Back to resultsCo-Administration Of Methotrexate And CP-690,550
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CP-690,550 (tofacitinib)
Methotrexate (MTX)
Sponsored by
About this trial
This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring Pharmacokinetics, oral JAK inhibitor, methotrexate (MTX), rheumatoid arthritis (RA)
Eligibility Criteria
Inclusion Criteria:
- Adults diagnosed with moderate to severe RA (Rheumatoid Arthritis)
- Diagnosis of RA based on the American College of Rheumatology 1987 revised criteria.
- Treatment with an oral stable weekly dose of Methotrexate (MTX) (15-25 mg/week, administered as a single dose [SD]) for a minimum of 4 doses (4 weeks)
Exclusion Criteria:
- Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.2 x 109/L; Platelet count <100 x 109/L
- Evidence or history of clinically significant infections within the past 6 months (eg, those requiring hospitalization, requiring parenteral antimicrobial therapy, or those with recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the trial.
- Total bilirubin, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) more than 1.2 times the upper limit of normal at the Screening visit, or a history of clinically significant elevated liver function tests (LFTs) while on current MTX dose or chronic liver disease, recent or active hepatitis.
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CP-690,550 (tofacitinib) 30 mg q12h
Arm Description
Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h
Outcomes
Primary Outcome Measures
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).
Maximum Observed Plasma Concentration (Cmax) for CP-690,550
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Methotrexate (MTX)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)
Secondary Outcome Measures
Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550
Plasma Decay Half-Life (t1/2) for CP-690,550
Plasma decay half-life is the time measured for the plasma concentration of CP-690,550 to decrease by one half.
Apparent Oral Clearance (CL/F) for CP-690,550
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Methotrexate (MTX)
Plasma Decay Half-Life (t1/2) for Methotrexate (MTX)
Plasma decay half-life is the time measured for the plasma concentration of MTX to decrease by one half.
Apparent Oral Clearance (CL/F) for Methotrexate (MTX)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 12 Hours (Ae[0-12]) for CP-690,550
Renal Clearance (CL R) for CP-690,550
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 24 Hours (Ae[0-24]) for Methotrexate (MTX)
Renal Clearance (CL R) for Methotrexate (MTX)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01745055
Brief Title
Co-Administration Of Methotrexate And CP-690,550
Official Title
A Phase 1, Open Label Study Of The Pharmacokinetics Of Multiple Doses Of Oral CP-690,550 And Single Doses Of Oral Methotrexate In Rheumatoid Arthritis Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
June 2006 (Actual)
Study Completion Date
June 2006 (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 designed to estimate the effects of methotrexate (MTX) on the pharmacokinetics (PK) of CP-690,550 when administered to subjects with rheumatoid arthritis (RA), to estimate the effects of CP-690,550 on the PK of MTX and to evaluate the short-term safety and tolerability of co-administration of CP-690,550 and MTX.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Pharmacokinetics, oral JAK inhibitor, methotrexate (MTX), rheumatoid arthritis (RA)
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CP-690,550 (tofacitinib) 30 mg q12h
Arm Type
Experimental
Arm Description
Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h
Intervention Type
Drug
Intervention Name(s)
CP-690,550 (tofacitinib)
Intervention Description
CP-690,550 30 mg q12h for 5 days
Intervention Type
Drug
Intervention Name(s)
Methotrexate (MTX)
Intervention Description
individual dose of methotrexate (stably dosed)
Primary Outcome Measure Information:
Title
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
Description
AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Title
Maximum Observed Plasma Concentration (Cmax) for CP-690,550
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Methotrexate (MTX)
Description
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours post-dose on Day 1 and Day 7
Title
Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 24 and 48 hours post-dose on Day 1 and Day 7
Secondary Outcome Measure Information:
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Title
Plasma Decay Half-Life (t1/2) for CP-690,550
Description
Plasma decay half-life is the time measured for the plasma concentration of CP-690,550 to decrease by one half.
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Title
Apparent Oral Clearance (CL/F) for CP-690,550
Description
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Methotrexate (MTX)
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 ,12, 24 and 48 hours post-dose on Day 1 and Day 7
Title
Plasma Decay Half-Life (t1/2) for Methotrexate (MTX)
Description
Plasma decay half-life is the time measured for the plasma concentration of MTX to decrease by one half.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 , 12, 24 and 48 hours post-dose on Day 1 and Day 7
Title
Apparent Oral Clearance (CL/F) for Methotrexate (MTX)
Description
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 , 12, 24 and 48 hours post-dose on Day 1 and Day 7
Title
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 12 Hours (Ae[0-12]) for CP-690,550
Time Frame
0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7
Title
Renal Clearance (CL R) for CP-690,550
Time Frame
0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7
Title
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 24 Hours (Ae[0-24]) for Methotrexate (MTX)
Time Frame
0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7
Title
Renal Clearance (CL R) for Methotrexate (MTX)
Time Frame
0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults diagnosed with moderate to severe RA (Rheumatoid Arthritis)
Diagnosis of RA based on the American College of Rheumatology 1987 revised criteria.
Treatment with an oral stable weekly dose of Methotrexate (MTX) (15-25 mg/week, administered as a single dose [SD]) for a minimum of 4 doses (4 weeks)
Exclusion Criteria:
Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.2 x 109/L; Platelet count <100 x 109/L
Evidence or history of clinically significant infections within the past 6 months (eg, those requiring hospitalization, requiring parenteral antimicrobial therapy, or those with recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the trial.
Total bilirubin, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) more than 1.2 times the upper limit of normal at the Screening visit, or a history of clinically significant elevated liver function tests (LFTs) while on current MTX dose or chronic liver disease, recent or active hepatitis.
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
Daytona Beach
State/Province
Florida
ZIP/Postal Code
32114
Country
United States
Facility Name
Pfizer Investigational Site
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33301
Country
United States
Facility Name
Pfizer Investigational Site
City
Miramar
State/Province
Florida
ZIP/Postal Code
33025
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75247
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921013&StudyName=Co-Adminstration%20Of%20Methotrexate%20And%20CP-690%2C550
Description
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Co-Administration Of Methotrexate And CP-690,550
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