Clinical trial NCT02719028
Conditions: Hyperlipidemias
Sponsor: Golden Biotechnology Corporation
Start date: 2016-05-01; Completion date: 2019-03-31
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Identified the efficacy of Antroquinonol (Hocena 50mg) in triglyceride, lipid-lowering and fatty liver.

Detailed description:
The primary efficacy objective is to demonstrate the reduction of triglyceride (TG) by Antroquinonol, in comparison with placebo, after 12 weeks of treatment in patients with hypercholesterolemia and hyperlipidemia. Secondary objectives include the evaluation of the effects of Antroquinonol in comparison with placebo on other lipid parameters after 12 weeks of treatment and the effects of Antroquinonol on left ventricular diastolic function, arterial stiffness and fatty liver. The safety and tolerability of Antroquinonol will be monitored as well.

Arms: arm 1: Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (antroquinnonol 50mg or Placebo) 3 capsules once a day. arm 2: Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (antroquinnonol 50mg or Placebo) 3 capsules once a day. arm 3: Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (antroquinnonol 50mg or Placebo) 3 capsules once a day. arm 4: Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (antroquinnonol 50mg or Placebo) 3 capsules once a day.
Interventions: intervention 1: Antroquinonol intervention 2: placebo
Intervention descriptions: intervention 1: Antroquinonol will be provided as capsules of 50 mg intervention 2: The matching placebo will be packaged as Antroquinonol with appearance identical in all aspects, however, don't have the active compound(antroquinonol)

Protocol documents:
Prot_001.pdf: 
All the information disclosed or provided by the Golden Biotechnology Corporation or produced during the 
clinical trial, including this protocol, the CRFs, the Investigator Brochure, and the results obtained during the 
clinical trial, is confidential and is intended for the use of clinical investigators, and any person under his/her 
authority agree to keep confidential. This protocol is the property of Golden Biotechnology Corporation and 
should not be copied, distributed to persons not involved in this clinical trial, or published without the 
permission of Golden Biotechnology Corporation. 
 
 
 
CLINICAL STUDY PROTOCOL 
 
 
 
A Prospective, Double Blind, Randomized, 
Placebo-controlled Trial of Antroquinonol in 
Patients with Hypercholesterolemia and 
Hyperlipidemia 
Protocol Number: GHLIP-2-001 
Study Product: Antroquinonol (Hocena® ) 
 
 
 
 
 
Phase of Development: Research (Phase II) 
Indication: 
Hyperlipidemia 
Principal Investigator: 
Fu-Tien Chiang, M.D. 
Sponsor: 
Golden Biotechnology Corporation 
Version Number: 
V2.1 
Date 
03-Feb-2017 
 
 
 
 
 
 


Protocol No.: GHLIP-2-001 
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AMENDMENT HISTORY 
 
 
Amendment 
No. 
Version No. Version Date 
Authors of 
changes 
Summary of Revisions 
1 
V1.2 
07-Dec-2015 Sponsor 
Revise criteria based on 
TFDA’s comments 
2 
V2.0 
05-Feb-2016 
Sponsor 
1. open for sites join 
2. revise criteria 
3. revise cfPWV to baPWV 
4. add ABI measurement 
3 
V2.1 
03-Feb-2017 Sponsor 1. Remove 
NSAID 
as 
prohibited medication 
2. Accept laboratory data 
obtained within 3 days 
from screening visit. 
3. Accept Doppler color 
flow mapping and liver 
CT scan images 
obtained within 14 days  
from visit 2 


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SIGNATURE PAGES 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
The study will be carried out in accordance with the protocol, the International Conference on 
Harmonisation guidelines for Good Clinical Practice (ICH E6), and in accordance to local legal 
and regulatory requirements. All personnel involved in the conduct of this study have 
completed human subject protection training. 
 
 
 
 
Study Site: 
Investigator: 
Date: 
(yyyy/mm/dd) 


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SPONSOR SIGNATURE PAGE 
 
 
The study will be carried out in accordance with the protocol, the International Conference on 
Harmonisation guidelines for Good Clinical Practice (ICH E6), and in accordance to local legal 
and regulatory requirements. All personnel involved in the conduct of this study have 
completed human subject protection training. 
 
 
 
 
Representative: 
Signature: 
Date: 
Sheng-Yung Liu, CEO 
Name, Title 
   
(yyyy/mm/dd) 


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CONTACT INFORMATION OF KEY ROLES 
 
 
CHIEF PRINCIPAL INVESTIGATOR 
Name 
Fu-Tien Chiang, M.D. 江福田 教授 
Address 
National Taiwan University Hospital 
No.7, Zhongshan S. Rd., Zhongzheng District, Taipei City 10002, Taiwan 
SPONSOR’S REPRESENTATIVE 
Name 
Golden Biotechnology Corp. 
Address 
15F., No.27-6, Sec. 2, Zhongzheng E. Rd., Tamsui Dist., New Taipei City 251, 
Taiwan 
Tel 
+886-2-2808-6006 
Fax 
+886-2-2808-6007 
CRO REPRESENTATIVE 
Name 
Bestat Pharmaservices Corp. 
Address 
6F., No.277, Sec. 3, Chengde Rd., Datong Dist., Taipei City 103, Taiwan 
Tel 
+886-2-2595-5590 
Fax 
+886-2-2595-5290 


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TABLE OF CONTENT 
AMENDMENT HISTORY ........................................................................................................................................................... 2 
SIGNATURE PAGES ..................................................................................................................................................................... 3 
CONTACT INFORMATION OF KEY ROLES ........................................................................................................ 5 
TABLE OF CONTENT ................................................................................................................................................. 6 
LIST OF ABBREVIATIONS ....................................................................................................................................... 9 
PROTOCOL SUMMARY ............................................................................................................................................ 11 
1. INTRODUCTION ............................................................................................................................................... 17 
1.1. Background Information ................................................................................................................... 17 
1.2. Study Rationale ..................................................................................................................................................... 18 
1.3. Potential Risks and Benefits ......................................................................................................................... 18 
1.3.1. 
Potential risk ............................................................................................................................ 18 
1.3.2. 
Potential benefits ................................................................................................................................. 18 
2. STUDY OBJECTIVES ........................................................................................................................................ 19 
2.1. Primary objective ................................................................................................................................. 19 
2.2. Secondary objectives ........................................................................................................................... 19 
3. STUDY DESIGNS ............................................................................................................................................... 20 
3.1. General Design ....................................................................................................................................... 20 
3.2. Primary Study Endpoints ................................................................................................................................ 21 
3.3. Secondary Study Endpoints............................................................................................................................ 21 
3.4. Safety Endpoints .................................................................................................................................................. 22 
4. SUBJECTS SELECTION AND WITHDRAWAL ................................................................................................... 23 
4.1. Number of Subjects ............................................................................................................................................ 23 
4.2. Inclusion Criteria ................................................................................................................................... 23 
4.3. Exclusion Criteria .................................................................................................................................. 24 
4.4. Strategies for Recruitment and Retention ................................................................................... 25 
4.5. Treatment Assignment Procedures .................................................................................................... 25 
4.5.1. 
Randomization procedures ...................................................................................................... 25 
4.5.2. 
Blinding procedures .................................................................................................................... 25 
4.5.3. 
Subject identifier .................................................................................................................................. 26 
4.5.4. 
Reasons for withdrawal ................................................................................................................... 27 
4.5.5. 
Handling of withdrawals ................................................................................................................. 27 
4.5.6. 
Termination of study ............................................................................................................................... 28 
5. STUDY DRUG/INTERVENTION .................................................................................................................. 29 


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5.1. Description of Study Drug .................................................................................................................. 29 
5.1.1. 
Drugs manufacture and supplier ...................................................................................... 29 
5.1.2. 
Formulation, packaging and labeling ........................................................................................ 29 
5.1.3. 
Product storage and stability ........................................................................................................ 29 
5.2. Dosage, Preparation and Administration of Study Drug ......................................................... 30 
5.3. Modification of Study Drug for a Subject ...................................................................................... 30 
5.4. Accountability Procedures and Assessment of Subject Compliance for the Study 
Drug(s) ................................................................................................................................................................ 30 
5.5. Treatment for Study Drug Overdose ...............................................................................................................31 
5.6. Concomitant Medications/Treatments ................................................................................................... 31 
5.6.1 
Prohibited medications/treatments ......................................................................................... 31 
5.6.2 
Permitted medications/treatments ........................................................................................... 31 
6. STUDY PROCEDURES ..................................................................................................................................... 32 
6.1. Flow Chart ................................................................................................................................................ 32 
6.2. Study Procedures ......................................................................................................................................... 35 
6.2.1. 
Screening (Day -14) ............................................................................................................... 35 
6.2.2. 
Enrollment/Randomization (Day 1) ................................................................................ 35 
6.2.3. 
On treatment visits (Day 29±3, Day 57±3, Day 85±3) ............................................... 36 
6.2.4. 
Final study visit (Day 99±3)................................................................................................ 37 
6.2.5. 
Early termination visit /Withdrawal visit ..................................................................... 38 
6.2.6. 
Unscheduled Visit .................................................................................................................... 39 
7. STUDY EVALUATIONS ...........................................................................................................................................................40 
7.1. Informed Consent ................................................................................................................................. 40 
7.2. Eligibility Assessments.............................................................................................................................. 40 
7.3. Demography Data and Medical History ........................................................................................ 41 
7.4. Urine Pregnancy Test/Contraception Methods ................................................................................. 42 
7.4.1. 
Urine pregnancy test ............................................................................................................. 42 
7.4.2. 
Contraception methods .................................................................................................................... 42 
7.5. Laboratory Evaluations ................................................................................................................................... 43 
7.5.1 Clinical laboratory evaluations ................................................................................................... 43 
7.5.2 Specimen preparation, handling, and storage ................................................................. 44 
7.6. Adverse event ......................................................................................................................................... 44 
7.7. Concomitant medications .................................................................................................................. 45 
8. ASSESSMENT OF SAFETY ............................................................................................................................. 46 
8.1. Adverse Events (AE)............................................................................................................................. 46 
8.2. Expected Adverse Reactions............................................................................................................. 48 
8.3. Serious Adverse Events (SAE) .......................................................................................................... 48 


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8.4. Reporting Procedures ............................................................................................................................... 49 
8.4.1. 
Reporting procedures for AEs and SAEs ........................................................................ 49 
8.4.2. 
Reporting pregnancy ............................................................................................................ 50 
9. STATISTICAL CONSIDERATIONS AND ANALYTICAL PLAN ............................................................. 52 
9.1. Study Hypothesis ................................................................................................................................... 52 
9.2. Sample Size Considerations ........................................................................................................................... 52 
9.3. Analyzed Population ......................................................................................................................................... 52 
9.4. Analysis Plan ................................................................................................................................................................. 53 
9.5. Premature Termination and Missing Values ............................................................................................ 54 
10. DATA HANDLING AND RECORD KEEPING ............................................................................................. 55 
10.1. Data Management Responsibilities ................................................................................................ 55 
10.2. Investigator’s File/Retention of Documents......................................................................................... 55 
10.3. Source Documentation and Background Data ........................................................................................ 55 
10.4. Case Report Form (CRF) .................................................................................................................... 56 
10.5. Data Capture Methods....................................................................................................................................... 56 
10.6. Study Records Retention .................................................................................................................... 56 
10.7. Protocol Deviations ............................................................................................................................. 56 
11. STUDY MONITORING, AUDIT AND INSPECTION ................................................................................. 58 
11.1. Study Monitoring................................................................................................................................... 58 
11.2. Study Audit and Inspection ............................................................................................................... 58 
12. QUALITY CONTROL AND QUALITY ASSURANCE ................................................................................ 59 
13. ETHICAL CONSIDERATIONS ....................................................................................................................... 60 
13.1. Ethical Standard ..................................................................................................................................................................... 60 
13.2. Research Ethics Committees (REC) ............................................................................................... 60 
13.3. Informed Consent Process ................................................................................................................ 60 
13.4. Subject Confidentiality ...................................................................................................................................... 61 
13.5. Protocol Amendments ...................................................................................................................................... 61 
14. PUBLICATION POLICY .................................................................................................................................... 62 
15.   APPENDIX................................................................................................................. 錯誤!   尚未定義書籤。 
Appendix 1. TFDA approval letter................................................................... 錯誤!  尚未定義書籤。 
Appendix 2. TSGH IRB Approval Letter........................................................ 錯誤!  尚未定義書籤。 
16. REFERENCES ..................................................................................................................................................... 62 


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LIST OF ABBREVIATIONS 
 
 
ABI 
Ankle-brachial index 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
baPWV 
Brachial-ankle pulse wave velocity 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CAD 
Coronary artery disease 
CCR 
Creatinine clearance rate 
CPK 
Creatine phosphokinase 
CRF 
Case report form[s] 
CRO 
Contract research organization 
CT 
Computer-assisted tomography 
CVD 
Cardiovascular disease 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EENT 
Eyes, ears, nose, throat 
eGFR 
Estimated glomerular filtration rate 
HDL-C 
High density lipoprotein cholesterol 
HF 
Heart failure 
hsCRP 
High sensitivity assay of C-reactive protein 
HU 
Hounsfield unit 
IB 
Investigator Brochure 
ICH 
International Conference on Harmonization 
IL-1 
Interleukin 1 
IL-6 
Interleukin 6 
ITT 
Intent to treat 
LDL-C 
Low density lipoprotein cholesterol 
LVAD 
Left ventricular assist device 
MCH 
Mean corpuscular hemoglobin 


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MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
MTD 
Maximum tolerated dose 
NSCLC 
Non-small cell lung cancer 
PK 
Pharmacokinetic 
PR 
Pulse rate 
REC 
Research ethics committee 
RBC 
Red blood cell 
SAE 
Serious adverse event 
TC 
Total cholesterol 
TG 
Triglycerides 
TNF-α 
Tumor necrosis factor alpha 
ULN 
Upper limit of normal range 
US 
United States 
WBC 
White blood cell 


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PROTOCOL SUMMARY 
 
 
Title: 
A Prospective, Double Blind, Randomized, Placebo-controlled 
Trial of Antroquinonol in Patients with Hypercholesterolemia 
and Hyperlipidemia 
Study Phase: 
Research (Phase II) 
Sponsor: 
Golden Biotechnology Corporation 
Chief Principal 
Investigator: 
Fu-Tien Chiang, M.D. 江福田 教授 
National Taiwan University Hospital 
Indication: 
Hypercholesterolemia and Hyperlipidemia 
Study product: 
Antroquinonol (Hocena® ) 
Dose/Route: 
Antroquinonol 150 mg, Antroquinonol 100 mg, Antroquinonol 
50 mg, placebo, once daily/oral administration 
Objectives: 
The primary efficacy objective is to demonstrate the reduction 
of triglyceride (TG) by Antroquinonol, in comparison with 
placebo, after 12 weeks of treatment in patients with 
hypercholesterolemia and hyperlipidemia. Secondary objectives 
include the evaluation of the effects of Antroquinonol in 
comparison with placebo on other lipid parameters after 12 
weeks of treatment and the effects of Antroquinonol on left 
ventricular diastolic function, arterial stiffness and fatty liver. 
The safety and tolerability of Antroquinonol will be monitored 
as well. 
Population: 
Patients with hypercholesterolemia and hyperlipidemia 
Sample Size: 
120 enrolments to achieve 96 completed subjects (drop-out 
rate: 20%) 
Study Design: 
A multi-center, prospective, double blind, randomized, 
placebo-controlled trial 
Study Duration: 
Approximately 24 months 
Subject Participation 
Duration: 
16 weeks including a two-week screening visit, a 12-week 
study treatment and a 2-week follow-up 
The end of the study is defined as all patients complete the 


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study treatment OR all patients are withdrawn and have been 
followed for two weeks, depending on which comes earlier. 
Estimated Time for 
Recruitment: 
The recruitment period of this study will be approximately 12 
months. 
Eligibility Criteria: 
Inclusion criteria: 
1. 
Adults of either sex 20 to 75 years of age, inclusive, with a 
diagnosis of nonfamilial hypercholesterolemia or mixed 
hyperlipidemia as one of the following: 
- TG between 150 mg/dL and 500 mg/dL, and cholesterol 
between 160 mg/dL and 250 mg/dL; 
- TG between 150 mg/dL and 500 mg/dL, and LDL-C > 
130 mg/dL; 
2. 
Subject must be free of any clinically significant disease, 
other than nonfamilial hypercholesterolemia or mixed 
hyperlipidemia that would knowingly interfere with study 
evaluations; 
3. 
A wash-out period of 2 weeks will be applied to patients 
prior treated with lipid-lowering medication; 
4. 
Subject 
must 
be 
willing 
to 
adhere 
to 
protocol 
requirements, and provide written informed consent; 
5. 
Female of child-bearing potential must agree to use 
adequate contraception (hormonal or barrier method of 
birth control; abstinence) prior to study entry and for the 
duration of study participation. 
Exclusion criteria: 
1. 
Patients with secondary dyslipidemia caused by diabetes 
mellitus, hypothyroidism, obstructive liver disease, 
chronic renal failure or drugs which can increase LDL-C 
level (e.g. retinoids, cyclosporine A and phenothiazines) 
or decrease HDL-C level (e.g. progestins, androgens, β 
-blockers, probucol and anabolic steroid); 
2. 
Patients with lifestyle that may interfere treatment 
efficacy, such as alcoholism or drinking habits more than 
3 times per week, late dinner, late night supper, frequent 


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oversea business traveler, frequent social gathering, and 
patients who cannot anticipate a diet control and lifestyle 
changes; 
3. 
Patients with diabetes or history of coronary artery 
disease 
(has 
had 
myocardial 
infarction, 
cardiac 
intervention, 
cerebrovascular 
accident/stroke 
or 
transient ischemic attack less than 6 months prior to Visit 
1); 
4. 
Patients with hypertension that is uncontrolled defined as 
2 consecutive measurements of sitting blood pressure of 
systolic >140 mmHg or diastolic > 90 mmHg at Visit 1; 
5. 
Patient has a known hypersensitivity to Antroquinonol or 
related compounds; 
6. 
Patient with uncontrolled intercurrent illness including, 
but not limited to, acute decompensated HF (exacerbation 
of chronic HF manifested by signs and symptoms that may 
require IV therapy), right heart failure due to severe 
pulmonary 
disease, 
diagnosed 
peripartum 
or 
chemotherapy induced cardiomyopathy within the 12 
months prior to visit 1, or psychiatric illness/social 
situations that would limit compliance with study 
requirements; 
7. 
Patients with a history of heart transplant or who are on a 
transplant list or with left ventricular assistance device 
(LVAD device); 
8. 
Patients with documented ventricular arrhythmia with 
syncopal episodes within the past 3 months prior to visit 1 
that remained untreated; 
9. 
Patients with confirmed severe primary pulmonary, renal 
(eGFR<30 ml/min/1.73 m2) or hepatic (Child-Pugh B/C 
classification) disease; 
10. Patients who can’t stop current lipid lowering drug 
treatments based on investigator’s judgement; 
11. Patients with any malignancy, treated or untreated,  
within the past 5 years of Visit 1 whether or not there is 


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evidence of local recurrence or metastases, with the 
exception of localized basal cell carcinoma of the skin or 
carcinoma in situ of the cervix; 
12. Female 
patient 
during 
pregnancy, 
lactation 
or 
breastfeeding; 
13. Patient has any other life-threatening complications; 
14. Patient who is considered unreliable as to medication 
compliance or adherence to scheduled appointments, or 
inappropriate 
for 
inclusion 
determined 
by 
the 
investigators; 
15. Any other reasons addressed by the investigators. 
Endpoints: 
Primary endpoint: 
The primary efficacy endpoint is the percentage change from 
baseline of TG by Antroquinonol, in comparison with placebo, 
after 
12 
weeks 
of 
treatment 
in 
patients 
with 
hypercholesterolemia and hyperlipidemia. 
Secondary endpoints: 
Secondary endpoints include the evaluation of the effect of 
Antroquinonol 
in 
comparison 
with 
placebo 
on 
total 
cholesterol, LDL-C, HDL-C, LDL/HDL ratio after 12 weeks of 
treatment; the effect of Antroquinonol on the ratio of mitral 
velocity to early diastolic velocity of the mitral annulus (E/E’ 
ratio) with tissue Doppler imaging and brachial-ankle pulse 
wave velocity (baPWV) and ankle-brachial index (ABI) via a 
non-invasive arterial stiffness measurement; in addition, the 
evaluation of the effect of Antroquinonol on fatty liver by using 
CT scan. 
Safety endpoints: 
 
Changes 
in 
laboratory 
examination 
including 
hematological, biochemical parameters and urinary 
analysis 
 
Changes in electrocardiogram test, vital signs, and physical 


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examinations 
 
Compliance and tolerability of the study drug 
 
Analysis of adverse events 
Statistical Methodology: 
There will be three populations in this study, Intent-To Treat 
(ITT) population, Per-Protocol (PP) population and Safety 
population for statistical analysis. 
- 
The ITT population includes all randomized patients 
who meet all inclusion criteria and exclusion criteria, 
take at least one study medication and have at least 
one post-baseline measurement 
- 
The PP population is a subset of the ITT population 
and includes all randomized patients who complete 
12 weeks of treatment without major protocol 
violation. 
- 
All subjects who received at least one study 
medication will be included in the safety analysis 
population. 
 
Primary efficacy analysis will be performed in ITT and PP 
population, secondary efficacy analyses will be performed 
in ITT population and safety analyses will be performed 
using safety population. 
 
Last observation carried forward (LOCF) will be used to 
approach the missing data of primary endpoint in ITT 
population. No missing data will be imputed for the 
secondary efficacy or safety analyses. 
 
Descriptive statistics will be summarized as n, mean, 
standard deviation, median and range for continuous 
parameters, and will be tabulated as frequency and 
percentage for categorical parameters. 
 
To  compare TG percentage  change from baseline to  week 
12 between 3 treatment groups, the ANOVA with 


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Bonferroni adjustment will be performed, or if assumption 
of normality is not met, then Kruskal-Wallis Test will be 
performed. If the differences in baseline characteristics, 
such as gender, age, weight etc., are observed, the ANCOVA 
will adjust for the significant variables in the primary 
analysis. The within-group change from baseline in each 
treatment group will be assessed using the paired-T test. If 
the normal assumption is violated, Wilcoxon signed-rank 
test will replace the paired-T test. 
 
Other continuous variable at each visit and change at post-
baseline visits will be summarized by descriptive statistics 
and be analyzed by means of ANOVA with Bonferroni 
adjustment. Paired T-Test will be used to compare the 
change from baseline within treatment groups. If the 
normal assumption is violated, non-parametric statistical 
methods such as Kruskal-Wallis Test or Wilcoxon Signed-
Rank Test will be used. 
 
Categorical variables will be tabulated with related 
frequency and percentages and be compared by using Chi-
square or Fisher’s exact test. 
 
AEs, laboratory parameters, and vital signs will be 
reported descriptively, based on the safety population (all 
randomized patients who received at least one dose or 
partial dose of study treatment). Safety will also be 
assessed by a review of all safety endpoints including 
adverse events (AEs), laboratory examinations, and 
electrocardiogram test. 
Unless otherwise specified, all statistical assessments will be 
two-sided under significant level of 0.05. 


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1. INTRODUCTION 
1.1. Background Information 
Dyslipidemia is a health risk, and epidemiologic studies have shown a link between total 
cholesterol levels and the risk of cardiovascular diseases (CVD), in particular coronary artery 
disease (CAD). Studies have shown that lowering the levels of total and low-density lipoprotein 
cholesterol (LDL-C) can result in a decrease in cardiac morbidity and mortality, whilst 
epidemiological evidence consistently indicate moderate and highly significant associations 
between triglyceride (TG) values and coronary heart disease risk 1. CVD is influenced by many 
potential factors, including gender, age, genetics, smoking, high blood pressure, diabetes, and 
altered plasma lipids. Specifically, disturbances in plasma lipoprotein profiles, including 
elevations of plasma total and low density lipoprotein cholesterol (LDL-C), elevated plasma TG, 
and decreased high density lipoprotein cholesterol (HDL-C), have all been linked to an 
increased risk of developing CVD. Furthermore, LDL-C and HDL-C contents have been shown to 
be closely related to the occurrence of CVD. Therefore, lowering blood cholesterol level is an 
important way to reduce the chances of suffering CVDs. While statins are the treatment of 
choice for lowering LDL-C in the majority of patients, many patients retain a high CVD risk 
despite achieving the recommended LDL-C targets with statins, mainly due to elevated TG and 
low HDL-C levels. Following statin therapy optimisation additional pharmacotherapy, addition of 
a fibrate or niacin, should be considered as part of a multifaceted approach to risk reduction 2. 
Antroquinonol is a new chemical entity isolated from the mycelium of Antrodia camphorata, 
which showed interesting anticancer and anti-inflammatory activities 3,4,5. Previous studies 
have indicated that signaling molecules, such as PI3K, AMPK, and mTOR, participate in 
Antroquinonol-induced cancer cell death, whereas Nrf2 and NF-kB are involved in the anti-
inflammatory effects of Antroquinonol 4,5,6. Recently, we also provide evidence that 
Antroquinonol plays a role in the inhibition of Ras and Ras-related small GTP-binding protein 
functions through the inhibition of protein isoprenyl transferase activity in cancer cells 7. 
Studies on lipid-lowering effects of Antroquinonol®  has been conducted and the results 
indicated that Antroquinonol®  enhances the expression of low-density lipoprotein receptor 
(LDLR) genes in liver cells responsible for the removal of cholesterol in low-density 
lipoprotein cholesterol (LDL-C) from the blood stream. In a diet-induced hyperlipidemic rat 
model, Antroquinonol®  significantly increased high-density lipoprotein cholesterol (HDL-C) 
level (p<0.001) in plasma compared to vehicle control. Additionally, in a carotid artery 
ligation mouse model, the neotima-media area ratio was significantly reduced (p<0.001) 
compared with control. These results demonstrate the potential applications of 
Antroquinonol®  in treating hyperlipidemia and prevent associated cardio vascular diseases. 


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1.2. Study Rationale 
Statins-cholesterol lowering drugs are the first-choice treatments for the primary and secondary 
prevention of CVD, if the patient still has elevated TG and/or low HDL-C despite intensive 
lifestyle intervention, and addressing compliance with pharmacotherapy and secondary causes 
of dyslipidemia, additional lipid-modifying therapy may be considered. Along with the long-term 
treatment with statins in combination with other hypolipidemic drugs or alone, the safety has 
drawn a particular attention in clinic, such as the elevation of transaminase and rhabdomyolysis, 
which have raised an idea of developing the other types of lipid-lowering agents from botanic 
materials. 
The primary hypothesis is that Antroquinonol treatment will be well tolerated and will result 
in greater lowering of TG at week 12 than placebo in patients with hypercholesterolemia and 
hyperlipidemia. The primary goal is to determine if Antroquinonol will provide greater TG 
lowering effect than placebo. 
 
1.3. Potential Risks and Benefits 
1.3.1. Potential risk 
The phase I study determining MTD and evaluating PK, safety/tolerability and efficacy 
profiles of Hocena®  in NSCLC subjects (NCT01134016) results showed that the study drug 
may be accompanied by gastrointestinal disorders such as diarrhea, vomiting, and nausea. 
 
1.3.2. Potential benefits 
The possible benefit of treating patients with hyperlipidemia with the trial is that subjects’ 
health will be closely monitored and the investigator will provide the support of health care 
when patients take part in the study. In addition, this study expects to observe the effects on 
TG lowering in patients with hypercholesterolemia and hyperlipidemia. 


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2. STUDY OBJECTIVES 
The primary efficacy objective is to demonstrate the reduction of TG by Antroquinonol, in 
comparison with placebo, after 12 weeks of treatment in patients with hypercholesterolemia 
and hyperlipidemia. Secondary objectives include the evaluation of the effects of 
Antroquinonol, in comparison with placebo, on other lipid parameters, left ventricular 
diastolic function, arterial stiffness, and fatty liver after a 12-week treatment. The safety and 
tolerability of Antroquinonol will be monitored as well. 
 
2.1. Primary objective 
To evaluate the effect of 12-week oral administration of Antroquinonol on the percentage 
change in TG from baseline as lipid-lowering therapy compared with placebo. 
 
2.2. Secondary objectives 
Secondary objectives are: 
(1) To evaluate the effects of 12 weeks of oral administration Antroquinonol compared with 
placebo on percentage change from baseline in other lipid parameters as lipid-lowering 
therapy. 
(2) To evaluate the effects of Antroquinonol on left ventricular diastolic function and arterial 
stiffness. 
(3) To evaluate the effect of Antroquinonol on fatty liver via computed tomography (CT) 
scanning. 
(4) To evaluate the safety and tolerability of 12 weeks of oral administration of Antroquinonol 
compared with placebo in subjects with hypercholesterolemia and hyperlipidemia 


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3. STUDY DESIGNS 
3.1. General Design 
This is a multi-center, phase 2, double blind, randomized, placebo-controlled trial of 
Antroquinonol in patients with hypercholesterolemia and hyperlipidemia. Subjects with a 
diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 
150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C > 
130 mg/dL) and meet all eligible criteria will be randomized to 4 groups: 
1. Antroquinonol 150 mg PO QD 
2. Antroquinonol 100 mg PO QD 
3. Antroquinonol 50 mg PO QD 
4. Placebo 
After the end of 12 weeks treatment period, subjects will be followed up for an additional 2 
weeks. 
Study visits will occur every 4 weeks. During these visits study drug will be administered at the 
site, new AEs/SAEs as well as follow-up for AEs and SAEs that have not been resolved will be 
recorded, changes to concomitant medications will be noted, vital signs will be taken, and 
efficacy evaluations will be performed as well. The studies include collection of biomarker 
samples, brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI), E/E’, and 
CT scan of the liver will be performed. The end-of-treatment visit and the last efficacy 
assessments will occur at week 13 (visit 5) for all subjects. In addition, a 2-week follow-up final 
visit will be at week 15 (visit 6) in order to collect safety data after the last study drug 
administration. Subjects will be encouraged to complete all planned visits regardless of their 
adherence to study drug administration. 


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Schematic diagram: 
The study design (Figure 3-1) is shown as follows: 
 
Screening 
Randomization 
Treatment Period
Follow-up 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
 
150 mg Antroquinonol (N=30) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day -14 
Day 1 
Day 29 
Day 57 
Day 85 
Day 99 
Week -2 
Week 1 
Week 5 
Week 9 
Week 13 
Week 15 
 
Figure 3- 1 Schematic diagram of the study design 
 
3.2. Primary Study Endpoints 
The primary efficacy endpoint is the percentage change of TG by Antroquinonol, in comparison 
with placebo, after 12 weeks of treatment in patients with hypercholesterolemia and 
hyperlipidemia. 
 
3.3. Secondary Study Endpoints 
Secondary endpoints include: 
(1) To evaluate the effect of 12-week oral administration of Antroquinonol compared with 
placebo, on percentage change in total cholesterol, HDL-C, LDL-C, LDL/HDL ratio from 
baseline as lipid-lowering therapy. 
(2) To evaluate the effect of Antroquinonol on the ratio of mitral velocity to early diastolic 
velocity of the mitral annulus (E/E’ ratio) via tissue Doppler imaging and baPWV and ABI 
via a non-invasive arterial stiffness measurement. 
(3) To evaluate the effect of Antroquinonol on fatty liver via computed tomography (CT) 
100 mg Antroquinonol (N=30) 
N=120 
50 mg Antroquinonol (N=30) 
Placebo (N=30) 


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scanning. 
 
3.4. Safety Endpoints 
Safety endpoints include the compliance and tolerability of the study drug, incidence of 
treatment emergent adverse events, safety laboratory values, vital signs, physical examinations, 
ECG, and the frequency and severity of muscle symptoms at each scheduled visit. 


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4. SUBJECTS SELECTION AND WITHDRAWAL 
The investigators or designee must ensure that all enrolled patients meet all the following 
inclusion criteria and none of the exclusion criteria for the study enrollment. The inform 
consent will be obtained from each subject after the nature of the study is explained. A subject 
who has been entered (signed a inform consent) into the study is potentially eligible to be 
enrolled in the study, however, only he/she who meets all criteria for enrollment specified in 
the protocol will be randomized (assigned to a treatment group) and receive the study 
intervention. No additional exclusion should be applied by the investigator, in order that the 
study population will be representative of all eligible patients. 
 
4.1. Number of Subjects 
Considering an estimated dropout rate of 20%, 120 subjects will be projected to provide 96 
evaluable subjects. Competitive recruitment will be applied in the present study. In average, 
each site may screen approximately 30-40 patients, and enroll around 25-30 subjects. 
 
4.2. Inclusion Criteria 
Subjects are eligible if the following inclusion criteria are satisfied: 
(1) Adults of either sex 20 to 75 years of age, inclusive, with a diagnosis of nonfamilial 
hypercholesterolemia or mixed hyperlipidemia as one of the following: 
- TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 
mg/dL 
- TG between 150 mg/dL and 500 mg/dL and LDL-C > 130 mg/dL); 
(2) Subject must be free of any clinically significant disease, other than nonfamilial 
hypercholesterolemia or mixed hyperlipidemia that would knowingly interfere with study 
evaluations; 
(3) A wash-out period of 2 weeks will be applied to patients prior treated with lipid-lowering 
medication; 
(4) Subject must be willing to adhere to protocol requirements, and provide written informed 
consent; 
(5) Female of child-bearing potential must agree to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) prior to study entry and for the duration of 
study participation. 


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4.3. Exclusion Criteria 
Subjects are eligible if no exclusion criterion applies: 
(1) Patients with secondary dyslipidemia caused by diabetes mellitus, hypothyroidism, 
obstructive liver disease, chronic renal failure or drugs which can increase LDL-C level (e.g. 
retinoids, cyclosporine A and phenothiazines) or decrease HDL-C level (e.g. progestins, 
androgens, β-blockers, probucol and anabolic steroid) 
(2) Patients with lifestyle that may interfere treatment efficacy, such as alcoholism or  
drinking habits more than 3 times per week, late dinner, late night supper, frequent 
oversea business traveler, frequent social gathering, and patients who cannot anticipate a 
diet control and lifestyle changes; 
(3) Patients with diabetes or history of coronary artery disease (has had myocardial infarction, 
cardiac intervention, cerebrovascular accident/stroke or transient ischemic attack less than 
6 months prior to Visit 1); 
(4) Patients with hypertension that is uncontrolled defined as 2 consecutive measurements of 
sitting blood pressure of systolic >140 mmHg or diastolic > 90 mmHg at Visit 1; 
(5) Patient has a known hypersensitivity to Antroquinonol or related compounds; 
(6) Patient with uncontrolled intercurrent illness including, but not limited to, acute 
decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that 
may require IV therapy), right heart failure due to severe pulmonary disease, diagnosed 
peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 
1, or psychiatric illness/social situations that would limit compliance with study 
requirements; 
(7) Patients with a history of heart transplant or who are on a transplant list or with left 
ventricular assistance device (LVAD device); 
(8) Patients with documented ventricular arrhythmia with syncopal episodes within the past 3 
months prior to visit 1 that remained untreated; 
(9) Patients with confirmed severe primary pulmonary, renal (eGFR<30 ml/min/1.73 m2) or 
hepatic (Child-Pugh B/C classification) disease; 
(10) Patients who can’t stop current lipid lowering drug treatments based on investigator’s 
judgement; 
(11) Patients with any malignancy, treated or untreated, within the past 5 years of Visit 1 
whether or not there is evidence of local recurrence or metastases, with the exception of 
localized basal cell carcinoma of the skin or carcinoma in situ of the cervix; 


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(12) Female patient during pregnancy, lactation or breastfeeding; 
(13) Patient has any other life-threatening complications; 
(14) Patient who is considered unreliable as to medication compliance or adherence to 
scheduled appointments, or inappropriate for inclusion determined by the investigators; 
(15) Any other reasons addressed by the investigators. 
 
 
4.4. Strategies for Recruitment and Retention 
Most subjects will be recruited from out-patients of the investigator’s specialized clinic for 
cardiology. Other potential subjects could also be patients who referred from other clinicians. 
The time of subjects’ participation in the present study will be a fixed duration for 16 weeks. 
Only subjects who benefit from study treatment will be expected to retain in this study. If 
subject fail to show response to study drug, he/she will be withdrawn by investigator’s 
determination. No further intervention will be conducted to enhance subject retention. 
 
