Study of LX3305 and Methotrexate in Subjects With Stable Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of LX3305 on methotrexate (MTX) pharmacokinetics and to evaluate the safety and tolerability of LX3305 given over 14 days in subjects with stable rheumatoid arthritis that are receiving stable doses of MTX.

Official Title
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A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study to Determine the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LX3305 and Methotrexate in Subjects With Stable Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: LX3305
* Drug: LX3305 Placebo
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years old Must be willing to practice 2 adequate methods of contraception for the duration of the study Rheumatoid arthritis present for at least 3 months; functional class I, II, or III as defined by ACR criteria Treatment with methotrexate (7.5 to 25 mg per week) for at least the last 3 months, and currently receiving stable dose methotrexate for at least one month prior to the start of the study Ability to provide written informed consent Exclusion Criteria: Women who are pregnant or nursing History of other current inflammatory arthritis History of opportunistic infection History of recurrent infections or current infection 2 weeks prior to start of study Presence of significant, uncontrolled medical problems Treatment with any disease-modifying anti-rheumatoid drugs other than methotrexate within 4 weeks prior to start of study Use of chondroitin sulfate, glucosamine sulfate, minocycline, or matrix metalloproteinase inhibitors, H-2 blockers, proton pump inhibitors, or misoprostol within 4 weeks prior to study start Receipt of live vaccine within 8 weeks prior to study start Rheumatoid arthritis, functional class IV as defined by ACR criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LX3305<br>Daily oral intake of LX3305 for 14 days. | Drug: LX3305<br>* Daily oral intake of LX3305 for 14 days.<br>Drug: Methotrexate<br>* Once weekly stable-dose methotrexate.<br>|
| Placebo Comparator: LX3305 Placebo<br>Matching placebo dosing with daily oral intake for 14 days. | Drug: LX3305 Placebo<br>* Matching placebo dosing with daily oral intake for 14 days.<br>Drug: Methotrexate<br>* Once weekly stable-dose methotrexate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methotrexate Maximum Plasma Concentration |  | Day 15 | 
| Time to Reach Maximum Plasma Concentration of Methotrexate |  | Day 15 | 
| Half-life of Methotrexate in Plasma |  | Day 15 | 
| Amount of Methotrexate Excreted in the Urine |  | Day 15 | 
| 7-Hydroxymethotrexate (7-OH-MTX) Maximum Plasma Concentration | 7-OH-MTX is the primary metabolite of methotrexate. | Day 15 | 
| Time to Reach Maximum Plasma Concentration of 7-OH-MTX |  | Day 15 | 
| Amount of 7-OH-MTX Excreted in the Urine |  | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration of LX3305 in the Presence of MTX |  | Day 15 | 
| Time to Maximum Plasma Concentration of LX3305 in the Presence of MTX |  | Day 15 | 
| Half-life of LX3305 in Plasma in the Presence of MTX |  | Day 15 | 
| Percentage of Change From Baseline in Absolute Total Lymphocyte Count at Day 15 | Baseline was defined as pre-dose on Day 1. | Day 15 |