Co-Administration Of Methotrexate And CP-690,550

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01745055
• Other study ID #: A3921013
• Status: Completed
• Phase: Phase 1
• First received: December 4, 2012
• Last updated: January 29, 2013
• Start date: April 2005
• Est. completion date: June 2006

Study information

• Verified date: January 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• CP-690,550 (tofacitinib)
CP-690,550 30 mg q12h for 5 days
• Methotrexate (MTX)
individual dose of methotrexate (stably dosed)

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Daytona Beach	Florida
United States	Pfizer Investigational Site	Fort Lauderdale	Florida
United States	Pfizer Investigational Site	Miramar	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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.	0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7	No
Secondary	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.	0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7	No
Secondary	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	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 12 Hours (Ae[0-12]) for CP-690,550		0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7	No
Secondary	Renal Clearance (CL R) for CP-690,550		0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7	No
Secondary	Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 24 Hours (Ae[0-24]) for Methotrexate (MTX)		0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7	No
Secondary	Renal Clearance (CL R) for Methotrexate (MTX)		0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7	No

External Links

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