Study of LX3305 and Methotrexate in Subjects With Stable Rheumatoid Arthritis

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

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 Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: LX3305; Drug: Methotrexate; Drug: LX3305 Placebo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • Metroplex Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Philip M. Brown, MD, JD, Lexicon Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: February 17, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (Estimate): February 19, 2009

Study Record Updates

• Last Update Posted (Estimate): June 3, 2010
• Last Update Submitted That Met QC Criteria: June 1, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: Protocol LX3305.1-104-DDI; LX3305.104; LX2931