Trial Outcomes & Findings for Study of LX3305 and Methotrexate in Subjects With Stable Rheumatoid Arthritis (NCT NCT00847886)

NCT ID: NCT00847886

Last Updated: 2010-06-03

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 15 participants
• Primary outcome timeframe: Day 15
• Results posted on: 2010-06-03

Participant Flow

This study was performed at one center in Dallas, TX. Recruitment began in January 2009 and the last subject completed the study in March 2009.

One subject did not complete the study due to an adverse event of uveitis on Day 1 and was not dosed with study drug. This subject was not included in any population analyses. Therefore, the participant flow includes 15 subjects, 12 receiving active drug and 3 receiving placebo.

Participant milestones

Measure	LX3305 + Methotrexate Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate Matching placebo dosing with daily oral intake for 14 days.
Overall Study STARTED	12	4
Overall Study COMPLETED	12	3
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	LX3305 + Methotrexate Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate Matching placebo dosing with daily oral intake for 14 days.
Overall Study Adverse Event	0	1

Baseline Characteristics

Study of LX3305 and Methotrexate in Subjects With Stable Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.	Total n=15 Participants Total of all reporting groups
Age Continuous	59.8 years STANDARD_DEVIATION 10.25 • n=5 Participants	58.7 years STANDARD_DEVIATION 14.74 • n=7 Participants	59.5 years STANDARD_DEVIATION 10.67 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	3 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 15

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Methotrexate Maximum Plasma Concentration	215 ng/mL Standard Deviation 71.4	177 ng/mL Standard Deviation 72.1

PRIMARY outcome

Timeframe: Day 15

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Time to Reach Maximum Plasma Concentration of Methotrexate	0.98 hours Interval 0.9 to 2.98	1.25 hours Interval 1.0 to 3.0

PRIMARY outcome

Timeframe: Day 15

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Half-life of Methotrexate in Plasma	3.80 hours Standard Deviation 0.520	3.80 hours Standard Deviation 0.693

PRIMARY outcome

Timeframe: Day 15

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Amount of Methotrexate Excreted in the Urine	3861 µg Standard Deviation 1720	4022 µg Standard Deviation 1218

PRIMARY outcome

Timeframe: Day 15

7-OH-MTX is the primary metabolite of methotrexate.

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
7-Hydroxymethotrexate (7-OH-MTX) Maximum Plasma Concentration	25.5 ng/mL Standard Deviation 12.8	25.5 ng/mL Standard Deviation 15.4

PRIMARY outcome

Timeframe: Day 15

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Time to Reach Maximum Plasma Concentration of 7-OH-MTX	6.01 hours Interval 5.9 to 11.98	8.00 hours Interval 4.0 to 12.0

PRIMARY outcome

Timeframe: Day 15

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Amount of 7-OH-MTX Excreted in the Urine	285 µg Standard Deviation 106	281 µg Standard Deviation 109

SECONDARY outcome

Timeframe: Day 15

Population: This outcome was not measured in the Methotrexate + LX3305 placebo subjects.

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate Matching placebo dosing with daily oral intake for 14 days.
Maximum Plasma Concentration of LX3305 in the Presence of MTX	588 ng/mL Standard Deviation 233	—

SECONDARY outcome

Timeframe: Day 15

Population: This outcome was not measured in the Methotrexate + LX3305 placebo subjects.

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate Matching placebo dosing with daily oral intake for 14 days.
Time to Maximum Plasma Concentration of LX3305 in the Presence of MTX	2.25 hours Interval 1.42 to 4.0	—

SECONDARY outcome

Timeframe: Day 15

Population: This outcome was not measured in the Methotrexate + LX3305 placebo subjects.

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate Matching placebo dosing with daily oral intake for 14 days.
Half-life of LX3305 in Plasma in the Presence of MTX	5.89 hours Standard Deviation 1.54	—

SECONDARY outcome

Timeframe: Day 15

Baseline was defined as pre-dose on Day 1.

Outcome measures

Measure	LX3305 + Methotrexate n=12 Participants Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 Participants Matching placebo dosing with daily oral intake for 14 days.
Percentage of Change From Baseline in Absolute Total Lymphocyte Count at Day 15	-14.049 Percent Standard Deviation 29.1505	-6.152 Percent Standard Deviation 15.0143

Adverse Events

LX3305 + Methotrexate

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Methotrexate

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LX3305 + Methotrexate n=12 participants at risk Daily oral intake of 100 mg LX3305 for 14 days.	Methotrexate n=3 participants at risk Matching placebo dosing with daily oral intake for 14 days.
Gastrointestinal disorders Abdominal Pain	25.0% 3/12 • Number of events 3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Nausea	25.0% 3/12 • Number of events 3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Vomiting	16.7% 2/12 • Number of events 2 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Abdominal Discomfort	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Abdominal Pain Upper	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Constipation	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Diarrhea	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Diarrhea hemorrhagic	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Gastrointestinal disorders Dyspepsia	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
General disorders Fatigue	16.7% 2/12 • Number of events 2 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
General disorders Non-cardiac chest pain	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
General disorders Pain	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
General disorders Pyrexia	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Infections and infestations Urinary tract infection	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	33.3% 1/3 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Infections and infestations Upper respiratory tract infection	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Nervous system disorders Headache	25.0% 3/12 • Number of events 4 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	33.3% 1/3 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Musculoskeletal and connective tissue disorders Athralgia	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Musculoskeletal and connective tissue disorders Back Pain	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/12 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	33.3% 1/3 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Eye disorders Eye swelling	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Eye disorders Ocular hyperemia	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Metabolism and nutrition disorders Fluid retention	0.00% 0/12 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	33.3% 1/3 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.
Respiratory, thoracic and mediastinal disorders Dyspnea	8.3% 1/12 • Number of events 1 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.	0.00% 0/3 • 22 days An adverse event is defined as any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to the study medication.

Additional Information

Joel P. Freiman, MD, MPH - Medical Director, Drug Safety

Lexicon Pharmaceuticals, Inc.

Phone: 281-863-3000

Results disclosure agreements

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

Restriction type: OTHER