Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01736696
First received: November 26, 2012
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

This study was conducted in subjects with psoriasis to evaluate drug activity in this patient population by analysis of changes in psoriatic lesion biopsy characteristics. This subject population was selected to evaluate potentially relevant biological activity of CP-690,550 as well as assessing safety and pharmacokinetics.


Condition Intervention Phase
Psoriasis
Immunomodulation
Drug: tofacitinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase 1, Investigator-Blind, Subject-Blind, Sponsor-Open, Placebo-Controlled, Two-Week, Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of CP-690,550

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 1 [ Time Frame: 23 hours (hrs) prior to morning dose on Day 1 (Baseline for HPD 1), 1 hour (hr) post morning dose on Day 1 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. For each scheduled hour post morning dose (HPD), except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 1 [ Time Frame: 22 hrs prior to morning dose on Day 1 (Baseline for HPD 2), 2 hrs post morning dose on Day 1 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. For each scheduled hour post morning dose (HPD), except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 1 [ Time Frame: 20 hrs prior to morning dose on Day 1 (Baseline for HPD 4), 4 hrs post morning dose on Day 1 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 1 [ Time Frame: 16 hrs prior to morning dose on Day 1 (Baseline for HPD 8), 8 hrs post morning dose on Day 1 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 1 [ Time Frame: 12 hrs prior to morning dose on Day 1 (Baseline for HPD 12), 12 hrs post morning dose on Day 1 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 16 Hour Post Morning Dose (HPD 16) on Day 1 [ Time Frame: 8 hrs prior to morning dose on Day 1 (Baseline for HPD 16), 16 hrs post morning dose on Day 1 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.Change from baseline in QT interval at HPD 16 was planned to be analyzed for participants who received CP-690,550 60 mg and matching placebo.

  • Change From Baseline in QT Interval at 0 Hour Post Morning Dose (HPD 0) on Day 14 [ Time Frame: Hour 0 (pre-dose) on Day 1 (Baseline for HPD 0), 0 hr on Day 14 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. The mean of the triplicates at HPD=0 on Day 1 will be defined as the baseline for HPD=0.

  • Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 14 [ Time Frame: 23 hrs prior to morning dose on Day 1 (Baseline for HPD 1), 1 hr post morning dose on Day 14 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 14 [ Time Frame: 22 hrs prior to morning dose on Day 1 (Baseline for HPD 2), 2 hrs post morning dose on Day 14 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 14 [ Time Frame: 20 hrs prior to morning dose on Day 1 (Baseline for HPD 4), 4 hrs post morning dose on Day 14 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 14 [ Time Frame: 16 hrs prior to morning dose on Day 1 (Baseline for HPD 8), 8 hrs post morning dose on Day 14 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 14 [ Time Frame: 12 hrs prior to morning dose on Day 1 (Baseline for HPD 12), 12 hrs post morning dose on Day 14 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

  • Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval [ Time Frame: 1, 2, 4, 8, 12 hrs post dose, additional 16 hrs post dose for 60 mg once daily group on Day 1; 1, 2 hrs post dose on Day 4, 7, 10;1,2,4,8,12 hrs post dose on Day 14; Day 21 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.

  • Number of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 500 Millisecond [ Time Frame: 1, 2, 4, 8, 12 hrs post dose, additional 16 hrs post dose for 60 mg once daily group on Day 1; 1, 2 hrs post dose on Day 4, 7, 10;1,2,4,8,12 hrs post dose on Day 14; Day 21 ] [ Designated as safety issue: Yes ]
    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum QTc >=500 msec were reported.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 1 [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1 ] [ Designated as safety issue: No ]
    AUCtau = area under the curve from time zero to end of dosing interval.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 14 [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14 ] [ Designated as safety issue: No ]
    AUCtau = area under the curve from time zero to end of dosing interval.

  • Maximum Observed Plasma Concentration (Cmax) at Day 1 [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1 ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) at Day 14 [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 1 [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 14 [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14 ] [ Designated as safety issue: No ]
  • Accumulation Ratio (R0) [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1 and Day 14 ] [ Designated as safety issue: No ]
    Accumulation ratio was calculated as, R0 = area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 1 [ Time Frame: Baseline, 1 hr post-dose on Day 1 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 2 [ Time Frame: Baseline, hr 0 on Day 2 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 4 [ Time Frame: Baseline, hr 0 on Day 4 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 7 [ Time Frame: Baseline, hr 0 on Day 7 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 10 [ Time Frame: Baseline, hr 0 on Day 10 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 14 [ Time Frame: Baseline; hr 0, 8 hr post-dose on Day 14 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 18 [ Time Frame: Baseline, Hour 0 on Day 18 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 21 [ Time Frame: Baseline, hr 0 on Day 21 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 28 [ Time Frame: Baseline, hr 0 on Day 28 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 42 [ Time Frame: Baseline, hr 0 on Day 42 ] [ Designated as safety issue: Yes ]
    Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

