480.80 ± 0.31
sVEGF1.80 ± 0.361.84 ± 0.28
sVCAM-14.91 ± 0.155.00 ± 0.14
sICAM-14.61 ± 0.094.71 ± 0.22
PrimaryBlood Cytokine Level at 8 Hours Post-dose on Day 28

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Blood Cytokine Level at 8 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1alpha0.76 ± 0.680.63 ± 0.69
IL-1beta0.29 ± 0.350.34 ± 0.39
IL-40.23 ± 0.270.14 ± 0.12
IL-60.71 ± 0.390.79 ± 0.34
IL-70.67 ± 0.400.66 ± 0.31
IL-81.10 ± 0.211.17 ± 0.26
IL-100.15 ± 0.110.29 ± 0.30
IL-12p700.28 ± 0.280.33 ± 0.42
IL-17A0.44 ± 0.420.29 ± 0.36
IL-211.58 ± 1.041.30 ± 1.13
IP-101.85 ± 0.222.14 ± 0.35
TNFalpha0.36 ± 0.430.35 ± 0.48
IFNgamma0.10 ± 0.000.12 ± 0.07
G-CSF0.65 ± 0.370.83 ± 0.28
GM-CSF0.48 ± 0.450.38 ± 0.46
MCP12.11 ± 0.312.02 ± 0.40
MIP1a0.71 ± 0.450.71 ± 0.35
sVEGF1.71 ± 0.361.82 ± 0.25
sVCAM-14.87 ± 0.165.05 ± 0.15
sICAM-14.59 ± 0.094.74 ± 0.24
PrimaryBlood Cytokine Level at 24 Hours Post-dose on Day 28

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Blood Cytokine Level at 24 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1alpha0.73 ± 0.660.66 ± 0.64
IL-1beta0.38 ± 0.410.38 ± 0.41
IL-40.26 ± 0.270.15 ± 0.15
IL-60.93 ± 0.420.99 ± 0.47
IL-70.79 ± 0.350.64 ± 0.31
IL-81.21 ± 0.321.18 ± 0.29
IL-100.22 ± 0.170.30 ± 0.33
IL-12p700.25 ± 0.250.37 ± 0.44
IL-17A0.44 ± 0.440.32 ± 0.32
IL-211.54 ± 0.981.64 ± 0.87
IP-102.02 ± 0.312.27 ± 0.39
TNFalpha0.42 ± 0.470.42 ± 0.51
IFNgamma0.16 ± 0.190.10 ± 0.00
G-CSF0.67 ± 0.390.71 ± 0.28
GM-CSF0.46 ± 0.460.31 ± 0.44
MCP12.33 ± 0.242.10 ± 0.35
MIP1a0.86 ± 0.490.88 ± 0.28
sVEGF1.89 ± 0.411.84 ± 0.23
sVCAM-14.88 ± 0.145.06 ± 0.17
sICAM-14.58 ± 0.104.74 ± 0.21
PrimaryBlood Cytokine Level at Pre-dose on Day 35 or Early Termination

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · pg/mL
Blood Cytokine Level at Pre-dose on Day 35 or Early Termination
pg/mLCP-690,550Placebo
IL-1alpha0.70 ± 0.680.66 ± 0.66
IL-1beta0.43 ± 0.430.38 ± 0.41
IL-40.29 ± 0.310.14 ± 0.13
IL-60.81 ± 0.460.66 ± 0.44
IL-70.85 ± 0.310.52 ± 0.35
IL-81.08 ± 0.261.04 ± 0.23
IL-100.22 ± 0.170.34 ± 0.37
IL-12p700.32 ± 0.260.33 ± 0.45
IL-17A0.43 ± 0.480.36 ± 0.35
IL-211.41 ± 1.041.58 ± 0.99
IP-102.20 ± 0.272.28 ± 0.38
TNFalpha0.46 ± 0.480.43 ± 0.51
IFNgamma0.17 ± 0.220.10 ± 0.00
G-CSF0.57 ± 0.550.58 ± 0.28
GM-CSF0.45 ± 0.460.35 ± 0.42
MCP12.17 ± 0.262.07 ± 0.35
MIP1a0.82 ± 0.500.85 ± 0.31
sVEGF1.92 ± 0.421.88 ± 0.29
sVCAM-14.97 ± 0.135.05 ± 0.16
sICAM-14.65 ± 0.124.76 ± 0.15
PrimaryBlood T, B and NK Lymphocyte Counts at Pre-dose on Day 1

Blood samples were collected for fluorescence-activated cell sorting \[FACS\] analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, Bone-marrow cells (B cells) and natural killer (NK) cells were analyzed using fluorescent-labeled antibodies against clusters of differentiation (CD) markers.

Time frame:
Pre-dose on Day 1
Reported as:
Mean · cells per microliter (cells/mcL)
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1
cells per microliter (cells/mcL)CP-690,550Placebo
B Cells (CD19)214.09 ± 134.72389.17 ± 190.27
Total T Cells (CD3)1516.27 ± 567.381579.00 ± 628.89
CD8 T Cells (CD3 CD8)402.73 ± 205.74376.67 ± 189.14
CD4 T Cells (CD3 CD4)1114.82 ± 415.591199.17 ± 496.66
NK Cells (CD16 CD56)276.45 ± 134.62190.67 ± 121.20
Immature B Cells10.27 ± 11.238.83 ± 5.65
Naive Cells165.64 ± 113.99273.67 ± 178.51
Marginal B Cells17.55 ± 7.6281.50 ± 168.29
Memory B Cells20.45 ± 12.3625.00 ± 14.83
Central Memory CD4 Cells627.45 ± 306.86673.33 ± 291.75
Effector Memory CD4 Cells130.09 ± 138.9893.92 ± 97.30
Naive CD4 Cells311.09 ± 245.67420.92 ± 294.76
Terminally Differentiated(Diff) EffectorCD4 Cells45.82 ± 83.6010.25 ± 15.15
Central Memory CD8 Cells117.73 ± 102.47136.58 ± 77.79
Effector Memory CD8 Cells38.55 ± 29.8868.25 ± 88.65
Naive CD8 Cells111.91 ± 81.86113.08 ± 50.56
Terminally Diff Effector Memory CD8 Cells134.36 ± 140.9758.83 ± 52.87
CD4 T-Cells81.91 ± 34.7681.92 ± 42.95
CD56 Bright NK-Cells9.27 ± 3.857.00 ± 4.13
CD56 Dim NK-Cell209.09 ± 124.61143.83 ± 103.97
CD56 Null NK-Cells57.82 ± 61.0539.58 ± 27.28
CD56 Dim Null NK-Cells266.73 ± 132.17183.42 ± 118.39
PrimaryBlood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
1 Hour Post-dose on Day 1
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1
cells/mcLCP-690,550Placebo
B Cells (CD19)207.07 ± 128.57312.69 ± 216.36
Total T Cells (CD3)1533.53 ± 631.421596.54 ± 754.87
CD8 T Cells (CD3 CD8)431.07 ± 229.21372.38 ± 157.96
CD4 T Cells (CD3 CD4)1102.60 ± 450.531208.08 ± 651.25
NK Cells (CD16 CD56)422.87 ± 182.11179.15 ± 107.03
Immature B Cells8.40 ± 9.638.92 ± 7.49
Naive Cells166.60 ± 111.95222.75 ± 185.92
Marginal B Cells16.20 ± 6.6578.17 ± 151.67
Memory B Cells16.07 ± 8.0425.75 ± 17.78
Central Memory CD4 Cells640.07 ± 314.78706.42 ± 360.34
Effector Memory CD4 Cells121.07 ± 127.9861.83 ± 45.05
Naive CD4 Cells298.47 ± 197.32459.75 ± 382.27
Terminally Diff Effector CD4 Cells42.93 ± 87.654.50 ± 6.78
Central Memory CD8 Cells134.40 ± 102.91141.75 ± 87.65
Effector Memory CD8 Cells49.00 ± 37.4446.58 ± 64.47
Naive CD8 Cells114.20 ± 50.74137.33 ± 69.67
Terminally Diff Effector Memory CD8 Cells133.53 ± 168.9239.58 ± 36.34
CD4 T-Cells76.13 ± 39.6591.92 ± 55.68
CD56 Bright NK-Cells10.00 ± 4.757.23 ± 4.38
CD56 Dim NK-Cell358.33 ± 171.65136.92 ± 97.23
CD56 Null NK-Cells54.40 ± 44.6534.77 ± 23.81
CD56 Dim Null NK-Cells412.60 ± 180.18171.62 ± 104.39
PrimaryBlood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
4 Hours Post-dose on Day 1
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1
cells/mcLCP-690,550Placebo
B Cells (CD19)222.79 ± 154.52380.33 ± 220.41
Total T Cells (CD3)1841.07 ± 880.141710.42 ± 959.80
CD8 T Cells (CD3 CD8)505.64 ± 298.97393.00 ± 205.06
CD4 T Cells (CD3 CD4)1338.79 ± 633.151312.92 ± 834.04
NK Cells (CD16 CD56)428.50 ± 207.39201.83 ± 192.98
Immature B Cells8.29 ± 10.4110.92 ± 10.09
Naive Cells177.50 ± 129.90265.00 ± 209.57
Marginal B Cells19.86 ± 12.6074.83 ± 129.24
Memory B Cells17.07 ± 10.9829.17 ± 23.94
Central Memory CD4 Cells785.43 ± 388.64720.50 ± 383.62
Effector Memory CD4 Cells155.71 ± 165.4993.42 ± 129.36
Naive CD4 Cells352.43 ± 307.49488.75 ± 499.88
Terminally Diff Effector CD4 Cells45.57 ± 103.3910.42 ± 18.37
Central Memory CD8 Cells159.21 ± 119.89140.42 ± 90.69
Effector Memory CD8 Cells64.07 ± 52.8761.33 ± 104.75
Naive CD8 Cells127.71 ± 54.79142.42 ± 69.46
Terminally Diff Effector Memory CD8 Cells154.43 ± 201.1348.67 ± 58.85
CD4 T-Cells86.36 ± 42.8997.83 ± 78.84
CD56 Bright NK-Cells11.21 ± 6.057.17 ± 3.95
CD56 Dim NK-Cell364.57 ± 191.50157.17 ± 158.85
CD56 Null NK-Cells52.57 ± 48.3237.33 ± 37.57
CD56 Dim Null NK-Cells417.00 ± 204.21194.50 ± 191.68
PrimaryBlood T, B and NK Lymphocyte Counts at Pre-dose on Day 10

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10
cells/mcLCP-690,550Placebo
B Cells (CD19)290.50 ± 144.94310.92 ± 154.13
Total T Cells (CD3)1732.29 ± 581.981477.08 ± 696.45
CD8 T Cells (CD3 CD8)413.64 ± 169.81384.15 ± 216.57
CD4 T Cells (CD3 CD4)1314.64 ± 475.641084.62 ± 547.23
NK Cells (CD16 CD56)258.79 ± 177.98205.38 ± 138.20
Immature B Cells11.21 ± 9.968.85 ± 7.99
Naive Cells218.57 ± 121.71211.38 ± 133.45
Marginal B Cells32.29 ± 20.2869.23 ± 135.70
Memory B Cells28.50 ± 14.5321.31 ± 13.01
Central Memory CD4 Cells696.21 ± 294.16603.54 ± 300.56
Effector Memory CD4 Cells130.86 ± 139.7978.92 ± 102.26
Naive CD4 Cells453.86 ± 314.82393.08 ± 296.88
Terminally Diff Effector CD4 Cells33.43 ± 52.479.31 ± 18.40
Central Memory CD8 Cells126.71 ± 95.74132.46 ± 76.09
Effector Memory CD8 Cells37.57 ± 27.1169.38 ± 104.84
Naive CD8 Cells136.93 ± 66.75122.54 ± 91.92
Terminally Diff Effector Memory CD8 Cells112.50 ± 114.1459.77 ± 70.15
CD4 T-Cells93.64 ± 57.4479.69 ± 43.04
CD56 Bright NK-Cells5.07 ± 2.378.23 ± 4.80
CD56 Dim NK-Cell207.50 ± 162.82149.54 ± 115.63
CD56 Null NK-Cells46.29 ± 52.4547.46 ± 35.83
CD56 Dim Null NK-Cells253.64 ± 176.82196.92 ± 136.36
PrimaryBlood T, B and NK Lymphocyte Counts at Pre-dose on Day 28

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28
cells/mcLCP-690,550Placebo
B Cells (CD19)399.62 ± 208.61392.25 ± 235.63
Total T Cells(CD3)1730.38 ± 730.181451.92 ± 622.86
CD8 T Cells (CD3 CD8)363.85 ± 143.45346.58 ± 206.22
CD4 T Cells (CD3 CD4)1352.46 ± 618.781102.08 ± 454.72
NK Cells (CD16 CD56)184.92 ± 103.73180.33 ± 123.31
Immature B Cells13.85 ± 8.9911.25 ± 11.86
Naive Cells304.77 ± 177.06280.50 ± 212.30
Marginal B Cells44.31 ± 36.3873.75 ± 159.25
Memory B Cells36.69 ± 18.1426.50 ± 19.50
Central Memory CD4 Cells736.00 ± 272.68623.67 ± 259.72
Effector Memory CD4 Cells118.54 ± 91.2090.00 ± 98.80
Naive CD4 Cells475.23 ± 421.51378.50 ± 193.71
Terminally Diff Effector CD4 Cells22.69 ± 28.469.50 ± 14.13
Central Memory CD8 Cells120.69 ± 65.03120.50 ± 68.09
Effector Memory CD8 Cells32.92 ± 25.6955.50 ± 67.08
Naive CD8 Cells131.38 ± 85.53121.75 ± 86.96
Terminally Diff Effector Memory CD8 Cells78.46 ± 81.5349.00 ± 61.65
CD4 T-Cells84.38 ± 54.7175.08 ± 43.97
CD56 Bright NK-Cells4.15 ± 2.037.17 ± 4.41
CD56 Dim NK-Cell127.15 ± 78.63134.25 ± 103.99
CD56 Null NK-Cells53.77 ± 51.2138.83 ± 35.54
CD56 Dim Null NK-Cells180.77 ± 103.02173.17 ± 119.76
PrimaryBlood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28
cells/mcLCP-690,550Placebo
B Cells (CD19)343.21 ± 159.97329.00 ± 202.97
Total T Cells(CD3)1705.57 ± 621.551630.64 ± 816.41
CD8 T Cells (CD3 CD8)409.71 ± 158.79482.07 ± 388.11
CD4 T Cells (CD3 CD4)1281.00 ± 491.921145.50 ± 522.79
NK Cells (CD16 CD56)309.43 ± 112.95339.50 ± 426.91
Immature B Cells12.43 ± 7.849.14 ± 9.04
Naive Cells261.57 ± 140.28233.86 ± 171.68
Marginal B Cells36.43 ± 20.1463.00 ± 141.24
Memory B Cells32.57 ± 15.2723.07 ± 17.84
Central Memory CD4 Cells723.43 ± 253.15614.50 ± 219.76
Effector Memory CD4 Cells117.21 ± 99.96143.14 ± 237.16
Naive CD4 Cells418.93 ± 321.41370.43 ± 199.66
Terminally Diff Effector CD4 Cells21.07 ± 31.3217.43 ± 36.50
Central Memory CD8 Cells141.50 ± 82.12128.14 ± 70.76
Effector Memory CD8 Cells36.07 ± 23.82114.79 ± 187.14
Naive CD8 Cells135.29 ± 83.65140.07 ± 101.82
Terminally Diff Effector Memory CD8 Cells97.21 ± 109.2798.93 ± 154.16
CD4 T-Cells88.50 ± 51.9378.64 ± 41.50
CD56 Bright NK-Cells4.71 ± 2.438.14 ± 5.53
CD56 Dim NK-Cell258.43 ± 111.98284.14 ± 394.73
CD56 Null NK-Cells46.29 ± 25.3846.93 ± 52.57
CD56 Dim Null NK-Cells304.64 ± 112.88331.14 ± 422.93
PrimaryBlood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28
cells/mcLCP-690,550Placebo
B Cells (CD19)336.45 ± 194.70347.67 ± 233.30
Total T Cells(CD3)1483.00 ± 495.981445.83 ± 712.35
CD8 T Cells (CD3 CD8)355.27 ± 111.71346.00 ± 209.68
CD4 T Cells (CD3 CD4)1122.91 ± 419.021095.00 ± 565.70
NK Cells (CD16 CD56)188.36 ± 59.25200.75 ± 191.26
Immature B Cells10.73 ± 8.3310.33 ± 10.82
Naive Cells256.91 ± 156.81247.17 ± 207.69
Marginal B Cells38.73 ± 38.6967.17 ± 129.67
Memory B Cells29.91 ± 17.2723.17 ± 19.64
Central Memory CD4 Cells675.55 ± 270.78631.50 ± 260.76
Effector Memory CD4 Cells110.09 ± 69.3485.92 ± 134.06
Naive CD4 Cells312.00 ± 237.45369.50 ± 314.06
Terminally Diff Effector CD4 Cells24.91 ± 30.278.17 ± 20.56
Central Memory CD8 Cells118.09 ± 78.61112.83 ± 60.76
Effector Memory CD8 Cells37.09 ± 27.5060.17 ± 91.98
Naive CD8 Cells126.00 ± 90.18133.17 ± 98.02
Terminally Diff Effector Memory CD8 Cells73.91 ± 58.7940.00 ± 75.37
CD4 T-Cells64.09 ± 33.0565.36 ± 36.70
CD56 Bright NK-Cells4.55 ± 2.426.83 ± 4.71
CD56 Dim NK-Cell143.55 ± 49.57163.50 ± 158.10
CD56 Null NK-Cells40.36 ± 25.7430.50 ± 35.48
CD56 Dim Null NK-Cells183.64 ± 58.53193.92 ± 188.21
PrimaryBlood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28
cells/mcLCP-690,550Placebo
B Cells (CD19)382.33 ± 204.55318.27 ± 253.87
Total T Cells(CD3)1557.58 ± 601.361616.00 ± 934.75
CD8 T Cells (CD3 CD8)348.33 ± 135.33420.18 ± 226.60
CD4 T Cells (CD3 CD4)1203.67 ± 491.021186.73 ± 788.19
NK Cells (CD16 CD56)174.58 ± 82.07217.91 ± 148.22
Immature B Cells11.25 ± 7.107.30 ± 8.08
Naive Cells291.33 ± 165.84243.10 ± 220.30
Marginal B Cells46.50 ± 38.5776.60 ± 142.34
Memory B Cells33.00 ± 20.8222.70 ± 19.96
Central Memory CD4 Cells726.75 ± 293.12725.00 ± 424.16
Effector Memory CD4 Cells119.17 ± 87.9285.64 ± 127.90
Naive CD4 Cells338.17 ± 270.26367.73 ± 378.39
Terminally Diff Effector CD4 Cells19.83 ± 21.418.27 ± 18.79
Central Memory CD8 Cells115.92 ± 51.47149.27 ± 86.30
Effector Memory CD8 Cells35.33 ± 25.2785.09 ± 110.75
Naive CD8 Cells133.25 ± 95.54133.64 ± 111.11
Terminally Diff Effector Memory CD8 Cells64.08 ± 56.4752.27 ± 72.48
CD4 T-Cells79.00 ± 53.9289.50 ± 72.98
CD56 Bright NK-Cells3.36 ± 1.807.27 ± 4.29
CD56 Dim NK-Cell117.18 ± 59.33164.36 ± 125.72
CD56 Null NK-Cells41.91 ± 29.3646.27 ± 38.40
CD56 Dim Null NK-Cells158.91 ± 74.78210.64 ± 145.85
PrimaryBlood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28
cells/mcLCP-690,550Placebo
B Cells (CD19)276.00 ± 167.25300.92 ± 191.57
Total T Cells(CD3)1044.08 ± 505.601619.33 ± 913.77
CD8 T Cells (CD3 CD8)239.92 ± 113.32382.75 ± 200.38
CD4 T Cells (CD3 CD4)799.50 ± 408.071223.17 ± 779.67
NK Cells (CD16 CD56)92.92 ± 52.30196.67 ± 152.83
Immature B Cells10.00 ± 4.209.75 ± 9.52
Naive Cells215.83 ± 146.07245.33 ± 173.16
Marginal B Cells25.58 ± 18.7824.08 ± 27.05
Memory B Cells24.83 ± 11.1021.75 ± 16.10
Central Memory CD4 Cells431.92 ± 186.89626.00 ± 339.12
Effector Memory CD4 Cells59.58 ± 41.8479.50 ± 119.68
Naive CD4 Cells297.17 ± 287.44508.83 ± 483.29
Terminally Diff Effector CD4 Cells11.00 ± 18.399.00 ± 18.01
Central Memory CD8 Cells85.50 ± 72.10133.33 ± 83.39
Effector Memory CD8 Cells16.75 ± 8.5859.17 ± 93.93
Naive CD8 Cells89.25 ± 62.57142.08 ± 131.13
Terminally Diff Effector Memory CD8 Cells48.42 ± 55.6848.17 ± 60.46
CD4 T Cells61.67 ± 41.3292.58 ± 59.44
CD56 Bright NK-Cells1.83 ± 1.118.50 ± 4.76
CD56 Dim NK-Cell65.42 ± 47.76158.17 ± 137.82
CD56 Null NK-Cells25.50 ± 12.7230.08 ± 26.57
CD56 Dim Null NK-Cells91.08 ± 51.61187.92 ± 149.63
PrimaryBlood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · cells/mcL
Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination
cells/mcLCP-690,550Placebo
B Cells (CD19)173.86 ± 95.29344.17 ± 211.00
Total T Cells (CD3)1044.07 ± 529.371411.75 ± 474.97
CD8 T Cells (CD3+CD8)253.64 ± 190.57364.92 ± 202.70
CD4 T Cells (CD3 CD4)781.57 ± 350.401046.00 ± 328.08
NK Cells (CD16 CD56)162.21 ± 116.20179.67 ± 142.64
Immature B Cells5.57 ± 3.5911.17 ± 9.99
Naive Cells136.43 ± 80.37252.92 ± 206.67
Marginal B Cells15.50 ± 8.7257.58 ± 102.20
Memory B Cells16.36 ± 12.7322.50 ± 13.93
Central Memory CD4 Cells416.93 ± 167.72605.00 ± 222.14
Effector Memory CD4 Cells56.29 ± 51.2497.25 ± 103.24
Naive CD4 Cells290.36 ± 244.79333.83 ± 132.59
Terminally Diff Effector CD4 Cells18.00 ± 24.889.75 ± 16.44
Central Memory CD8 Cells73.71 ± 58.46109.42 ± 49.90
Effector Memory CD8 Cells17.93 ± 13.7470.58 ± 99.36
Naive CD8 Cells101.79 ± 126.51133.75 ± 97.93
Terminally Diff Effector Memory CD8 Cells60.07 ± 67.1051.08 ± 61.27
CD4 T Cells66.64 ± 40.5873.50 ± 39.02
CD56 Bright NK-Cells3.62 ± 2.606.33 ± 3.52
CD56 Dim NK-Cell99.00 ± 89.92141.17 ± 130.25
CD56 Null NK-Cells66.23 ± 72.5932.25 ± 19.30
CD56 Dim Null NK-Cells165.15 ± 115.88173.25 ± 141.06
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific Enzyme-Linked Immunosorbent Assay \[ELISA\] method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples).

Time frame:
Pre-dose on Day 1
Reported as:
Mean · nanogram per milliliter (ng/mL)
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1
nanogram per milliliter (ng/mL)CP-690,550Placebo
MMP338.31 ± 32.2424.52 ± 12.65
Osteocalcin19.54 ± 8.2318.54 ± 12.31
Osteopontin108.40 ± 42.5998.11 ± 37.04
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
1 Hour Post-dose on Day 1
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1
ng/mLCP-690,550Placebo
MMP337.30 ± 32.4022.42 ± 12.06
Osteocalcin18.90 ± 8.1218.01 ± 11.38
Osteopontin101.10 ± 40.2394.37 ± 39.02
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
4 Hours Post-dose on Day 1
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1
ng/mLCP-690,550Placebo
MMP336.98 ± 30.7222.09 ± 12.08
Osteocalcin18.17 ± 7.3019.01 ± 13.17
Osteopontin99.82 ± 36.7795.23 ± 38.37
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10
ng/mLCP-690,550Placebo
MMP332.10 ± 26.8921.05 ± 12.28
Osteocalcin21.35 ± 8.8718.60 ± 11.28
Osteopontin91.13 ± 29.1691.12 ± 34.13
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28
ng/mLCP-690,550Placebo
MMP325.18 ± 22.3319.26 ± 11.64
Osteocalcin22.05 ± 9.2816.51 ± 9.06
Osteopontin78.23 ± 17.2379.93 ± 18.63
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28
ng/mLCP-690,550Placebo
MMP321.59 ± 19.3018.86 ± 11.73
Osteocalcin21.45 ± 9.6517.37 ± 8.85
Osteopontin78.60 ± 19.2486.66 ± 29.65
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28
ng/mLCP-690,550Placebo
MMP319.71 ± 17.6516.67 ± 10.70
Osteocalcin21.09 ± 8.2615.45 ± 7.22
Osteopontin71.52 ± 24.9286.56 ± 33.00
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28
ng/mLCP-690,550Placebo
MMP317.94 ± 14.3816.68 ± 11.75
Osteocalcin20.93 ± 6.3716.67 ± 8.63
Osteopontin75.32 ± 21.3289.84 ± 33.02
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28
ng/mLCP-690,550Placebo
MMP324.48 ± 20.8226.20 ± 15.56
Osteocalcin20.96 ± 9.4517.49 ± 9.57
Osteopontin82.60 ± 22.2895.51 ± 28.50
PrimaryMatrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · ng/mL
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination
ng/mLCP-690,550Placebo
MMP328.98 ± 21.3628.72 ± 24.48
Osteocalcin21.79 ± 9.3816.60 ± 10.48
Osteopontin95.93 ± 29.7386.48 ± 29.69
PrimaryParathyroid Hormone (PTH) Level at Pre-dose on Day 1

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
Pre-dose on Day 1
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at Pre-dose on Day 1
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at Pre-dose on Day 138.40 ± 17.4433.32 ± 5.80
PrimaryParathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
1 Hour Post-dose on Day 1
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 133.89 ± 13.4431.48 ± 8.77
PrimaryParathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
4 Hours Post-dose on Day 1
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 132.97 ± 13.3133.35 ± 7.12
PrimaryParathyroid Hormone (PTH) Level at Pre-dose on Day 10

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at Pre-dose on Day 10
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at Pre-dose on Day 1034.93 ± 11.7631.48 ± 8.37
PrimaryParathyroid Hormone (PTH) Level at Pre-dose on Day 28

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at Pre-dose on Day 28
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at Pre-dose on Day 2838.46 ± 12.6433.39 ± 8.94
PrimaryParathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 2837.97 ± 14.0533.93 ± 7.51
PrimaryParathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 2838.70 ± 13.2536.65 ± 12.54
PrimaryParathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 2837.76 ± 15.9037.82 ± 18.84
PrimaryParathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 2835.91 ± 19.9436.08 ± 10.17
PrimaryParathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · pg/mL
Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination
pg/mLCP-690,550Placebo
Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination37.30 ± 14.8634.59 ± 10.40
PrimaryOsteoprotegerin (OPG) Level at Pre-dose on Day 1

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 1
Reported as:
Mean · picomole per liter (pmol/L)
Osteoprotegerin (OPG) Level at Pre-dose on Day 1
picomole per liter (pmol/L)CP-690,550Placebo
Osteoprotegerin (OPG) Level at Pre-dose on Day 15.99 ± 2.046.21 ± 1.91
PrimaryOsteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
1 Hour Post-dose on Day 1
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 16.13 ± 1.995.72 ± 2.16
PrimaryOsteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
4 Hours Post-dose on Day 1
Reported as:
Mean · picomole per liter (pmol/L)
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1
picomole per liter (pmol/L)CP-690,550Placebo
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 15.50 ± 1.535.35 ± 1.86
PrimaryOsteoprotegerin (OPG) Level at Pre-dose on Day 10

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at Pre-dose on Day 10
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at Pre-dose on Day 106.02 ± 1.885.82 ± 2.22
PrimaryOsteoprotegerin (OPG) Level at Pre-dose on Day 28

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at Pre-dose on Day 28
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at Pre-dose on Day 285.53 ± 1.795.64 ± 2.48
PrimaryOsteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 285.72 ± 1.865.56 ± 2.14
PrimaryOsteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 285.18 ± 1.555.69 ± 2.13
PrimaryOsteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 284.64 ± 1.285.64 ± 2.39
PrimaryOsteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · pmol/L
Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28
pmol/LCP-690,550Placebo
Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 287.22 ± 2.746.20 ± 2.07
PrimaryOsteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · pmol/L
Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination
pmol/LCP-690,550Placebo
Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination6.31 ± 1.705.65 ± 2.01
PrimaryPlasma 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

No measurements were reported for this outcome.

PrimaryPlasma 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

No measurements were reported for this outcome.

PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1

Serum samples were analyzed for SAA concentrations using meso scale discovery (MSD) single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific Electro ChemiLuminescent ImmunoAssay (ECLIA).

Time frame:
Pre-dose on Day 1
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1
ng/mLCP-690,550Placebo
SAA (n=14, 14)26383.03 ± 43196.3723427.00 ± 43431.26
CTX-1 (n=14, 12)0.43 ± 0.260.37 ± 0.27
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
1 Hour Post-dose on Day 1
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1
ng/mLCP-690,550Placebo
SAA25716.93 ± 42986.7023308.57 ± 41911.51
CTX-10.36 ± 0.250.32 ± 0.22
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
4 Hours Post-dose on Day 1
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1
ng/mLCP-690,550Placebo
SAA26460.26 ± 46059.6427297.36 ± 52346.36
CTX-10.25 ± 0.120.25 ± 0.19
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10
ng/mLCP-690,550Placebo
SAA5968.89 ± 5509.1831666.50 ± 92833.52
CTX-10.34 ± 0.160.35 ± 0.22
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28
ng/mLCP-690,550Placebo
SAA4094.94 ± 2527.7214818.88 ± 18346.19
CTX-10.36 ± 0.190.35 ± 0.19
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28
ng/mLCP-690,550Placebo
SAA3921.49 ± 2291.3318976.74 ± 29228.65
CTX-10.32 ± 0.160.35 ± 0.25
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28
ng/mLCP-690,550Placebo
SAA4042.21 ± 2974.0320123.97 ± 31463.56
CTX-10.29 ± 0.170.20 ± 0.12
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28
ng/mLCP-690,550Placebo
SAA (n=14, 12)4113.05 ± 2939.8615403.08 ± 24616.14
CTX-1 (n=12, 12)0.28 ± 0.170.31 ± 0.21
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28
ng/mLCP-690,550Placebo
SAA6643.14 ± 6504.5514627.28 ± 16685.62
CTX-10.28 ± 0.160.28 ± 0.13
PrimarySerum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · ng/mL
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination
ng/mLCP-690,550Placebo
SAA22174.19 ± 25387.7933853.61 ± 88542.43
CTX-10.27 ± 0.150.34 ± 0.16
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 1
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1
pg/mLCP-690,550Placebo
IL-1ra545.71 ± 279.48449.38 ± 163.85
IL-158.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
1 Hour Post-dose on Day 1
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1
pg/mLCP-690,550Placebo
IL-1ra565.43 ± 262.73479.93 ± 167.61
IL-158.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
4 Hours Post-dose on Day 1
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1
pg/mLCP-690,550Placebo
IL-1ra518.29 ± 297.33477.25 ± 142.17
IL-158.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10
pg/mLCP-690,550Placebo
IL-1ra487.00 ± 265.16465.00 ± 176.17
IL-158.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28
pg/mLCP-690,550Placebo
IL-1ra437.73 ± 171.93617.38 ± 624.81
IL-158.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
1 Hour Post-dose on Day 28
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1ra421.00 ± 196.57501.31 ± 337.85
IL-158.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
4 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1ra (n= 13, 13)388.15 ± 147.27552.85 ± 415.32
IL-15 (n=11, 12)8.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
8 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1ra (n=12, 12)399.08 ± 157.84414.67 ± 152.99
IL-15 (n=12, 10)8.00 ± 0.008.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28
pg/mLCP-690,550Placebo
IL-1ra500.38 ± 187.55462.57 ± 175.80
IL-158.26 ± 0.948.00 ± 0.00
PrimaryInterleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · pg/mL
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination
pg/mLCP-690,550Placebo
IL-1ra520.87 ± 282.88486.57 ± 317.27
IL-158.00 ± 0.008.00 ± 0.00
PrimaryUrine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as nanogram per millimoles of creatinine (ng/mmol Cr).

Time frame:
Pre-dose on Day 1
Reported as:
Mean · ng/mmol Cr
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1
ng/mmol CrCP-690,550Placebo
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1454.74 ± 216.74345.87 ± 259.83
PrimaryUrine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Time frame:
Pre-dose on Day 10
Reported as:
Mean · ng/mmol Cr
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10
ng/mmol CrCP-690,550Placebo
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10318.10 ± 208.07423.76 ± 389.15
PrimaryUrine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Time frame:
Pre-dose on Day 28
Reported as:
Mean · ng/mmol Cr
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28
ng/mmol CrCP-690,550Placebo
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28320.42 ± 192.31409.89 ± 338.67
PrimaryUrine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Time frame:
24 Hours Post-dose on Day 28
Reported as:
Mean · ng/mmol Cr
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28
ng/mmol CrCP-690,550Placebo
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28267.86 ± 159.63284.87 ± 202.92
PrimaryUrine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Time frame:
Pre-dose on Day 35 or Early Termination
Reported as:
Mean · ng/mmol Cr
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination
ng/mmol CrCP-690,550Placebo
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination278.55 ± 198.90340.83 ± 379.42
SecondaryPercentage of Participants Achieving American College of Rheumatology 20% Response

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Time frame:
Day 28, 35 or Early Termination
Reported as:
Number · percentage of participants
Percentage of Participants Achieving American College of Rheumatology 20% Response
percentage of participantsCP-690,550Placebo
Day 2860.00.0
Day 35 or Early Termination33.30.0
SecondaryPercentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response

ACR50 response: \>=50% improvement in TJC; \>= 50% improvement in SJC; and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

Time frame:
Day 28, 35 or Early Termination
Reported as:
Number · percentage of participants
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
percentage of participantsCP-690,550Placebo
Day 2840.00.0
Day 35 or Early Termination13.30.0
SecondaryPercentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response

ACR70 response: \>=70% improvement in TJC; \>= 70% improvement in SJC; and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

Time frame:
Day 28, 35 or Early Termination
Reported as:
Number · percentage of participants
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
percentage of participantsCP-690,550Placebo
Day 286.70.0
Day 35 or Early Termination6.70.0
SecondaryDisease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])

DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP) (milligram per liter \[mg/L\]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (\<=) 3.2 implied low disease activity, greater than (\>) 3.2 to 5.1 implied moderate to high disease activity and less than (\<) 2.6 implied remission.

Time frame:
Day -7, 1 (Baseline), 28, 35 or Early Termination
Reported as:
Mean · units on a scale
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
units on a scaleCP-690,550Placebo
Day -75.58 ± 0.875.06 ± 1.16
Day 1 (Baseline)5.57 ± 0.785.22 ± 0.96
Day 284.06 ± 0.974.91 ± 0.92
Day 35 or Early Termination4.91 ± 1.104.79 ± 1.10
SecondaryChange From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 28 and 35

DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

Time frame:
Day 1 (Baseline), 28, 35 or Early Termination
Reported as:
Mean · units on a scale
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
units on a scaleCP-690,550Placebo
Day 28-1.51 ± 0.97-0.31 ± 0.49
Day 35 or Early Termination-0.66 ± 0.96-0.43 ± 0.40
SecondaryPercentage of Participants With Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) <=3.2 and <2.6

DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

Time frame:
Day -7, 1 (Baseline), 28, 35 or Early Termination
Reported as:
Number · percentage of participants
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
percentage of participantsCP-690,550Placebo
Day -7: DAS28-3 (CRP) <=3.20.07.1
Day -7: DAS28-3 (CRP) <2.60.00.0
Day 1 (Baseline): DAS28-3 (CRP) <=3.20.00.0
Day 1 (Baseline): DAS28-3 (CRP) <2.60.00.0
Day 28: DAS28-3 (CRP) <=3.220.014.3
Day 28: DAS28-3 (CRP) <2.60.00.0
Day 35 or Early Termination: DAS28-3 (CRP) <=3.26.77.1
Day 35 or Early Termination: DAS28-3 (CRP) <2.60.00.0
SecondaryDisease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])

DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity, \> 3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

Time frame:
Day -7, 1 (Baseline), 28, 35 or Early Termination
Reported as:
Mean · units on a scale
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
units on a scaleCP-690,550Placebo
Day -76.60 ± 0.986.17 ± 1.12
Day 1 (Baseline)6.55 ± 0.986.32 ± 1.01
Day 284.90 ± 1.116.03 ± 0.98
Day 35 or Early Termination5.83 ± 1.236.00 ± 1.01
SecondaryChange From Baseline in Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Day 28 and 35

DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR \[mm/hour\] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity, \> 3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

Time frame:
Day 1 (Baseline), 28, 35 or Early Termination
Reported as:
Mean · units on a scale
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
units on a scaleCP-690,550Placebo
Day 28-1.58 ± 1.02-0.30 ± 0.60
Day 35 or Early Termination-0.73 ± 0.91-0.32 ± 0.50
SecondaryPercentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) <=3.2 and <2.6

DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR \[mm/hour\] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity, \> 3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

Time frame:
Day -7, 1 (Baseline), 28, 35 or Early Termination
Reported as:
Number · percentage of participants
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
percentage of participantsCP-690,550Placebo
Day -7: DAS28-4 (ESR) =<3.20.00.0
Day -7: DAS28-4 (ESR) <2.60.00.0
Day 1 (Baseline): DAS28-4 (ESR) =<3.20.00.0
Day 1 (Baseline): DAS28-4 (ESR) <2.60.00.0
Day 28: DAS28-4 (ESR) =<3.27.10.0
Day 28: DAS28-4 (ESR) <2.60.00.0
Day 35 or Early Termination: DAS28-4 (ESR) =<3.20.00.0
Day 35 or Early Termination: DAS28-4 (ESR) <2.60.00.0

Adverse events

Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CP-690,550—0/15 (0%)7/15 (46.7%)
Placebo—0/14 (0%)10/14 (71.4%)
Most frequent other events
Showing 10 of 30
Most frequent other events
EventCP-690,550Placebo
NauseaGastrointestinal disorders2/151/14
FatigueGeneral disorders2/150/14
HypoaesthesiaNervous system disorders2/150/14
Oedema peripheralGeneral disorders1/151/14
PyrexiaGeneral disorders0/151/14
Herpes simplexInfections and infestations0/151/14
Upper respiratory tract infectionInfections and infestations0/151/14
Urinary tract infectionInfections and infestations0/151/14
Viral infectionInfections and infestations0/151/14
Procedural painInjury, poisoning and procedural complications1/151/14

Baseline characteristics

Age Continuous
Age Continuous(years)CP-690,550PlaceboTotal
Mean53.5 ± 9.253.1 ± 14.353.3 ± 11.7
Sex: Female, Male
Sex: Female, Male(Participants)CP-690,550PlaceboTotal
Female141226
Male123
08

Study locations

15 sites
  • Pfizer Investigational Site
    Birmingham, Alabama 35205, United States
  • Pfizer Investigational Site
    Birmingham, Alabama 35209, United States
  • Pfizer Investigational Site
    Birmingham, Alabama 35216, United States
  • Pfizer Investigational Site
    La Jolla, California 92037, United States
  • Pfizer Investigational Site
    Frederick, Maryland 21702, United States
  • Pfizer Investigational Site
    Battle Creek, Michigan 49015, United States
  • Pfizer Investigational Site
    Mayfield Village, Ohio 44143, United States
  • Pfizer Investigational Site
    Mentor, Ohio 44060, United States
  • Pfizer Investigational Site
    Willoughby, Ohio 44094, United States
  • Pfizer Investigational Site
    Dallas, Texas 75231, United States
  • Pfizer Investigational Site
    Dallas, Texas 75251, United States
  • Pfizer Investigational Site
    Mesquite, Texas 75150, United States
  • Pfizer Investigational Site
    Sunnyvale, Texas 75182, United States
  • Pfizer Investigational Site
    Seattle, Washington 98104, United States
  • Pfizer Investigational Site
    Seattle, Washington 98122, United States
09

References and documents

Publications

  • Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6. PubMed 34870800 ↗
  • Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395. PubMed 33127856 ↗
  • Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2021 Sep;66(9):3214-3215. doi: 10.1007/s10620-020-06638-z. PubMed 32816215 ↗
  • Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31. PubMed 28143815 ↗
  • Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, Shurmur R, Singhal AK, Wei N, Rosengren S, Kaplan I, Krishnaswami S, Luo Z, Bradley J, Firestein GS. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6):1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14. PubMed 25398374 ↗
  • Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779. PubMed 25047021 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 9, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00976599
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Sep 14, 2009
Start date
Nov 2009
Primary completion
Jul 2011
Completion
Jul 2011
Results posted
Jan 9, 2013
Last update
Jan 9, 2013

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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