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

NCT01090570 | Withdrawn Phase 1

• 1 other identifier: PLX108-02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis

  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.

  2 weeks + 2 weeks follow up

Secondary Outcomes (3)

• To assess the safety and tolerability of PLX3397 when taken once daily with concomitant methotrexate administration

  4 weeks

• To assess the pharmacokinetics of PLX3397 when taken once daily for 2 weeks at either a 25, 50, 100, 200 or 300 mg dose.

  2 weeks

• To assess the pharmacodynamics of PLX3397 when taken once daily for 2 weeks at either a 25, 50, 100, 200 or 300 mg dose.

  4 weeks

Study Arms (6)

PLX3397 25 mg

EXPERIMENTAL

Drug: PLX3397

PLX3397 50 mg

EXPERIMENTAL

Drug: PLX3397

PLX3397 100 mg

EXPERIMENTAL

Drug: PLX3397

PLX3397 200 mg

EXPERIMENTAL

Drug: PLX3397

PLX3397 300 mg

EXPERIMENTAL

Drug: PLX3397

Placebo

PLACEBO COMPARATOR

Drug: PLX3397

Interventions

PLX3397 DRUG

Once-daily oral capsules

PLX3397 100 mg; PLX3397 200 mg; PLX3397 25 mg; PLX3397 300 mg; PLX3397 50 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Plexxikon: lead

Study Sites (5)

Unknown Facility

Tuscaloosa, Alabama, United States

Location

Unknown Facility

Little Rock, Arkansas, United States

Location

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Altoona, Pennsylvania, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

pexidartinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 22, 2010
• Study Start: May 1, 2010
• Primary Completion: December 1, 2010
• Last Updated: March 17, 2015

Record last verified: 2015-03

Locations

US (5)