Co-Administration Of Methotrexate And CP-690,550

Phase 1

Completed

Conditions: Rheumatoid Arthritis

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

Registration Number: NCT01745055

Lead Sponsor: Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CP-690,550 (tofacitinib) 30 mg q12h	Methotrexate (MTX)	Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h
CP-690,550 (tofacitinib) 30 mg q12h	CP-690,550 (tofacitinib)	Individual dose of methotrexate with the addition of CP-690,550 30 mg q12h

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] 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	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	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)	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).
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 Outcome Measures

Name	Time	Method
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
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	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	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.
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	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)	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.
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
Renal Clearance (CL R) for CP-690,550	0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7
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
Renal Clearance (CL R) for Methotrexate (MTX)	0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7