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

• Register: ClinicalTrials.gov
• Last refreshed on: 23 March 2015
• Main ID: NCT01090570
• Date of registration: 15/03/2010
• Prospective Registration: Yes
• Primary sponsor: Plexxikon
• Public title: Safety, Pharmacokinetic (PK), Pharmcodynamic (PD), and Drug-Drug Interaction of PLX3397 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate
• Date of first enrolment: May 2010
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT01090570
• Study type: Interventional
• Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: PLX3397

Primary Outcome(s)

To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis [Time Frame: 2 weeks + 2 weeks follow up]

Secondary Outcome(s)

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]

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]

To assess the safety and tolerability of PLX3397 when taken once daily with concomitant methotrexate administration [Time Frame: 4 weeks]

Secondary ID(s)

PLX108-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors