A Study to Determine the Safety and Efficacy of LX3305 in Subjects With Active Rheumatoid Arthritis

A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects With Active Rheumatoid Arthritis (RA)

The primary objective of this study is to determine the safety of LX3305 in a dose escalation compared with placebo over 12 weeks in subjects with active rheumatoid arthritis (RA).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: 50 mg LX3305 QD; Drug: 100 mg LX3305 QD; Drug: 150 mg LX3305 QD; Drug: 200 mg LX3305 QD; Drug: 250 mg LX3305 QD; Drug: 300 mg LX3305 QD; Drug: 400 mg LX3305 QD; Drug: 250 mg LX3305 BID; Drug: 500 mg LX3305 QD; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75231
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult subjects, aged 18 to 75 years
• Active rheumatoid arthritis (RA), class I to III (defined by the American College of Rheumatology), diagnosed at least 3 months prior to Screening
• Minimum of 4 swollen joints (at Screening and Day 1), minimum of 4 tender joints (at Screening and Day 1), and serum C-reactive protein (CRP) level >1.2x the upper limit of normal and/or elevated erythrocyte sedimentation rate (ESR)
• If receiving methotrexate (7.5 mg to 25 mg/week), subject must have been treated for at least 6 weeks prior to Screening and currently receiving a stable dose of methotrexate (MTX) with a stable route of administration, and have no plans to change MTX dose during the study
• Ability to give written informed consent

Exclusion Criteria:

• Women who are pregnant or nursing
• RA diagnosis prior to 16 years of age (juvenile RA)
• Intra-articular and/or parenteral corticosteroids within 4 weeks of study Day 1
• Receipt of live vaccine within 4 weeks prior to Day 1
• Major surgical procedure within 8 weeks prior to Day 1
• Blood donation within 4 weeks prior to Day 1
• Any systemic inflammatory condition
• History of bleeding diathesis
• History of medically significant opportunistic infection
• History of drug or alcohol abuse within 3 years prior to Day 1
• History of cancer within 5 years prior to Day 1
• Presence of hepatic or biliary disease
• History of tuberculosis
• History of human immunodeficiency virus (HIV)
• Any clinically significant laboratory test results, in the opinion of the investigator
• Use of any investigational agent or participation in an investigative trial within 30 days of Day 1
• Concurrent use of any biologic agent for the treatment of RA or concomitant disease modifying antirheumatoid drugs (other than MTX, hydroxychloroquine, leflunomide, and sulfasalazine - at stables doses for 8 weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo dosing in capsule form
Experimental: 50 mg LX3305 QD	Drug: 50 mg LX3305 QD; 50 mg LX3305 once daily in capsule form
Experimental: 100 mg LX3305 QD	Drug: 100 mg LX3305 QD; 100 mg LX3305 once daily in capsule form
Experimental: 150 mg LX3305 QD	Drug: 150 mg LX3305 QD; 150 mg LX3305 once daily in capsule form
Experimental: 200 mg LX3305 QD	Drug: 200 mg LX3305 QD; 200 mg LX3305 once daily in capsule form
Experimental: 250 mg LX3305 QD	Drug: 250 mg LX3305 QD; 250 mg LX3305 once daily in capsule form
Experimental: 300 mg LX3305 QD	Drug: 300 mg LX3305 QD; 300 mg LX3305 once daily in capsule form
Experimental: 400 mg LX3305 QD	Drug: 400 mg LX3305 QD; 400 mg LX3305 once daily in capsule form
Experimental: 250 mg LX3305 BID	Drug: 250 mg LX3305 BID; 250 mg LX3305 twice daily in capsule form
Experimental: 500 mg LX3305 QD	Drug: 500 mg LX3305 QD; 500 mg LX3305 once daily in capsule form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects experiencing an adverse event (AE)	14 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in absolute lymphocyte counts	14 weeks
Maximum observed plasma concentration	14 weeks
Time at which maximum observed plasma concentration occurs	14 weeks
Half-life of drug in plasma	14 weeks
Changes from baseline in global health	14 weeks

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Joel Freiman, MD, MPH, Lexicon Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: August 12, 2011
• First Submitted That Met QC Criteria: August 12, 2011
• First Posted (Estimate): August 16, 2011

Study Record Updates

• Last Update Posted (Estimate): August 2, 2012
• Last Update Submitted That Met QC Criteria: August 1, 2012
• Last Verified: August 1, 2012

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
• Other Study ID Numbers: LX3305.1-106-RA; LX3305.106 (Other Identifier: Lexicon Pharmaceuticals, Inc.)