Trial Outcomes & Findings for Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate (NCT NCT00903383)

NCT ID: NCT00903383

Last Updated: 2011-12-15

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 208 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2011-12-15

Participant Flow

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.

There was a 4 week screening period prior to the 12-week treatment period.

Participant milestones

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

Reasons for withdrawal

Measure	Low Dose A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose A mid dose of LX3305; daily oral intake for 12 weeks	High Dose A high dose of LX3305; daily oral intake for 12 weeks	Placebo Matching placebo dosing with daily oral intake for 12 weeks
Overall Study Adverse Event	1	2	3	1
Overall Study Physician Decision	1	2	0	0
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Decision of Sponsor	1	0	0	0
Overall Study Withdrawal by Subject	4	1	0	2
Overall Study Patient Decision - Lack of Efficacy	0	1	0	0
Overall Study Patient Decision	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks	Total n=208 Participants Total of all reporting groups
Age Continuous	56.5 years STANDARD_DEVIATION 9.25 • n=5 Participants	55.8 years STANDARD_DEVIATION 9.20 • n=7 Participants	56.4 years STANDARD_DEVIATION 10.89 • n=5 Participants	57.5 years STANDARD_DEVIATION 10.19 • n=4 Participants	56.5 years STANDARD_DEVIATION 9.83 • n=21 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	43 Participants n=7 Participants	37 Participants n=5 Participants	41 Participants n=4 Participants	168 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	8 Participants n=4 Participants	40 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Population

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).

Outcome measures

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks
ACR20 Response at Week 12	24 Participants	22 Participants	30 Participants	24 Participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Population

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).

Outcome measures

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks
ACR50 Response at Week 12	6 Participants	5 Participants	11 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Population

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).

Outcome measures

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks
ACR70 Response at Week 12	2 Participants	4 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Population

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.

Outcome measures

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks
Hybrid ACR Response at Week 12	26.595 Percent change Standard Deviation 23.2280	27.422 Percent change Standard Deviation 24.3453	37.356 Percent change Standard Deviation 26.1357	35.290 Percent change Standard Deviation 24.4368

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Population

The C-reactive protein value (mg/L) at baseline was subtracted from the value for each of the treatment groups at Week 12.

Outcome measures

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks
Change From Baseline in C-reactive Protein (mg/L) at Week 12	-0.026 mg/L Standard Deviation 15.7225 • Interval -1.5071 to 17.4208	5.342 mg/L Standard Deviation 26.5937 • Interval 2.0924 to 24.5573	-5.316 mg/L Standard Deviation 19.1959 • Interval -7.3324 to 12.6649	-7.983 mg/L Standard Deviation 28.5387 • Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to Treat Population

The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12.

Outcome measures

Measure	Low Dose n=55 Participants A low dose of LX3305; daily oral intake for 12 weeks	Mid Dose n=54 Participants A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 Participants A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 Participants Matching placebo dosing with daily oral intake for 12 weeks
Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12	-2.5 mm Standard Deviation 21.23 • Interval -3.0 to 13.18	-3.3 mm Standard Deviation 20.23 • Interval -3.59 to 12.07	-9.7 mm Standard Deviation 21.76 • Interval -10.32 to 6.17	-7.6 mm Standard Deviation 18.05 • Interval 0.0 to 0.0

Adverse Events

Mid Dose

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

High Dose

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Low Dose

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Mid Dose n=54 participants at risk A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 participants at risk A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 participants at risk Matching placebo dosing with daily oral intake for 12 weeks	Low Dose n=55 participants at risk A low dose of LX3305; daily oral intake for 12 weeks
Gastrointestinal disorders Nausea and Vomiting	0.00% 0/54 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	0.00% 0/50 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	0.00% 0/49 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	1.8% 1/55 • Number of events 1 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.
Cardiac disorders Atrial Fibrillation	0.00% 0/54 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	0.00% 0/50 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	0.00% 0/49 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	1.8% 1/55 • Number of events 1 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.

Other adverse events

Measure	Mid Dose n=54 participants at risk A mid dose of LX3305; daily oral intake for 12 weeks	High Dose n=50 participants at risk A high dose of LX3305; daily oral intake for 12 weeks	Placebo n=49 participants at risk Matching placebo dosing with daily oral intake for 12 weeks	Low Dose n=55 participants at risk A low dose of LX3305; daily oral intake for 12 weeks
Infections and infestations Urinary Tract Infection	1.9% 1/54 • Number of events 1 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	6.0% 3/50 • Number of events 5 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	12.2% 6/49 • Number of events 6 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	5.5% 3/55 • Number of events 4 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.
Gastrointestinal disorders Diarrhea	5.6% 3/54 • Number of events 3 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	4.0% 2/50 • Number of events 3 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	2.0% 1/49 • Number of events 1 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	3.6% 2/55 • Number of events 2 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	1.9% 1/54 • Number of events 1 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	6.0% 3/50 • Number of events 3 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	4.1% 2/49 • Number of events 2 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	3.6% 2/55 • Number of events 2 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.
Nervous system disorders Headache	0.00% 0/54 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	4.0% 2/50 • Number of events 2 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	6.1% 3/49 • Number of events 3 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.	5.5% 3/55 • Number of events 3 • Adverse events were followed during the 12-week Treatment period and during the 30-day Follow-up period.

Additional Information

Joel Freiman, MD, MPH

Lexicon Pharmaceuticals, Inc.

Phone: 281-863-3070

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor requires that written permission be given before the PI can release any data publicly.
• Publication restrictions are in place

Restriction type: OTHER