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

A Phase 1 study testing PLX3397 in people with Rheumatoid Arthritis, run by Plexxikon at 5 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Trial summary

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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: PLX3397
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: 5 sitesUnited States
Study dates: May 2010to Dec 2010
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 9Show fewer

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 locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Study site
Altoona, Pennsylvania
Study site
Dallas, Texas
Study site
Little Rock, Arkansas
Study site
San Francisco, California
Study site
Tuscaloosa, Alabama

Other trials in United States

About this study

Conditions: Rheumatoid Arthritis
Being tested: PLX3397
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PLX3397Drug
Once-daily oral capsules

Study groups in NCT01090570
Study group	Role	What they receive
PLX3397 25 mg	Experimental	Not described Receives: Drug: PLX3397
PLX3397 50 mg	Experimental	Not described Receives: Drug: PLX3397
PLX3397 100 mg	Experimental	Not described Receives: Drug: PLX3397
PLX3397 200 mg	Experimental	Not described Receives: Drug: PLX3397
PLX3397 300 mg	Experimental	Not described Receives: Drug: PLX3397
Placebo	Placebo comparator	Not described Receives: Drug: PLX3397

What is being measured

The primary outcome is the main question the study is designed to answer.

To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis
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.
Measured: 2 weeks + 2 weeks follow up

Secondary outcomes (3)

To assess the safety and tolerability of PLX3397 when taken once daily with concomitant methotrexate administration
Adverse events and safety lab tests (including a hematology panel, blood chemistry panel, coagulation and urinalysis) will be monitored throughout the study time frame.
Measured: 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.
The pharmacokinetic profile of plasma PLX3397 will be analyzed by measurement of area under the plasma concentration-time curve (AUC0-t, AUC0-inf), peak concentration (Cmax), time to peak concentration (Tmax), half-life (t1/2), and terminal elimination rate constant (Kel).
Measured: 2 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.
Measured by looking at the factors in the blood that may include, but are not limited to pro- and anti-inflammatory cytokines and mediators of the inflammatory process that may correlate with the activity of the disease and the response to PLX3397 in combination with methotrexate
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2010Dec 2010

First posted22 Mar 2010 (estimated)
Study startMay 2010
Primary completionDec 2010 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01090570
Sponsor's protocol ID: PLX108-02
Status last verified: Mar 2015
First submitted: 15 Mar 2010
Last updated: 17 Mar 2015
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of PTC844 in Participants With Active Rheumatoid Arthritis
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R-2487 in Patients With Sjogren's Syndrome (SjD)
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Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
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All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety, Pharmacokinetic (PK), Pharmcodynamic (PD), and Drug-Drug Interaction of PLX3397 in Patients With Rheumatoid Arthritis Who Are Receiving Methotrexate
ClinicalTrials.gov ID: NCT01090570
Acronym / sponsor ID: PLX108-02
Conditions: Rheumatoid Arthritis
Phase: Phase 1
Study type: Interventional
Recruitment status: Withdrawn
Enrolment: 0 participants (actual)
Lead sponsor: PlexxikonIndustry (pharma, biotech, devices)
Study start: May 2010
Primary completion: Dec 2010 (estimated)
First posted: 22 Mar 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
PLX3397 25 mg	Experimental	Drug: PLX3397
PLX3397 50 mg	Experimental	Drug: PLX3397
PLX3397 100 mg	Experimental	Drug: PLX3397
PLX3397 200 mg	Experimental	Drug: PLX3397
PLX3397 300 mg	Experimental	Drug: PLX3397
Placebo	Placebo comparator	Drug: PLX3397

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PLX3397Once-daily oral capsules	Drug	PLX3397 100 mg, PLX3397 200 mg, PLX3397 25 mg, PLX3397 300 mg, PLX3397 50 mg, Placebo

Primary outcome

To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis
Time frame: 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.

3 secondary outcomes

To assess the safety and tolerability of PLX3397 when taken once daily with concomitant methotrexate administration
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 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

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2015.

Related trials for Rheumatoid Arthritis

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PLX3397 in people with Rheumatoid Arthritis, run by Plexxikon at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 17 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess the drug-drug interaction of PLX3397 and Methotrexate in patients with rheumatoid arthritis (time frame: 2 weeks + 2 weeks follow up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01090570.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2015.