Supplements, Placebo, or Rosuvastatin Study
Phase: PHASE2
Conditions: Hypercholesterolemia
Sponsor: The Cleveland Clinic

Cleveland Clinic 
CONFIDENTIAL 
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 Supplements, Placebo, or RosuvastaTin Study 
 
SPORT Trial Protocol Version 1.0 
 
23February 2021 
 
 
 
 
 
IND Number: 154728 
 
Study Chair: Steven E. Nissen, MD, MACC 
 
Principal Investigator: Luke Laffin, MD,  
 
Co-Investigator: Dennis Bruemmer, MD, PhD 
 
Sponsor: Cleveland Clinic Investigator Initiated Trial 
 
Funded by: Astra Zeneca 
 
 
 
 

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Study Chairman Protocol Approval Page 
 
 
 
Study Title: 
Supplements, Placebo, or RosuvastaTin Study 
 
 
SPORT Trial Protocol Version 1.0 
 
 
23February 2021 
 
Study Sponsor: Cleveland Clinic Investigator Initiated Trial 
 
 
I, the undersigned, have read and approve this protocol and agree on its content. It is confirmed that the 
information and guidance given in this protocol complies with scientific principles, the guidelines of 
Good Clinical Practice. 
 
 
Study Chairman Signature:    _
 
 
 
23Feb2021 
 
 
 
 
     
Steven Nissen, MD, MACC  
 
(Date) 
 
 
 
 
     
Cleveland Clinic  
 
 
 
                      
 
 
 
 
 
 
 
 

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Table of Contents 
List of abbreviations/definitions .......................................................................................... 5 
1 
Introduction ......................................................................................................................... 6 
1.1 
Background .............................................................................................................. 6 
1.2 
Purpose .................................................................................................................... 6 
2 
Objectives and endpoints ..................................................................................................... 6 
3 
Study design ........................................................................................................................ 7 
3.1 
Rationale for duration of administration ................................................................. 7 
3.2 
Risks and benefits .................................................................................................... 7 
4 
Population ............................................................................................................................ 7 
4.1 
Inclusion criteria ...................................................................................................... 7 
4.2 
Exclusion criteria ..................................................................................................... 8 
4.3 
Study medication/supplements ................................................................................ 8 
4.3.1 
Study medication/supplement groups ..................................................... 8 
4.3.2 
Medication/supplement study groups ..................................................... 9 
4.3.3 
Concomitant therapy ............................................................................... 9 
4.3.4 
Prohibited medication/supplement and therapies ................................... 9 
4.3.5 
Study group assignment, randomization ................................................. 9 
4.4 
Study group blinding ............................................................................................. 10 
5 
Informed consent procedures ............................................................................................ 10 
6 
Visit schedule and assessments ......................................................................................... 10 
6.1 
Subject demographics/other baseline characteristics ............................................ 13 
6.1.1 
Pregnancy assessments ......................................................................... 13 
7 
Study discontinuation and completion .............................................................................. 13 
7.1 
Discontinuation ...................................................................................................... 13 
7.1.1 
Discontinuation of study medication/supplement ................................. 13 
7.1.2 
Withdrawal of informed consent ........................................................... 14 
7.1.3 
Lost to follow-up ................................................................................... 14 
7.1.4 
Early study termination by the sponsor ................................................. 14 
7.2 
Study completion ................................................................................................... 15 
8 
Safety monitoring and reporting ........................................................................................ 15 
8.1 
Definition of adverse events and reporting requirements ...................................... 15 

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8.1.1 
Adverse events ...................................................................................... 15 
8.1.2 
Pregnancy reporting .............................................................................. 16 
8.1.3 
Executive Committee ............................................................................ 16 
9 
Data collection and database management ........................................................................ 16 
9.1 
Data collection ....................................................................................................... 16 
9.2 
Safety monitoring .................................................................................................. 17 
10 Data analysis and statistical methods ................................................................................ 17 
10.1 
Analysis sets .......................................................................................................... 17 
10.2 
Subject disposition ................................................................................................. 17 
10.3 
Subject demographics and baseline characteristics ............................................... 17 
10.4 
Study evaluations ................................................................................................... 17 
10.5 
Analysis of the primary endpoint .......................................................................... 18 
10.6 
Analysis of secondary endpoints ........................................................................... 18 
10.6.1 
Adverse events ...................................................................................... 19 
11 Ethical considerations and administrative procedures ...................................................... 19 
11.1 
Regulatory and ethical compliance........................................................................ 19 
11.2 
Responsibilities of the investigator and IRB ......................................................... 19 
12 References ......................................................................................................................... 20 
 
 

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List of abbreviations/definitions 
AE 
Adverse Event 
ASCVD 
Atherosclerotic Cardiovascular Disease 
eCRF 
Electronic Case Report Form  
dL 
Deciliter 
GCP 
Good Clinical Practice 
mg 
milligram(s) 
OTC 
Over the Counter 
SAE 
Serious adverse event 
Study 
Medication 
Study medication refers to FDA approved rosuvastatin 
Supplement 
Refers to over the counter fish oil, cinnamon, garlic, turmeric, plant sterol 
Sponsor 
Cleveland Clinic 

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1 
Introduction 
1.1 
Background 
Few well-controlled trials have studied the LDL-lowering effects of dozens of marketed “cholesterol 
health” dietary supplements. These products combine for sales of billions of dollars annually, primarily 
via online marketing.  The business model for the dietary supplement industry often relies on efforts to 
undermine FDA-approved cholesterol lowering medications in favor of “all natural” alternatives for 
“heart protection” and “cholesterol management.” Marketing of dietary supplements (without evidence 
of benefit) is protected by the Dietary Supplement Health and Education Act of 1994, which assigns 
oversight of this industry primarily to the Federal Trade Commission, rather than the Food and Drug 
Administration. The supplement industry markets against prescription statins on eCommerce platforms, 
but rarely, if ever, perform comparative studies. Furthermore, prior research suggests most U.S. 
consumers believe cholesterol health supplements are safer than statins, and a majority of the public also 
believe supplements are as effective, or more effective, than prescription statins.   Approximately one 
third of US adults who have been told they have elevated cholesterol are using a supplement to provide 
heart health protection rather than a statin.  This represents a significant public health concern. 1-6 
1.2 
Purpose 
The purpose of this study is to evaluate the effect of select dietary supplements on cholesterol health 
compared with a low dose of a statin. 
2 
Objectives and endpoints 
Primary Objective 
The primary objective of this study is to compare the LDL lowering of rosuvastatin with the effect of 
six commonly used dietary supplements on cholesterol health  
Secondary Objective 
Assess the effect of each supplement on inflammatory markers compared with rosuvastatin 5 mg. 
Primary Endpoint 
The percent change in LDL-C for rosuvastatin 5 mg compared with dietary supplements after 4 weeks. 
Secondary Endpoints 
 The percent change in high sensitivity C reactive protein (hsCRP) for rosuvastatin 5 mg and 
dietary supplements compared with placebo after 4 weeks. 
 The percent change in HDL-C, total cholesterol, and triglycerides for each supplement compared 
with rosuvastatin. 
 The percent change in HDL-C, total cholesterol, and triglycerides for each supplement compared 
with placebo. 

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3 
Study design 
A randomized, single blind study design will be used to evaluate rosuvastatin 5 mg. vs. placebo and 6 
commercially available over the counter supplements in a hierarchical testing order. Each participant 
will take study medication/supplement for a total of 4 weeks.  
3.1 
Rationale for duration of administration 
The duration of 4 weeks is sufficient as steady-state LDL-C levels are reached for rosuvastatin 5mg 
within two weeks.  
3.2 
Risks and benefits 
The risks may include a lack of effect on cholesterol health with supplements over a short duration, or 
an adverse effect of one of the study medication/supplements. Undeclared ingredients are a possibility 
with over-the-counter supplements. 
The benefits may include the potential to have an effect on cholesterol health with one or more of the 
study medication/supplements. 
4 
 Population 
The study will randomize primary prevention patients who are considered borderline and intermediate 
risk for ASCVD based upon the 2018 Cholesterol Treatment Guidelines7 and are not taking any of the 
studied medication/supplements at the time of randomization. 
4.1 
Inclusion criteria 
Subjects eligible for inclusion in this study must meet all of the following criteria: 
1. Written informed consent must be obtained before any assessment is performed. 
2. U.S. adults with primary hypercholesterolemia, 40-75 years of age. 
3. Not currently taking statins or one of the dietary supplements included in the trial. Patients 
willing to discontinue a prohibited supplement for 4 weeks prior to enrollment will be allowed to 
participate. 
4. LDL-cholesterol between 70 and 189 mg/dL. 
5. Patients without diabetes mellitus and a 10-year risk of ASCVD between 5 and <20% using the 
pooled cohort risk equation. * 
Or 
Patients with diabetes mellitus in females 50-60 years of age or males 40-50 years of age with an 
LDL-C between 70-189 mg/dL and with an ASCVD risk below 20%. 
 
 
 
*http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/ 

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4.2 
Exclusion criteria 
Subjects meeting any of the following criteria are not eligible for inclusion in this study: 
1. Age < 40  or >75 years of age 
2. Women who are pregnant, plan to become pregnant within the next 6 months, or are 
breastfeeding. 
3. Documented liver dysfunction or history of elevated LFTs indicating active liver disease 
4. Documented chronic renal dysfunction within the past two years defined as an 
eGFR<30mL/min/m2. 
5. Known hypersensitivity to rosuvastatin or any supplement under investigation (i.e. shellfish 
allergy, etc.). 
6. Currently taking any prescription statin, or other prescription medication/supplements to treat 
elevated cholesterol or triglycerides.  
7. Currently taking a medication/supplement that has known interaction with rosuvastatin, including 
fenofibrate, gemfibrozil, HIV medications, colchicine, cyclosporine, warfarin, anti-viral 
medications to treat Hepatitis C, regorafenib, and darolutamide. 
8. Are unwilling to discontinue prohibited dietary supplement(s) for 4 weeks prior to participation 
or during the course of the trial. Other non-prohibited supplements will be permitted if doses 
have been stable for at least 4 weeks. 
9. Known cardiovascular disease including a history of prior MI, stroke/TIA, PAD or prior 
revascularization procedures of the heart or vasculature (e.g. CABG, stenting, PCI etc.). 
10. Fasting Triglycerides >200mg/dl.  
11.  In the opinion of the investigator, any other condition that will preclude participation in the 
study. 
 
4.3 
Study medication/supplements 
4.3.1 
 Study medication/supplement groups 
Eight groups will be studied, Rosuvastatin 5 mg compared with the following: 
1. Placebo (comparable to rosuvastatin 5mg) 
2. Fish oil (Nature Made™ 2 soft gels / day) 
3. Cinnamon (1200mg,  2 capsules / day) 
4. Garlique™ (1 tablet / day) 
5. Turmeric (Bio Schwartz Turmeric Curcumin, 1500mg, 3 capsules / day)  
6. Plant sterol (Nature Made CholestOff™ Plus, 2 soft gels 2x / day)  
7. Red yeast rice (Arazo Nutrition, Red Yeast Rice, 1200mg, 2 capsules / day) 
 

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4.3.2 
Medication/supplement study groups 
Eligible subjects will be randomized 1:1:1:1:1:1:1:1 to the study groups in a blinded fashion. There will 
be 25 subjects per study group. The total sample size will be 200 patients. 
Sample Size and Power 
Assuming a common standard deviation of 15 and an alpha of 0.05, enrolling a total of 25 in each group 
will have 90% power to detect an average difference in percent change in LDL of 15 between 
rosuvastatin and each study group. 
4.3.3 
Concomitant therapy 
Medication/supplement classification used by the subject prior to randomization will be recorded in the 
eCRF pages. 
4.3.4 
Prohibited medication/supplement and therapies 
New use of prescription medication/supplements for elevated cholesterol or triglycerides during 
participation in the trial. 
New use of over the counter dietary supplements marketed for cholesterol health or triglyceride health 
for 4 weeks prior to or during participation in this study are prohibited. Chronic use of supplement types 
other than those being assessed in the trial will be permitted if doses have been stable for 4 weeks or 
longer.   
Patients will be encouraged to maintain lifestyle habits present at the time of trial enrollment during the 
course of the trial. Significant dietary and physical activity modifications will be discouraged over the 4 
weeks of participation. Participants are not to enroll in weight loss programs during the trial. 
4.3.5 
Study group assignment, randomization 
Randomization 
will 
occur 
using 
REDCap 
Cloud 
electronic 
database 
platform. 
Study 
medication/supplement will be dispensed by the investigational pharmacy in a blinded fashion for in 
person visits to study personnel or shipped to the subjects by the investigational pharmacy following 
randomization. Day 1 of the study is the first day that subjects start study medication/supplement. In the 
event that study medication/supplement is shipped to subjects, study personnel will verify the start of 
study medication/supplement (Day1) for medication/supplement accountability.  
 
The study medication/supplement will be supplied from commercially available products and 
administered according to the package insert. The rosuvastatin 5mg and placebo will be provided by 
Astra Zeneca.  The over the counter supplements will be purchased and due to documented history of 
supplement tainting, supplements may be tested for unlabeled enhancing impurities retrospectively if 
deemed necessary per data findings. If we observe > 15% lowering in LDL cholesterol, we will test for 
impurities. 
 
 

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4.4 
Study group blinding 
Subjects, investigator staff, persons performing the assessments, and the clinical trial team will be 
blinded to assigned study group. Baseline laboratory values will not be blinded to the subjects, 
investigator staff, and the clinical team. Additional lipid labs will be prohibited for the 4 week 
participation period. The Day 28 labs will not be blinded.  
 
It is expected that the need for unblinding of a patient’s study group will be extremely rare.  Every 
effort should be made to preserve the blind unless there is a compelling reason that knowledge of the 
specific treatment would alter the medical care of the patient. 
5 
Informed consent procedures 
Eligible subjects may only be included in the study after providing IRB approved informed consent. 
Informed consent must be obtained before conducting any study-specific procedures.  Subjects will be 
prescreened using historical laboratory values within 13 months of screening prior to consenting.  
Subjects that screen fail will not be eligible for rescreening.  
6 
Visit schedule and assessments 
Subjects should be seen for all visits/assessments as outlined in the assessment schedule.  The baseline 
and final visits will be completed in-person or remotely. 
The fasting lipid draw and complete metabolic panel (CMP) at Day 0 and Day 28 must be obtained from 
a Cleveland Clinic lab. Recently acquired lipid labs and complete metabolic panel may be used in place 
of a Day 0 lab draw if acquired within 4 weeks of screening at a Cleveland Clinic lab and performed in 
the fasting state. Subjects are to remain on study medication/supplement until Day 28 labs are drawn.  
 
Study personnel will use the following historical information to input into the ASCVD risk calculator to 
determine eligibility:  
 Age 
 Gender 
 Race 
 Systolic blood pressure 
 Diastolic blood pressure 
 Treatment for high blood pressure and diabetes 
 Current smoking status 
If a historical blood pressure is not found within 1 year of screening, patient reported is acceptable. 

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Lipid panel, hs-CRP will be collected at the initial visit and Day 28.   
 
 Lipids: Indirect LDL-C (Total Cholesterol, HDL-C, and Triglycerides)  
 Inflammatory markers:  hs-CRP    

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Table 7-1 
Assessment Schedule 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a  Females of child-bearing potential only, urine or serum at investigator’s discretion.  
b The baseline (0) and 28 Day visit may be completed remotely. Consent will be obtained 
prior to completion of the baseline visit and may be completed remotely in accordance with 
Cleveland Clinic guidelines 
c Fasting lipid panel and complete metabolic panel should be drawn a Cleveland Clinic lab 
facility. Patients should fast for approximately 8 hours. 
d Recently acquired lipid and complete metabolic panel labs may be used in place of a Day 0 
lab draw if acquired within 4 weeks of screening at a Cleveland Clinic lab. 
e  Study medication/supplement adherence will be assessed with a pill count.  The bottle will 
be returned to the study site to retain until the end of study. 
f  If enrolled for over 14 days and the patient discontinues study medication/supplement 
perform Day 28 lab work (ITT principle). 
g Historical documented height and weight may be used.  Weight to be within the last 3 
months.  Subject reported is acceptable. 
h Randomization and eligibility confirmation may occur on different days from baseline 
pending lab results 
i Study medication/supplement will be dispensed by the investigational pharmacy for in 
person visits to study personnel or shipped to the subjects by the investigational pharmacy 
following randomization. 
  