4.5. Treatment Assignment Procedures 
4.5.1. Randomization procedures 
A permuted block randomization method with 1: 1: 1 :1 ratio will be employed to allocate 
subjects into one of the four treatment arms as follows (1) Antroquinonol 150 mg PO QD; (2) 
Antroquinonol 100 mg PO QD; (3) Antroquinonol 50 mg PO QD; or (4) Placebo arm. 
Randomization code list will be generated by the CRO and provided to Golden Biotechnology 
Corporation in order to pack and label the study drugs. Randomization data will not be 
accessible by anyone else involved in the study. The corresponding study group of individual 
subjects will be recorded in a sealed envelope and should be kept strictly confidential until the 
time of data lock. 
For this multi-center study, centralized randomization will be applied. The investigator 
confirms the subject fulfills the inclusion and exclusion criteria and informs the randomization 
center. The sponsor’s independent staff will then provide the randomization number in order. 
The study drugs labeled with randomization number will be provided according to the request 
from each site. 
 
4.5.2. Blinding procedures 
After enrollment, subjects will be randomly assigned to receive one of the study treatments in a 
double-blind fashion. The identity of the treatments will be concealed. The placebo will be 
masked by the same appearance, odor and taste as the study drug (Antroquinonol). Subjects, 


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investigator, site staff, persons performing study assessments and data analysts will remain 
blind to the treatment assignment from the time of randomization until data lock. 
All patients enrolled should take 3 capsules within 15 minutes after the first meal every day. In 
the study group, subjects will be treated with (1) 3* Antroquinonol 50 mg capsule; (2) 2* 
Antroquinonol 50 mg capsule and 1 capsule of placebo; (3) 1* Antroquinonol  50 mg capsule  
and 2 capsules of placebo and (4) in the control group, subjects will be treated with 3 capsules 
of placebo. 
The blinding during the study is maintained by administration of matching placebo capsules to 
patients in the placebo group. Furthermore, the project teams of Golden Biotechnology 
Corporation and the CRO as well as the investigator and his/her study personnel will be 
blinded with respect to patients’ assignment to one of the four treatment groups. 
Treatment codes should not be broken except in the case of emergency situations. If the 
investigator wishes to know the identity of the treatment given to study patients for any other 
purpose, this request should first be discussed with Golden Biotechnology Corporation. 
As per regulatory reporting requirement, Golden Biotechnology Corporation will unblind the 
identity of the study medication for all unexpected (as per the Investigator Brochure [IB]) 
serious adverse events that are considered by the investigator to be related to study drug. 
Details of patients who are unblinded during the study will be included in the Clinical Study 
Report. 
All other individuals directly involved in this study will remain blinded until the final analysis of 
the primary parameter. 
 
4.5.3. Subject identifier 
Each subject will be assigned a consecutive numbers as he/she enters the study. In the study, 
the screening and randomization numbers are used as subject identifiers. The subject who 
signed the informed consent form will be assigned a sequential screening number starting 
with an alphabet “S” and following with 3 digits at visit 1 (Screening visit) by each site. The 
subject who meet the eligible criteria will be enrolled and granted a random number by 
randomization process before visit 2. The random number is composed of 3 digits and an initial 
alphabet “R”. Once assigned to a subject, the screening numbers at each site and randomization 
numbers will not be reused. This random number will be used to identify the subject 
throughout the clinical study and must be used on all study documentation related to that 
subject. A two-digit site number will also be indicated on case report form as well as related 
working sheets. In that case, National Taiwan University Hospital will be coded as site “01”.  
Once a new institution participates in the present study, the site number will be increased 
sequentially, e.g. site “02” for the second institution. 


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4.5.4. Reasons for withdrawal 
Subjects may be discontinued from study drug at the discretion of the investigator of any 
untoward effects occur or for one of the following reasons: 
(1) Subject who cannot comply with the medical practices and the schedule of follow-up visit; 
(2) Subjects (or their legally acceptable representatives, if applicable) decide to withdraw their 
inform consent forms; 
(3) Investigator considers that the subject is no longer physically or psychologically feasible to 
be included in this study; 
(4) Adverse effects occur in subjects that the investigator considers a permanent cessation of 
the study treatment is necessary; 
(5) Violation of enrollment criteria which is not recognized at the time of enrollment; 
(6) Lost to follow-up; 
(7) Lack of response to study treatment and the investigator considers that the subject shall  
be withdrawn to receive other treatments. 
Subjects who are withdrawn because of lost to follow-up will be contacted by telephone, and  
the information will be record on the “Study Termination” of Case Report Form (CRF), 
including the date of the event and the reasons for not returning to the clinic by study staff. 
 
4.5.5. Handling of withdrawals 
Subjects have the right to withdraw from the study at any time for any reason. The investigator 
also has the right to withdraw patients from the study in the event of intercurrent illness, 
adverse events, protocol violations, administrative reasons or other reasons. An excessive rate 
of withdrawals can render the study un-interpretable; therefore, unnecessary withdrawal of 
patients should be avoided. Should a patient decide to withdraw, all efforts will be made to 
complete and report the observations prior to withdrawal as thoroughly as possible. 
The investigator should contact the subject or a responsible relative either by telephone or 
through a personal visit to establish as completely as possible the reason for the withdrawal. A 
complete final evaluation at the time of the subject’s withdrawal should be made with an 
explanation of why the subject is withdrawing from the study. If the reason for removal of a 
subject from the study is an adverse event, the principal specific event will be recorded on the 
case report form (CRF). 
Subjects withdrawing from the study should be followed for occurrence of adverse events  
unless the patient refuses to give further information. 
Any subjects withdraw from the study, the study staff shall inform the sponsor and CRO within 
5 working days. 


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4.5.6. Termination of study 
This study may be prematurely terminated if, in the opinion of the investigator, the sponsor or 
due to health authority’s review, there is sufficient reasonable cause. Written notification, 
documenting the reason for study termination, will be provided to the investigator or sponsor 
by the terminating party. 


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5. STUDY DRUG/INTERVENTION 
5.1. Description of Study Drug 
5.1.1. Drugs manufacture and supplier 
The study drug Antroquinonol is provided and manufactured by Golden Biotechnology 
Corporation. The matching placebo of Antroquinonol used during the study will also be 
supplied by Golden Biotechnology Corporation. 
 
5.1.2. Formulation, packaging and labeling 
Antroquinonol will be provided as a 50 mg capsule. Study drug is capsule-shaped, identical in 
appearance to placebo. The study drug and matching placebo will be packaged as 
Antroquinonol with appearance identical in all aspects. The study drug will be packaged in a 
light-proof polypropylene pill box and will be labeled with following information: 
 
Sponsor identification 
 
Manufacturer 
 
Protocol number 
 
Randomization number 
 
Quantity of contents 
 
Prescription instructions 
 
Storage conditions 
 
Expiration date 
 
Caution statements: 
“FOR CLINICAL TRIAL USE ONLY” 
“KEEP OUT OF REACH OF CHILDREN” 
 
Blank spaces to write the data while dispensing. 
Detailed instructions and training for the administration of study supplies will be provided by 
investigator or designees of the study site. 
 
5.1.3. Product storage and stability 
The study drugs will be handled by the investigator or the designated pharmacist for 
management and dispensation. The storage area for study drugs at the site must be monitored 
by the site staff for temperature consistency with the acceptable storage temperature range 
specified in this protocol or in the product label. Documentation of temperature monitoring 
should be maintained. Importantly, the study drug supplied for this study must be maintained 
under adequate security and stored under the conditions specified on the label until dispensed 
for subject use or returned to Golden Biotechnology Corporation. 


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The optimal storage condition for study drugs is described as below: 
The individually labeled double-blind study medication kits should be kept under  28  , away  
from moisture and heat in a cool place away from light. The study drug supplies should be 
stored in a locked and secure area with limited access. 
 
5.2. Dosage, Preparation and Administration of Study Drug 
Participants will receive medication supplies at scheduled visits in sufficient quantity until the 
next scheduled visit. Patients will take their daily dose of Antroquinonol and/or  placebo  as follow: 
in the study group, subjects will be treated with (1) 3* Antroquinonol 50 mg capsule; (2) 2* 
Antroquinonol 50 mg capsule and 1 capsule of placebo; (3) 1* Antroquinonol 50 mg capsule and 
2 capsules of placebo within 15 minutes after first meal every day; and in the control group, 
subjects will be treated with 3 capsules of placebo within 15 minutes after meal every day. 
 
5.3. Modification of Study Drug for a Subject 
No modification of dose will be conducted in the present study. If any drug toxicity occurs to  
the subject, he/she may be withdrawn from the study by the investigator’s determination. 
5.4. Accountability Procedures and Assessment of Subject 
Compliance for the Study Drug(s) 
Accountability and subject compliance will be assessed by maintaining adequate drug 
dispensing and return records. 
Patients will be asked to return all used and unused drug supply containers from visit 3 to visit 
5 as a measure of compliance. 
Drug record section on CRF and drug dispensing logs must be kept current and should contain 
the following information: 
 
the identification of the subject to whom the study medication was dispensed 
 
the date[s], quantity of the study medication dispensed to the subject 
 
the date[s] and quantity of the study medication returned by the subject 
This inventory must be available for inspection by the Monitor. All supplies, including partially 
used or empty containers and the dispensing logs, must be returned to the Golden 
Biotechnology Corporation or Golden Biotechnology Corporation designee at the end of the 
study. The investigational staff must record quantity of medication dispensed and returned on 


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CRF. In addition, a dispensing log for each subject shall also be completed by the staff. This 
dispensing log will be supplied to the institution before study initiation. The log will include the 
subject’s identification, drug lot/batch number, dispensed and returned date and quantity, 
signature of site staff, comments which is used to record any unusual situation and verification 
section by CRO, 
 
5.5. Treatment for Study Drug Overdose 
The effects of overdose of study drug are under investigation. Per the phase I and ongoing  
phase II study in oncology patients, no single event of overdose is recorded. In the event of 
overdose, standard measures to remove any unabsorbed drug should be considered. 
Symptomatic and supportive treatment is recommended. 
 
5.6. Concomitant Medications/Treatments 
5.6.1 Prohibited medications/treatments 
The following treatments are not permitted during the study 
 
Statin therapy, 
 
Steroids, 
 
Fibrates, 
 
Anti-lipid medication 
Patients will also be informed that they should avoid foods including broccoli, Brussels sprouts, 
charbroiled food, cruciferous vegetables, star fruit, and grapefruit juice within four hours after 
taking Antroquinonol. Cigarette smoking is also prohibited during the study. 
 
5.6.2 Permitted medications/treatments 
Throughout the study, investigators may prescribe any concomitant medications or treatments 
deemed necessary to provide adequate supportive care which does not affect serum lipid level 
except for those listed in Section 5.6.1. 


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6. STUDY PROCEDURES 
This is a, randomized, double-blind, placebo-controlled study composed of the following: 
(1) a screening visit including a wash-out period of 2 weeks will be applied to patients prior 
to the treatment of Antroquinonol; 
(2) randomization of subjects who meet the eligibility criteria in 1: 1: 1 :1 ratio into the four 
treatment groups (Antroquinonol 150 mg, Antroquinonol 100 mg, Antroquinonol 50 mg or 
placebo); 
(3) three on-treatment visits scheduled at four-week interval during which efficacy and safety 
assessments will be performed; 
(4) and a follow-up visit after the end of treatment, during which safety assessments will be 
performed. 
 
6.1. Flow Chart 
Scheduled examination components are shown by visit in Tables below, all of the assessments 
are indicated with an “X” at the visits when they will be performed. 


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STUDY SCHEDULE: 
Procedure 
Screening * 
Randomization 
Treatment Period 
Follow-up 
Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Interval 
Day -14 
Day 1 
(Week 1) 
Day 29 
(Week 5) 
Day 57 
(Week 9) 
Day 85 
(Week 13) 
Day 99 
(Week 15) 
Allow Window 
- 
- 
±3 
±3 
±3 
±3 
Informed Consent 
X 
Assessment of Eligibility Criteria 
X 
Medical History 
X 
Demographic 
X 
Vital Signs 1 
X 
X 
X 
X 
X 
X 
Anthropometric measures 2 
X 
X 
X 
X 
X 
X 
Electrocardiogram 
X 
X 
Physical Examination 
X 
X 
X 
X 
X 
X 
Urine Pregnancy Test 
X 
Randomization 3 
X 
Drug Dispense 
X 
X 
X 
Drug Return 
X 
X 
X 
Efficacy Assessment 
Serum Lipid 4 
X 
X 
X 
X 
X 
X 
baPWV and ABI 
X 
X 
Image Monitoring 5 
X 
X 
Biomarker Assessment 


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Procedure 
Screening * 
Randomization 
Treatment Period 
Follow-up 
Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Interval 
Day -14 
Day 1 
(Week 1) 
Day 29 
(Week 5) 
Day 57 
(Week 9) 
Day 85 
(Week 13) 
Day 99 
(Week 15) 
Allow Window 
- 
- 
±3 
±3 
±3 
±3 
CRP and Cytokine 6 
X 
X 
X 
Safety Assessment 
CBC and WBC differential 7 
X 
X 
X 
Biochemistry 8 
X 
X 
X 
X 
X 
X 
Urinary Exam 9 
X 
X 
X 
Concomitant Therapy 
X 
X 
X 
X 
X 
X 
Adverse Event 
X 
X 
X 
X 
X 
* A wash-out period of 2 weeks will not be applied to patients prior treated with medication which does not affect serum lipid level. 
1. Vital signs: pulse rate, body temperature, respiratory rate, and blood pressure (including systolic blood pressure (SBP) and diastolic blood pressure (DBP)). 
2. Including height, weight, waist circumference, and BMI (calculated by kg/m2) 
3. Subjects who meet the eligibility criteria will be randomized into treatment arms. If the eligibility is confirmed and a wash-out period is not needed for the  subject, 
based on investigator’s judgements the blood test required at V2 can be replaced by the data obtained 14 days before V2. 
4. Serum lipids: total cholesterol, triglycerides, HDL-C, LDL-C, LDL/HDL ratio. Serum lipid results obtained 3 days prior to V1 is acceptable. 
5. Doppler color flow mapping and CT scan of the liver. CT scan will not be scheduled at visit 5 on subjects without fatty liver. Results of Doppler color  flow 
mapping and CT scan of the liver obtained between V1 and V2 are acceptable. 
6. hsCRP, IL-1, IL-6, and TNF-alpha. 
7. WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, neutrophil-band and segment, lymphocyte, monocyte, eosinophil, and basophil. 
8. Biochemical exam: AST, ALT, CPK, BUN and serum creatinine: visit 2 to visit 6; albumin, total bilirubin, direct bilirubin, ALP, total protein: V2, V5 and V6. At 
screening visit, serum creatinine shall be run for estimating glomerular filtration rate (GFR) and data obtained 3 days prior to V1 is acceptable. 
9. Urinary exam: routine urine test (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, leukocyte) and clinical microscopy. 


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6.2. Study Procedures 
6.2.1. Screening (Day -14) 
All patients must provide written informed consent before any study specific assessments or 
procedures are performed. A subject enrollment form documenting the investigator’s 
assessment of each screened subject with regard to the protocol’s inclusion and exclusion 
criteria has to be completed by the investigator. 
Based on the results of Visit 1 assessments (see below 'Screening Assessments at Visit 1'), 
potentially eligible patients will enter a wash-out period as necessary. Blood test data generated 
by the study site or central laboratory 3 days prior to Visit 1 can be accepted. 
Screening Assessments at Visit 1 
 Demographics, medical history, including previous and concomitant diseases and 
treatments 
 Physical examination 
 Anthropometric measures (Height, Weight, Waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 
 Urine Pregnancy Test 
 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and LDL/HDL ratio) 
- 
biochemistry (serum creatinine for estimating GFR) 
Patients will be instructed to come in fasted state for all subsequent study visits. Patients should 
receive information on a heart healthy diet and counseling on lifestyle changes as appropriate. 
 
6.2.2. Enrollment/Randomization (Day 1) 
Randomization Assessments at Visit 2 
Once a patient has fulfilled the entry criteria, he/she will be randomized into either 
Antroquinonol 150 mg, Antroquinonol 100 mg, Antroquinonol 50 mg or placebo treatment 
group using a permuted block randomization method with 1: 1: 1: 1 ratio. The subject will be 
registered with a randomization number, and the study drug will be administered. The 
importance of compliance with study drug should be emphasized. 
The assessments listed below will be performed. If the eligibility is confirmed and a wash-out 
period is not needed for the subject, based on investigator’s judgements, the blood test, CT Scan, 
and Doppler color flow mapping required at visit 2 can be replaced by data obtained 14 days 
before V2. 
 Physical examination 
 Anthropometric measures (Height, weight, waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 


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 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and HDL-C /LDL-C ratio) 
- 
hematology (WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, neutrophil-band 
and segment, lymphocyte, monocyte, eosinophil, basophil) 
- 
serum chemistry (AST, ALT, CPK, BUN, serum creatinine, albumin, total bilirubin, 
direct bilirubin, ALP, total protein) 
- 
biomarkers (hsCRP, IL-1, IL-6, and TNF-alpha) 
 12-lead electrocardiogram 
 Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) 
 Doppler color flow mapping, and CT scan of the liver 
 Urinalysis 
- 
routine urine test (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, 
leukocyte) 
- 
clinical microscopy 
 
In addition, information on adverse events during the wash-out period and new concomitant 
medications will be collected. 
 
