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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00903383
• Other study ID #: Protocol LX3305.1-201-RA
• Secondary ID: LX3305.201, LX29
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2009
• Last updated: November 11, 2011
• Start date: July 2009

Study information

• Verified date: November 2011
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• LX3305 low dose
A low dose of LX3305; daily oral intake for 12 weeks
• LX3305 mid dose
A mid dose of LX3305; daily oral intake for 12 weeks
• LX3305 high dose
A high dose of LX3305; daily oral intake for 12 weeks
• Placebo
Matching placebo dosing with daily oral intake for 12 weeks

Locations

Country	Name	City	State
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
Czech Republic	Lexicon Investigational Site	Bruntal
Czech Republic	Lexicon Investigational Site	Hlucin
Czech Republic	Lexicon Investigational Site	Sokolov
Czech Republic	Lexicon Investigational Site	Zlin
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
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
Serbia	Lexicon Investigational Site	Belgrade
Serbia	Lexicon Investigational Site	Niska Banja
United States	Lexicon Investigational Site	Cumberland	Maryland
United States	Lexicon Investigational Site	Dallas	Texas
United States	Lexicon Investigational Site	Flowood	Mississippi
United States	Lexicon Investigational Site	Gainesville	Florida
United States	Lexicon Investigational Site	Hagerstown	Maryland
United States	Lexicon Investigational Site	Hickory	North Carolina
United States	Lexicon Investigational Site	Kalamazoo	Michigan
United States	Lexicon Investigational Site	La Crosse	Wisconsin
United States	Lexicon Investigational Site	Nashville	Tennessee
United States	Lexicon Investigational Site	Orange Park	Florida
United States	Lexicon Investigational Site	Orlando	Florida
United States	Lexicon Investigational Site	Philadelphia	Pennsylvania
United States	Lexicon Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Czech Republic,  Hungary,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ACR20 Response at Week 12	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).	Baseline and 12 weeks	No
Secondary	ACR50 Response at Week 12	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).	Baseline and 12 weeks	No
Secondary	ACR70 Response at Week 12	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).	Baseline and 12 weeks	No
Secondary	Hybrid ACR Response at Week 12	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.	Baseline and 12 weeks	No
Secondary	Change From Baseline in C-reactive Protein (mg/L) at Week 12	The C-reactive protein value (mg/L) at baseline was subtracted from the value for each of the treatment groups at Week 12.	Baseline and 12 weeks	No
Secondary	Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12	The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12.	Baseline and 12 weeks	No