Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00302952
• Collaborator: Autoimmunity Centers of Excellence (Other)
• Enrollment: 64
• Locations: 15
• Arms: 2
• Actual Duration (Months): 53.8
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Rheumatoid arthritis (RA) is the most common inflammatory arthritis and a major health problem. The purpose of this study is to determine the safety and effectiveness of lovastatin for controlling inflammation in mildly active RA.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Lovastatin; Drug: Placebo	Phase 2

Detailed Description

RA is characterized by persistent inflammation of peripheral joints, causing pain, stiffness, swelling, and warmth. The inflammation may cause progressive joint damage and destruction, resulting in deformity and loss of function. Both traditional and biologic disease-modifying antirheumatic drugs (DMARDs) have been prescribed for RA patients to control existing inflammatory symptoms and affect long-term prognosis. However, DMARD use is expensive, and the long-term safety of DMARDs is unknown. Lovastatin is an HMG-CoA reductase inhibitor (also known as a statin) used to lower levels of cholesterol and other fats in the blood. The purpose of this study is to examine the safety and efficacy of lovastatin in controlling inflammation in individuals with RA who have mildly active RA disease despite treatment.

Participants will be randomly assigned to one of two study arms (Experimental or Placebo). There will be four study visits over 12 weeks. At each visit, a physical exam, vital signs measurement, medication history, a pregnancy test (if applicable), and blood collection will occur. Additional safety blood testing will occur at Week 2. Tender and swollen joint counts and a Physician Global Assessment will occur at study entry and Week 12. Participants will also be asked to complete self-assessments at study entry and Week 12.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Double Blind, Placebo Controlled, Phase II, Randomized Study of Lovastatin Therapy in the Treatment of Mildly Active Rheumatoid Arthritis
• Actual Study Start Date: Nov 6, 2007
• Actual Primary Completion Date: Apr 30, 2012
• Actual Study Completion Date: Apr 30, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lovastatin Participants are randomized to take two 40 mg lovastatin 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 40 mg lovastatin tablet or treatment could be discontinued. 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.	Drug: Lovastatin; Two 40 mg lovastatin tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion; Other Names: Altoprev Mevacor Mevinolin
Placebo Comparator: Placebo Participants are 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.	Drug: Placebo; Two placebo tablets orally once daily for a total of 12 weeks in a blinded (masked) fashion; Other Names: Inactive drug (pharmacologically)

Outcome Measures

Primary Outcome Measures

1. Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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.

2. Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

3. Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

4. Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

5. Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

6. Change From Baseline in CPK at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

7. Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

8. Change From Baseline in Hematocrit (Hct) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

9. Change From Baseline in Red Cell Distribution Width (RDW) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

   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

10. Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

    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

11. Change From Baseline in Mean Corpuscular Volume (MCV) at Day 84 [Baseline (Day 0), Day 84 (Wk 12)]

    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

Secondary Outcome Measures

1. Adjusted Mean Change From Baseline in the Disease Activity Score Using C-reactive Protein (DAS28-CRP) on Day 84 [Baseline (Day 0) to Day 84 (Wk 12)]

   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.

2. Percentage of Participants Meeting ACR20 Response Criteria at Day 84 (ACR: American College of Rheumatology) [Day 84 (Wk 12)]

   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.

3. Adjusted Mean Change From Baseline in Serum IgM Rheumatoid Factor by ELISA (ELISA: Enzyme-linked Immunosorbent Assay) [Baseline (Day 0), Day 84 (Wk 12)]

   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.

4. Adjusted Mean Change From Baseline in Serum Anti-cyclic Citrullinated Peptide (Anti-CCP) by ELISA (ELISA: Enzyme-linked Immunosorbent Assay) [Baseline ( Day 0), Day 84 (Wk 12)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of RA as defined by 1987 American College of Rheumatology (ACR) criteria

• Functional Class I, II, or III RA as defined by 1987 ACR criteria

• Serum C-reactive protein (CRP) measurement of greater than 5 mg/L

• Mildly active disease with at least one swollen and two tender joints, but no more than six swollen and eight tender joints

• If on corticosteroids, dose must be stable and 10 mg/day prednisone (or equivalent) or less for at least 4 weeks prior to study entry

• If on DMARD, dose must be stable for at least 4 weeks (methotrexate, leflunomide, azathioprine, etanercept, adalimumab, anakinra) or at least 3 months (hydroxychloroquine, gold, or abatacept)

• Willing to use acceptable means of contraception

Exclusion Criteria:

• Serum creatinine level greater than 1.5 mg/dL

• Currently taking a statin or have taken a statin within 12 weeks of study entry

• History of an adverse reaction to a statin

• Active or recent infection within 4 weeks of study entry

• Myositis or an unexplained elevation in creatine phosphokinase (CPK)

• Joint replacement surgery within 60 days of study entry or plan to undergo joint replacement surgery during the course of the study

• Intra-articular cortisone injections within 4 weeks of study entry

• Chronic disorders other than RA affecting the joints, including systemic lupus erythematosus (SLE), psoriatic arthritis, gout, scleroderma, or known reactive arthritis (Reiter's syndrome)

• HIV infection

• Hepatitis B surface antigen positive

• Hepatitis C antibody positive

• Treatment with infliximab within 12 weeks of study entry

• Treatment with rituximab

• Treatment with medications known to be metabolized by the cytochrome P3A4 pathway. More information about this criterion can be found in the protocol.

• Require amiodarone or verapamil

• Investigational drug or treatment during the 4 weeks or seven half-lives prior to study entry

• History of alcohol abuse

• History of liver disease, current liver disease (e.g., hepatitis, cirrhosis), or abnormal liver function (AST or ALT greater than 2 times the upper limit of normal [ULN])

• Any condition that, in the opinion of the investigator, may interfere with the study

• Pregnancy or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	University of California, San Francisco	San Francisco	California	United States	94143
3	University of Colorado	Aurora	Colorado	United States	80095
4	University of Chicago Medical Center	Chicago	Illinois	United States	60637
5	Justus J. Fiechtner, MD, PLLC	Lansing	Michigan	United States	48910
6	Feinstein Institute for Medical Research NS-LIJ Health System	Manhasset	New York	United States	11030
7	University of Rochester	Rochester	New York	United States	14642
8	Carolina Bone and Joint	Charlotte	North Carolina	United States	29425
9	Duke University Medical Center	Durham	North Carolina	United States	27710
10	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
11	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
12	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15261
13	Medical University of South Carolina	Charleston	South Carolina	United States	29425
14	Baylor Research Institute	Dallas	Texas	United States	75231
15	University of Utah	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Autoimmunity Centers of Excellence

Investigators

• Study Chair: Cynthia Aranow, MD, Feinstein Institute for Medical Research NS-LIJ Health System
• Study Chair: Betty Diamond, MD, Feinstein Institute for Medical Research NS-LIJ Health System

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Autoimmunity Centers of Excellence (ACE)

Publications

• Abud-Mendoza C, de la Fuente H, Cuevas-Orta E, Baranda L, Cruz-Rizo J, González-Amaro R. Therapy with statins in patients with refractory rheumatic diseases: a preliminary study. Lupus. 2003;12(8):607-11.
• McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004 Jun 19;363(9426):2015-21.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00302952
• Other Study ID Numbers: DAIT ARA02
• First Posted: Mar 15, 2006
• Last Update Posted: Nov 4, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Arthritis, Rheumatoid
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Lovastatin; L 647318; Dihydromevinolin

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	34	30
Started Intent-to-Treat (ITT)	34	30
Completed Intent-to-Treat (ITT)	34	29
COMPLETED	31	25
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Lovastatin 80 mg	Placebo	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	34	29	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.8 (7.1)	52.6 (10.4)	54.3 (8.8)
Sex: Female, Male (Count of Participants)
Female	32 94.1%	28 96.6%	60 95.2%
Male	2 5.9%	1 3.4%	3 4.8%
Region of Enrollment (participants) [Number]
United States	34 100%	29 100%	63 100%
Years with Rheumatoid Arthritis at Baseline (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.5 (9.6)	11.9 (12.6)	12.2 (11.0)
Number of Participants at Baseline Who Were Taking Methotrexate (Number) [Number]
Number [Participants]	20 58.8%	16 55.2%	36 57.1%
Number of Participants at Baseline Who Were Taking an Anti-TNF Drug (Number) [Number]
Number [Participants]	16 47.1%	10 34.5%	26 41.3%
Number of Participants at Baseline Who Were Taking a Biologic Drug (Number) [Number]
Number [Participants]	20 58.8%	11 37.9%	31 49.2%
C-reactive Protein (CRP) Level at Baseline (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	12.2 (11.4)	12.6 (16.4)	12.4 (13.8)
Tender Joint Count at Baseline (tender joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [tender joints]	4.4 (2.5)	4.8 (2.2)	4.6 (2.4)
Swollen Joint Count at Baseline (swollen joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [swollen joints]	3.5 (1.4)	3.8 (1.6)	3.6 (1.5)
Patient Global Assessment of Disease Activity - Visual Analog Scale (VAS) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	3.5 (2.3)	4.5 (1.6)	4.0 (2.0)
Disease Activity Score Using C-reactive Protein (DAS28-CRP) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	3.9 (0.7)	4.2 (0.4)	4.0 (0.6)

Outcome Measures

1. Primary Outcome

Title	Adjusted Mean Change From Baseline in Log Transformed C - Reactive Protein (CRP) at Day 84
Description	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.
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with available data

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	30	25
Mean (Standard Error) [mg/L]	-0.4 (0.2)	-0.3 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lovastatin 80 mg, Placebo
	Comments	The p-value compares Lovastatin with the Placebo treatment group. Log transformed CRP was analyzed to meet the heterogeneity assumption for ANCOVA models.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments	Adjustments were made for baseline ln(CRP), baseline DAS28-CRP score, race, methotrexate use, anti-TNF use, and disease duration.
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Alkaline Phosphatase	-3.0 (20.4)	0.4 (15.6)
ALT	-1.8 (10.2)	0.7 (10.2)
AST	-1.2 (19.7)	0.8 (7.3)

3. Secondary Outcome

Title	Adjusted Mean Change From Baseline in the Disease Activity Score Using C-reactive Protein (DAS28-CRP) on Day 84
Description	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.
Time Frame	Baseline (Day 0) to Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with Available Data

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	31	25
Mean (Standard Error) [Scores on a scale]	-0.5 (0.2)	-0.5 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lovastatin 80 mg, Placebo
	Comments	The p-value compares Lovastatin with the Placebo treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	Adjustments were made for baseline DAS28-CRP score.
	Method	ANCOVA
	Comments	ANOVA was performed on participants with a DAS28-CRP score at Day 84.

4. Secondary Outcome

Title	Percentage of Participants Meeting ACR20 Response Criteria at Day 84 (ACR: American College of Rheumatology)
Description	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.
Time Frame	Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with Available Data

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	31	25
Number [Percentage of participants]	29.0 85.3%	40.0 137.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lovastatin 80 mg, Placebo
	Comments	The p-value compares Lovastatin with the Placebo treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-11.0
	Confidence Interval	(2-Sided) 95%; -35.9 to 14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in percentages is calculated as Lovastatin - Placebo.

5. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Serum IgM Rheumatoid Factor by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)
Description	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.
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with Available Data

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	31	25
Mean (Standard Error) [IU/mL]	-5.4 (4.0)	2.8 (4.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lovastatin 80 mg, Placebo
	Comments	The p-value compares Lovastatin with the Placebo treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	Adjustments were made for baseline serum IgM RF by ELISA test result. In the ANCOVA model, baseline value was a covariate; therefore, an adjustment was performed.
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Serum Anti-cyclic Citrullinated Peptide (Anti-CCP) by ELISA (ELISA: Enzyme-linked Immunosorbent Assay)
Description	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.
Time Frame	Baseline ( Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with Available Data

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	31	25
Mean (Standard Error) [IU/mL]	16.3 (12.1)	-1.0 (13.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lovastatin 80 mg, Placebo
	Comments	The p-value compares Lovastatin with the Placebo treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments	Adjustments were made for baseline serum anti-CCP by ELISA
	Method	ANCOVA
	Comments

7. Primary Outcome

Title	Change From Baseline in Total Bilirubin, Creatinine, BUN, Phosphorus, Calcium, and Glucose at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Total Bilirubin	0.0 (0.2)	0.1 (0.2)
Creatinine	0.0 (0.1)	0.0 (0.1)
BUN	-0.4 (3.2)	-0.5 (2.3)
Phosphorus	0.0 (0.5)	0.0 (0.5)
Calcium	0.0 (0.4)	0.0 (0.3)
Glucose	-4.3 (16.5)	-1.2 (18.6)

8. Primary Outcome

Title	Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscular Hemoglobin Concentration (MCHC) at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Albumin	0.0 (0.2)	0.1 (0.3)
Total Protein	0.0 (0.4)	0.1 (0.5)
Hemoglobin	-0.3 (0.6)	-0.3 (0.6)
MCHC	-0.3 (0.9)	-0.4 (1.0)

9. Primary Outcome

Title	Change From Baseline in Potassium, Sodium, Chloride, and Total CO2 at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Potassium	0.0 (0.3)	0.0 (0.5)
Sodium	-0.2 (1.8)	-0.2 (2.7)
Chloride	-0.1 (2.3)	0.5 (3.0)
Total CO2	0.7 (2.6)	-0.5 (2.3)

10. Primary Outcome

Title	Change From Baseline in CPK at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Mean (Standard Deviation) [U/L]	-2.4 (51.2)	8.0 (54.0)

11. Primary Outcome

Title	Change From Baseline in Counts: White Blood Cells (WBC), Neutrophils, Bands, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, and Reticulocytes at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
WBC	0.1 (1.0)	-0.4 (1.3)
Neutrophils	0.2 (1.0)	-0.6 (1.3)
Bands	0.0 (0.1)	0.0 (0.1)
Lymphocytes	-0.1 (0.4)	0.1 (0.8)
Monocytes	0.1 (0.1)	0.0 (0.2)
Eosinophils	0.0 (0.1)	0.0 (0.2)
Basophils	0.0 (0.0)	0.0 (0.0)
Platelet Count	-8.2 (34.2)	-5.6 (56.8)
Reticulocytes	-4.7 (15.6)	0.0 (0.0)

12. Primary Outcome

Title	Change From Baseline in Hematocrit (Hct) at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Mean (Standard Deviation) [% of packed red blood cells by volume]	-0.5 (2.2)	-0.5 (2.2)

13. Primary Outcome

Title	Change From Baseline in Red Cell Distribution Width (RDW) at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Mean (Standard Deviation) [% of mean corpuscle volume]	-0.4 (2.0)	0.2 (1.1)

14. Primary Outcome

Title	Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Mean (Standard Deviation) [pg]	-0.4 (0.7)	0.0 (1.3)

15. Primary Outcome

Title	Change From Baseline in Mean Corpuscular Volume (MCV) at Day 84
Description	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
Time Frame	Baseline (Day 0), Day 84 (Wk 12)

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Lovastatin 80 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	34	30
Mean (Standard Deviation) [fL]	-0.4 (2.3)	0.7 (3.2)

Adverse Events

Time Frame	Beginning of study to end of study.
Adverse Event Reporting Description	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)
Arm/Group Title	Lovastatin 80 mg		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Lovastatin 80 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lovastatin 80 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		1/30 (3.3%)
Gastrointestinal disorders
Haematemesis	0/34 (0%)	0	1/30 (3.3%)	1
Infections and infestations
Upper respiratory tract infection	1/34 (2.9%)	1	0/30 (0%)	0
Other (Not Including Serious) Adverse Events
	Lovastatin 80 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/34 (67.6%)		25/30 (83.3%)
Blood and lymphatic system disorders
Anaemia	9/34 (26.5%)	9	6/30 (20%)	8
Leukopenia	2/34 (5.9%)	2	3/30 (10%)	3
Lymphopenia	3/34 (8.8%)	3	3/30 (10%)	3
Gastrointestinal disorders
Diarrhoea	1/34 (2.9%)	1	4/30 (13.3%)	5
Nausea	2/34 (5.9%)	2	4/30 (13.3%)	5
Infections and infestations
Upper respiratory tract infection	3/34 (8.8%)	4	1/30 (3.3%)	1
Investigations
Alanine aminotransferase increased	3/34 (8.8%)	3	4/30 (13.3%)	5
Aspartate aminotransferase increased	4/34 (11.8%)	4	4/30 (13.3%)	5
Blood creatine phosphokinase increased	4/34 (11.8%)	4	3/30 (10%)	3
Metabolism and nutrition disorders
Hyperglycaemia	1/34 (2.9%)	1	3/30 (10%)	3
Hypoalbuminaemia	3/34 (8.8%)	3	3/30 (10%)	3
Hypocalcaemia	2/34 (5.9%)	2	3/30 (10%)	3
Hypoglycaemia	4/34 (11.8%)	4	3/30 (10%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	4/34 (11.8%)	8	2/30 (6.7%)	2
Synovitis	3/34 (8.8%)	3	2/30 (6.7%)	2

Limitations/Caveats

Enrollment was slow and the full sample size was not obtained.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.