  • Change From Baseline in Immune Cell Function at Day 14 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 14 ] [ Designated as safety issue: Yes ]
    The degree of immunosuppression induced by the study drug administration was evaluated using a bioluminescent assay in which the concentration of Adenosine-5-Triphosphate (ATP) released by CD4 cells was measured. ATP concentrations released from stimulated and unstimulated cells were evaluated. ATP Concentration less than or equal to (<=) 225: low immune cell response, 226 to 524: Moderate immune cell response, >= 525: strong immune cell response. Baseline was defined as the mean of the samples collected during the pre-dose biopsy.

  • Change From Baseline in Reticulocyte Count at Day 2 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 2 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 4 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 4 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 7 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 7 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 10 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 10 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 15 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 15 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 21 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 21 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 28 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 28 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Change From Baseline in Reticulocyte Count at Day 42 [ Time Frame: Baseline (Within 7 days prior to Day 1), Day 42 ] [ Designated as safety issue: Yes ]
    Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

  • Time to Reach Maximum Change From Baseline and Time to Return to Baseline Value for Fluorescence-Activated Cell Sorting (FACS), Reticulocyte Counts and Immune Cell Function [ Time Frame: Day 0 (pre-dose), 1, 2, 4, 7, 10, 14, 15, 18, 21, 28, 42 ] [ Designated as safety issue: Yes ]
  • Half Maximal Effective Area Under the Concentration-Time Curve 50 (EAUC 50) [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    EAUC 50 was calculated from a regression analyses using area under the concentration-time curve (AUC) as the independent variable. A sigmoid maximum effect (Emax) model was used to explain the relationship between AUC and modified Psoriasis Severity Index (mPASI) score, where Emax was the maximum effect (100 percent reduction in the total mPASI score from baseline), and EAUC 50 was the AUC where 50 percent of the maximum effect was measured.


Secondary Outcome Measures:
  • Number of Participants With Modified Psoriasis Severity Index (mPASI) at Day 14 [ Time Frame: Baseline (Within 7 days prior to Day 1) up to Day 14 ] [ Designated as safety issue: No ]
    Modified Psoriasis Area and Severity Index (mPASI) assessed lesion severity but not the body surface area affected. Severity was estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final mPASI = sum of the each component scores. Total score range 0-12 , higher score indicated more severity.

  • Number of Participants With Physician's Global Assessment (PGA) of Psoriasis [ Time Frame: Baseline (Within 7 days prior to Day 1) up to Day 14 ] [ Designated as safety issue: No ]
    Physician global assessment (PGA) of Psoriasis is a 7-point scale used to assess severity of psoriatic plaques, scaling and/or erythema. Severity scale ranged from 1 to 7: 1=severe, 2=moderate to severe, 3=moderate, 4=mild to moderate, 5=mild, 6=almost clear, 7=clear (no sign of psoriasis).

  • Gene Expression in Psoriatic Plaque Biopsies [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Gene expression by quantitative polymerized chain reaction (PCR) using standard curve (SC) method generated by linear regression using log threshold cycle versus log(cell number). Keratin (K)-16, inducible nitric oxide synthase (iNOS), Interleukin 8 (IL-8), CD25, Granzyme B, IL-2, IL-7, IL-15, Interferon-gamma (INF-gamma), C-X-C motif chemokine(CXCL10), perforin 1, B-cell Lymphoma 2 (BCL-2), BCL2 associated X Protein (BAX), Tumor Necrosis Factor Fas Ligand (TNF-FasL), and proliferating cell nuclear antigen (PCNA) presented as control gene normalized expression (relative expression) within SC.

  • Immunohistochemistry From Psoriatic Plaque Biopsies [ Time Frame: Baseline (within 7 days prior to Day 1), Day 14 ] [ Designated as safety issue: No ]
    Immunohistochemical staining of skin biopsies was performed with monoclonal antibodies directed against cluster of differentiation 3 (CD3) and cluster of differentiation 8 (CD8) T-lymphocytes, cluster of differentiation 16/56 (CD16/56) natural killer cells, and cluster of differentiation 83 (CD83) mature dendritic cells. Baseline was defined as mean of samples obtained at the screening visit within 7 days prior to Day 1, at the baseline biopsy, and Day 0. Immunohistochemistry results were planned to be analyzed for participants who received CP-690,550 5, 20, 30 mg and matching placebo.

  • Number of Participants With Keratin 16 (K16) Expression [ Time Frame: Baseline (within 7 days prior to Day 1) up to Day 14 ] [ Designated as safety issue: No ]
    Immunohistochemical staining of skin biopsies was performed with monoclonal antibodies directed against K16. Number of participants with K16 expression were assessed qualitatively using suprabasal keratinocytes.

  • Number of Participants With Intracellular Adhesion Molecule (ICAM-1) by Epidermal Keratinocytes Expression [ Time Frame: Baseline (within 7 days prior to Day 1) up to Day 14 ] [ Designated as safety issue: No ]
    Immunohistochemical staining of skin biopsies was performed with monoclonal antibodies directed against ICAM-1. Number of participants with ICAM-1 expression was to be assessed qualitatively using epidermal keratinocytes.

  • Gene Expression in Peripheral Blood [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Punch biopsy and serum blood were assayed for messenger Ribonucleic acid (mRNA) gene expression by quantitative PCR using standard curve(SC) method generated by linear regression using log threshold cycle versus log(cell number). granzyme B, IFN-gamma, TNF-alpha (FasL and superfamily member 5 [SF5]), BCL2, BAX, iNOS, and CD 25 presented as control gene normalized expression(relative expression) within SC. The Relative mRNA Gene Expression Level is relative to baseline and normalized to the housekeeping gene 18 Svedberg unit ribosomal RNA (18S rRNA).


Enrollment: 59
Study Start Date: November 2002
Study Completion Date: April 2004
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5 mg BID
5 mg BID for 13 days and once on Day 14
Drug: tofacitinib
5 mg BID For 13 days and once on Day 14
Experimental: 10 mg BID
10 mg BID for13 days and once on Day 14*
Drug: tofacitinib
10 mg BID for 13 days and once on Day 14*
Experimental: 20 mg BID
20 mg BID for 13 days and once on Day 14
Drug: tofacitinib
20 mg BID for 13 days and once on Day 14
Experimental: 30 mg BID
30 mg BID for 13 days and once on Day 14
Drug: tofacitinib
30 mg BID for 13 days and once on Day 14
Experimental: 60 mg QD
60 mg QD for 14 days
Drug: tofacitinib
60 mg tablet once a day (QD) for 14 days
Experimental: 50 mg BID
50 mg BID x 13 days and once on day 14
Drug: tofacitinib
50 mg tablets two times a day (BID) for 13 days and once on day 14

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and/or female subjects between the ages of 18 and 65 years, inclusive, with active psoriasis lesion(s).
  • Subjects should be healthy with the exception of psoriasis, where healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination. Blood pressure must be < 140/89. Body Mass Index (BMI) between 18-36 kg/m2, inclusive; and a total body weight >50 kg (110 lbs)
  • The following laboratory variables must be no more than 10% below the lower limit of the normal reference range: RBC, hemoglobin, hematocrit, WBC, absolute neutrophil count. The absolute lymphocyte count must be greater than or equal to the lower limit of the reference range. Values for AST, ALT, bilirubin and alkaline phosphatase must be no more than 10% above the upper limit of the normal reference range. Values for total cholesterol and LDL must be no more than 20% above the upper limit of the normal reference range except for subjects being treated for hyperlipidemia. Normal glomerular filtration rate (> 80 mL/min).

Exclusion Criteria:

  • Subjects with evidence or history of clinically significant hematological, renal, urological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic disorder.
  • Subjects with controlled essential hypertension and/or hyperlipidemia may be eligible for the study provided that any medications that are administered.
  • Screening 12-lead ECG demonstrating at least one of the following: heart rate > 100 bpm, QRS >120 msec, QTc > 430 msec (males), QTc > 450 msec (females) or PR > 220 msec.
  • Abnormal chest radiographs including, but not limited to, evidence of past or present tuberculosis infection. History of tuberculosis without treatment and/or positive tuberculin reaction without known vaccination with BCG.
  • Subjects with a history of tumors with the exception of adequately treated basal cell carcinoma of the skin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736696

Locations
United States, Arkansas
Pfizer Investigational Site
Little Rock, Arkansas, United States, 72202
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01736696     History of Changes
Other Study ID Numbers: A3921003
Study First Received: November 26, 2012
Results First Received: December 6, 2012
Last Updated: January 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Psoriasis
PASI
plaques
skin biopsy
immunomodulation

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014