Back to resultsMultiple Dose Escalation Study In Medically Stable Subjects With Psoriasis
Primary Purpose
Psoriasis, Immunomodulation
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tofacitinib
tofacitinib
tofacitinib
tofacitinib
tofacitinib
tofacitinib
Sponsored by
About this trial
This is an interventional treatment trial for Psoriasis focused on measuring Psoriasis, PASI, plaques, skin biopsy, immunomodulation
Eligibility 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.
Sites / Locations
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
5 mg BID
10 mg BID
20 mg BID
30 mg BID
60 mg QD
50 mg BID
Arm Description
5 mg BID for 13 days and once on Day 14
10 mg BID for13 days and once on Day 14*
20 mg BID for 13 days and once on Day 14
30 mg BID for 13 days and once on Day 14
60 mg QD for 14 days
50 mg BID x 13 days and once on day 14
Outcomes
Primary Outcome Measures
Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 1
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
AUCtau = area under the curve from time zero to end of dosing interval.
Maximum Observed Plasma Concentration (Cmax) at Day 1
Maximum Observed Plasma Concentration (Cmax) at Day 14
Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) at Day 14
Accumulation Ratio (R0)
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
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
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
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
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
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
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
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
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
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
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
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
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 4
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 7
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 10
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 15
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 21
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 28
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Change From Baseline in Reticulocyte Count at Day 42
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
Half Maximal Effective Area Under the Concentration-Time Curve 50 (EAUC 50)
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
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
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
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
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
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
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
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01736696
Brief Title
Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
November 2002 (undefined)
Primary Completion Date
April 2004 (Actual)
Study Completion Date
April 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis, Immunomodulation
Keywords
Psoriasis, PASI, plaques, skin biopsy, immunomodulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
5 mg BID
Arm Type
Experimental
Arm Description
5 mg BID for 13 days and once on Day 14
Arm Title
10 mg BID
Arm Type
Experimental
Arm Description
10 mg BID for13 days and once on Day 14*
Arm Title
20 mg BID
Arm Type
Experimental
Arm Description
20 mg BID for 13 days and once on Day 14
Arm Title
30 mg BID
Arm Type
Experimental
Arm Description
30 mg BID for 13 days and once on Day 14
Arm Title
60 mg QD
Arm Type
Experimental
Arm Description
60 mg QD for 14 days
Arm Title
50 mg BID
Arm Type
Experimental
Arm Description
50 mg BID x 13 days and once on day 14
Intervention Type
Drug
Intervention Name(s)
tofacitinib
Intervention Description
5 mg BID For 13 days and once on Day 14
Intervention Type
Drug
Intervention Name(s)
tofacitinib
Intervention Description
10 mg BID for 13 days and once on Day 14*
Intervention Type
Drug
Intervention Name(s)
tofacitinib
Intervention Description
20 mg BID for 13 days and once on Day 14
Intervention Type
Drug
Intervention Name(s)
tofacitinib
Intervention Description
30 mg BID for 13 days and once on Day 14
Intervention Type
Drug
Intervention Name(s)
tofacitinib
Intervention Description
60 mg tablet once a day (QD) for 14 days
Intervention Type
Drug
Intervention Name(s)
tofacitinib
Intervention Description
50 mg tablets two times a day (BID) for 13 days and once on day 14
Primary Outcome Measure Information:
Title
Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 1
Description
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.
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
Title
Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 1
Description
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.
Time Frame
22 hrs prior to morning dose on Day 1 (Baseline for HPD 2), 2 hrs post morning dose on Day 1
Title
Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 1
Description
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.
Time Frame
20 hrs prior to morning dose on Day 1 (Baseline for HPD 4), 4 hrs post morning dose on Day 1
Title
Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 1
Description
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.
Time Frame
16 hrs prior to morning dose on Day 1 (Baseline for HPD 8), 8 hrs post morning dose on Day 1
Title
Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 1
Description
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.
Time Frame
12 hrs prior to morning dose on Day 1 (Baseline for HPD 12), 12 hrs post morning dose on Day 1
Title
Change From Baseline in QT Interval at 16 Hour Post Morning Dose (HPD 16) on Day 1
Description
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.
Time Frame
8 hrs prior to morning dose on Day 1 (Baseline for HPD 16), 16 hrs post morning dose on Day 1
Title
Change From Baseline in QT Interval at 0 Hour Post Morning Dose (HPD 0) on Day 14
Description
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.
Time Frame
Hour 0 (pre-dose) on Day 1 (Baseline for HPD 0), 0 hr on Day 14
Title
Change From Baseline in QT Interval at 1 Hour Post Morning Dose (HPD 1) on Day 14
Description
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.
