NCT01090570撤回1 期
Safety, Pharmacokinetic (PK), Pharmcodynamic (PD), and Drug-Drug Interaction of PLX3397 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate
Plexxikon0 个研究点开始时间: 2010年5月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 CYP3A
- •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.
研究组 & 干预措施
PLX3397 25 mg
Experimental
干预措施: PLX3397 (Drug)
PLX3397 50 mg
Experimental
干预措施: PLX3397 (Drug)
PLX3397 100 mg
Experimental
干预措施: PLX3397 (Drug)
PLX3397 200 mg
Experimental
干预措施: PLX3397 (Drug)
PLX3397 300 mg
Experimental
干预措施: PLX3397 (Drug)
Placebo
Placebo Comparator
干预措施: PLX3397 (Drug)
结局指标
主要结局
To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis
时间窗: 2 weeks + 2 weeks follow up
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.
次要结局
- To assess the safety and tolerability of PLX3397 when taken once daily with concomitant methotrexate administration(4 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)
- 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)
研究者
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