Co-Administration Of Methotrexate And CP-690,550

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01745055
First received: December 4, 2012
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: CP-690,550 (tofacitinib)
Drug: Methotrexate (MTX)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7 ] [ Designated as safety issue: No ]
  • Renal Clearance (CL R) for CP-690,550 [ Time Frame: 0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Renal Clearance (CL R) for Methotrexate (MTX) [ Time Frame: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7 ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: April 2005
Study Completion Date: June 2006
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CP-690,550 (tofacitinib) 30 mg q12h
Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h
Drug: CP-690,550 (tofacitinib)
CP-690,550 30 mg q12h for 5 days
Drug: Methotrexate (MTX)
individual dose of methotrexate (stably dosed)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01745055

Locations
United States, Florida
Pfizer Investigational Site
Daytona Beach, Florida, United States, 32114
Pfizer Investigational Site
Fort Lauderdale, Florida, United States, 33301
Pfizer Investigational Site
Miramar, Florida, United States, 33025
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75247
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: NCT01745055     History of Changes
Other Study ID Numbers: A3921013
Study First Received: December 4, 2012
Results First Received: December 6, 2012
Last Updated: January 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Pharmacokinetics
oral JAK inhibitor
methotrexate (MTX)
rheumatoid arthritis (RA)

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Tofacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014