Time Frame
23 hrs prior to morning dose on Day 1 (Baseline for HPD 1), 1 hr post morning dose on Day 14
Title
Change From Baseline in QT Interval at 2 Hour Post Morning Dose (HPD 2) on Day 14
Description
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.
Time Frame
22 hrs prior to morning dose on Day 1 (Baseline for HPD 2), 2 hrs post morning dose on Day 14
Title
Change From Baseline in QT Interval at 4 Hour Post Morning Dose (HPD 4) on Day 14
Description
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.
Time Frame
20 hrs prior to morning dose on Day 1 (Baseline for HPD 4), 4 hrs post morning dose on Day 14
Title
Change From Baseline in QT Interval at 8 Hour Post Morning Dose (HPD 8) on Day 14
Description
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.
Time Frame
16 hrs prior to morning dose on Day 1 (Baseline for HPD 8), 8 hrs post morning dose on Day 14
Title
Change From Baseline in QT Interval at 12 Hour Post Morning Dose (HPD 12) on Day 14
Description
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.
Time Frame
12 hrs prior to morning dose on Day 1 (Baseline for HPD 12), 12 hrs post morning dose on Day 14
Title
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval
Description
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.
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
Title
Number of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 500 Millisecond
Description
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.
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
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 1
Description
AUCtau = area under the curve from time zero to end of dosing interval.
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Day 14
Description
AUCtau = area under the curve from time zero to end of dosing interval.
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 14
Title
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
Title
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
Title
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
Title
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
Title
Accumulation Ratio (R0)
Description
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.
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12 hrs post dose on Day 1 and Day 14
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 1
Description
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.
Time Frame
Baseline, 1 hr post-dose on Day 1
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 2
Description
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.
Time Frame
Baseline, hr 0 on Day 2
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 4
Description
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.
Time Frame
Baseline, hr 0 on Day 4
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 7
Description
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.
Time Frame
Baseline, hr 0 on Day 7
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 10
Description
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.
Time Frame
Baseline, hr 0 on Day 10
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 14
Description
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.
Time Frame
Baseline; hr 0, 8 hr post-dose on Day 14
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 18
Description
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.
Time Frame
Baseline, Hour 0 on Day 18
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 21
Description
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.
Time Frame
Baseline, hr 0 on Day 21
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 28
Description
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.
Time Frame
Baseline, hr 0 on Day 28
Title
Percent Change From Baseline in Fluorescence-Activated Cell Sorting (FACS) Analysis at Day 42
Description
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.
Time Frame
Baseline, hr 0 on Day 42
Title
Change From Baseline in Immune Cell Function at Day 14
Description
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.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 14
Title
Change From Baseline in Reticulocyte Count at Day 2
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 2
Title
Change From Baseline in Reticulocyte Count at Day 4
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 4
Title
Change From Baseline in Reticulocyte Count at Day 7
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 7
Title
Change From Baseline in Reticulocyte Count at Day 10
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 10
Title
Change From Baseline in Reticulocyte Count at Day 15
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 15
Title
Change From Baseline in Reticulocyte Count at Day 21
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 21
Title
Change From Baseline in Reticulocyte Count at Day 28
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 28
Title
Change From Baseline in Reticulocyte Count at Day 42
Description
Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.
Time Frame
Baseline (Within 7 days prior to Day 1), Day 42
Title
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
Title
Half Maximal Effective Area Under the Concentration-Time Curve 50 (EAUC 50)
Description
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.
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Number of Participants With Modified Psoriasis Severity Index (mPASI) at Day 14
Description
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.
Time Frame
Baseline (Within 7 days prior to Day 1) up to Day 14
Title
Number of Participants With Physician's Global Assessment (PGA) of Psoriasis
Description
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).
Time Frame
Baseline (Within 7 days prior to Day 1) up to Day 14
Title
Gene Expression in Psoriatic Plaque Biopsies
Description
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.
Time Frame
Day 14
Title
Immunohistochemistry From Psoriatic Plaque Biopsies
Description
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.
Time Frame
Baseline (within 7 days prior to Day 1), Day 14
Title
Number of Participants With Keratin 16 (K16) Expression
Description
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.
Time Frame
Baseline (within 7 days prior to Day 1) up to Day 14
Title
Number of Participants With Intracellular Adhesion Molecule (ICAM-1) by Epidermal Keratinocytes Expression
Description
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.
Time Frame
Baseline (within 7 days prior to Day 1) up to Day 14
Title
Gene Expression in Peripheral Blood
Description
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).
Time Frame
Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921003&StudyName=Multiple%20Dose%20Escalation%20Study%20In%20Medically%20Stable%20Subjects%20With%20Psoriasis%20
Description
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Learn more about this trial
Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis
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