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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01329991
Recruitment Status : Completed
First Posted : April 6, 2011
Last Update Posted : April 12, 2012
Sponsor:
Information provided by:
Plexxikon

Tracking Information
First Submitted Date  ICMJE April 4, 2011
First Posted Date  ICMJE April 6, 2011
Last Update Posted Date April 12, 2012
Study Start Date  ICMJE May 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2011)
Safety-Number of patients with adverse events [ Time Frame: 22 days ]
Subjects will take oral doses of PLX5622 once a day for 14 days. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology, serum chemistry, coagulation, and urinalysis will be used to assess safety throughout Day 1-14 of the study, Day 17 and the follow up study visit on day 22. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01329991 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2011)
  • Pharmacokinetic profile: Measurement of area under the plasma-concentration-time curve [ Time Frame: 22 days ]
    The pharmacokinetic profile of plasma PLX5622 and Methotrexate will be analyzed by measurement of area under the plasma concentration-time curve [AUC0-t, AUC0-inf, AUC0-24].
  • Pharmacokinetic evaluation: Measurement of Peak Concentration [ Time Frame: 22 days ]
    The pharmacokinetic profile of plasma PLX5622 and Methotrexate will be analyzed by measurement of peak concentration (Cmax) and time to peak concentration (Tmax).
  • Pharmacokinetic profile: Measurement of half life, apparent systemic clearance, and apparent volume of distribution, terminal phase. [ Time Frame: 22 days ]
    The pharmacokinetic profile of plasma PLX5622 and Methotrexate will be analyzed by measurement of half-life (T1/2), apparent systemic clearance (CL/F), and apparent volume of distribution, terminal phase (Vz/F).
  • Pharmacodynamics-Effect of PLX5622 on the body [ Time Frame: 22 days ]
    The effects of PLX5622 on the body will be measured by observing early response biomarkes of disease activity.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1b Study of PLX5622 in Rheumatoid Arthritis Patients Who Are Receiving Methotrexate
Official Title  ICMJE A Phase 1b Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Drug-Drug Interaction of PLX5622 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: PLX5622
    PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in a dosage strength of 100 mg with matching placebo
  • Drug: Placebo
    Matching placebo for PLX5622
Study Arms  ICMJE
  • Active Comparator: oral dose of 200 mg PLX5622
    6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.
    Intervention: Drug: PLX5622
  • Active Comparator: oral dose of 400 mg PLX5622
    6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.
    Intervention: Drug: PLX5622
  • Active Comparator: oral dose of 800 mg PLX5622
    6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.
    Intervention: Drug: PLX5622
  • Active Comparator: oral dose of PLX5622-dose to be determined
    6 subjects will be randomized to take an oral dose of PLX5622 for 14 days and 2 subjects will be randomized to take placebo.
    Intervention: Drug: PLX5622
  • Placebo Comparator: Placebo Comparator
    2 patients per cohort will be randomly assigned to take placebo. 8 patients total will be randomized to take placebo in this study.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2012)
26
Original Estimated Enrollment  ICMJE
 (submitted: April 5, 2011)
32
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01329991
Other Study ID Numbers  ICMJE PLX115-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Keith Nolop, MD, Plexxikon
Study Sponsor  ICMJE Plexxikon
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Plexxikon
Verification Date April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP