Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate - Full Text View

Purpose

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	Intervention	Phase
Rheumatoid Arthritis	Drug: LX3305 low dose Drug: LX3305 mid dose Drug: LX3305 high dose Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Genetics Home Reference related topics: rheumatoid arthritis

MedlinePlus related topics: Arthritis Rheumatoid Arthritis

Drug Information available for: Methotrexate

U.S. FDA Resources

Further study details as provided by Lexicon Pharmaceuticals:

Primary Outcome Measures:

ACR20 Response at Week 12 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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:

ACR50 Response at Week 12 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12.


Enrollment:	208
Study Start Date:	July 2009
Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903383

Show 38 Study Locations

Sponsors and Collaborators

Lexicon Pharmaceuticals

Investigators


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

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
Study First Received:	May 14, 2009
Results First Received:	October 3, 2011
Last Updated:	November 11, 2011
Health Authority:	United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 29, 2016