Safety, Pharmacokinetic (PK), Pharmcodynamic (PD), and Drug-Drug Interaction of PLX3397 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate

NCT ID: NCT01090570

Last Updated: 2015-03-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

PLX3397 25 mg

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Once-daily oral capsules

PLX3397 50 mg

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Once-daily oral capsules

PLX3397 100 mg

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Once-daily oral capsules

PLX3397 200 mg

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Once-daily oral capsules

PLX3397 300 mg

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Once-daily oral capsules

Placebo

Group Type: PLACEBO_COMPARATOR

PLX3397

Intervention Type: DRUG

Once-daily oral capsules

Interventions

PLX3397

Once-daily oral capsules

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Plexxikon

INDUSTRY

Sponsor Role: lead

Locations

Tuscaloosa, Alabama, United States

Little Rock, Arkansas, United States

San Francisco, California, United States

Altoona, Pennsylvania, United States

Dallas, Texas, United States

Countries

United States

Other Identifiers

PLX108-02

Identifier Type: -

Identifier Source: org_study_id