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

• ClinicalTrials.gov Identifier: NCT00903383
• Recruitment Status: Completed
• First Posted: May 18, 2009
• Results First Posted: December 15, 2011
• Last Update Posted: December 15, 2011
• Sponsor: Lexicon Pharmaceuticals
• Information provided by (Responsible Party): Lexicon Pharmaceuticals

Study Description

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

• 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

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

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

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• 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

Locations

United States, Florida

Lexicon Investigational Site

Gainesville, Florida, United States, 32607

Lexicon Investigational Site

Orange Park, Florida, United States, 32073

Lexicon Investigational Site

Orlando, Florida, United States, 32804

Lexicon Investigational Site

Tampa, Florida, United States, 33614

United States, Maryland

Lexicon Investigational Site

Cumberland, Maryland, United States, 21502

Lexicon Investigational Site

Hagerstown, Maryland, United States, 21740

United States, Michigan

Lexicon Investigational Site

Kalamazoo, Michigan, United States, 49009

United States, Mississippi

Lexicon Investigational Site

Flowood, Mississippi, United States, 39232

United States, North Carolina

Lexicon Investigational Site

Hickory, North Carolina, United States, 28601

United States, Pennsylvania

Lexicon Investigational Site

Philadelphia, Pennsylvania, United States, 19152

United States, Tennessee

Lexicon Investigational Site

Nashville, Tennessee, United States, 37205

United States, Texas

Lexicon Investigational Site

Dallas, Texas, United States, 75235

United States, Wisconsin

Lexicon Investigational Site

La Crosse, Wisconsin, United States, 54601

Bulgaria

Lexicon Investigational Site

Pleven, Bulgaria

Lexicon Investigational Site

Plovdiv, Bulgaria

Lexicon Investigational Site

Ruse, Bulgaria

Lexicon Investigational Site

Sofia, Bulgaria

Lexicon Investigational Site

Veliko Tarnovo, Bulgaria

Czech Republic

Lexicon Investigational Site

Bruntal, Czech Republic

Lexicon Investigational Site

Hlucin, Czech Republic

Lexicon Investigational Site

Sokolov, Czech Republic

Lexicon Investigational Site

Zlin, Czech Republic

Hungary

Lexicon Investigational Site

Bekescsaba, Hungary

Lexicon Investigational Site

Budapest, Hungary

Lexicon Investigational Site

Kecskemet, Hungary

Lexicon Investigational Site

Mako, Hungary

Lexicon Investigational Site

Sopron, Hungary

Lexicon Investigational Site

Veszprem, Hungary

Poland

Lexicon Investigational Site

Bialystok, Poland

Lexicon Investigational Site

Dzialdowo, Poland

Lexicon Investigational Site

Gdynia, Poland

Lexicon Investigational Site

Katowice, Poland

Lexicon Investigational Site

Lublin, Poland

Lexicon Investigational Site

Warszawa, Poland

Lexicon Investigational Site

Wloszczowa, Poland

Lexicon Investigational Site

Wroclaw, Poland

Serbia

Lexicon Investigational Site

Belgrade, Serbia

Lexicon Investigational Site

Niska Banja, Serbia

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
• 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