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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: LX3305 low dose; Drug: LX3305 mid dose; Drug: LX3305 high dose; Drug: Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	208 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Multi-center, Randomized, Double Blind, Placebo-controlled, Multiple-dose Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects With Active Rheumatoid Arthritis (RA) on Stable Methotrexate (MTX) Therapy
Study Start Date :	July 2009
Actual Primary Completion Date :	September 2010

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Low Dose; A low dose of LX3305; daily oral intake for 12 weeks	Drug: LX3305 low dose; A low dose of LX3305; daily oral intake for 12 weeks
Experimental: Mid Dose; A mid dose of LX3305; daily oral intake for 12 weeks	Drug: LX3305 mid dose; A mid dose of LX3305; daily oral intake for 12 weeks
Experimental: High Dose; A high dose of LX3305; daily oral intake for 12 weeks	Drug: LX3305 high dose; A high dose of LX3305; daily oral intake for 12 weeks
Placebo Comparator: Placebo; Matching placebo dosing with daily oral intake for 12 weeks	Drug: Placebo; Matching placebo dosing with daily oral intake for 12 weeks

Outcome Measures

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Primary Outcome Measures :

1. ACR20 Response at Week 12 [ Time Frame: 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 :

1. ACR50 Response at Week 12 [ Time Frame: 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).
2. ACR70 Response at Week 12 [ Time Frame: 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).
3. Hybrid ACR Response at Week 12 [ Time Frame: 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.
4. Change From Baseline in C-reactive Protein (mg/L) at Week 12 [ Time Frame: 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.
5. Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12 [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

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  Show 38 Study Locations

Sponsors and Collaborators

Lexicon Pharmaceuticals

Investigators

Study Director:	Joel P. Freiman, MD, MPH	Lexicon Pharmaceuticals, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00903383 History of Changes
Other Study ID Numbers:	Protocol LX3305.1-201-RA; LX3305.201, LX2931
First Posted:	May 18, 2009
Results First Posted:	December 15, 2011
Last Update Posted:	December 15, 2011
Last Verified:	November 2011

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents	Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors