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

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00903383
• Collaborator: (none)
• Enrollment: 208
• Locations: 38
• Arms: 4
• Patients Per Site: 5.5

Study Details

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
• 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: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 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 [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 [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 [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Lexicon Investigational Site	Gainesville	Florida	United States	32607
2	Lexicon Investigational Site	Orange Park	Florida	United States	32073
3	Lexicon Investigational Site	Orlando	Florida	United States	32804
4	Lexicon Investigational Site	Tampa	Florida	United States	33614
5	Lexicon Investigational Site	Cumberland	Maryland	United States	21502
6	Lexicon Investigational Site	Hagerstown	Maryland	United States	21740
7	Lexicon Investigational Site	Kalamazoo	Michigan	United States	49009
8	Lexicon Investigational Site	Flowood	Mississippi	United States	39232
9	Lexicon Investigational Site	Hickory	North Carolina	United States	28601
10	Lexicon Investigational Site	Philadelphia	Pennsylvania	United States	19152
11	Lexicon Investigational Site	Nashville	Tennessee	United States	37205
12	Lexicon Investigational Site	Dallas	Texas	United States	75235
13	Lexicon Investigational Site	La Crosse	Wisconsin	United States	54601
14	Lexicon Investigational Site	Pleven		Bulgaria
15	Lexicon Investigational Site	Plovdiv		Bulgaria
16	Lexicon Investigational Site	Ruse		Bulgaria
17	Lexicon Investigational Site	Sofia		Bulgaria
18	Lexicon Investigational Site	Veliko Tarnovo		Bulgaria
19	Lexicon Investigational Site	Bruntal		Czech Republic
20	Lexicon Investigational Site	Hlucin		Czech Republic
21	Lexicon Investigational Site	Sokolov		Czech Republic
22	Lexicon Investigational Site	Zlin		Czech Republic
23	Lexicon Investigational Site	Bekescsaba		Hungary
24	Lexicon Investigational Site	Budapest		Hungary
25	Lexicon Investigational Site	Kecskemet		Hungary
26	Lexicon Investigational Site	Mako		Hungary
27	Lexicon Investigational Site	Sopron		Hungary
28	Lexicon Investigational Site	Veszprem		Hungary
29	Lexicon Investigational Site	Bialystok		Poland
30	Lexicon Investigational Site	Dzialdowo		Poland
31	Lexicon Investigational Site	Gdynia		Poland
32	Lexicon Investigational Site	Katowice		Poland
33	Lexicon Investigational Site	Lublin		Poland
34	Lexicon Investigational Site	Warszawa		Poland
35	Lexicon Investigational Site	Wloszczowa		Poland
36	Lexicon Investigational Site	Wroclaw		Poland
37	Lexicon Investigational Site	Belgrade		Serbia
38	Lexicon Investigational Site	Niska Banja		Serbia

Sponsors and Collaborators

• Lexicon Pharmaceuticals

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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
• Last Update Posted: Dec 15, 2011
• Last Verified: Nov 1, 2011

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Recruitment Details	There were 43 study centers in 6 countries (10 in the US, 8 in Bulgaria, 4 in Czech Republic, 7 in Hungary, 11 in Poland, and 3 in Serbia). The first subject was enrolled on 31 August 2009, and the last subject completed the study on 30 September 2010.
Pre-assignment Detail	There was a 4 week screening period prior to the 12-week treatment period.

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Period Title: Overall Study
STARTED	55	54	50	49
COMPLETED	48	48	47	44
NOT COMPLETED	7	6	3	5

Baseline Characteristics

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo	Total
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks	Total of all reporting groups
Overall Participants	55	54	50	49	208
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (9.25)	55.8 (9.20)	56.4 (10.89)	57.5 (10.19)	56.5 (9.83)
Sex: Female, Male (Count of Participants)
Female	47 85.5%	43 79.6%	37 74%	41 83.7%	168 80.8%
Male	8 14.5%	11 20.4%	13 26%	8 16.3%	40 19.2%

Outcome Measures

1. Primary Outcome

Title	ACR20 Response at Week 12
Description	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).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Measure Participants	55	54	50	49
Number [Participants]	24 43.6%	22 40.7%	30 60%	24 49%

2. Secondary Outcome

Title	ACR50 Response at Week 12
Description	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).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Measure Participants	55	54	50	49
Number [Participants]	6 10.9%	5 9.3%	11 22%	12 24.5%

3. Secondary Outcome

Title	ACR70 Response at Week 12
Description	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).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Measure Participants	55	54	50	49
Number [Participants]	2 3.6%	4 7.4%	5 10%	3 6.1%

4. Secondary Outcome

Title	Hybrid ACR Response at Week 12
Description	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.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Measure Participants	55	54	50	49
Mean (Standard Deviation) [Percent change]	26.595 (23.2280)	27.422 (24.3453)	37.356 (26.1357)	35.290 (24.4368)

5. Secondary Outcome

Title	Change From Baseline in C-reactive Protein (mg/L) at Week 12
Description	The C-reactive protein value (mg/L) at baseline was subtracted from the value for each of the treatment groups at Week 12.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Measure Participants	55	54	50	49
Mean (Standard Deviation) [mg/L]	-0.026 (15.7225)	5.342 (26.5937)	-5.316 (19.1959)	-7.983 (28.5387)

6. Secondary Outcome

Title	Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12
Description	The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose	Mid Dose	High Dose	Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks	A mid dose of LX3305; daily oral intake for 12 weeks	A high dose of LX3305; daily oral intake for 12 weeks	Matching placebo dosing with daily oral intake for 12 weeks
Measure Participants	55	54	50	49
Mean (Standard Deviation) [mm]	-2.5 (21.23)	-3.3 (20.23)	-9.7 (21.76)	-7.6 (18.05)

Adverse Events

Time Frame	Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.
Arm/Group Title	Low Dose		Mid Dose		High Dose		Placebo
Arm/Group Description	A low dose of LX3305; daily oral intake for 12 weeks		A mid dose of LX3305; daily oral intake for 12 weeks		A high dose of LX3305; daily oral intake for 12 weeks		Matching placebo dosing with daily oral intake for 12 weeks
All Cause Mortality
	Low Dose		Mid Dose		High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Dose		Mid Dose		High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/55 (3.6%)		0/54 (0%)		0/50 (0%)		0/49 (0%)
Cardiac disorders
Atrial Fibrillation	1/55 (1.8%)	1	0/54 (0%)	0	0/50 (0%)	0	0/49 (0%)	0
Gastrointestinal disorders
Nausea and Vomiting	1/55 (1.8%)	1	0/54 (0%)	0	0/50 (0%)	0	0/49 (0%)	0
Other (Not Including Serious) Adverse Events
	Low Dose		Mid Dose		High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/55 (18.2%)		5/54 (9.3%)		10/50 (20%)		12/49 (24.5%)
Gastrointestinal disorders
Diarrhea	2/55 (3.6%)	2	3/54 (5.6%)	3	2/50 (4%)	3	1/49 (2%)	1
Infections and infestations
Urinary Tract Infection	3/55 (5.5%)	4	1/54 (1.9%)	1	3/50 (6%)	5	6/49 (12.2%)	6
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis	2/55 (3.6%)	2	1/54 (1.9%)	1	3/50 (6%)	3	2/49 (4.1%)	2
Nervous system disorders
Headache	3/55 (5.5%)	3	0/54 (0%)	0	2/50 (4%)	2	3/49 (6.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor requires that written permission be given before the PI can release any data publicly.