Co-Administration Of Methotrexate And CP-690,550

NCT01745055 | Completed Phase 1 Results

• 1 other identifier: A3921013
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

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.

Conditions

Rheumatoid Arthritis

Keywords

Pharmacokinetics; oral JAK inhibitor; methotrexate (MTX); rheumatoid arthritis (RA)

Outcome Measures

Primary Outcomes (4)

• 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).

  0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7

• Maximum Observed Plasma Concentration (Cmax) for CP-690,550

  0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7

• 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).

  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

• Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)

  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 Outcomes (10)

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550

  0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7

• Plasma Decay Half-Life (t1/2) for CP-690,550

  0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7

• Apparent Oral Clearance (CL/F) for CP-690,550

  0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for Methotrexate (MTX)

  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

• Plasma Decay Half-Life (t1/2) for Methotrexate (MTX)

  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

Study Arms (1)

CP-690,550 (tofacitinib) 30 mg q12h

EXPERIMENTAL

Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h

Drug: CP-690,550 (tofacitinib); Drug: Methotrexate (MTX)

Interventions

CP-690,550 (tofacitinib) DRUG

CP-690,550 30 mg q12h for 5 days

CP-690,550 (tofacitinib) 30 mg q12h

Methotrexate (MTX) DRUG

individual dose of methotrexate (stably dosed)

CP-690,550 (tofacitinib) 30 mg q12h

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

Pfizer Investigational Site

Daytona Beach, Florida, 32114, United States

Location

Pfizer Investigational Site

Fort Lauderdale, Florida, 33301, United States

Location

Pfizer Investigational Site

Miramar, Florida, 33025, United States

Location

Pfizer Investigational Site

Dallas, Texas, 75247, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Results were summarized for Ae(0-12) instead of planned Ae(0-24), as CP-690,550 was administered every 12 hours.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2012
• First Posted: December 7, 2012
• Study Start: April 1, 2005
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: February 4, 2013
• Results First Posted: December 7, 2012

Record last verified: 2013-01

Locations

US (4)