Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: LX3305 low dose
Drug: LX3305 mid dose
Drug: LX3305 high dose
Drug: Placebo

Registration Number: NCT00903383

Lead Sponsor: Lexicon Pharmaceuticals

Brief Summary: The purpose of the study is to evaluate the safety, tolerability, and effectiveness of LX3305 versus a placebo control in subjects with active rheumatoid arthritis on stable methotrexate therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 208

Inclusion Criteria

Males and females aged 18-75 years old
Rheumatoid arthritis present for at least 6 months, functional class I, II, or III as defined by ACR criteria
Active disease as determined by the presence of ≥6 swollen joints, ≥6 tender joints, and serum C-reactive protein level > upper limit of normal
Receiving stable dose of MTX (≥10 mg/wk) and folate supplementation at least 8 weeks prior to Day 1
Ability to provide written informed consent

Exclusion Criteria

RA diagnosis prior to 16 years of age (Juvenile RA)
Lack of response to >3 disease modifying anti-rheumatic drugs (DMARDs) or exposure to >1 biologic DMARD
Use of DMARDs other than MTX within 12 weeks prior to Day 1
Intra-articular and/or parenteral corticosteroids within 4 weeks prior to study Day 1
Blood donation or receipt of live vaccine within 4 weeks prior to Day 1
Major surgical procedure within 8 weeks prior to Day 1
Any systemic inflammatory condition, recurrent infection, or current infection other than onychomycosis
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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Dose	LX3305 low dose	A low dose of LX3305; daily oral intake for 12 weeks
Mid Dose	LX3305 mid dose	A mid dose of LX3305; daily oral intake for 12 weeks
High Dose	LX3305 high dose	A high dose of LX3305; daily oral intake for 12 weeks
Placebo	Placebo	Matching placebo dosing with daily oral intake for 12 weeks

Primary Outcome Measures

Name	Time	Method
ACR20 Response at Week 12	Baseline and 12 weeks	Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 20% response criteria (ACR20) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR20, there had to be ≥20% improvement in swollen joint count, ≥20% improvement in painful/tender joint count, and ≥20% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).

Secondary Outcome Measures

Name	Time	Method
ACR50 Response at Week 12	Baseline and 12 weeks	Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 50% response criteria (ACR50) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR50, there had to be ≥50% improvement in swollen joint count, ≥50% improvement in painful/tender joint count, and ≥50% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).
ACR70 Response at Week 12	Baseline and 12 weeks	Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 70% response criteria (ACR70) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR70, there had to be ≥70% improvement in swollen joint count, ≥70% improvement in painful/tender joint count, and ≥70% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).
Hybrid ACR Response at Week 12	Baseline and 12 weeks	Evaluates the improvement in active RA by combining elements of the ACR20/50/70 with a continuous score of the mean change in core set measures. The percentage improvement from baseline was computed in each of the components of the ACR. The average percent improvement was calculated and used with the subject's ACR20, ACR50, and ACR70 status to compute the hybrid ACR response, with a positive change indicating improvement.
Change From Baseline in C-reactive Protein (mg/L) at Week 12	Baseline and 12 weeks	The C-reactive protein value (mg/L) at baseline was subtracted from the value for each of the treatment groups at Week 12.
Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12	Baseline and 12 weeks	The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12.