6.2.3. On treatment visits (Day 29±3, Day 57±3, Day 85±3) 
During the treatment period, subjects will visit the clinic every 4 weeks. Subjects have to come 
in fasted state for all visits. Therefore, subjects will be instructed not to take study drug in the 
morning of study visits but to wait until all study assessments have been completed. Subjects 
will receive new drug supply at each visit and will be required to bring in all unused study 
drugs for assessment of compliance. 
Treatment Period Assessments at Visit 3 and 4 ( ± 3 days) 
The following evaluations will be performed at each visit throughout treatment: 
 Physical examination 
 Anthropometric measures (Height, weight, waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 
 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and LDL/HDL ratio) 
- 
serum chemistry (AST, ALT, CPK, BUN, serum creatinine) 
 Information on adverse events 
 Information on new concomitant medications 
 Record of drug dispense and drug return 


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End of Treatment Assessments at Visit 5 ( ± 3 days) 
The following evaluations will be performed: 
 Physical examination 
 Anthropometric measures (Height, weight, waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 
 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and LDL/HDL ratio) 
- 
hematology (WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, neutrophil-band 
and segment, lymphocyte, monocyte, eosinophil, basophil) 
- 
serum chemistry (AST, ALT, CPK, BUN, serum creatinine, albumin, total bilirubin, 
direct bilirubin, ALP, total protein) 
- 
biomarkers (hsCRP, IL-1, IL-6, and TNF-alpha) 
 12-lead electrocardiogram 
 Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) 
 Doppler color flow mapping, and CT scan of the liver for patients with confirmed fatty 
liver at Visit 2 
 Urinalysis 
- 
routine urine test (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, 
leukocyte) 
- 
clinical microscopy 
 Information on adverse events 
 Information on new concomitant medications 
 Record of drug return 
 
6.2.4. Final study visit (Day 99±3) 
Safety Follow-Up Assessments at Visit 6 ( ± 3 days) 
A safety follow-up for all patients will be conducted 2 weeks after the end of treatment visit.  
The following assessments will be performed: 
 Physical examination 
 Anthropometric measures (Height, weight, waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 
 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and LDL/HDL ratio) 
- 
hematology (WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, neutrophil-band 
and segment, lymphocyte, monocyte, eosinophil, basophil) 
- 
serum chemistry (AST, ALT, CPK, BUN, serum creatinine, albumin, total bilirubin, 
direct bilirubin, ALP, total protein) 


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- 
biomarkers (hsCRP, IL-1, IL-6, and TNF-alpha) 
 Urinalysis 
- 
routine urine test (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, 
leukocyte) 
- 
clinical microscopy 
 Information on adverse events 
 Information on new concomitant medications 
 Provide final instructions to subject 
 
6.2.5. Early termination visit /Withdrawal visit 
For subjects who prematurely withdraw from treatment, the same procedures as the one at the 
end of the treatment will be applied. An end of treatment visit should be scheduled as soon as 
possible and the assessments listed below should be performed. Subjects will be required to 
bring in all study drugs for assessment of compliance. If the decision of discontinuation is being 
taken while the subject is in the clinic for a visit, the end of treatment assessments may be 
performed on that day. 
 Physical examination 
 Anthropometric measures (Height, weight, waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 
 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and LDL/HDL ratio) 
- 
hematology (WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, neutrophil-band 
and segment, lymphocyte, monocyte, eosinophil, basophil) 
- 
serum chemistry (AST, ALT, CPK, BUN, serum creatinine, albumin, total bilirubin, 
direct bilirubin, ALP, total protein) 
- 
biomarkers (hsCRP, IL-1, IL-6, and TNF-alpha) 
 12-lead electrocardiogram 
 Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) 
 CT scan of the liver for patients with confirmed fatty liver at Visit 2 
 Urinalysis 
- 
routine urine test (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, 
leukocyte) 
- 
clinical microscopy 
 Information on adverse events 
 Information on new concomitant medications 
 
A safety follow-up should be conducted for subjects who prematurely withdraw from treatment 


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2 weeks after the end of treatment visit. A clinic visit is recommended unless the subject 
refused to return. If so, the safety follow-up may be conducted via telephone. 
Subjects willing to provide information should be followed for assessments of adverse events 
until the end of the trial. At a minimum, the investigator should make every effort to obtain 
information on whether or not the subject is alive or dead at the end of the study. 
 
6.2.6. Unscheduled Visit 
An unscheduled visit may be performed at any time during the study at the subject’s request or 
as deemed necessary by the site investigator. The date and reason for the unscheduled visit will 
be recorded in the source documentation and CRFs. Following procedures/assessments will be 
performed at unscheduled visits if applicable: 
 Physical examination 
 Anthropometric measures (Height, weight, waist circumference, BMI) 
 Vital signs (pulse rate, body temperature, respiratory rate, and blood pressure) 
 Blood samples for 
- 
lipid profile (total cholesterol, TG, HDL-C, LDL-C and LDL/HDL ratio) 
- 
serum chemistry (AST, ALT, CPK, BUN, serum creatinine, albumin, total bilirubin, 
direct bilirubin, ALP, total protein) 
 12-lead electrocardiogram 
 Information on adverse events 
 Information on new concomitant medications 


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7. STUDY EVALUATIONS 
A detailed scheduled examination components are shown by visit in Table 6.1. 
 
7.1. Informed Consent 
Consent to participate in a research study includes the elements listed below. The consent 
process will include all elements. 
 Participants must be advised that the study involves research. Staff must explain the 
purposes of the research, the expected duration of participation, and a description of the 
procedures to be followed, including identification of experimental procedures. 
 Anticipated benefits of the trial must be explained to the participant. 
 Attendant discomforts and risks “reasonably to be expected” must be described. 
 Appropriate alternative procedures that might be advantageous for the participant must 
be disclosed. 
 The extent, if any, to which confidentiality of records identifying the participant will be 
maintained must be described. 
 Prospective participants must be advised of the availability or non-availability of 
medical treatment or compensation for physical injuries incurred as a result of 
participation in the study, and if available, what they consist of, or where further 
information can be obtained. 
 Persons responsible for the study must explain whom a participant can contact for 
answers to pertinent questions about the research and his or her rights, and whom to 
contact in the event of a research-related injury. 
 Participants must be told that participation is voluntary, refusal to participate will 
involve no penalty or loss of benefits to which the participant is otherwise entitled, and 
the participant may discontinue participation at any time without penalty or loss of 
benefits to which he or she is otherwise entitled. 
 
7.2. Eligibility Assessments 
The objective of setting inclusion/exclusion criteria is to identify a trial population that will 
ensure adequate event rates for statistical power, provide maximum generalizability, and 
maximize safety. Inclusion criteria is defined in section 4.2, and exclusion criteria selected to 
enhance safety and adherence are defined in section 4.3. The following assessments are 
performed at screening visit to determine eligibility: 
(1) Check Patients’ Medical History: Eligible patients must have confirmed diagnoses of 


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hyperlipidemia according to European guidelines on cardiovascular disease prevention 
in clinical practice. 
(2) Vital Signs: Examination items include pulse rate, body temperature, respiratory rate, and 
blood pressure (including systolic blood pressure (SBP) and diastolic blood pressure 
(DBP)). 
(3) Physical Examinations: A physical examination will be completed and recorded in the 
source documents at Visit 1 prior to any study-related procedures. This evaluation will 
include an examination of general appearance, HEENT (head, eyes, ears, nose, and 
throat), mouth, skin, neck (including thyroid), lymph nodes, spine, cardiovascular 
system, respiratory system, gastro-intestinal system, nervous system, musculoskeletal 
system, blood and blood forming organs, mental status, and other body systems if 
applicable for describing the status of subject’s health. Anthropometric measures 
gathered include standing height, weight, BMI, and waist circumference. Height is 
measured for the subject not wearing shoes at Visit 1. The measurement of height will 
be rounded to the nearest tenth of a centimeter. Body weight is measured for  the 
subject not wearing shoes but wearing light clothing at Visit 1. The measurement of 
weight will also be rounded to the nearest tenth of a kilogram (if this procedure, 
measuring the height and weight, cannot be performed, obtaining this information from 
patients’ medical chart (within 1 month) is acceptable). Other anthropometric measures 
include waist circumference and body mass index (BMI, calculated as kg/m2) has been 
shown to be predictive of cardiovascular disease. 
(4) Check Patients’ Drug Records: Check record of use of lipid-lowering drugs within 2 
months. Patients taking lipid-lowering drugs shall have a 14-day wash-out period. In 
addition, patients shall not take any prohibited drugs mentioned in section 5.6.1 during 
the study period. If a subject is currently taking lipid-lowering drugs, the investigators 
shall determine whether discontinuation of these drugs will have impacts on his/her 
health status. If so, he/she is not recommended to enroll in the study. 
 
7.3. Demography Data and Medical History 
(1) Date of Birth 
(2) Gender: Male or Female 
(3) Race 
(4) Medical History: Review any diagnosis of liver or renal impairment, skin disorders or other 
severe diseases. Medical history data are collected at baseline in the form  of a detailed  
initial medical history and collected at specified follow-up visits in the form of an 
abbreviated interval history. The medical history shall be reviewed thoroughly to ensure 


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that eligible patients don’t have any symptoms/diseases specified in exclusion criteria 
(Section 4.3). Important aspects of the medical history include eligibility criteria, allergies, 
cardiovascular disease, smoking status, and diabetes. Any disease occurred within one 
year before visit 1 shall be recorded in CRF. 
(5) Drug Records: Review and record drug medication within 2 months before patient 
enrollment till the end of the study. Information regarding the participants’ concomitant 
medication therapy is collected and documented at baseline and then reviewed and 
revised at follow-up visits. Appropriate sources for obtaining this information include 
participant (significant other) report, current pharmacy action profiles, and 
verification of medications documented in the medical record. Although data are 
collected on all standing therapies, emphasis is placed on concurrent antihypertensive, 
glycemic and lipid-lowering therapy as well as background risk reduction (e.g., aspirin) 
therapy. 
 
7.4. Urine Pregnancy Test/Contraception Methods 
7.4.1. Urine pregnancy test 
All the female subjects with childbearing potential must perform urine pregnancy test (or 
serum pregnancy test if urine is not available) at the screening visit, and they should avoid 
pregnancy during this trial. Subjects must be permanently discontinued if pregnancy is 
confirmed by a positive urine (or serum) pregnancy test. Notably, subject shall  avoid 
pregnancy using an efficient contraception method (recommendation listed in Section 7.4.2, 
including but not limited to) during the entire 16 weeks of the study. Once any pregnancy event 
is known during the study, this pregnant subject must be withdrawn from the study 
immediately, and will be followed up. Pregnancies and pregnancy follow-up should be reported 
on the Adverse Event Form. Pregnancy follow-up should describe the outcome of the pregnancy, 
including any voluntary or spontaneous termination, details of the birth, the presence or 
absence of any congenital abnormalities, birth defect, maternal or newborn complications. 
Monitoring of the patient should continue until conclusion of the pregnancy. 
 
7.4.2. Contraception methods 
Non-pregnant, non-breast-feeding women may be enrolled if they are considered highly 
unlikely to conceive. A highly effective method of birth control is defined as one that results in a 
low failure rate (i.e., less than 1 percent per year) when used consistently and correctly, such as 
implants, injectables, combined oral contraceptives, some intrauterine devices, sexual 
abstinence, or a vasectomized partner. For subjects using a hormonal contraceptive method, 
information regarding the product under evaluation and its potential effect on the 


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contraceptive should be addressed. 
A female patient who is not of reproductive potential and therefore eligible to participate  in 
this study without requiring the use of contraception is defined as: one who has either (1) 
reached natural menopause (defined as ≥6 months of spontaneous amenorrhea with serum 
follicle-stimulating hormone levels in the postmenopausal range as determined by the 
laboratory, or ≥12 months of spontaneous amenorrhea), or (2) ≥6 weeks post surgical 
hysterectomy, or bilateral oophorectomy with or without hysterectomy, or (3) bilateral tubal 
ligation. 
The following are considered adequate barrier methods of contraception (including but not 
limited to): intrauterine device, diaphragm with spermicide, contraceptive sponge, condom, or 
vasectomy. For the purposes of this study, use of oral contraceptive pills are permitted but are 
not to be considered one of the two forms of birth control required. Patients  should  be 
informed that taking the study medication may involve unknown risks to the fetus (unborn 
baby) if pregnancy were to occur during the study and agree that in order to participate in the 
study they must adhere to the contraception requirement (described above) for the duration of 
the study. 
 
7.5. Laboratory Evaluations 
7.5.1 Clinical laboratory evaluations 
Laboratory tests (including hematology, biochemistry, and urinalysis) will be scheduled as 
below. The examination items are included in Table 7- 1. 
Lipid Profile: Blood samples to assess total cholesterol, triglycerides, HDL-C, LDL-C, LDL/HDL 
ratio will be obtained from visit 1 to visit 5. 
Hematology: Blood samples to assess WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, 
neutrophil-band and segment, lymphocyte, monocyte, eosinophil, basophil will be obtained at 
visit 2 and visit 5. 
Serum Biochemistry: Blood samples to assess AST, ALT, CPK, BUN and serum creatinine  will 
be obtained from visit 2 to visit 5, albumin, total bilirubin, direct bilirubin, ALP, total protein 
will be obtained at visit 2 and visit 5. At screening visit, serum creatinine shall be run for 
estimating glomerular filtration rate (GFR). 
Urinalysis: Assessments of urine pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, 
nitrite, leukocyte and clinical microscopy will be tested at visit 2 and visit 5. 
Pregnancy Test: Urine HCG test will be performed at visit 1. 
12-lead ECG: ECG will be performed in accordance with the standard procedures at the site at 
visit 2 and visit 5. 
baPWV and ABI measurement: baPWV is used to assess arterial stiffness and will be 


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obtained using VP 1000 or VP 1000 plus (Omron) at visit 2 and visit 5/early termination visit. 
ABI is a surrogate marker of atherosclerosis and will be obtained using the same device at visit 
2 and visit 5/early termination visit. 
Echocardiography: Values for S’, E’, and A’ will be measured and averaged over three 
consecutive cardiac cycles. A composite mean for each of these parameters is then formed by 
taking the average of the values from the septal, lateral, and inferior wall. The ratio of the 
transmitral Doppler E wave velocity and the composite mean of E’ will then be used to calculate 
the E/E’ ratio. E/E’ ratio will be obtained at visit 2 and visit 5. 
CT scan of the liver: Each participant will undergo non-enhanced liver computed tomography 
(CT) scans at visit 2. The Hounsfield Unit (HU) attenuation of liver on CT scans will be utilized 
for determination of fatty liver (L/S ratio <1.0 and liver attenuation <40HU). Subjects who are 
confirmed with fatty liver will undergo liver CT scans again at visit 5. 
 
Table 7- 1 Laboratory tests planned to be performed 
Hematology 
Biochemistry 
Urinalysis 
Others 
WBC, RBC, Hb, Hct, 
RDW, platelet, MCV, 
MCH, MCHC, neutrophil 
band and segment, 
lymphocyte, monocyte, 
eosinophil, basophil 
AST, ALT, CPK, BUN, serum 
creatinine, albumin, total 
bilirubin, direct bilirubin, 
ALP, total protein 
eGFR will be counted based 
on MDRD (Modification of 
Diet in Renal Disease) 
formulation: 
GFR (mL/min/1.73 m2)= 
186 x Scr -1.154 x Age 
-0.203 x 0.742 (if female) 
pH, protein, glucose, 
ketone, blood, 
urobilinogen, bilirubin, 
nitrite, leukocyte, and 
clinical microscopy 
Lipid Profile: total 
cholesterol, triglycerides, 
HDL-C, LDL-C, LDL/HDL 
ratio 
Biomarker: hsCRP, IL-1, 
IL-6, TNF-α 
 
7.5.2 Specimen preparation, handling, and storage 
The blood and urine samples will be examined at Union Clinical Laboratory in line with the 
SOPs during the study. The blood and urine samples will be examined at the site 
laboratory as well only for eligibility measurement at screening visit. 
 
7.6. Adverse event 
The subject will be asked to report adverse event (AE) voluntarily and an investigator will also 
examine a subject for identifying adverse event at each visit during the study, starting from  
Visit 2 until the end of the trial. The methods and procedures for recording, assessing and 
reporting AEs are described in Section 8. 


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7.7. Concomitant medications 
All concomitant medication used, either prescription or over-the-counter, and over-the-
counter supplements (vitamins and herbal supplements) throughout the study period will be 
recorded. 


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8. ASSESSMENT OF SAFETY 
8.1. Adverse Events (AE) 
An adverse event is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in the research, 
whether or not considered related to the subject’s participation in the research. 
All AEs including local and systemic reactions not meeting the criteria for “serious adverse 
events” will be captured on the appropriate AE page of CRF. Information to be collected 
includes event description, time of onset, clinician’s assessment of severity, relationship  to 
study product (assessed only by those with the training and authority to make a diagnosis) and 
time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship. All AEs will be followed to adequate 
resolution which means subjects experiencing AEs shall be followed until recovery, recovery 
with residual effects, continuing, death or lost to follow-up and be recorded on CRF AE page. 
Pre-existing conditions will be recorded as baseline on the “Medical History” of CRF. If the pre-
existing condition does not change, it does not have to be reported as an AE on subsequent 
cycles. However, if it deteriorates at any time during the study, it will be recorded as an AE. 
All AEs must be graded for severity and relationship to study product. The adverse event 
toxicity grading scale used will be the CTCAE v4.03 grading score. 
 
Severity of AEs 
All AEs will be assessed by the clinician using a protocol defined grading system. For events not 
included in the protocol defined grading system, the following guidelines will be used to 
quantify intensity. 
 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADL. 
Grade 3 
Severe 
or 
medically significant  but not 
immediately 
life-threatening; 
hospitalization 
or 
prolongation 
of 
hospitalization indicated; disabling; limiting self care ADL. 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE. 
ADL: activities of Daily Living 


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Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of intensity to be performed. Adverse events characterized as 
intermittent require documentation of onset and duration of each episode. 
 
Relationship to Study Drugs 
The clinician’s assessment of an AE's relationship to test article (study drug) is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event will be 
reported. All AEs must have their relationship to study product assessed using the terms 
defined as follows. In a clinical trial, the study product must always be suspect. To help assess, 
the following guidelines are used. 
 
Causality 
 Certain: There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable timeframe after study procedure(s) 
and cannot be explained by concurrent disease or other drugs or chemicals.
 Probable: There is evidence to suggest a causal relationship, and the influence of 
other factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after study procedure(s), is unlikely to be 
attributed to concurrent disease or other drugs or chemicals, and follows a clinically 
reasonable response to study events.
 Possible: There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after study  procedure(s)).  However,  the 
influence of other factors may have contributed to the event (e.g., the subject’s 
clinical condition, other concomitant events). Although an adverse event may be 
judged only as “possibly related” soon after discovery, it can be flagged as requiring 
more information and later be upgraded to “probably related” or “definitely related”, 
as appropriate.
 Unlikely: A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study procedure(s) makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after study procedure(s)) and 
in which other drugs or chemicals or underlying disease provides plausible 
explanations (e.g., the participant’s clinical condition, other concomitant treatments).
 Unrelated: The AE is completely independent of study  procedure(s),  and/or 
evidence exists that the event is definitely related  to another cause. There must be 
an alternative, definitive cause documented by the clinician.


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8.2. Expected Adverse Reactions 
In clinical trials, observed adverse effects of Antroquinonol are summarized as following: 
 
Diarrhea (92.31%) 
 
Vomiting (69.23 %) 
 
Nausea (53.85 %) 
If a GI event occurs, adequate drugs/therapies could be administered based on investigator’s 
judgements. If the event is judged as grade 3 according to CTCAE v4.03, this event will be seen 
as a serious adverse event. 
 
8.3. Serious Adverse Events (SAE) 
An SAE is any adverse event/experience occurring at any study drug dose that results in any of 
the following outcomes: 
 
Death 
 
Life-threatening (defined as an event in which the subject is at immediate risk of 
death at the time of the event; life-threatening does not refer to an event that 
hypothetically might have caused death if it were more severe, resulting in 
permanent or significant disability/incapacity) 
 
Requires inpatient hospitalization or prolongation of existing  inpatient 
hospitalization (excluding the hospitalization for the protocol specified image taking) 
 
Results in congenital anomaly or birth defect 
 
Results in persistent or significant disability or incapacity 
 
Events requiring medical and/or surgical intervention to prevent permanent 
impairment of function or permanent damage to a body structure 
 
All SAEs will be: 
 
recorded on the appropriate SAE CRF 
 
followed through resolution by a study clinician 
 
reviewed and evaluated by a study clinician 
 
An adverse event would meet the criterion of “requires hospitalization”, if the event 
necessitated an admission to a health care facility (e.g., overnight stay). Hospitalization does not 
include the following: 
 
Rehabilitation facilities 
 
Hospice facilities 
 
Respite care (e.g., caregiver relief) 


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 
Skilled nursing facilities 
 
Nursing homes 
 
Hospitalization or prolongation of hospitalization is not in itself an SAE. Examples include: 
 
Admission for treatment of a preexisting condition not associated with the development of 
a new adverse event or with a worsening of the preexisting condition (e.g., for work-up of 
persistent pretreatment lab abnormality) 
 
Administrative admission (e.g., for yearly physical exam) 
 
Protocol-specified admission during a clinical trial (e.g., for a procedure required by the 
trial protocol) 
 
Preplanned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject 
 
The study will adhere to the full requirements of the ICH Guideline for Clinical Safety Data 
Management, Definitions and Standards for Expedited Reporting, Topic E2 and comply with 
local regulatory requirements. 
 
8.4. Reporting Procedures 
8.4.1. Reporting procedures for AEs and SAEs 
All AEs and SAEs must be documented in the source documents and the relevant CRF and ADR 
form when applicable. The investigator may be asked to provide photocopies of the medical 
records for completion of AE or SAE report. The subjects’ names on the medical records 
submitted to the relevant parties will be concealed. It is the investigator’s responsibility to record 
AEs and SAEs by diagnosis terminologies, if possible. When the diagnosis is not possible for AE or 
SAE recording/reporting, signs and symptoms will be used for reporting instead. 
According the amended provision 106 of “Good Clinical Practice” (2010, by Department of 
Health, Taiwan), serious adverse events that are unexpected (i.e., SAEs that are not identified  
or recorded on protocol Section 8.3, investigator brochure and ICF) and related or possibly 
related to study drugs must be immediately reported to the “National Reporting System of 
Adverse Drug Reaction in Taiwan” using Adverse Drug Reaction (ADR) forms, which will be 
completed by the investigator. A copy of the ADR form will be filed in the site files. Those SAEs 
that are unexpected and related or possible related to study drugs should also be reported to 
local Research Ethics Committees (REC) according to its regulations. 
When any mentioned event happens to a subject between the times a participant signs the 
informed consent form and the time a subject departs the study at the end of the final visit 
should be reported to ADR center and local REC. All new serious adverse events occurring 


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beyond this time frame and coming to the attention of the investigator must be recorded only if 
they are considered (based on the investigator’s opinion) causally-related to the study drug. 
It is very important that the investigator should take information of underlying diseases, 
concomitant drugs, temporal relationship of the onset of the event to the time of dosing the 
study drugs, and re-challenging outcomes, into account when the investigator is making a 
causal relation decision (as described in Section 8.1). 
It is also investigator’s responsibility to proactively follow the outcome of each AE/SAE until 
resolution or stabilization of the condition or loss of follow-up. Serious, alarming and/or 
unusual adverse events must be reported to local Research Ethics Committees (REC) within 
24 hours of the investigator's knowledge of the event. 
 
An ADR form should be completed for all SAEs that are unexpected and related or possibly 
related to study drugs (SUSARs, suspected unexpected serious adverse reactions) and 
forwarded to the ADR center and the REC in according to the requirements of the institutions. 
Investigators should follow subjects as far as possible until an outcome of the events is known. 
The investigator will notify health authority of all the SAEs that are “death” or “life-threatening” 
in 7 calendar days, followed by a report within additional 8 calendar days. All of the remaining SAE 
events should be reported to health authority within 15 calendar days. The copy of each report 
will be kept in investigator’s files. Also, the investigator must inform SAE to local REC within the 
time frame regulated by REC. 
Lastly, all AEs, regardless of severity, will be followed by the investigator until the resolution is 
satisfactory. All the information must be collected on the action taken with the study drug. 
Serious, alarming and/or unusual adverse events must be reported to the following 
individuals within 24 hours of the investigator's knowledge of the event: 
 
AFFILIATION 
DEPARTMENT 
TELEPHONE 
NUMBER 
FAX NUMBER 
 
Bestat 
Pharmaservices Corp. 
Clinical Research 
+886-2-25955590 
+886-2-25955290 
 
8.4.2. Reporting pregnancy 
If a pregnancy occurs in a female subject while the subject is taking protocol-required therapies, 
subject pregnancy must be reported by the investigational staff within 24 hours of their 
knowledge. If a pregnancy occurs in a female partner of a male subject, while the subject is 
taking protocol-required therapies, it will be reported by the investigational staff within 24 


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hours of their knowledge. Any subject who becomes pregnant during the study must be 
promptly withdrawn from the study. Follow-up information regarding the outcome of the 
pregnancy and any postnatal sequelae in the infant will be required. The investigational staff 
shall record pregnancy on adverse event page on CRF, fill in an ADR form and inform both 
Sponsor and CRO designee aforementioned. 


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9. STATISTICAL CONSIDERATIONS AND ANALYTICAL 
PLAN 
9.1. Study Hypothesis 
Several hypotheses will be tested regarding the lipid change to determine if the benefits of 
Antroquinonol in the context of desirable levels of primary endpoint TG, and secondary  
endpoint TC, HDL-C, LDL-C, and LDL/HDL ratio. As well as the effect of Antroquinonol on E/E’, 
baPWV and ABI and HU parameters. 
 
9.2. Sample Size Considerations 
The primary efficacy endpoint in this trial is “to compare the percentage change of  
triglyceride (TG) from baseline following a 12-week regimen of Antroquinonol versus 
placebo.” The objective of this trial is to assess the efficacy of the study treatment compared 
with control treatment. According to the literature review (FDA statistical reviews of Fibrate), 
the TG reduction percentage change of Fibrate from baseline to last visit was 36.6% for 
subjects who were treated with the study treatment, and 0.7% increased for the control 
treatment. According to prior published clinical reference, it is assumed that the mean TG 
percentage reduction is 27.5% and standard deviation is 40. The evaluable patient number 
should be at least 24 patients for each group under one-sided significance level 0.025 and 
power 90%. Considering a 20% drop-out rate, a sample size of 30 patients should be enrolled 
to each group, and a total of 120 patients will be recruited into this study. The sample size 
calculation was derived using PASS 2008. 
 
9.3. Analyzed Population 
There will be three populations in this study, Intent-To Treat (ITT) population, Per-Protocol (PP) 
population and Safety populations for statistical analysis. Primary efficacy analysis will be 
performed in both ITT and PP population, while secondary efficacy analyses will be performed 
in ITT population only. Safety population will be used in analysis of safety variables. The 
populations for analysis applied into this study are defined as following: 
 
Intent to Treat Population (ITT): 
The ITT population includes all randomized patients who meet all inclusion criteria and 
exclusion criteria, take at least one study medication and have at least one post-baseline 


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measurement. 
 
Per-Protocol Population (PP): 
The PP population is a subset of the ITT population and includes all randomized patients who 
complete 12 weeks of treatment without major protocol violation. 
The definition of major protocol violations include (1) violate the enrollment criteria, (2) use 
prohibited medications indicated to treat dyslipidemia, and (3) drug compliance less than 
70%. 
 
Safety Analysis Population: 
All subjects who received at least one study medication will be included in the safety analysis 
population. 
 
9.4. Analysis Plan 
General data analysis 
For continuous endpoints, descriptive statistics including number, mean, median, standard 
deviation, minimum, maximum, and 95% confidence intervals will be presented. Continuous 
variables will be analyzed by means of ANOVA with Bonferroni adjustment. Paired T-Test will 
be used to compare the change from baseline within treatment groups. If the data strongly 
indicate a violation of the normal assumption, the non-parametric method of Kruskall Wallis 
test or Wilcoxon Signed-Rank Test will be applied for analysis. 
For categorical endpoints, the count and percentages will be used to summarize the categorical 
data. The Chi-square test will be performed to test the difference between groups while 
Fisher’s exact test will be applied for any counting of the frequency is less than 5. 
All statistical analyses will be conducted using SAS software. 
 
Endpoints 
The primary efficacy endpoint for assessing the superiority of Antroquinonol to placebo will be 
analyzed using analysis of covariance (ANCOVA) model and baseline measurement as 
covariates, if the differences in baseline characteristics, such as gender, age, weight etc., are 
observed, for comparing the effectiveness between the treatment groups. 
Analysis of other secondary efficacy endpoints (TC, HDL-C, LDL-C, and LDL/HDL ratio as well 
as the effect of Antroquinonol on E/E’, baPWV and ABI and HU parameters) will be similar to 
the primary analysis of the primary endpoint. All tests will be based on a significance level of 
0.05, without adjustment for multiple endpoints. 
For the safety assessments, the information of adverse events will be described in detail. Count 


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and percentage will be tabulated for the number of patients with AEs, number of total AEs, 
number of patients with AEs associated to study dosing and intensity. Adverse events will be 
coded by the Medical Dictionary for Regulatory Activities (MedDRA® ) adverse event dictionary. 
All the AEs will be categorized by each represented Preferred Terms (PT) and System Organ 
Class (SOC), which will be tabulated by body system with related incidence rates. The clinical 
laboratory tests and electrocardiogram tests will be analyzed to separate subjects into normal 
and abnormal categories, with number of subjects and percentage of subjects in each category, 
and McNemar’s test or Fisher’s exact test will then be applied to test the changes between 
each visit. 
 
9.5. Premature Termination and Missing Values 
Subjects may be withdrawn from the study prematurely for lost to follow-up, withdrawal the 
consent or other conditions as mentioned in Section 4.5.4. The reason of premature  
termination will be summarized. For drop-out subjects, the listing table will list the detailed 
reason and date for patients’ withdrawals. For subjects who terminate study drug early, values 
measured after termination of study drug will be censored. 
Last observation carried forward (LOCF) will be used to approach the missing data of primary 
endpoint in ITT population. No missing data will be imputed for the secondary efficacy or  
safety analyses. 


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10. DATA HANDLING AND RECORD KEEPING 
10.1. Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff under the 
supervision of the investigator. All source documents and laboratory reports must be 
reviewed by the study team and data entry staff, who will ensure that they are accurate and 
complete. Unanticipated problems and adverse events must be reviewed by the investigator 
or designee. 
The assigned CRO will be responsible for data management, quality review, analysis, and 
reporting of the study data. 
 
10.2. Investigator’s File/Retention of Documents 
A file for each subject must be maintained that includes the signed informed consent form and 
copies of all source documentation related to that subject. For each subject treated with the 
study drug(s), the Principal Investigator is required to prepare and maintain case histories that 
include all observations and other data pertinent to the investigation. This will include all 
source documents needed to verify the accuracy of all observations and other data contained in 
the Case Report Forms (CRFs) on each study patient. 
The Investigator or his/her designee is required to retain the records related to the trial for a 
period of 2 years following the date of marketing application is approved for the indication of 
being investigated. If no application is to be filed or if the application is not approved for such 
indication, the records must still be retained until 2 years after the investigation is 
discontinued and the regulatory agencies are notified. 
The Investigator shall retain study drug disposition records and source documents for the 
maximum period required by the country and the institution in which the study has been 
conducted, or for the period specified by the Sponsor, whichever is longer. The Investigator 
must contact the Sponsor prior to destroying any records associated with the study. 
 
10.3. Source Documentation and Background Data 
The investigator shall supply the REC and the authority(ies) on request with any required 
background data from the study documentation or clinic records. This is particularly important 
when CRFs are illegible or when errors in data transcription are suspected. In case of special 
problems and/or governmental queries or requests for audit inspections, it is also necessary to 
have access to the complete study records, providing protection of subject’s confidentiality. 


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10.4. Case Report Form (CRF) 
CRFs will be used for recording all data from each subject. CRFs must be typewritten or printed 
legibly using black ballpoint pen or completed electronically. The investigator or his/her 
designee is responsible for recording all data relating to the trial on the CRFs. The investigator 
must verify that all data entries on the CRFs are accurate and correct by signing and dating the 
CRFs on the designated pages. 
If an item is not available or is not applicable, it should be documented as such; no blank spaces 
should be left on a CRF. 
 
10.5. Data Capture Methods 
Case report form (CRF) is the method for recording the data of this study. Clinical data will be 
written to case report forms (CRFs). All entries on the CRF are made in English and are 
supported by the source data. 
 
10.6. Study Records Retention 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study drug. These documents should be 
retained for a longer period, however, if required by local regulations. 
 
10.7. Protocol Deviations 
 
A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical 
Practice, or Manual of Procedures requirements. The noncompliance may be on the part of the 
subject, the investigator, or study staff. As a result of deviations, corrective actions are to be 
developed by the study staff and implemented promptly. 
It is the responsibility of the site to use continuous vigilance to identify, record deviations in 
the “Protocol Deviation Form”. 
All deviations from the protocol must be addressed in study subject source documents. A 
completed copy of the “Protocol Deviation Form” must be maintained in the regulatory file, as 
well as in the subject’s source document. Protocol deviations must be sent to the local REC per 


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their guidelines. The site PI and study staff are responsible for knowing and adhering to their 
REC requirements. 


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11. STUDY MONITORING, AUDIT AND INSPECTION 
 
11.1. Study Monitoring 
All aspect of the study will be conducted under ICH, GCP (Good Clinical Practice) guidelines and 
government regulations. Monitoring (by phone, fax, or on site) will be done by a representative 
of the study monitor designated by the sponsor. If the monitoring is done on site the monitor 
will check the case report forms and questionnaires for completeness and clarity, and 
crosscheck them with source documents. In addition to the monitoring visits, frequent 
communications (letter, telephone, and fax), by the study monitor will ensure that the 
investigation is conducted according to protocol design and regulatory requirements. Study 
closeout (by phone, fax or on site) will be performed by the study monitor upon closure of the 
study. The investigator agrees to all these monitors access to the clinical supplies, dispensing, 
and storage area, and to the clinical files of the study subjects, and if requested, agrees to assist 
the monitor. 
A separate monitoring plan document should be developed to describe who will conduct the 
monitoring, at what frequency monitoring will be done, and at what level of detail monitoring 
will be conducted. 
 
11.2. Study Audit and Inspection 
In accordance with the principles of GCP, the study may be subjected to internal audits. 
Domestic authorities and the REC may request access to all source documents, case report 
forms, and other study documentation for on-site audit or inspection. Direct access to these 
documents must be guaranteed by the investigator, who must provide support at all times for 
these activities. Medical records and other study documents may be copied during audit or 
inspection. Subject names are obliterated on the copies to ensure confidentiality. The purpose 
of the audits should be to evaluate study conduct and compliance with protocol, SOPs, GCP, 
and the applicable regulatory requirements. The observations and findings should be 
documented. 


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12. QUALITY CONTROL AND QUALITY ASSURANCE 
Quality control is the ongoing, concurrent review of data collection forms for completion and 
logic. Quality assurance is a comprehensive, retrospective review of all components of research 
records to assess adherence to protocol, standard operation procedures, and regulations, and to 
evaluate the accuracy of the records. Quality management is the process of assessing  the 
quality of processes within a system and encompasses quality assurance and quality control. 
 
For the assurance of the data accuracy, completeness, and reliability, the investigator or the 
study staff assigned by the investigator will evaluate the CRFs by visual review and standard 
computer editing to detect errors in data collection will be performed by the assigned CRO. 
 
To protect the safety of the subjects and to ensure the data accuracy, completeness, and 
reliability, the research staff would preserve documented data from all sources on CRF,  
including lab test results, chart records, treatment conditions, physical examination, 
concomitant medication, and any adverse events. 


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13. ETHICAL CONSIDERATIONS 
13.1. Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the principles 
set forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, as drafted by the US National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research (April 18, 1979), the Declaration of Helsinki 
(2013), the ICH E6, and local regulations. 
 
13.2. Research Ethics Committees (REC) 
The protocol, informed consent form(s), recruitment materials, and all subject materials will  
be submitted to the REC for review and approval. Approval of both the protocol and the 
consent form must be obtained before any subject is enrolled. Any amendment to the protocol 
will require review and approval by the REC before the changes are implemented in the study. 
 
13.3. Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate in 
the study and continues throughout study participation. Extensive discussion of risks and 
possible benefits of study participation will be provided to subjects and their families, if 
applicable. A consent form describing in detail the study procedures and risks will be given to 
the subject. Consent forms will be REC-approved, and the subject is required to read and 
review the document or have the document read to him or her. The investigator or designee 
will explain the research study to the subject and answer any questions that may arise. The 
subject will sign the informed consent document prior to any study-related assessments or 
procedures. Subjects will be given the opportunity to discuss the study with their surrogates 
or think about it prior to agreeing to participate. They may withdraw consent at any time 
throughout the course of the study. A copy of the signed informed consent document will be 
given to subjects for their records. The rights and welfare of the subjects will be protected by 
emphasizing to them that the quality of their clinical care will not be adversely affected if they 
decline to participate in this study. 
The consent process will be documented in the clinical or research record. 


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13.4. Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators and their staff. 
This confidentiality is extended to cover testing of biological samples and genetic tests in 
addition to the clinical information relating to participating subjects. All patients will be 
identified by the subject number, initials, date of birth and gender in the CRFs. Subject’s name 
will only be maintained at site. The investigator must assure that subjects' anonymity will be 
maintained and that their identities are protected from unauthorized parties. The subjects 
should be informed about the possibility of audits by authorized representatives of the 
company and regulatory authorities when audit or review is required. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the investigator. 
The study monitor or other authorized representatives of the investigator may inspect all 
documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the subjects in this 
study. The clinical study site will permit access to such records. 
 
13.5. Protocol Amendments 
Any change of this protocol that affect study objectives, study design, study procedures, 
patient population, or significant administrative procedures will require a formal amendment 
to the protocol. Any proposed protocol amendments must be sent in written form to the 
REC/TFDA. Prior to implementation, an amendment must be approved by the Sponsor, the 
Investigator and the REC/TFDA. 


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14. PUBLICATION POLICY 
Following completion of the study, the investigator is expected to publish the results of this 
research in a scientific journal. Member journals of The International Committee of Medical 
Journal Editors have adopted a trials-registration policy as a condition for publication. This 
policy requires that all clinical trials be registered in a public trials registry such as 
ClinicalTrials.gov, which is sponsored by the National Library of Medicine. Other biomedical 
journals are considering adopting similar policies. For grants and cooperative agreements, it is 
the Golden Biotechnology Corporation’s responsibility to register the trial in an acceptable 
registry. 
The ICMJE defines a clinical trial as any research project that prospectively assigns human 
subjects to intervention or comparison groups to study the cause-and-effect relationship 
between a medical intervention and a health outcome. Studies designed for other purposes, 
such as to study pharmacokinetics or major toxicity (e.g., Phase I trials), would be exempt from 
registering trials in a public registry such as ClinicalTrials.gov. The sponsor shall have the right 
to publish or present any results or information, including the study results. Once if the sponsor 
or the institution, investigator or the staff intend to publish the study results, mutual agreement 
shall be obtained at least thirty (30) business days prior to the submission for publication or 
presentation. 
 
15. REFERENCES 
[1] Curr Atheroscler Rep. 2008 Oct;10(5):386-90. Triglycerides and risk for coronary artery 
disease. McBride P. 
[2] Nutr Metab Cardiovasc Dis. 2013 Sep;23(9):799-807. Managing the residual cardiovascular 
disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical 
update. Reiner Z. 
[3] Mutat Res. 2011 Feb 10;707(1-2):42-52. Antroquinonol inhibits NSCLC proliferation by 
altering PI3K/mTOR proteins and miRNA expression profiles. Kumar VB, Yuan TC, Liou JW, Yang 
CJ, Sung PJ, Weng CF. 
[4] Crit Care Med. 2011 May;39(5):984-92. Plasma levels of tumor necrosis factor-α and 
interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic 
reticulum Ca2+ ATPase. Wu CK, Lee JK, Chiang FT, Yang CH, Huang SW, Hwang JJ, Lin JL, Tseng 
CD, Chen JJ, Tsai CT. 
[5] Free Radic Biol Med. 2011 Jun 1;50(11):1503-16. Antroquinonol reduces oxidative stress by 
enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental 
glomerulosclerosis mice. Tsai PY, Ka SM, Chao TK, Chang JM, Lin SH, Li CY, Kuo MT, Chen P, Chen 


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A. 
[6] Biochem Pharmacol. 2010 Jan 15;79(2):162-71. Antroquinonol displays anticancer potential 
against human hepatocellular carcinoma cells: a crucial role of AMPK and mTOR pathways. 
Chiang PC, Lin SC, Pan SL, Kuo CH, Tsai IL, Kuo MT, Wen WC, Chen P, Guh JH. 
[7] Biomed Pharmacother. 2014 Oct;68(8):1007-14. Antroquinonol blocks Ras and Rho 
signaling via the inhibition of protein isoprenyltransferase activity in cancer cells. Ho CL, Wang 
JL, Lee CC, Cheng HY, Wen WC, Cheng HH, Chen MC. 

SAP_000.pdf: 
  
 
 
 
 
SAP_V1.0, 09-FEB-2018 
 
Confidential 
Statistical Analysis Plan 
 
 
A Prospective, Double Blind, 
Randomized, Placebo-controlled 
Trial of Antroquinonol in Patients 
with Hypercholesterolemia and 
Hyperlipidemia 
 
 
PROTOCOL NO. 
GHLIP-2-001 
SAP VERSION 
V1.0 
SAP DATE 
09-Feb-2018 
SPONSOR 
Golden Biotechnology Corporation 
PREPARED BY  
Isa Chen/Bestat Pharmaservices Corp. 
CONFIDENTIAL: This document and the information in it are confidential and legally privileged. Any 
confidential information may not be disclosed unless such disclosure is required by applicable law or regulations. 
In any event, persons to whom the information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure will apply equally to all 
future information supplied to you which is indicated as privileged or confidential. 


 
 
 
 
SAP_V1.0, 09-FEB-2018 
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Confidential 
TITLE PAGE 
A Prospective, Double Blind, Randomized, Placebo-controlled Trial of Antroquinonol in 
Patients with Hypercholesterolemia and Hyperlipidemia 
PROTOCOL NO. 
GHLIP-2-001 
INVESTIGATIONAL DRUG 
Antroquinonol (Hocena®) 
INDICATION 
Hypercholesterolemia and Hyperlipidemia 
SPONSOR 
Golden Biotechnology Corporation 
PRINCIPAL INVESTIGATOR(S) 
Fu-Tien Chiang, M.D. 江福田 教授 
National Taiwan University Hospital 
DATE OF FIRST ENROLLMENT 
02-Nov-2016 
DATE OF STUDY COMPLETION  
(LAST PATIENT LAST VISIT): 
Expected on 30-Sep-2018 
DATE OF DATABASE LOCK 
Expected on 15-Oct-2018 
SAP VERSION/DATE: 
V1.0/ 09-Feb-2018 
This study was performed in compliance with Good Clinical Practices (GCP) including the archiving of essential 
documents.




 
 
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TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................................................... 2 
APPROVALS .............................................................................................................................................................. 3 
TABLE OF CONTENTS ............................................................................................................................................... 4 
ABBREVIATIONS ...................................................................................................................................................... 8 
1 
PREFACE .........................................................................................................................................................11 
2 
PURPOSE.........................................................................................................................................................11 
3 
STUDY OBJECTIVES AND ENDPOINTS .........................................................................................................12 
 
STUDY OBJECTIVES ........................................................................................................................................... 12 
 
Primary Objective ..................................................................................................................................... 12 
 
Secondary Objectives................................................................................................................................ 12 
 
STUDY ENDPOINTS ........................................................................................................................................... 12 
 
Primary Endpoint ..................................................................................................................................... 12 
 
Secondary Endpoints ............................................................................................................................... 13 
 
Safety Endpoints ...................................................................................................................................... 13 
4 
STUDY METHOD .............................................................................................................................................13 
 
OVERALL STUDY DESIGN AND PLAN ................................................................................................................... 13 
 
Study Flow Chart ...................................................................................................................................... 14 
 
Schedule of Assessments........................................................................................................................... 15 
 
SELECTION OF POPULATION ............................................................................................................................... 16 


 
 
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Inclusion Criteria ...................................................................................................................................... 16 
 
Exclusion Criteria ..................................................................................................................................... 17 
 
RANDOMIZATION AND BLINDING ........................................................................................................................ 18 
5 
SAMPLE SIZE DETERMINATION ...................................................................................................................19 
6 
SEQUENCE OF PLANNED ANALYSES .............................................................................................................19 
 
INTERIM ANALYSES AND DATA MONITORING ....................................................................................................... 19 
 
FINAL ANALYSES AND REPORTING ...................................................................................................................... 20 
7 
GENERAL CONSIDERATIONS .........................................................................................................................20 
 
RELEVANT SOPS AND POLICIES.......................................................................................................................... 20 
 
TIMING OF ANALYSES ........................................................................................................................................ 21 
 
MISSING DATA .................................................................................................................................................. 21 
 
ANALYSIS POPULATIONS .................................................................................................................................... 21 
 
Intent-to-Treat Population (ITT) ............................................................................................................. 21 
 
Per Protocol Population ........................................................................................................................... 22 
 
Safety Population ..................................................................................................................................... 22 
 
COVARIATES AND SUBGROUPS ............................................................................................................................ 22 
 
DERIVED AND COMPUTED VARIABLES ................................................................................................................ 22 
 
ADJUSTMENTS FOR MULTIPLICITY ...................................................................................................................... 23 
 
MULTI-CENTER STUDIES.................................................................................................................................... 23 
 
DATA MANAGEMENT SYSTEM AND ANALYSIS SOFTWARE ...................................................................................... 24 
 
CODING DICTIONARY ......................................................................................................................................... 24 
 
DATA HANDLING AND TRANSFER ....................................................................................................................... 24 


 
 
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PROGRAMMING SPECIFICATIONS ........................................................................................................................ 25 
8 
SUMMARY OF STUDY DATA ...........................................................................................................................25 
 
DISPOSITION OF SUBJECT AND WITHDRAWS ........................................................................................................ 26 
 
PROTOCOL VIOLATION AND DEVIATIONS ............................................................................................................. 26 
 
DEMOGRAPHICS ................................................................................................................................................ 26 
 
BASELINE AND SCREENING CONDITIONS ............................................................................................................. 27 
 
Baseline Medical History .......................................................................................................................... 27 
 
Baseline Physical Exam ............................................................................................................................ 27 
 
PRIOR AND CONCURRENT MEDICATIONS ............................................................................................................. 27 
 
TREATMENT COMPLIANCE ................................................................................................................................. 27 
9 
STATISTICAL METHODS ................................................................................................................................28 
 
PRIMARY HYPOTHESIS ...................................................................................................................................... 28 
 
TEST OF ASSUMPTIONS ..................................................................................................................................... 28 
 
PRIMARY ENDPOINT ANALYSIS ........................................................................................................................... 29 
 
SECONDARY ENDPOINT ANALYSES ...................................................................................................................... 30 
 
SAFETY ANALYSES ............................................................................................................................................ 30 
 
SUBGROUP ANALYSES ........................................................................................................................................ 31 
 
INTERPRETATION AND CONCLUSION ................................................................................................................... 31 
10 
SAFETY ANALYSES .........................................................................................................................................31 
 
ADVERSE EVENTS ............................................................................................................................................. 32 
 
All Adverse Events................................................................................................................................ 32 
 
Adverse Events Leading to Withdrawal .............................................................................................. 33 


 
 
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Serious Adverse Events ........................................................................................................................ 33 
 
Deaths .................................................................................................................................................. 34 
 
Other AE Assessments .......................................................................................................................... 34 
 
CLINICAL LABORATORY EVALUATIONS ................................................................................................................. 34 
 
OTHER SAFETY MEASURES ................................................................................................................................ 34 
11 
REPORTING CONVENTIONS ..........................................................................................................................35 
 
GENERAL REPORTING CONVENTIONS .................................................................................................................. 35 
 
POPULATION/STATISTIC SUMMARY CONVENTIONS .............................................................................................. 36 
12 
SUMMARY OF CHANGES TO THE PROTOCOL ..............................................................................................36 
13 
REFERENCES ..................................................................................................................................................37 
14 
APPENDIX .......................................................................................................................................................37 
 
MOCK-UP TABLES ............................................................................................................................................. 37 
 
PLANNED TABLES ............................................................................................................................................. 40 
Statistical Tables ..................................................................................................................................................... 40 
Data Listing ............................................................................................................................................................ 44 
 
 
 


 
 
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ABBREVIATIONS 
ABBREVIATIONS 
DEFINITION 
ABI 
Ankle-brachial Index 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate Aminotransferase 
baPWV 
Brachial-ankle Pulse Wave Velocity 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CDMS 
Clinical Data Management Systems 
CPK 
Creatine Phosphokinase 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C-reactive Protein 
CV 
Cardiovascular 
CV(%) 
Coefficient of Variation 
CVD 
Cardiovascular Diseases 
DBP 
Diastolic Blood Pressure 
eGFR 
Estimated glomerular filtration rate 
GCP 
Good Clinical Practice 
ECG 
Electrocardiogram 


 
 
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HDL-C 
High-density Lipoprotein Cholesterol 
HF 
Heart Failure 
hsCRP 
High Sensitivity assay of C-reactive Protein 
HU 
Hounsfield Unit 
ICH 
International Conference on Harmonization 
IL-1 
Interleukin 1 
IL-6 
Interleukin 6 
ITT 
Intent-to-Treat 
kg 
Kilogram 
LDL-C 
Low-density Lipoprotein Cholesterol  
LDL-R 
Low-density Lipoprotein Receptor 
m 
Meter 
m2 
Meters Squared 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
PT 
Preferred Term 
PP 
Per-Protocol 
RBC 
Red blood cell 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis System® 
SBP 
Systolic Blood Pressure  
SD  
Standard Deviation 
SOC 
System Organ Class 


 
 
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SOP 
Standard Operating Procedure 
TC 
Total Cholesterol 
TG 
Triglyceride  
WBC 
White blood cell 
 
 
 


 
 
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1 PREFACE 
Dyslipidemia is a health risk, and epidemiologic studies have shown a link between total 
cholesterol levels and the risk of cardiovascular diseases (CVD). Previous studies have shown 
that lowering the levels of total and low-density lipoprotein cholesterol (LDL-C) are associated 
with decreasing in cardiac morbidity and mortality, whilst epidemiological evidence 
consistently indicate moderate and highly significant associations between triglyceride (TG) 
values and coronary heart disease risk 1. Studies have shown that Antroquinonol® enhances the 
expression of low-density lipoprotein receptor (LDLR) genes in liver cells responsible for the 
removal of cholesterol in low-density lipoprotein cholesterol (LDL-C) from the blood stream 
and significantly increased high-density lipoprotein cholesterol (HDL-C) level (p<0.001) in 
plasma compared to vehicle control. These results demonstrate the potential applications of 
Antroquinonol® in treating hyperlipidemia and prevent associated CVDs. In this study, 
Antroquinonol® will be served as the study treatment to assess the reduction of TG in 
comparison with placebo in patients with hypercholesterolemia and hyperlipidemia after 12 
weeks. 
2 PURPOSE 
The purpose of this SAP is to outline the planned statistical analyses to be completed to support 
the completion of the Clinical Study Report (CSR) for protocol GHLIP-2-001. The planned 
analyses identified in this SAP will be included in regulatory submission and/or future 
manuscripts. Also exploratory analyses not necessarily identified in this SAP may be performed 
to support the clinical development program. Any post-hoc, or unplanned, analyses not 


 
 
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identified in this SAP performed will be clearly identified in the respective CSR.
3
STUDY OBJECTIVES AND ENDPOINTS 
Study Objectives 
Primary Objective 
The primary objective is to demonstrate the reduction of TG by Antroquinonol, in comparison 
with placebo, after 12 weeks of treatment in patients with hypercholesterolemia and 
hyperlipidemia.
Secondary Objectives 
Secondary objectives include the evaluation of the effects of Antroquinonol in comparison with 
placebo on other lipid parameters, left ventricular diastolic function, arterial stiffness, and fatty 
liver after 12 weeks of treatment. The safety and tolerability of Antroquinonol will be monitored 
as well.

Study Endpoints 
Primary Endpoint 
The primary efficacy endpoint is the percentage change of TG by Antroquinonol, in comparison 
with placebo, after 12 weeks of treatment in patients with hypercholesterolemia and 
hyperlipidemia.


 
 
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Secondary Endpoints 
ͳǤ  The effect of Antroquinonol in comparison with placebo on the percentage change in total 
cholesterol, HDL-C, LDL-C and HDL/LDL ratio from baseline after 12 weeks of treatment. 
ʹǤ  The effect of Antroquinonol on the ratio of mitral velocity to early diastolic velocity of the 
mitral annulus (E/E’ ratio) with tissue Doppler imaging and baPWV and ABI via a non-
invasive arterial stiffness measurement.
͵Ǥ  The effect of Antroquinonol on the fatty liver prognostic with CT scan.
Safety Endpoints 
ͳǤ
Changes in laboratory examination including hematological, biochemical parameters, and 
urinary analysis.
ʹǤ
Changes in electrocardiogram test, vital signs, and physical examinations.
͵Ǥ
Analysis of adverse events.
ͶǤ
Compliance and tolerability of the study drug
4
STUDY METHOD 
Overall Study Design and Plan 
The study design is constructed as a multi-center, prospective, double-blind, randomized, 
placebo-controlled study to assess the reduction of TG by Antroquinonol, in comparison with 
placebo, after 12 weeks of treatment in patients aged between 20 and 75 years with 
hypercholesterolemia and hyperlipidemia. Enrolled patients are randomized in 1: 1: 1: 1 ratio 
to Antroquinonol 150 mg, Antroquinonol 100 mg, Antroquinonol 50 mg, or placebo.


 
 
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Study Flow Chart 
Flow Chart of the Study Schedule
Procedure
Screening *
Randomize 
Treatment Period
Follow-up
Visit
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Interval
Day -14
Day 1
(Week 1)
Day 29 
(Week 5)
Day 57
(Week 9)
Day 85
(Week 13)
Day 99
(Week 15)
Allow Window
-
-
±3
±3
±3
±3
Informed Consent
X





Assessment of 
Eligibility Criteria
X





Medical History
X





Demographic
X





Vital Signs 1
X
X
X
X
X
X
Anthropometric 
measures 2
X
X
X
X
X
X
Electrocardiogram

X


X

Physical Examination
X
X
X
X
X
X
Urine Pregnancy Test
X





Randomization 3

X




Drug Dispense 

X
X
X


Drug Return


X
X
X

Efficacy Assessment






Serum Lipid 4
X
X
X
X
X
X
baPWV and ABI

X


X

Image Monitoring 5

X


X

Biomarker Assessment






CRP and Cytokine 6

X


X
X
Safety Assessment






CBC and WBC 
differential 7

X


X
X
Biochemistry 8
  X
X
X
X
X
X
Urinary Exam 9

X


X
X


 
 
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Concomitant Therapy
X
X
X
X
X
X
Adverse Event

X
X
X
X
X
* A wash-out period of 2 weeks will not be applied to patients prior treated with medication which does not affect 
serum lipid level.
ͳǤ Vital signs: pulse rate, body temperature, respiratory rate, and blood pressure (including systolic blood pressure 
(SBP) and diastolic blood pressure (DBP)).
ʹǤ Including height, weight, waist circumference, and BMI (calculated by kg/m2)
͵Ǥ Subjects who meet the eligibility criteria will be randomized into treatment arms. If the eligibility is confirmed 
and a wash-out period is not needed for the subject, based on investigator’s judgements the blood test required 
at V2 can be replaced by the data obtained 14 days before V2.
ͶǤ Serum lipids: total cholesterol, triglycerides, HDL-C, LDL-C, LDL/HDL ratio. Serum lipid results obtained 3 days 
prior to V1 is acceptable.
ͷǤ Doppler color flow mapping, and CT scan of the liver. CT scan will not be scheduled at visit 5 on subjects without 
fatty liver. Results of Doppler color flow mapping and CT scan of the liver obtained between V1 and V2 are 
acceptable.
͸Ǥ hsCRP, IL-1, IL-6, and TNF-alpha.
͹Ǥ WBC, RBC, Hb, Hct, RDW, platelet, MCV, MCH, MCHC, neutrophil-band and segment, lymphocyte, monocyte, 
eosinophil, and basophil.
ͺǤ Biochemical exam: AST, ALT, CPK, BUN and serum creatinine: visit 2 to visit 6; albumin, total bilirubin, direct 
bilirubin, ALP, total protein: V2, V5 and V6. At screening visit, serum creatinine shall be run for 
estimatingglomerular filtration rate(GFR) and data obtained 3 days prior to V1 is acceptable.
ͻǤ Urinary exam: routine urine test (pH, protein, glucose, ketone, blood, urobilinogen, bilirubin, nitrite, leukocyte) 
and clinical microscopy.

Schedule of Assessments 
Screening activities: 
Before being enrolled to the study, patients should complete informed consent, review of 
medical history, physical examination, blood samples for lipid profile and biochemistry, 
demographic, anthropometric measures, urine pregnancy test, vital signs, and concomitant 
therapy record. 


 
 
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Every study visit day including Day1, 29, 57, 85, 99: 
The patient who meets all the entry criteria are eligible for the study. During the study period, 
the patient have to undergo biochemistry assessment, vital signs measurements, 
anthropometric measures, physical examination, serum lipid test, concomitant therapy record, 
and adverse event assessment.
Every study visit day including Day 1, 85, 99: 
During the study period, biomarker assessment, CBC and WBC differential, and urinary exam 
are conducted.
Every study visit day including Day 1, 85: 
During the study period, electrocardiogram, baPWV, ABI, and image monitoring are performed.
Every study visit day including Day 1, 29, 57, 85: 
Dispense new study drug pack to the patient (Day 1, 29, 57), collect unused portion of previous 
pack from the patient (Day 29, 57, 85), and ensure accountability information on patients’ drug 
accountability log.
Selection of Population 
Inclusion Criteria 
ͳǤ
Adults of either sex 20 to 75 years of age, inclusive, with a diagnosis of nonfamilial 
hypercholesterolemia or mixed hyperlipidemia as one of the following: 
- TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 
mg/dL 
- TG between 150 mg/dL and 500 mg/dL and LDL-C > 130 mg/dL).
ʹǤ
Subject must be free of any clinically significant disease, other than nonfamilial 
hypercholesterolemia or mixed hyperlipidemia that would knowingly interfere with study 
evaluations.


 
 
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͵Ǥ
A wash-out period of 2 weeks will be applied to patients prior treated with lipid-lowering 
medication.
ͶǤ
Subject must be willing to adhere to protocol requirements, and provide written informed 
consent.
ͷǤ
Female of child-bearing potential must agree to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) prior to study entry and for the duration of 
study participation.
Exclusion Criteria 
ͳǤ
       ǡ ǡ
ǡǦȋǤǤ
ǡȌǦȋǤǤǡ
androgens, βǦǡȌǤ
ʹǤ
ǡ
   ͵   ǡ  ǡ   ǡ  
 ǡ   ǡ       
Ǥ
͵Ǥ
Patients with diabetes or history of coronary artery disease (has had myocardial infarction, 
cardiac intervention, cerebrovascular accident/stroke or transient ischemic attack less 
than 6 months prior to Visit 1).
ͶǤ
Patients with hypertension that is uncontrolled defined as 2 consecutive measurements of 
sitting blood pressure of systolic >140 mmHg or diastolic > 90 mmHg at Visit 1.
ͷǤ
Patient has a known hypersensitivity to Antroquinonol or related compounds.
͸Ǥ
Patient with uncontrolled intercurrent illness including, but not limited to, acute 
decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that 
may require IV therapy), right heart failure due to severe pulmonary disease, diagnosed 
peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 
1, or psychiatric illness/social situations that would limit compliance with study 
requirements.
͹Ǥ
Patients with a history of heart transplant or who are on a transplant list or with left 
ventricular assistance device (LVAD device).


 
 
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ͺǤ
Patients with documented ventricular arrhythmia with syncopal episodes within the past 
3 months prior to visit 1 that remained untreated.
ͻǤ
Patients with confirmed severe primary pulmonary, renal (eGFR<30 ml/min/1.73 m2) or 
hepatic (Child-Pugh B/C classification) disease.
ͳͲǤ Patients who can’t stop current lipid lowering drug treatments based on investigator’s 
judgement.
ͳͳǤ    ǡ   ǡ    ͷ    ͳ
ǡ
Ǥ
ͳʹǤ Female patient during pregnancy, lactation or breastfeeding.
ͳ͵Ǥ Patient has any other life-threatening complications.
ͳͶǤ Patient who is considered unreliable as to medication compliance or adherence to 
scheduled appointments, or inappropriate for inclusion determined by the investigators.
ͳͷǤ Any other reasons addressed by the investigators.
Randomization and Blinding 
According to the double-blind study design, enrolled patients are randomized in 1: 1: 1 :1 ratio 
to receive either Antroquinonol 150 mg, Antroquinonol 100 mg, Antroquinonol 50 mg, or 
placebo. The randomization sequence was generated using SAS version 9.3 with blocks of 
variable size and random seeds to ensure that allocation concealment is not violated through 
guessing of the allocation sequence at the end of each block. The aforementioned randomization 
code list was generated by the CRO and provided to Golden Biotechnology Corporation in order 
to pack and label the study drugs. Randomization data would not be accessible by anyone else 
involved in the study. The corresponding study group of individual subjects were recorded in a 
sealed envelope and were kept strictly confidential until the time of data lock. For this multi-
center study, centralized randomization was applied. The investigator confirmed the subject 


 
 
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fulfilled the inclusion and exclusion criteria and informed the randomization center. The 
sponsor’s independent staff provided the randomization number in order. The study drugs 
labeled with randomization number was provided according to the request from each site.
After enrollment, subjects were randomly assigned to receive one of the study treatments in a 
double-blind fashion. The identity of the treatments were concealed by the use of study drugs. 
The placebo was masked by the same appearance, odor and taste as the study drug 
(Antroquinonol), and used as well. Subjects, investigator, site staff, persons performing study 
assessments and data analysts remain blinded to the treatment assignment from the time of 
randomization until data lock.
5
SAMPLE SIZE DETERMINATION 
The sample size estimation of this study is using two-sample T-test Ǧ
ͲǤͲʹͷǡͻͲΨǤDavidson’sǡ

ͳ͵Ͳ	͵͸Ǥ͸Ψ
ǡʹǤͶΨͷǤ͵Ψ
Ǥssuming a drop-out rate of 20%ǡa sample size of ͳʹͲpatients(30 
patients per arm) were required to provideͻ͸patientsȋʹͶȌ
which indicates an achievement of 80% completion rateǤ 
6
SEQUENCE OF PLANNED ANALYSES 
Interim Analyses and Data Monitoring 
No interim analysis will be performed for this study.


 
 
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Final Analyses and Reporting 
All final planned analyses identified in the protocol and in this SAP will be performed only after 
the last patient has completed assessments scheduled for the 12-week study period and the 
database has been cleaned and locked. A blinded data review will be conducted prior to 
database lock and completion of the final analyses. In addition, no database may be locked, 
random code un-blinded, or analyses completed until this SAP has been approved. 
Key Statistics and study results will be made available to Bestat Pharmaservices Corp. following 
database lock and prior to completion of the final CSR.
Any post-hoc, exploratory analyses completed to support planned study analyses, which were 
not identified in this SAP, all be documented and reported in appendices to the CSR. Any results 
from unplanned analyses will also be clearly identified in the text of the CSR.
7
GENERAL CONSIDERATIONS 
Relevant SOPs and Policies 
The data manager (DM) will carry out verification procedures upon double data entry 
completion. Data entered in the first database has to be verified against the data entered in the 
second database for comparison and verification purposes. All discrepancies shall be recorded 
and data verification output shall be generated after this process. The DM verify the 
discrepancies between first entry and second entry against the hard copy CRF. All verified data 
must be uploaded to the updated database(s). Data verification output and relevant records will 
be stored properly and securely. 
ǡ


 
 
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Ǥ
Ǥ
Timing of Analyses 
The final analyses will be performed when the last subjects have completed the study or 
permanently discontinued the study, all queries are solved, protocol deviation/violation has 
been identified, database has been locked and the statistical analysis plan with detail methods 
has been finalized and approved.
Missing Data 
Last observation carried forward (LOCF) will be used to approach the missing data of primary 
endpoint in Intent-To-Treat (ITT) population. For each individual, missing values occurs in 
efficacy variable (i.e., TG) will be replaced by the later point. If more than two data are missing 
the following assessment, the last non-missing value will be used to fill in each missing 
observation. The variable TG related with the primary endpoint assessment will be presented 
by LOCF method.
No missing data will be imputed for the secondary efficacy or safety analyses.
Analysis Populations 
ITT population, Per-Protocol (PP) population and Safety populations are three populations for 
statistical analysis. The ITT population and PP population are used in analysis of efficacy 
variables, and the safety population perform in analysis of safety variables. 
Intent-to-Treat Population (ITT) 
The ITT population includes all randomized patients who meet all inclusion criteria and 


 
 
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exclusion criteria, take at least one study medication and have at least one post-baseline 
measurement.
Per Protocol Population 
The PP population is a subset of the ITT population and includes all randomized patients who 
complete 12 weeks of treatment without major protocol violation. 


ǡ 

ǡ

͹ͲΨǤ
Safety Population 
All subjects who received at least one study medication will be included in the safety analysis 
population.
Covariates and Subgroups 
The primary efficacy endpoint for assessing the superiority of Antroquinonol (50mg, 100mg, 
and 150mg) to placebo is the mean percentage reduction change of TG in patients with 
hyperlipidemia by using analysis of covariance (ANCOVA) model using baseline measurement 
as covariates, if the differences in baseline characteristics, such as gender, age, weight etc., are 
observed, for comparing the effectiveness between the treatment groups and placebo. 
Derived and Computed Variables 
The following derived and computed variables have been initially identified. It is expected that 


 
 
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additional variables will be required. The SAP will not be amended for additional variables that 
are not related to the primary endpoint or key secondary endpoints. An additional derived or 
computed variables will be identified and document in the SAS programs that create analysis 
files.
•
Age (years) = (date of giving inform consent – date of birth)/365.25
•
BMI (kg/m2) = Weight (kg) / Height2 (m2)
•
Treatment Compliance (%) = 
Quantity of total dispensed − Quantity of total returned
Treatment period (84 days) 
× 100%
•
Percentage change from baseline of TG (%) =
𝐷𝑎𝑦85 (𝑇𝐺)−𝐷𝑎𝑦1 (𝑇𝐺)
𝐷𝑎𝑦1 (𝑇𝐺)
× 100%
Adjustments for Multiplicity 
For comparison of percentage change in TG of three groups with placebo, 100mg vs. 50 mg, and 
150mg vs. 100mg, the post hoc tests will be used to detect which group differ from the rest 
while statistical significance of ANCOVA or Kruskal-Wallis test. For ANCOVA, the required 
significance criterion alpha is 0.05 divided by the total number of tests. To correct the multiple 
testing for primary endpoint, the p-value will be adjusted according to Bonferroni’s method to 
reject the null hypothesis (p-value <0.05/m, m= number of tests). In addition, two independent 
t-test will also be used for pairwise comparison (p-value=0.05 for all multiple tests). For 
Kruskal-Wallis test, two independent t-test or Wilcoxon rank-sum test will be used for pairwise 
comparison (p-value=0.05 for all multiple tests).  
Multi-center Studies 
Total efficacy-evaluable patients will be enrolled from multiple study sitesǡǤǤǡ
 ǡ    ǡ    


 
 
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ǡFar Eastern Memorial HospitalǡTaipei Veterans General Hospitalǡ Chang Gung 
Memorial Hospital, Linkou branchǤ With the intention of pooling the data for analysis, all the 
investigators from participating institutions will follow the study protocol and conduct the 
clinical trial to improve the consistency across centers. All collected clinical data will be 
managed, centralized and summarized with respect to demographic characteristics, and 
efficacy and safety observations.
Data Management System and Analysis Software 
The data collected will be entered into the study database against the paper CRF and stored in 
the Clinical Data Management Systems (CDMS). The data backup is exhibited by data 
management personnel. The data will be exported to Statistical Analysis System® (SAS) for 
Windows (Version 9.4, SAS Institute, Cary, North Carolina, USA) to generate the subject listings, 
tabulations, and statistical analyses.
Coding Dictionary 
In order to create a standard language that is comparable across all therapeutic teams and 
provide standardization for statistical analysis, adverse events recorded on the paper CRF will 
be coded by medical dictionaries/thesaurus. In this study, the Medical Dictionary for Regulatory 
Activities (MedDRA) version ʹͲǤͲwill be used to map adverse events verbatim to Preferred 
Terms (PT) and System Organ Class (SOC).
Data Handling and Transfer 
All collected clinical data or external data will be managed centralized and stored in the clinical 
data management systems. The system of variable coding will follow rules of Bestat 
Pharmaservices Corp.


 
 
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Programming Specifications 
The summary statistics for continuous variables will be entitled as Number, Mean±SD, Median, 
Range and 95% C.I. in the table, which represent the number of observations, mean value 
plus/minus standard deviation, median value of observations, minimum and maximum, lower 
bound and upper bound of the 95% confidence interval.   ͻͷΨ ǤǤ   
Ǥ
Unless otherwise noted, the summary statistics for continuous variables will be printed out to 
one decimal place except for the standard deviation and confidence interval. The standard 
deviation and confidence interval will be expressed to 2 decimal places.
In analysis of categorical variable, descriptive statistics will be entitled as frequencies and 
percentages. All table percentages will be reported with two decimal points unless otherwise 
specified.
ǦǡͲǤͲͷ
ǦǤ  Ǧ       Ǥ    
 Ǥ Ǧvalue less than 0.001 will be reported as “< 0.001*” and pǦ
greater than 0.999 will be expressed as “> 0.999”.
8
SUMMARY OF STUDY DATA 
Continuous variables will be summarized by descriptive statistics: number of observations, 
mean, median, standard deviation, range and 95% C.I. Frequency counts and percentages 
(based on non-missing sample size) of observed levels will be reported for categorical variables.


 
 
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Disposition of Subject and Withdraws 
Participants who signed the informed consent form will follow study-related procedures 
described in the protocol till the end of study. However, subjects are free to withdraw from the 
study at any time. The number of screened, randomized, reached study completion will be 
counted and summarized. The reason causing the discontinuation will be provided as listing 
report as well. The allocation in each treatment group will be specified and the size of analysis 
populations will be determined by treatment.
Protocol Violation and Deviations 
Protocol deviations includes but do not restrict to the following:
•
Out of visit and procedure window.
•
Deviations from the expected dispensing regimen.
•
Intentional deviation from the protocol, GCP or regulations by study personnel in a non-
emergency setting. 
Protocol violations includes the following:
•
Violate the eligibility founded after the randomization.
•
Failure to obtain valid informed consent.
Demographics 
The following demographic and baseline characteristics will be ascertained at the time of study 
recruitment: gender, age, height, weight, BMI, pregnancy status (females only), medical history, 
physical examination, and concomitant medications. Continuous data will be summarized by 
descriptive statistics using number of specific item, mean, median, standard deviation, 


 
 
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maximum and minimum. Frequencies and percentages are tabulated for categorical data. The 
analysis of baseline characteristics will be performed using safety population.
If the differences in baseline characteristics are observed, the multiple linear model will adjust 
for the significant variables in the primary analysis. The baseline demographic characteristics 
will be compared using Chi-square test or Fisher’s exact test for categorical variables and t-test 
or Wilcoxon Rank-Sum test for continuous variables. 
Baseline and Screening Conditions 
Baseline Medical History 
No coding or analysis items for medical history of subjects will be planned. The listing report 
will present the raw medical history record of subjects.
Baseline Physical Exam 
Results of baseline physical examination for abnormality will be listed. 
Prior and Concurrent Medications 
Data coding for Adverse Events will be based on pre-existing/concurrent conditions or 
treatments. All prior and concurrent data will be presented by patients and by treatment in the 
listing report.
Treatment Compliance 
Patients will be instructed to take a total of three capsules of Antroquinonol and/or placebo in 
different combination once per day and return to the study site on the next visit. A record of the 


 
 
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number of capsules dispensed, taken and returned for each patient must be documented on the 
CRF. Compliance will be assessed from the information recorded in the CRF, including study 
medication count, start and end date of therapy. The treatment compliance rate will be 
determined by the number of taken drugs divided by number of taken drugs divided by number 
of days of treatment taken × 3 capsules per day that should be taken and presented in the 
percentage format, given by:
•
Treatment Compliance (%) =  
Quantity of total dispensed − Quantity of total returned
Treatment period (84 days) 
× 100%
9
STATISTICAL METHODS 
Primary Hypothesis 
The primary endpoint in a study is the percentage change from baseline of TG by Antroquinonol 
compared to placebo after 12 weeks. The primary hypothesis of the study is that: 
H0: the percentage change of TG score in four groups are equal versus 
HA: at least one of the percentage change of TG score in four groups is different
Test of Assumptions 
The continuous variables will be compared using Student's t test (2 groups) or analysis of 
variance (> 2 groups). If the conditions for applying these tests are not met normality 
assumption, the Wilcoxon rank sum (2 groups) or Kruskal-Wallis (> 2 groups) non-parametric 
tests will be used. Comparison within group will be tested by using paired t test. If the normal 
assumption is violated, the Wilcoxon signed-rank test will be conducted. The category variables 
will be compared between groups using the Chi-square test if the theoretical total of each class 
studied is greater than 5. Otherwise Fisher's exact test will be used.


 
 
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Primary Endpoint Analysis 
The primary efficacy endpoint (percentage change of TG) for assessing the superiority of 
Antroquinonol (50mg, 100mg, 150mg) to placebo is the percentage change in patients with 
hyperlipidemia by using analysis of covariance (ANCOVA) model using baseline measurement 
as covariates (model 1). If the differences in baseline characteristics, such as gender, age, weight 
etc., are observed, for comparing the effectiveness between the treatment groups and placebo, 
the model will be performed by multiple linear model (model 2) to adjust characteristics. 
Model 1: Ypercentage change of TG (%)=β1+β2Xtreatment+β3Xbaseline of TG 
Model 2: Ypercentage change of TG (%)=β1+β2Xtreatment+β3Xbaseline of TG+β4X significant characteristic in baseline
If statistical significance of ANCOVA treatment effect is reached (p-value<0.05), Bonferroni’s 
method, and two independent t-test (section 7.7) will be performed post hoc analysis for 
pairwise comparison of percentage change in TG (Antroquinonol 50 mg vs. Placebo, 
Antroquinonol 100 mg vs. Placebo, Antroquinonol 150 mg vs. Placebo, Antroquinonol 100 mg 
vs. Antroquinonol 50 mg and Antroquinonol 150 mg vs. Antroquinonol 100 mg). 
If the normal assumption is violated for percentage change of TG in any treatments, Kruskal-
Wallis test will replace ANCOVA. If statistical significance of Kruskal-Wallis test treatment effect 
is reached (p-value<0.05), two independent t-test or Wilcoxon rank-sum test will be performed 
post hoc analysis for pairwise comparison of percentage change in TG (Antroquinonol 50 mg 
vs. Placebo, Antroquinonol 100 mg vs. Placebo, Antroquinonol 150 mg vs. Placebo, 
Antroquinonol 100 mg vs. Antroquinonol 50 mg and Antroquinonol 150 mg vs. Antroquinonol 
100 mg).


 
 
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Secondary Endpoint Analyses 
Analysis of other secondary efficacy endpoints (TC, HDL-C, LDL-C, and LDL/HDL ratio as well 
as the effect of Antroquinonol on E/E’, baPWV and ABI and HU parameters) will be similar to 
the primary analysis of the primary endpoint by using ANCOVA model using baseline 
measurement as covariates, or using Kruskal-Wallis test when normal assumption is violated. 
Pairwise comparison will use two independent t-test or Wilcoxon rank-sum test, and performed 
significance level of 0.05 while statistical significance of ANCOVA or Kruskal-Wallis test 
treatment effect is achieved (Antroquinonol 50 mg vs. Placebo, Antroquinonol 100 mg vs. 
Placebo, Antroquinonol 150 mg vs. Placebo, Antroquinonol 100 mg vs. Antroquinonol 50 mg 
and Antroquinonol 150 mg vs. Antroquinonol 100 mg).
Safety Analyses 
For the safety assessments, the information of adverse events will be described in detail. Count 
and percentage will be tabulated for the number of patients with AEs, number of total AEs, 
number of patients with AEs associated to study dosing and intensity. Adverse events will be 
coded by the Medical Dictionary for Regulatory Activities (MedDRA®) adverse event dictionary. 
All the AEs will be categorized by each represented Preferred Terms (PT) and System Organ 
Class (SOC), which will be tabulated by body system with related incidence rates. The clinical 
laboratory tests and electrocardiogram tests will be analyzed to separate subjects into normal 
and abnormal categories, with number of subjects and percentage of subjects in each category, 
and McNemar’s test or Fisher’s exact test will then be applied to test the changes between each 
visit.


 
 
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Subgroup Analyses 
The primary and secondary endpoints analyses will be performed by classified subgroup using 
ITT population and PP population. In addition, specified categorical or numeric characteristics 
if the demographic variables are statistically and clinically significant. The identified numeric 
variable will be classified by an appropriate cut-off point.
Interpretation and Conclusion 
All tests are two-tailed unless otherwise specified and the overall significant level is set to be 
0.05. When the number of hypothesis in a test is increased, the Bonferroni correction would be 
used to test each of the individual tests at a significance level of 0.05/m (m= number of tests=5, 
section 9.3). Statistical significance will be demonstrated if the p-value is less than the 
significance level of test. Regardless of the outcome declared statistically significant, all results 
could be stated on the Clinical Study Report (CSR).
10 SAFETY ANALYSES 
The analysis of safety assessments in this study will include summaries of the following 
categories of safety and tolerability data collected for each subject:

Adverse Events
Ǧ AEs and SAEs
Ǧ AEs leading to withdrawal
Ǧ Any Deaths


 
 
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
Clinical Laboratory Investigations

Other Safety measures: vital signs, ECG, physical examinations
Safety assessments consist of monitoring and recording all adverse events, laboratory tests, 
vital signs and physical examinations. Adverse event incidence rates in each group will be 
summarized by system organ class and preferred terms. Each subject will be counted only once 
within a system organ class or a preferred term and any repetitions will be ignored.
Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
central coding dictionary Version 20.0.
All Adverse Events 
Summaries of incidence rates (frequencies and percentages), intensity, and relationship to 
study drug of individual AEs by System Organ Class and Preferred Term (MedDRA) will be 
prepared. Each patient will be counted only once within each preferred term per study period. 
If a patient experiences more than one AE within a prepared item for the same recording period, 
only the AE with the strongest relationship or the greatest intensity, as appropriate, will be 
included in the summaries of relationship and intensity.
Summaries will be presented by treatment group for Antroquinonol. Fisher's exact test will he 
used to compare rates for System Organ Classes across treatment groups. A similar summary 
by treatment group will be presented for all patients in the Safety Population.
Counts of AEs by maximum intensity will be presented for patients in the Safety Population by 
treatment group, grouped by the treatment the patient had received most recently prior to the 


 
 
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AE. Only AEs beginning at or after the beginning of study drug administration will be included. 
Similarly, counts of AEs by strongest relationship to study drug will be presented.
A data listing will also be presented showing all AEs, which started prior to the administration 
of any study drug.
Adverse Events Leading to Withdrawal 
A summary of incidence rates (frequencies and percentages) of AEs leading to withdrawal, by 
treatment group, System Organ Class, and Preferred Terms, will be prepared for the Safety 
Population. No statistical tests will be performed.
A data listing of AEs leading to withdrawal will also be provided, displaying details of the event(s) 
captured on the CRF.
Serious Adverse Events 
Serious adverse events reconciliation will be performed by Data Management, Clinical Research, 
and Golden Drug Safety and Pharmacovigilance via data listings.
A summary of incidence rates (frequencies and percentages) of SAEs by treatment group. 
System Organ Class, and Preferred Term will be prepared for the Safety Population. No 
statistical tests will be performed.
A data listing of SAEs will also be provided, displaying details of the event(s) captured on the 
CRF. Serious adverse event narratives will be provided for the CSR by the Golden Drug Safety 
and Pharmacovigilance Department.


 
 
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Deaths 
If any patients die during the study, relevant information will be supplied in a data listing, and 
appropriate SAE narratives.
Other AE Assessments 
No other assessments or analysis are planned.
 Clinical Laboratory Evaluations 
Descriptive summaries (mean, SD, median. minimum. and maximum for each group with 
related 95% confidence interval.) of changes from baseline will be presented for clinical 
laboratory values by treatment for the Safety Population.
The number of patients with clinical laboratory values below, within, or above normal ranges, 
pre-procedure versus post-procedure will be tabulated for each test, for the Safety Population 
by treatment group. Pre- and post-procedure values will also be presented with an analysis of 
mean changes from baseline. Laboratory assessment results will be classified to normal or 
abnormal, and will be tabulated with related frequency and percentages. The shift tables of 
laboratory results will also be provided.
Laboratory values that are outside the normal range will also be flagged in the data listings, 
along with corresponding normal ranges. Any out-of-range values that are identified by the 
investigator as being clinically significant will also be shown in a data listing.
 Other Safety Measures 

Vital Signs


 
 
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Descriptive statistics of actual, values and changes from baseline will be calculated for heart 
rate, Blood pressure, body temperature, weight, waist circumference, hip circumference and 
body fat.

12-Lead ECG
Individual ECG values will be listed and summarized by descriptive analysis. Comparisons 
between baseline ECG and post-screening ECGs result will also be evaluated.

Physical Examinations
Results of physical examination for abnormality will be listed.
11 REPORTING CONVENTIONS 
The following reporting conventions will be adopted for the SAP. Theseconventions will 
enhance the review process and help to standardize presentation with common notations.
General Reporting Conventions 
All tables, figure, and data listings will have the name of the program and a date/time stamp on 
the bottom of each output and will be presented in Landscape Orientation. Unless presented as 
part of the text in a CSR.
All titles will be left justified and top of the page, and all footnotes will be left justified and the 
bottom of a page. Missing values for both numeric and character variables will be presented as 
blanks or “.” in a table or data listing.
All data values will be presented as MM/DD/YYYY (e.g., 08/29/2001) format. A four-digit year 
is preferred for all dates.


 
 
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Population/Statistic Summary Conventions 
Population(s) represented on the tables or data listings will be clearly identified in the last title 
of the Table as "Population: [name of population]” and will be identical in name to that identified 
in the protocol or SAP.
Consistent terminology will be used to define and identify a population. Common nomenclature 
may include (a) ITT, (b) PP or Per-Protocol, and (c) Safety.
Population sizes may be presented for each treatment or dosing category as totals in the column 
header as (N=xxxx), where appropriate.
All population summaries for categorical variables will include categories that the patients had 
a response in these categories.
All population summaries for continuous variables will include: N. mean, SD, minimum, and 
maximum. Other summaries (e.g. median, quartiles, 5%, 95% intervals, CV or %CV) may be 
used as appropriate. All percentages are rounded and reported to two decimal points.
Population summaries that include p-values will report the p-value to three decimal places with 
a leading zero (0.001). All p-values reported on default output from statistical software (i.e., 
SAS® Software) may be reported at the default level of precision. P-values <0.001 should be 
reported as <0.001 not 0.000.
12 SUMMARY OF CHANGES TO THE PROTOCOL 
No change in non-statistical and statistical analysis to the protocol.


 
 
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13  REFERENCES 
1.
Protocol No.: GHLIP-2-001 version 2.1
2.
ICH harmonized tripartite Guideline: E9 - Statistical Principles for Clinical Trials
3.
ICH harmonized tripartite Guideline: E3 – Structure and Content of Clinical Study Reports
14 APPENDIX 
Mock-up Tables 
•
Statistical Table 
•
Data Listing


 
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Confidential 
Statistical Table 
Page 1   (LAST PAGE) 
Table 14.1.2.1 Summary of Demographic and Baseline Characteristics (Safety Population) 
==================================================================================================== 
Characteristics       Antroquinonol     Antroquinonol        Antroquinonol      Placebo         P-Value 
                         50 mg (N=  )       100 mg (N=  )        150 mg (N=  )      (N=  ) 
---------------------------------------------------------------------------------------------------- 
Age & 
      NUMBER                       
      MEAN                         
      S.D.                         
      RANGE                      
      95% C.I.                  
 
Gender # 
      MALE                         
      FEMALE                       
 
Race # 
      ASIAN                         
      TAIWAN INDIGENOUS 
 
CAUCASIAN 
      BLACK 
      OTHER   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
========================================================================================== 
Program name: Antro_T_DEMO.sas   Programmer:               
RANGE: (Minimun, Maximum); S.D.: Standard Deviation; CI: 95% Confidence Interval 
&: P-value was conducted by T-test/Kruskal-Wallis test for Continuous Variables 
#: P-value was conducted by Chi-square/Fisher’s exact test for Categorical Variables


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Data Listing 
Listing 16.2.1.1 --- Subject Early Termination 
Page 1 of 2 
================================================================================================================================= 
                                                   Did Subject Complete    What Was the Primary Reason for 
 Site No.   Screening No.    Subject No.     the Study?                Early Termination/Withdrawal? 
--------------------------------------------------------------------------------------------------------------------------------- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
================================================================================================================================= 
Site No.: 1=National Taiwan University Hospital, 2=China Medical University Hospital, 3=National Cheng Kung University Hospital, 
3=National Cheng Kung University Hospital, 4=Taipei Veterans General Hospital, 5=Far Eastern Memorial Hospital, 6=Chang Gung 
Memorial Hospital, Linkou branch


CONFIDENTIAL 
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 Planned Tables 
The contents of Statistical analysis tables and data listing follow ICH E3 Guidelines for tables, figures and graphs.
Statistical Tables 
14.1 Demographic Data 
Table 14.1.1.1 Summary of Subject Disposition by Treatment Group
Table 14.1.1.2 Primary Reason for Discontinuation
Table 14.1.2.1 Summary of Demographic and Baseline Characteristics (Safety Population)

14.2 Efficacy Data 
Table 14.2.1.1 Primary Endpoint: Percentage change of TG after 12 Weeks (ITT)
Table 14.2.1.2 Primary Endpoint: Percentage change of TG after 12 Weeks (PP)
Table 14.2.2.1 Secondary Endpoint: Percentage change of TC, HDL-C, LDL-C, and LDL/HDL after 12 Weeks (ITT)
Table 14.2.2.2 Secondary Endpoint: Percentage Change of TC, HDL-C, LDL-C, and LDL/HDL after 12 Weeks (PP)
Table 14.2.3.1 Secondary Endpoint: Percentage Change of E/E', baPWV, ABI, and HU after 12 Weeks (ITT)


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Table 14.2.3.2 Secondary Endpoint: Percentage Change of E/E', baPWV, ABI, and HU after 12 Weeks (PP)  
 
14.3 Anthropometric measures 
Table 14.3.1.1 Summary of Anthropometric measures (Safety Population) 
Table 14.3.1.2 Summary of Mean Change from Baseline in Anthropometric measures (Safety Population) 
 
14.4 Safety Data 
Table 14.4.1.1 Summary of Vital Sign by Visit (Safety Population)  
Table 14.4.1.2 Summary of Mean Change from Baseline in Vital Sign (Safety Population)  
Table 14.4.2.1 Summary of of Physical Examinations (Normal/Abnormal) (Safety Population)  
Table 14.4.2.2 Transition Table of Physical Examinations (Safety Population)  
Table 14.4.3.1 Summary of baPWV, ABI, E/E', and HU (Safety Population)  
Table 14.4.3.2 Summary of of 12-Lead ECG, baPWV, ABI, E/E', and HU (Normal/Abnormal) (Safety Population)  
Table 14.4.3.3 Transition Table of 12-Lead ECG, baPWV, ABI, E/E', and HU after 12 Weeks (Safety Population) 
Table 14.4.4.1 Summary of Laboratory Assessment-Lipid Profile (Safety Population) 


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Table 14.4.4.2 Summary of Laboratory Assessment-Serum Chemistry (Safety Population)  
Table 14.4.4.3 Summary of Laboratory Assessment-Hematology (Safety Population)  
Table 14.4.4.4 Summary of Laboratory Assessment-Biomarkers (Safety Population) 
Table 14.4.4.5 Summary of Laboratory Assessment-Urinary Exam (Safety Population) 
Table 14.4.5.1 Summary of Laboratory Assessment-Lipid Profile (Normal/Abnormal) (Safety Population) 
Table 14.4.5.2 Summary of Laboratory Assessment-Serum Chemistry (Normal/Abnormal) (Safety Population) 
Table 14.4.5.3 Summary of Laboratory Assessment-Hematology (Normal/Abnormal) (Safety Population)  
Table 14.4.5.4 Summary of Laboratory Assessment-Biomarkers (Normal/Abnormal) (Safety Population) 
Table 14.4.5.5 Summary of Laboratory Assessment-Urinary Exam (Normal/Abnormal) (Safety Population) 
Table 14.4.5.6 Summary of Laboratory Assessment-Microscopy (Normal/Abnormal) (Safety Population) 
Table 14.4.6.1 Transition Table of Laboratory Assessment-Lipid Profile (Safety Population) 
Table 14.4.6.2 Transition Table of Laboratory Assessment-Serum Chemistry (Safety Population) 
Table 14.4.6.3 Transition Table of Laboratory Assessment-Hematology after 12 Weeks (Safety Population) 
Table 14.4.6.4 Transition Table of Laboratory Assessment-Biomarkers after 12 Weeks (Safety Population) 
Table 14.4.6.5 Transition Table of Laboratory Assessment-Urinary Exam after 12 Weeks (Safety Population) 


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Table 14.4.6.6 Transition Table of Laboratory Assessment-Microscopy after 12 Weeks (Safety Population) 
Table 14.4.7.1 Summary of Subject Compliance for the Study Drugs (Safety Population) 
Table 14.4.8.1 Summary of Adverse Events by Treatment Groups (Safety Population) 
Table 14.4.8.2 Summary of Adverse Events by MedDRA Coding (Safety Population) 
Table 14.4.9.1 Summary of Concomitant Medication by Treatment Groups (Safety Population) 
Table 14.4.10.1 Summary of Concomitant Therapies by Treatment Groups (Safety Population)  
 
 


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Data Listing 
16.2.1 Discontinued Subjects 
Listing 16.2.1.1 --- Subject Early Termination  
 
 
16.2.2 Subjects Eligibility 
Listing 16.2.2.1 ---Treatment groups and Population 
Listing 16.2.2.2 --- Inclusion Criteria  
Listing 16.2.2.3 --- Exclusion Criteria  
 
16.2.3 Demographics Data 
Listing 16.2.3.1 --- Demographics 
 
Listing 16.2.3.2 --- Medical History 
 
 
16.2.4 Safety Response 
Listing 16.2.4.1 --- Vital Sign Measurements 
 


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Listing 16.2.4.2 --- Urine Pregnancy Test  
Listing 16.2.4.3 --- Physical Examinations  
Listing 16.2.4.4 --- 12-Lead Echocardiogram 
 
Listing 16.2.4.5 --- Concomitant Medications 
 
Listing 16.2.4.6 --- Concomitant Therapies 
 
16.2.5 Efficacy Response 
Listing 16.2.5.1 ---TG, TC, HDL-C, LDL-C, and LDL/HDL ratio  
Listing 16.2.5.2 --- baPWV, ABI attenuation, E/E’ ratio, and HU attenuation 
16.2.8 Reporting Adverse Events 
 
Listing 16.2.8.1 --- Adverse Events  
16.2.9 Laboratory Measurements 
Listing 16.2.9.1 --- Hematology 
Listing 16.2.9.4 --- Serum Chemistry 


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Listing 16.2.9.5 --- Urinalysis 
Listing 16.2.9.2 --- Biomarkers 
Listing 16.2.9.3 --- Microscopy 
 
16.2.10 Other Correspondence 
Listing 16.2.10.1 --- Visit Date and Subject Initials 
Listing 16.2.10.2 --- Study Drug Dispensed 
Listing 16.2.10.3 --- Comments