Trial Outcomes & Findings for Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis (NCT NCT00302952)

Results Overview

Blood draw for CRP, an acute phase reactant used to identify the presence of nonspecific inflammation. Change=Day 84 value minus Baseline value. Normal serum CRP reference range in this study is 0-4 mg/L (log transformed: -4.2 to 1.4). Participants with measurements for designated time points were included in analysis. An increased CRP level indicates the presence of inflammation. Reduced CRP levels could mean a decrease in inflammation.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

Baseline (Day 0), Day 84 (Wk 12)

Results posted on

2022-09-07

Participant Flow

Fifteen sites in the United States participated. The first site was activated in August 2006. The first participant was randomized in November 2007 and the last participant was randomized in February 2012.

Participant milestones

Participant milestones
Measure	Lovastatin 80 mg Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Overall Study STARTED	34	30
Overall Study Started Intent-to-Treat (ITT)	34	30
Overall Study Completed Intent-to-Treat (ITT)	34	29
Overall Study COMPLETED	31	25
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Lovastatin 80 mg Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	2	3
Overall Study Elevated SGOT (AST) lab value	0	1

Baseline Characteristics

Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=29 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.	Total n=63 Participants Total of all reporting groups
Age, Continuous	55.8 years STANDARD_DEVIATION 7.1 • n=5 Participants	52.6 years STANDARD_DEVIATION 10.4 • n=7 Participants	54.3 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	34 participants n=5 Participants	29 participants n=7 Participants	63 participants n=5 Participants
Years with Rheumatoid Arthritis at Baseline	12.5 years STANDARD_DEVIATION 9.6 • n=5 Participants	11.9 years STANDARD_DEVIATION 12.6 • n=7 Participants	12.2 years STANDARD_DEVIATION 11.0 • n=5 Participants
Number of Participants at Baseline Who Were Taking Methotrexate	20 Participants n=5 Participants	16 Participants n=7 Participants	36 Participants n=5 Participants
Number of Participants at Baseline Who Were Taking an Anti-TNF Drug	16 Participants n=5 Participants	10 Participants n=7 Participants	26 Participants n=5 Participants
Number of Participants at Baseline Who Were Taking a Biologic Drug	20 Participants n=5 Participants	11 Participants n=7 Participants	31 Participants n=5 Participants
C-reactive Protein (CRP) Level at Baseline	12.2 mg/L STANDARD_DEVIATION 11.4 • n=5 Participants	12.6 mg/L STANDARD_DEVIATION 16.4 • n=7 Participants	12.4 mg/L STANDARD_DEVIATION 13.8 • n=5 Participants
Tender Joint Count at Baseline	4.4 tender joints STANDARD_DEVIATION 2.5 • n=5 Participants	4.8 tender joints STANDARD_DEVIATION 2.2 • n=7 Participants	4.6 tender joints STANDARD_DEVIATION 2.4 • n=5 Participants
Swollen Joint Count at Baseline	3.5 swollen joints STANDARD_DEVIATION 1.4 • n=5 Participants	3.8 swollen joints STANDARD_DEVIATION 1.6 • n=7 Participants	3.6 swollen joints STANDARD_DEVIATION 1.5 • n=5 Participants
Patient Global Assessment of Disease Activity - Visual Analog Scale (VAS)	3.5 cm STANDARD_DEVIATION 2.3 • n=5 Participants	4.5 cm STANDARD_DEVIATION 1.6 • n=7 Participants	4.0 cm STANDARD_DEVIATION 2.0 • n=5 Participants
Disease Activity Score Using C-reactive Protein (DAS28-CRP)	3.9 scores on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	4.2 scores on a scale STANDARD_DEVIATION 0.4 • n=7 Participants	4.0 scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Intent-to-Treat with available data

Blood draw for CRP, an acute phase reactant used to identify the presence of nonspecific inflammation. Change=Day 84 value minus Baseline value. Normal serum CRP reference range in this study is 0-4 mg/L (log transformed: -4.2 to 1.4). Participants with measurements for designated time points were included in analysis. An increased CRP level indicates the presence of inflammation. Reduced CRP levels could mean a decrease in inflammation.

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=30 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=25 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84	-0.4 mg/L Standard Error 0.2	-0.3 mg/L Standard Error 0.1

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84 Alkaline Phosphatase	-3.0 U/L Standard Deviation 20.4	0.4 U/L Standard Deviation 15.6
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84 ALT	-1.8 U/L Standard Deviation 10.2	0.7 U/L Standard Deviation 10.2
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84 AST	-1.2 U/L Standard Deviation 19.7	0.8 U/L Standard Deviation 7.3

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 Total Bilirubin	0.0 mg/dL Standard Deviation 0.2	0.1 mg/dL Standard Deviation 0.2
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 Creatinine	0.0 mg/dL Standard Deviation 0.1	0.0 mg/dL Standard Deviation 0.1
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 BUN	-0.4 mg/dL Standard Deviation 3.2	-0.5 mg/dL Standard Deviation 2.3
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 Phosphorus	0.0 mg/dL Standard Deviation 0.5	0.0 mg/dL Standard Deviation 0.5
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 Calcium	0.0 mg/dL Standard Deviation 0.4	0.0 mg/dL Standard Deviation 0.3
Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 Glucose	-4.3 mg/dL Standard Deviation 16.5	-1.2 mg/dL Standard Deviation 18.6

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84 Albumin	0.0 g/dL Standard Deviation 0.2	0.1 g/dL Standard Deviation 0.3
Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84 Total Protein	0.0 g/dL Standard Deviation 0.4	0.1 g/dL Standard Deviation 0.5
Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84 Hemoglobin	-0.3 g/dL Standard Deviation 0.6	-0.3 g/dL Standard Deviation 0.6
Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84 MCHC	-0.3 g/dL Standard Deviation 0.9	-0.4 g/dL Standard Deviation 1.0

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84 Potassium	0.0 mmol/L Standard Deviation 0.3	0.0 mmol/L Standard Deviation 0.5
Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84 Sodium	-0.2 mmol/L Standard Deviation 1.8	-0.2 mmol/L Standard Deviation 2.7
Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84 Chloride	-0.1 mmol/L Standard Deviation 2.3	0.5 mmol/L Standard Deviation 3.0
Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84 Total CO2	0.7 mmol/L Standard Deviation 2.6	-0.5 mmol/L Standard Deviation 2.3

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in CPK at Day 84	-2.4 U/L Standard Deviation 51.2	8.0 U/L Standard Deviation 54.0

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 WBC	0.1 10^3/uL Standard Deviation 1.0	-0.4 10^3/uL Standard Deviation 1.3
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Neutrophils	0.2 10^3/uL Standard Deviation 1.0	-0.6 10^3/uL Standard Deviation 1.3
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Bands	0.0 10^3/uL Standard Deviation 0.1	0.0 10^3/uL Standard Deviation 0.1
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Lymphocytes	-0.1 10^3/uL Standard Deviation 0.4	0.1 10^3/uL Standard Deviation 0.8
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Monocytes	0.1 10^3/uL Standard Deviation 0.1	0.0 10^3/uL Standard Deviation 0.2
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Eosinophils	0.0 10^3/uL Standard Deviation 0.1	0.0 10^3/uL Standard Deviation 0.2
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Basophils	0.0 10^3/uL Standard Deviation 0.0	0.0 10^3/uL Standard Deviation 0.0
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Platelet Count	-8.2 10^3/uL Standard Deviation 34.2	-5.6 10^3/uL Standard Deviation 56.8
Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 Reticulocytes	-4.7 10^3/uL Standard Deviation 15.6	0.0 10^3/uL Standard Deviation 0.0

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Hematocrit (Hct) at Day 84	-0.5 % of packed red blood cells by volume Standard Deviation 2.2	-0.5 % of packed red blood cells by volume Standard Deviation 2.2

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Red Cell Distribution Width (RDW) at Day 84	-0.4 % of mean corpuscle volume Standard Deviation 2.0	0.2 % of mean corpuscle volume Standard Deviation 1.1

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Day 84	-0.4 pg Standard Deviation 0.7	0.0 pg Standard Deviation 1.3

PRIMARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Safety

Blood samples were taken from participants at Baseline and Day 84. Participants with measurements for designated time points included in analysis. Change=Day 84 value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values. Reference: http://www.merckmanuals.com/professional/appendixes/normal\_laboratory\_values/blood\_tests\_normal\_values.html

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=34 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Change From Baseline in Mean Corpuscular Volume (MCV) at Day 84	-0.4 fL Standard Deviation 2.3	0.7 fL Standard Deviation 3.2

SECONDARY outcome

Timeframe: Baseline (Day 0) to Day 84 (Wk 12)

Population: Intent-to-Treat with Available Data

The DAS28-CRP score is on a scale of 0 to 10 and indicates current activity of rheumatoid arthritis (\>5.1=high disease activity; 3.2-\<=5.1=moderate disease activity; \<=3.2=low disease activity; \<2.6=remission). The score uses a combination of four variables: 1) the number of tender joints (of the 28 that are measured); 2) the number of swollen joints (of the 28 that are measured); 3) serum C-reactive protein (CRP) lab value in mg/L , and 4) Patient Global Assessment of Disease Activity. Using a formula, the physician determines the score. Participants with measurements for designated time points included in analysis.

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=31 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=25 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Adjusted Mean Change From Baseline in the Disease Activity Score Using C-reactive Protein (DAS28-CRP) on Day 84	-0.5 Scores on a scale Standard Error 0.2	-0.5 Scores on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Day 84 (Wk 12)

Population: Intent-to-Treat with Available Data

Patients were ACR20 Responders if they had: at least 20% improvement in both tender joint count (28 examined) and swollen joint count (28 examined), and 20% improvement in at least three of the following 5 remaining ACR core measures: • Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) • Patient's global assessment of disease activity (VAS 100 mm) • Physician's global assessment of disease activity (VAS 100 mm) • Patient self-assessed disability (Health Assessment Questionnaire (HAQ)) score • Acute phase reactant C-reactive protein. Participants with measurements for designated time points were included in analysis.

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=31 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=25 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Percentage of Participants Meeting ACR20 Response Criteria at Day 84 (ACR: American College of Rheumatology)	29.0 Percentage of participants	40.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 84 (Wk 12)

Population: Intent-to-Treat with Available Data

Rheumatoid factor (RF) is an antibody often present in the blood of a person with rheumatoid arthritis. In this study, a positive value for RF was 0.5 IU/mL or greater; a negative value for RF was \<0.5 IU/mL. Change= Day 84 value minus Baseline value. In general, presence of the antibody indicates aggressive rheumatoid arthritis and higher risk of joint damage. Participants with measurements for designated time points included in analysis.

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=31 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=25 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Adjusted Mean Change From Baseline in Serum IgM Rheumatoid Factor by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)	-5.4 IU/mL Standard Error 4.0	2.8 IU/mL Standard Error 4.5

SECONDARY outcome

Timeframe: Baseline ( Day 0), Day 84 (Wk 12)

Population: Intent-to-Treat with Available Data

Anti-CCP antibodies are autoantibodies frequently detected in the serum of individuals with rheumatoid arthritis. In this study, a positive value for anti-CCP was 8 IU/mL or greater; a negative value for anti-CCP was \<8 IU/mL. Change= subtraction of Day 0 from Day 84 anti-CCP value. In general, high levels of the antibody indicate an aggressive rheumatoid arthritis and a higher risk of joint damage. Participants with measurements for designated time points included in analysis.

Outcome measures

Outcome measures
Measure	Lovastatin 80 mg n=31 Participants Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=25 Participants Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Adjusted Mean Change From Baseline in Serum Anti-cyclic Citrullinated Peptide (Anti-CCP) by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)	16.3 IU/mL Standard Error 12.1	-1.0 IU/mL Standard Error 13.5

Adverse Events

Lovastatin 80 mg

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lovastatin 80 mg n=34 participants at risk Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 participants at risk Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Gastrointestinal disorders Haematemesis	0.00% 0/34 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	3.3% 1/30 • Number of events 1 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Upper respiratory tract infection	2.9% 1/34 • Number of events 1 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/30 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)

Other adverse events

Additional Information

Associate Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lovastatin 80 mg n=34 participants at risk Participants were randomized to take two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. In addition to the active ingredient lovastatin, each tablet contained the following ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, and pregelatinized starch. Butylated hydroxyanisole (BHA) was added as a preservative and D\&C Yellow #10, FD\&C Blue #1, and Yellow #6 were added as dyes.	Placebo n=30 participants at risk Participants were randomized to take two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion. For toxicity, the dose could either be adjusted to one placebo tablet or treatment could be discontinued. The placebo tablets contained microcrystalline cellulose, NF (Avicel PH 102) and Supro AA Swedish Orange Opaque Capsule Shells, Color 4188.
Blood and lymphatic system disorders Anaemia	26.5% 9/34 • Number of events 9 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	20.0% 6/30 • Number of events 8 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Blood and lymphatic system disorders Leukopenia	5.9% 2/34 • Number of events 2 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Blood and lymphatic system disorders Lymphopenia	8.8% 3/34 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Gastrointestinal disorders Diarrhoea	2.9% 1/34 • Number of events 1 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	13.3% 4/30 • Number of events 5 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Gastrointestinal disorders Nausea	5.9% 2/34 • Number of events 2 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	13.3% 4/30 • Number of events 5 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Upper respiratory tract infection	8.8% 3/34 • Number of events 4 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	3.3% 1/30 • Number of events 1 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Alanine aminotransferase increased	8.8% 3/34 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	13.3% 4/30 • Number of events 5 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Aspartate aminotransferase increased	11.8% 4/34 • Number of events 4 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	13.3% 4/30 • Number of events 5 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Blood creatine phosphokinase increased	11.8% 4/34 • Number of events 4 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hyperglycaemia	2.9% 1/34 • Number of events 1 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypoalbuminaemia	8.8% 3/34 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypocalcaemia	5.9% 2/34 • Number of events 2 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypoglycaemia	11.8% 4/34 • Number of events 4 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	10.0% 3/30 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Musculoskeletal and connective tissue disorders Arthralgia	11.8% 4/34 • Number of events 8 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	6.7% 2/30 • Number of events 2 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Musculoskeletal and connective tissue disorders Synovitis	8.8% 3/34 • Number of events 3 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	6.7% 2/30 • Number of events 2 • Beginning of study to end of study. This study graded the severity of adverse events experienced by the study participant according to criteria set forth by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)