Study Day 
Activity 
Day 0 b 
Day 28b,f +4/-4 days 
Informed consent obtainedb 
X 
 
Demographics 
X 
 
Medical history 
X 
 
Eligibility confirmed & subject randomizedh 
X 
 
Body weightg 
X 
 
Heightg 
X 
 
Concomitant Medication/supplements 
X 
X 
Hs-CRP  
X 
X 
CMP, LDL-C,  TC, HDL-C, and TGsc, d 
X 
X 
Pregnancy test a 
X 
 
Study medication/supplement dispensedi 
X 
 
Adverse events 
 
X 
Study medication/supplement adherencee 
 
X 

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6.1 
Subject demographics/other baseline characteristics 
Patient demographic and baseline characteristic data will be collected on all subjects. 
6.1.1 
Pregnancy assessments  
All pre-menopausal women who are not surgically sterile will have a urine or serum 
pregnancy test performed at the Day 0 visit. Pregnancy testing is not required for post-
menopausal women.  
7 
Study discontinuation and completion 
7.1 
Discontinuation 
7.1.1 
Discontinuation of study medication/supplement 
Discontinuation of study medication/supplement for a subject occurs when the study 
medication/supplement is stopped earlier than the protocol planned duration, and can be 
initiated by either the subject or the investigator. 
The investigator must discontinue study medication/supplement for a given subject if, he/she 
believes that continuation would negatively impact the subject's well-being. After study 
medication/supplement discontinuation, the patient should remain in the study, unless he/she 
withdraws consent, preferably in writing. 
Study medication/supplement must be discontinued under the following circumstances: 
 Subject decision 
 Pregnancy 
 Any situation in which study participation might result in a safety risk to the subject 
 Any laboratory abnormalities that in the judgment of the investigator prevents the 
subject from continuing study medication/supplement administration 
If discontinuation of study medication/supplement occurs, the investigator should make a 
reasonable effort to understand the primary reason for the subject’s premature discontinuation 
of study medication/supplement and record this information.  
Subjects who discontinue study medication/supplement or who decide they do not wish to 
participate in the study further should NOT be considered withdrawn from the study UNLESS 
they withdraw their consent. If discontinuation occurs after Day 14, study personnel should 
attempt to obtain Day 28 labs as close as possible to last dose of study medication/supplement 
taken. 
Where possible, they should return for the Day 28 assessments indicated in the assessment 
schedule. If they fail to return for these assessments for unknown reasons, every effort (e.g. 
telephone, e-mail, and letter) should be made to contact the subject/pre-designated contact per 
institutional guidelines to collect as much data as possible according to the visit schedule. 

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Patient’s vital status can also be verified by the study site upon contact with patient’s primary 
care physician or other sources according to local rules and regulations. 
After study medication/supplement discontinuation, at a minimum, in the abbreviated visit, the 
following data should be collected either during an in person visit or via telephone/email 
contact: 
 new / concomitant treatments 
 adverse events/Serious Adverse Events 
7.1.1.1 
Replacement policy 
Subjects will not be replaced on study.  
7.1.2 
Withdrawal of informed consent 
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a subject: 
 Does not want to participate in the study anymore 
And 
 Does not allow  further collection of personal data 
It is encouraged that patient provides withdrawal of consent in writing. 
In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the subject’s decision to withdraw his/her consent and 
record this information. Patient’s vital status can be verified upon contact with patient’s primary 
care physician or other sources according to local rules and regulations. 
Study medication/supplement must be discontinued and no further assessments conducted, and 
the data that would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the subject are not allowed unless safety findings require 
communicating or follow-up. 
The study will continue to keep and use collected study information (including any data 
resulting from the analysis of a subject’s samples until the time of withdrawal) according to 
applicable regulations. 
7.1.3 
Lost to follow-up 
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must continue to attempt to contact the 
subject until the end of the study per institutional guidelines. A subject should not be considered 
as lost to follow-up until the end of the study. Vital status can be determined using publically 
available information in accordance with institutional guidelines. 
7.1.4 
Early study termination by the sponsor 
The study can be terminated by the sponsor at any time. Reasons for early termination: 

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 Unexpected, significant, or unacceptable safety risk to subjects enrolled in the study 
 Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data 
In making the decision to terminate, the sponsor will always consider the subject welfare and 
safety. Should early termination be necessary, subjects must be seen as soon as possible and 
treated as a prematurely withdrawn subject. The investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the subject’s interests. The sponsor will be responsible for informing IRB of the 
early termination of the trial. 
7.2 
Study completion  
Study completion is defined as when the last subject finishes their Day 28 visit, and any repeat 
assessments associated with this visit have been documented and followed-up appropriately by 
the Investigator, or in the event of an early study termination decision, the date of that decision.  
8 
Safety monitoring and reporting 
8.1 
Definition of adverse events and reporting requirements 
8.1.1 
Adverse events 
An adverse event is an untoward event that affects the patient’s health or safety. When reporting 
an adverse event, the investigator will complete the AE report form. Adverse events that require 
reporting include any clinical changes in condition that could possibly be attributed to: 
 Any of the study medication/supplements 
 Any study required procedures (lab draws) 
Each adverse event will be evaluated by the investigator for relatedness and seriousness.  
i) Relatedness  
The relatedness of an adverse event to the study medication/supplement will be assessed by the 
Investigator for each submitted adverse event form.  
 Possibly Related: An adverse event that is noted in the package insert. 
 Unknown: An adverse event that cannot be determined to have a causal relationship with 
either the study medication/supplement or study procedure will be classified as unknown.  
 Not Related: An adverse event that is determined to not have a causal relationship with 
either the study medication/supplement or study procedure.  
ii) Seriousness  
Adverse events as described above will be evaluated for serious injury. Adverse events resulting 
in death or serious injury are to be reported to the sponsor within 24 hours of learning of the 
event. An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the 
view of either the investigator or sponsor, it results in any of the following outcomes: death, a 

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life-threatening adverse event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect. Important medical events 
that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the participant 
and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
iii) SUSARS 
All Suspected Unexpected Serious Adverse Reactions (SUSARS) related to Rosuvastatin or 
supplements (if required per regulatory guidelines) are to be reported to the sponsor within 24 
hours of learning of the event.  
8.1.2 
Pregnancy reporting 
Pregnancies 
To ensure subject safety, each pregnancy occurring after signing the informed consent must be 
reported by the investigator to the sponsor. The pregnancy should be followed up to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the presence 
or absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. Pregnancy follow-up should include an assessment of the possible relationship 
to the study medication/supplement of any pregnancy outcome. Any SAE experienced during 
pregnancy must be reported. 
8.1.3 
Executive Committee 
The Executive Committee (EC) will play an active role in providing scientific guidance and 
advice to the sponsor related to the design, conduct, results analysis, and publication strategy 
for the SPORT study. The EC will be composed of members who are experts in preventive 
cardiology with relevant clinical trial methodological expertise. Meeting frequency, 
membership, and specific responsibilities will be further described in the EC Charter. 
9 
Data collection and database management 
9.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF) within the REDCap Cloud database. The eCRFs have been built 
using fully validated secure web-enabled software that conforms to 21 CFR Part 11 
requirements.  
The investigator/designee is responsible for assuring that the data entered into eCRF is 
complete, accurate, and that entry and updates are performed in a timely manner. The 
Investigator must certify that the data entered are complete and accurate. 
After final database lock, the investigator will receive copies of the subject data for archiving 
at the investigational site. 

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All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. 
9.2 
Safety monitoring 
The investigator must maintain source documents for each subject in the study, consisting of 
case and visit notes (hospital or clinic medical records) which may include demographic and 
medical information, laboratory data, and the results of any other tests or assessments. All 
information on eCRFs must be traceable to these source documents in the subject’s file. The 
investigator must also keep the original informed consent form signed by the subject (a signed 
copy is given to the subject). 
A Medical Monitor will review safety data for the study as specified in the Medical Monitor 
Charter. 
10 
Data analysis and statistical methods 
10.1 
Analysis sets 
The following analysis populations will be defined for statistical analysis: 
The full analysis set (FAS) consists of all enrolled patients.  Efficacy variables will be analyzed 
based on the FAS as the primary population. 
The safety analysis set (SAS) consists of all patients who received at least one dose of study 
medication/supplement. The safety population will be used for the analyses of safety variables. 
10.2 
Subject disposition  
The number of patients screened will be presented by study group and overall for the screened 
set. In addition, the reasons of screen failures will be provided for screened set as well. The 
number and percentage of patients who completed the study, who discontinued the study and 
the reason for discontinuation will be presented for each study group and all patients. The 
frequency (%) of patients with major protocol deviations will be presented in separate tables.  
10.3 
Subject demographics and baseline characteristics 
 
All demographic and baseline characteristics summaries will be based on the FAS. They will 
be presented in summary tables by study group. Continuous data will be summarized by 
descriptive statistics, and categorical data will be summarized by frequency distributions. 
Finally, the number of enrolled patients by site will be presented descriptively. 
10.4 
Study evaluations 
10.4.1     Study medication/supplement 
The duration of the study medication/supplement use will be computed as the time from the 
first dose to the patient’s study completion visit during the study close-out period. 

