Clinical trial NCT01329991: Phase 1b Study of PLX5622 in Rheumatoid Arthritis Patients Who Are Receiving Methotrexate
Official title: A Phase 1b Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Drug-Drug Interaction of PLX5622 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: RA
Methotrexate
Lead sponsor: Plexxikon
Sponsor class: INDUSTRY
First posted: 2011-04-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


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 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.

Primary outcomes:
measure: Safety-Number of patients with adverse events
timeFrame: 22 days
Secondary outcomes:
measure: Pharmacokinetic profile: Measurement of area under the plasma-concentration-time curve
timeFrame: 22 days
measure: Pharmacokinetic evaluation: Measurement of Peak Concentration
timeFrame: 22 days
measure: Pharmacokinetic profile: Measurement of half life, apparent systemic clearance, and apparent volume of distribution, terminal phase.
timeFrame: 22 days
measure: Pharmacodynamics-Effect of PLX5622 on the body
timeFrame: 22 days
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Lansing
country: United States
facility: Medical Practice of Justus Fiechtner, MD
state: Michigan
city: Duncansville
country: United States
facility: Altoona Center for Clinical research
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
Study officials:
References: