Phase 1b Study of PLX5622 in Rheumatoid Arthritis Patients Who Are Receiving Methotrexate

Plexxikon

Status and phase: Completed; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: PLX5622; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01329991

PLX115-02

Details and patient eligibility

About

PLX115-02 is a phase 1b study to assess how the study drug, PLX5622: 1. affects the body, 2. how the body affects PLX5622 3. the interaction of PLX5622 with Methotrexate and 4. the safety of PLX5622 in rheumatoid arthritis patients taking Methotrexate

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients ≥ 18 years old with a diagnosis of rheumatoid arthritis by ACR criteria for ≥ 3 months.
• Prior to Day 1, 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 with study drug 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 nonchildbearing 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: 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 (rituximab).
• Use of Arava (leflunomide) within 12 weeks prior to Day 1 or any immunosuppressive agents, including hydroxychloroquine or sulfasalazine, within 4 weeks of Day 1.
• Investigational drug use within 4 weeks of Day 1.
• Positive urine drug screen for drugs of abuse (except for opiates if being used for RA).
• Concomitant use of DMARDs (other than methotrexate), biological response modifiers, or known strong inducers or inhibitors of CYP3A4 (see Appendix 2).
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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26 participants in 5 patient groups, including a placebo group

oral dose of 200 mg PLX5622

Active Comparator group

Description:

6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.

Treatment:

Drug: PLX5622

oral dose of 400 mg PLX5622

Active Comparator group

Description:

6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.

Treatment:

Drug: PLX5622

oral dose of 800 mg PLX5622

Active Comparator group

Description:

6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.

Treatment:

Drug: PLX5622

oral dose of PLX5622-dose to be determined

Active Comparator group

Description:

6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.

Treatment:

Drug: PLX5622

Placebo Comparator

Placebo Comparator group

Description:

2 patients per cohort will be randomly assigned to take placebo. 8 patients total will be randomized to take placebo in this study.

Treatment:

Drug: Placebo