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The duration of the study medication/supplement use will be summarized for the full analysis 
set and safety set by study group descriptively including by duration categories.  
The safety set will be used for the above analyses unless otherwise specified. 
10.4.2     Prior and concomitant therapies 
Prior or concomitant medication/supplements will be summarized for the safety set in separate 
tabulations based on a predetermined list of medication/supplements.  Prior 
medication/supplement are defined as any medication/supplement a subject was taking prior 
to randomization in the study.  Concomitant medication/supplements will include any 
medication/supplements taken during the study period. 
10.5 
Analysis of the primary endpoint 
To control the overall alpha of the study, the primary endpoint will be evaluated hierarchically. 
Each comparison to rosuvastatin will use an alpha of 0.05.  Once a comparison is not met (2-
sided p-value ≥ 0.05) all subsequent comparisons will be considered exploratory with nominal 
p-values. The change in LDL-C for rosuvastatin will be compared with the other 7 study groups 
using ANCOVA in a hierarchical fashion in the following order: 
 Rosuvastatin 5 mg compared with the following: 
1. Placebo (identical to rosuvastatin 5mg) 
2. Fish oil (Nature Made™ 2 soft gels / day) 
3. Cinnamon (1200mg,  2 capsules / day) 
4. Garlique™ (1 tablet / day) 
5. Turmeric (Bio Schwartz Turmeric Curcumin, 1500mg, 3 capsules / day)  
6. Plant sterol (Nature Made CholestOff™ Plus, 2 soft gels 2x / day)  
7. Red yeast rice (Arazo Nutrition, Red Yeast Rice, 1200mg, 2 capsules / day) 
 
If the percent change in LDL has a non-normal distribution (graphically assessed), median 
values will be used to summarize the endpoints and compared with a non-parametric test. At a 
minimum, adjustments for baseline LDL and age will be used in summarizing the endpoints.  
Other adjustments may be warranted if differences in factors across study groups are 
statistically significant. The primary endpoint will be analyzed in the FAS. 
10.6 
Analysis of secondary endpoints 
The following secondary endpoints will be analyzed in the FAS: 
 Percent change in high sensitivity C reactive protein (hsCRP) for each study group 
compared with rosuvastatin 5 mg  
 The percent changes in HDL-C, total cholesterol, and triglycerides for each study group 
compared with rosuvastatin 5 mg 

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 The percent changes in HDL-C, total cholesterol, and triglycerides for each study group 
compared with placebo  
 
The comparisons of each study group to placebo will utilize placebo-subtracted changes from 
baseline.  Percent change from baseline for each study group and placebo will first be 
calculated.  The difference found in the placebo arm will then be subtracted from each study 
group. The mean and 95% confidence intervals will be used to summarize the effect of each 
study group. 
 
No hierarchical testing of the secondary endpoints will be conducted.  Since the study was not 
powered to test secondary endpoints, all testing and p-values will be considered exploratory.  
No adjustments will be made for multiplicity. 
10.6.1 
Adverse events 
All information obtained on adverse events will be summarized by study group.  A subject with 
multiple adverse events of the same type is only counted once towards the total of that event.  
Serious adverse event and deaths resulting from an adverse events will be tabulated.   All 
adverse events, deaths and serious adverse events will be provided in patient listings. 
11 
Ethical considerations and administrative procedures 
11.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations US CFR 21), and with the ethical principles laid down in the Declaration of 
Helsinki. 
11.2 
Responsibilities of the investigator and IRB 
Before initiating a trial, the investigator will obtain approval/favorable opinion from the 
Institutional Review Board (IRB) for the trial protocol, written informed consent form, consent 
form updates, subject recruitment procedures and any other written information to be provided 
to subjects.  
The protocol will be registered in a publicly accessible database clinicaltrials.gov. In addition, 
after study completion and finalization of the study report the results of this trial will be 
submitted for publication and posted in a publicly accessible database of clinical trial results in 
clinicaltrials.gov. 

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12 
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