Clinical trial NCT01745055: Co-Administration Of Methotrexate And CP-690,550
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Pharmacokinetics
oral JAK inhibitor
methotrexate (MTX)
rheumatoid arthritis (RA)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-12-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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.

Primary outcomes:
measure: Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
measure: Maximum Observed Plasma Concentration (Cmax) for CP-690,550
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Methotrexate (MTX)
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)
timeFrame: 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:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
measure: Plasma Decay Half-Life (t1/2) for CP-690,550
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
measure: Apparent Oral Clearance (CL/F) for CP-690,550
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Methotrexate (MTX)
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2) for Methotrexate (MTX)
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) for Methotrexate (MTX)
timeFrame: 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
measure: Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 12 Hours (Ae[0-12]) for CP-690,550
timeFrame: 0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7
measure: Renal Clearance (CL R) for CP-690,550
timeFrame: 0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7
measure: Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 24 Hours (Ae[0-24]) for Methotrexate (MTX)
timeFrame: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7
measure: Renal Clearance (CL R) for Methotrexate (MTX)
timeFrame: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Miramar
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: