- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01090570
Safety, Pharmacokinetic (PK), Pharmcodynamic (PD), and Drug-Drug Interaction of PLX3397 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate
March 13, 2015 updated by: Plexxikon
PLX3397 is a selective inhibitor of Fms and Kit activity.
The objective of this study is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and drug-drug interaction (DDI) of orally administered PLX3397 during 2 weeks of dosing in patients with rheumatoid arthritis (RA) who are on maintenance methotrexate.
This study is planned to provide data to inform dose selection for a subsequent 12 week dose ranging study in RA.
Study Overview
Study Type
Interventional
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alabama
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Tuscaloosa, Alabama, United States
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Arkansas
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Little Rock, Arkansas, United States
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California
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San Francisco, California, United States
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Pennsylvania
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Altoona, Pennsylvania, United States
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Texas
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Dallas, Texas, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female patients ≥ 18 years old with a diagnosis of rheumatoid arthritis by ACR criteria for ≥ 3 months.
- Prior to Baseline, patients must be on oral or subcutaneous methotrexate (≥ 10 mg/week and ≤ 25 mg/week) for at least 12 weeks (with a stable dose for at least 4 weeks) and folate (≥ 5 mg/week) for at least 6 weeks, and willing to continue on this regimen for the duration of the study.
- Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥ 1.5 X 109/L, Hgb > 9 g/dL, platelet count ≥ 100 X 109/L, AST/ALT WNL, albumin ≥ 3 g/dL, calculated CrCl>60 mL/min using Cockcroft-Gault formula).
- Women of child-bearing potential must have a negative pregnancy test within 7 days prior to initiation of dosing and must agree to use a double barrier method of birth control from the time of the negative pregnancy test up to 30 days after the last dose of study drug. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year.
- Fertile men must agree to use an acceptable method of birth control while on study drug. Acceptable methods of contraception must include either abstinence from the first dose of study drug through 4 weeks after the last dose of study drug, or use of a condom with instructions to the female partner of child-bearing potential to also be protected as above.
- Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements.
Exclusion Criteria:
- Use of biologic response modifiers within the following periods prior to Day 1 Baseline: 4 weeks for Kineret (anakinra) and Enbrel (etanercept); 12 weeks for Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatacept), Actemra (tocilizumab), or Cimzia (certolizumab); 12 months for Rituxan.
- Use of Arava (leflunomide) within 12 weeks prior to Day 1 Baseline or any immunosuppressive agents other then hydroxychloroquine or sulfasalazine within 4 weeks of Day 1 Baseline.
- Investigational drug use within 4 weeks of Day 1 Baseline.
- Concomitant use of DMARDs (other than methotrexate), biological response modifiers, or known strong inducers or inhibitors of CYP3A4.
- Positive HepBsAg or HCV, or presence of clinically significant hepatic or biliary disease.
- Uncontrolled intercurrent illness.
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
- QTc ≥ 450 msec at Screening.
- The presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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Once-daily oral capsules
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Experimental: PLX3397 25 mg
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Once-daily oral capsules
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Experimental: PLX3397 50 mg
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Once-daily oral capsules
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Experimental: PLX3397 100 mg
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Once-daily oral capsules
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Experimental: PLX3397 200 mg
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Once-daily oral capsules
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Experimental: PLX3397 300 mg
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Once-daily oral capsules
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis
Time Frame: 2 weeks + 2 weeks follow up
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Blood samples will be taken at multiple time points during the 2 week time frame plus a 2 week follow up time frame to study the pharmacokinetics of PLX3397 and Methotrexate in patients.
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2 weeks + 2 weeks follow up
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the safety and tolerability of PLX3397 when taken once daily with concomitant methotrexate administration
Time Frame: 4 weeks
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Adverse events and safety lab tests (including a hematology panel, blood chemistry panel, coagulation and urinalysis) will be monitored throughout the study time frame.
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4 weeks
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To assess the pharmacokinetics of PLX3397 when taken once daily for 2 weeks at either a 25, 50, 100, 200 or 300 mg dose.
Time Frame: 2 weeks
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The pharmacokinetic profile of plasma PLX3397 will be analyzed by measurement of area under the plasma concentration-time curve (AUC0-t, AUC0-inf), peak concentration (Cmax), time to peak concentration (Tmax), half-life (t1/2), and terminal elimination rate constant (Kel).
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2 weeks
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To assess the pharmacodynamics of PLX3397 when taken once daily for 2 weeks at either a 25, 50, 100, 200 or 300 mg dose.
Time Frame: 4 weeks
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Measured by looking at the factors in the blood that may include, but are not limited to pro- and anti-inflammatory cytokines and mediators of the inflammatory process that may correlate with the activity of the disease and the response to PLX3397 in combination with methotrexate
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4 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2010
Primary Completion (Anticipated)
December 1, 2010
Study Registration Dates
First Submitted
March 15, 2010
First Submitted That Met QC Criteria
March 18, 2010
First Posted (Estimate)
March 22, 2010
Study Record Updates
Last Update Posted (Estimate)
March 17, 2015
Last Update Submitted That Met QC Criteria
March 13, 2015
Last Verified
March 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PLX108-02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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