Co-Administration Of Methotrexate And CP-690,550

• ClinicalTrials.gov Identifier: NCT01745055
• Recruitment Status: Completed
• First Posted: December 7, 2012
• Results First Posted: December 7, 2012
• Last Update Posted: February 4, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: CP-690,550 (tofacitinib); Drug: Methotrexate (MTX)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: April 2005
• Actual Primary Completion Date: June 2006
• Actual Study Completion Date: June 2006

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).
2. 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 ]
3. 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 ]
   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
4. 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 Measures :

1. 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 ]
2. 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 ]
   Plasma decay half-life is the time measured for the plasma concentration of CP-690,550 to decrease by one half.
3. 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 ]
   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.
4. 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 ]
5. 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 ]
   Plasma decay half-life is the time measured for the plasma concentration of MTX to decrease by one half.
6. 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 ]
   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.
7. 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 ]
8. Renal Clearance (CL R) for CP-690,550 [ Time Frame: 0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7 ]
9. 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 ]
10. Renal Clearance (CL R) for Methotrexate (MTX) [ Time Frame: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01745055
• Other Study ID Numbers: A3921013
• First Posted: December 7, 2012
• Results First Posted: December 7, 2012
• Last Update Posted: February 4, 2013
• Last Verified: January 2013

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; 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