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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Lexicon Pharmaceuticals
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Methotrexate Maximum Plasma Concentration
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
LX3305 Placebo
Matching placebo dosing with daily oral intake for 14 days.
Intervention: LX3305 Placebo (Drug)
LX3305
Daily oral intake of LX3305 for 14 days.
Intervention: LX3305 (Drug)
LX3305 Placebo
Matching placebo dosing with daily oral intake for 14 days.
Intervention: Methotrexate (Drug)
LX3305
Daily oral intake of LX3305 for 14 days.
Intervention: Methotrexate (Drug)
Outcomes
Primary Outcomes
Methotrexate Maximum Plasma Concentration
Time Frame: Day 15
Time to Reach Maximum Plasma Concentration of Methotrexate
Time Frame: Day 15
Half-life of Methotrexate in Plasma
Time Frame: Day 15
Amount of Methotrexate Excreted in the Urine
Time Frame: Day 15
7-Hydroxymethotrexate (7-OH-MTX) Maximum Plasma Concentration
Time Frame: Day 15
7-OH-MTX is the primary metabolite of methotrexate.
Time to Reach Maximum Plasma Concentration of 7-OH-MTX
Time Frame: Day 15
Amount of 7-OH-MTX Excreted in the Urine
Time Frame: Day 15
Secondary Outcomes
- 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(Day 15)