Co-Administration Of Methotrexate And CP-690,550
This study has been completed.
Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01745055
First received: December 4, 2012
Last updated: January 29, 2013
Last verified: January 2013
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Rheumatoid Arthritis |
Drug: CP-690,550 (tofacitinib) Drug: Methotrexate (MTX) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by Pfizer:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]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 [ 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
- 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]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 [ 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 ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]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) [ 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 ] [ Designated as safety issue: No ]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 [ Time Frame: 0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7 ] [ Designated as safety issue: No ]
- Renal Clearance (CL R) for CP-690,550 [ Time Frame: 0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Renal Clearance (CL R) for Methotrexate (MTX) [ Time Frame: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7 ] [ Designated as safety issue: No ]
| Enrollment: | 12 |
| Study Start Date: | April 2005 |
| Study Completion Date: | June 2006 |
| Primary Completion Date: | June 2006 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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)
|
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01745055
Please refer to this study by its ClinicalTrials.gov identifier: NCT01745055
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:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT01745055 History of Changes |
| Other Study ID Numbers: | A3921013 |
| Study First Received: | December 4, 2012 |
| Results First Received: | December 6, 2012 |
| Last Updated: | January 29, 2013 |
| Health Authority: | United States: Food and Drug Administration |
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 |
ClinicalTrials.gov processed this record on September 30, 2016