A Multicenter, Randomized, Open-Label, 4-Week Study to Investigate the Efficacy and Pharmacokinetic Profile of K-877-ER Once Daily Treatment Compared to K-877-IR Twice Daily Treatment in Adult Patients With Fasting Triglyceride Levels
Phase: PHASE2
Conditions: Dyslipidemia
Sponsor: Kowa Research Institute, Inc.

 
 
 
 
 
 
 
 
 
NCT #: 04447820 
 
Protocol Version Date: 17 September 2020 

CONFIDENTIAL 
Kowa Research Institute, Inc. 
K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
Page 3 of 66 
INVESTIGATOR AGREEMENT 
By signing below I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by Kowa Research Institute, Inc. to study personnel under my supervision. I will discuss this 
material with them to ensure they are fully informed about the study product and study procedures. 
I will let them know that this information is confidential and proprietary to Kowa Research 
Institute, Inc. and that it may not be further disclosed to third parties. I understand that the study 
may be terminated or enrollment suspended at any time by Kowa Research Institute, Inc., with or 
without cause, or by me if it becomes necessary to protect the best interests of the study subjects. 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board Regulations and International Council for Harmonisation Guidelines 
for Good Clinical Practices. 
 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name 
 

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Kowa Research Institute, Inc. 
K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
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TABLE OF CONTENTS 
Protocol Signature Page .................................................................................................................. 2 
Investigator Agreement ................................................................................................................... 3 
Synopsis .......................................................................................................................................... 4 
Table of Contents .......................................................................................................................... 14 
List of Tables ................................................................................................................................ 18 
List of Figures ............................................................................................................................... 19 
List of Abbreviations and Definition of Terms............................................................................. 20 
1  Introduction and Background Information ............................................................................. 22 
1.1 
Rationale ........................................................................................................................ 22 
1.2 
Risk/Benefit ................................................................................................................... 23 
2  Study Objectives ..................................................................................................................... 24 
2.1 
Primary Objective ......................................................................................................... 24 
2.2 
Secondary Objectives .................................................................................................... 24 
3  Study Description.................................................................................................................... 25 
3.1 
Summary of Study Design ............................................................................................ 25 
4  Selection and Withdrawal of Patients ..................................................................................... 27 
4.1 
Inclusion Criteria ........................................................................................................... 27 
4.2 
Exclusion Criteria .......................................................................................................... 28 
4.3 
Study Drug Discontinuation Criteria ............................................................................. 30 
4.4 
Withdrawal Criteria ....................................................................................................... 30 
4.5 
Re-Screening of Screen Failures ................................................................................... 31 
4.6 
Study Drug Discontinuation for Persistent Abnormal Clinical Laboratory Values ...... 32 
5  Study Treatments .................................................................................................................... 33 
5.1 
Treatment Groups .......................................................................................................... 33 
5.2 
Rationale for Dosing ..................................................................................................... 33 
5.3 
Randomization and Blinding ......................................................................................... 33 
5.4 
Breaking the Blind ........................................................................................................ 33 
5.5 
Drug Supplies ................................................................................................................ 33 
5.5.1  Formulation and Packaging ............................................................................... 33 
5.5.2  Study Drug Preparation and Dispensing ........................................................... 34 

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5.5.3  Study Drug Administration ............................................................................... 34 
5.5.4  Treatment Compliance ...................................................................................... 35 
5.5.5  Storage and Accountability ............................................................................... 35 
5.6 
Prior and Concomitant Medications and/or Procedures ................................................ 35 
5.6.1  Excluded Medications and/or Procedures ......................................................... 35 
5.6.2  Restricted Medications and/or Procedures ........................................................ 36 
5.6.3  Allowed Medications and/or Procedures .......................................................... 36 
5.6.4  Documentation of Prior and Concomitant Medication Use .............................. 36 
6  Study Procedures .................................................................................................................... 37 
6.1 
Informed Consent .......................................................................................................... 37 
6.2 
Screening Period ........................................................................................................... 37 
6.2.1  Screening Visit .................................................................................................. 37 
6.2.2  Qualification Period .......................................................................................... 37 
6.3 
Randomization .............................................................................................................. 38 
6.4 
Treatment Period ........................................................................................................... 38 
6.5 
Follow-Up Telephone Call ............................................................................................ 38 
6.6 
Early Termination Visit and Withdrawal Procedures ................................................... 38 
7  Efficacy and 
 Assessments ........................................................................... 39 
7.1 
Primary Efficacy Endpoint ............................................................................................ 39 
7.2 
Secondary Efficacy Endpoints ...................................................................................... 39 
 
 ....................................................................................... 39 
8  Safety Assessments ................................................................................................................. 41 
8.1 
Adverse Events .............................................................................................................. 41 
8.1.1  Adverse (Drug) Reaction .................................................................................. 41 
8.1.2  Unexpected Adverse Drug Reaction ................................................................. 42 
8.1.3  Assessment of Adverse Events by the Investigator .......................................... 42 
8.2 
Serious Adverse Events ................................................................................................. 43 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................ 43 
8.4 
Pregnancy Reporting ..................................................................................................... 44 
8.5 
Expedited Reporting ...................................................................................................... 45 
8.6 
Special Situation Reports .............................................................................................. 45 
8.7 
Clinical Laboratory Evaluations .................................................................................... 46 

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
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11.6  Retention of Records ..................................................................................................... 53 
11.7  Publication Policy ......................................................................................................... 53 
11.8  Financial Disclosure ...................................................................................................... 54 
12  Study Administrative Information .......................................................................................... 55 
12.1  Protocol Amendments ................................................................................................... 55 
13  References ............................................................................................................................... 56 
Appendix A: Schedule of Procedures ........................................................................................... 57 
Appendix B: Clinical Laboratory Analytes .................................................................................. 62 
 
 
 

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
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LIST OF FIGURES 
Figure 1.  Illustration of Study Design ........................................................................................ 25 

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to demonstrate the efficacy of K-877-ER 
 
 
compared to K-877-IR 
 
 from baseline to Day 28 in lowering fasting TG levels in 
patients with fasting TG levels 150 mg/dL and <500 mg/dL. 
2.2 
Secondary Objectives 
The secondary objectives of this study are the following: 
 To demonstrate the efficacy of K-877-ER 
 
 compared to K-877-IR 
 
 
from baseline to Day 28 in lowering fasting TG levels in patients with fasting TG levels 
150 mg/dL and <500 mg/dL; 
 To evaluate the efficacy of K-877-ER 
 treatments (from 
day to 
day) from 
baseline to Day 28 in altering PD properties, including lipid parameters, in patients with 
fasting TG levels 150 mg/dL and <500 mg/dL; and 
 To evaluate the multiple-dose 
 properties at steady state of K-877-ER 
 
 

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
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If the patient withdraws from the study, the reason should be captured and could include the 
following:  
1. The patient withdraws consent at any time or requests discontinuation from the study;  
2. The patient fails to comply with protocol requirements or study-related procedures if, in the 
opinion of the Investigator or the Sponsor, the non-compliance will significantly compromise 
data interpretation or safety;  
3. In the Investigator’s judgment, it is in the patient’s best interests;  
4. Violation of the protocol inclusion and exclusion criteria is discovered, if, in the opinion of the 
Investigator or the Sponsor, the violation will significantly compromise data interpretation or 
safety; or  
5. The Sponsor or the regulatory authority terminates the study. 
Patients who choose to withdraw consent will be asked to document withdrawal of consent in 
writing.  
Although a patient is not obligated to give his/her reason for withdrawing prematurely, the 
Investigator will make a reasonable effort to obtain the reason while fully respecting the patient’s 
rights. The reason for withdrawal from the study must be documented in the eCRF. The Clinical 
Study Report will include the reason(s) for withdrawal from the study.  
If a patient withdraws prematurely from the study, study staff will make every effort to complete 
the full panel of assessments scheduled for the Early Termination (ET) visit. 
If a patient withdraws from the study due to an AE, the patient will be asked to return to the site 
for, at a minimum, the evaluations scheduled for the ET Visit. If the AE has still not resolved, 
additional follow-up will be performed, as appropriate, and documented in the patient’s medical 
records. As a minimum requirement, ongoing AEs are to be followed for 30 days after the patient’s 
last dose of study drug. If patients are lost to follow-up, attempts to contact them must be made 
and documented in the study records. Withdrawn patients will not be replaced. 
4.5 
Re-Screening of Screen Failures 
Patients who are screen failures for a modifiable condition (such as elevated HbA1c or 
uncontrolled hypertension), other than failing the TG criteria, can be re-screened once, and 
enrolled in the study at a future date if they are then deemed eligible for study participation based 
on protocol entry criteria after having medications adjusted and stabilized. Before each patient is 
re-screened, the Investigator should discuss the case with the Medical Monitor. 
Patients who are screen failures or run-in failures under Protocol Version 1.0 Inclusion 3 TG 
criteria may rescreen once with the review and approval of the Medical Monitor. 

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K-877-ER 
 
 
17 September 2020 v2.0 
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4.6 
Study Drug Discontinuation for Persistent Abnormal Clinical Laboratory 
Values 
A patient will discontinue treatment with study drug if persistent elevations in ALT, AST, 
bilirubin, CK, or TG, or a persistent decrease in eGFR, occur according to the following criteria: 
1. ALT or AST >8 × ULN, confirmed on repeat; 
2. ALT or AST >3 × ULN and bilirubin >2 × ULN or international normalized ratio >1.5, 
confirmed on repeat (if patient has Gilbert’s syndrome, bilirubin will require Medical Monitor 
review); 
3. ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%) confirmed on repeat; 
4. ALT or AST >5 × ULN which persists for 2 weeks; 
5. Unexplained CK >5 × ULN confirmed on repeat. For patients with CK 10 × ULN, 
Investigators should immediately interrupt study drug while awaiting re-evaluation; 
Note: If the above CK elevation criteria are met with concerns of rhabdomyolysis, evaluations 
should include the patient being questioned about symptoms (e.g., muscle or tendinous pain, 
cramping, or weakness) and potential causes for the CK elevation (e.g., medications, exercise, 
or trauma). The following laboratory measurements should be obtained: CK, CK cardiac 
muscle isoenzyme (CK-MB), CK skeletal muscle isoenzyme (CK-MM), troponin, creatinine, 
myoglobin (serum and urine), transaminases, total bilirubin, and urinalysis including urine 
sediment. A physical examination should be performed, documenting findings such as muscle 
tenderness, weakness, or rash. An ECG should be collected as well. This information should 
be collected on the appropriate eCRF. For abnormalities to be reported as AEs, see Appendix E 
for a list of muscle AE definitions. Abnormalities should be followed until they have returned 
to baseline, or the Investigator considers them clinically stable;  
6. Fasting TG levels >2000 mg/dL (22.60 mmol/L) with signs or symptoms of pancreatitis at any 
time during the study. For repeated or persistent elevations of TG >2000 mg/dL 
(22.60 mmol/L) that are not accompanied by signs or symptoms of pancreatitis, Investigators 
may discontinue study drug at their discretion; or 
7. eGFR <30 mL/min/1.73 m2 occurring on or after Day 14 (Visit 5), confirmed on repeat. 
Note: Repeat testing should occur as soon as possible within 72 hours unless otherwise specified. 
If at any time during the study a patient develops elevations in ALT or AST >3 × ULN, 
CK >5 × ULN, TG >2000 mg/dL (>22.60 mmol/L), or a decrease in eGFR <30 mL/min/1.73 m2 
the study site will receive an alert from the central laboratory.  

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
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8 
SAFETY ASSESSMENTS 
8.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational medicinal product, whether or not related to the investigational medicinal product. 
All AEs, including observed or volunteered problems, complaints, or symptoms, are to be recorded 
on the appropriate eCRF. 
AEs, which include clinical laboratory test variables, will be monitored and documented from the 
time of informed consent until the Follow-Up Telephone Call. Patients should be instructed to 
report any AE that they experience to the Investigator, whether or not they think the event is due 
to study treatment. Beginning from the time of informed consent, Investigators should make an 
assessment for AEs at each visit and record the event on the appropriate AE eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. Additionally, 
the condition that led to a medical or surgical procedure (e.g., surgery, endoscopy, tooth extraction, 
or transfusion) should be recorded as an AE, not the procedure itself.  
Any medical condition already present at the Screening Visit should be recorded as medical history 
and not be reported as an AE unless the medical condition or signs or symptoms present at baseline 
changes in severity, frequency, or seriousness at any time during the study. In this case, it should 
be reported as an AE. 
Clinically significant abnormal laboratory or other examination (e.g., ECG) findings that are 
detected during the study or are present at the Screening Visit and significantly worsen during the 
study should be reported as AEs, as described below. The Investigator will exercise his or her 
medical and scientific judgment in deciding whether an abnormal laboratory finding or other 
abnormal assessment is clinically significant. Clinically significant abnormal laboratory values 
occurring during the clinical study will be followed until repeat tests return to normal, stabilize, or 
are no longer clinically significant. Abnormal test results that are determined to be an error should 
not be reported as an AE. Laboratory abnormalities or other abnormal clinical findings (e.g., ECG 
abnormalities) should be reported as an AE if any of the following are applicable: 
 If an intervention is required as a result of the abnormality; 
 If action taken with the study drug is required as a result of the abnormality; or 
 Based on the clinical judgment of the Investigator. 
8.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an adverse event is at least a reasonable possibility, 
i.e., the relationship cannot be ruled out. 

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
17 September 2020 v2.0 
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8.1.2 
Unexpected Adverse Drug Reaction 
An Unexpected Adverse Drug Reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information.  
8.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE as mild, moderate, or severe, and 
will also categorize each AE as to its potential relationship to study drug using the categories of 
yes or no. 
Assessment of Severity 
Mild – An event that is easily tolerated and generally not interfering with normal daily activities. 
Moderate – An event that is sufficiently discomforting to interfere with normal daily activities. 
Severe – An event that is incapacitating with inability to work or perform normal daily activities. 
Causality Assessment 
The relationship of an AE to the administration of the study drug is to be assessed according to the 
following definitions: 
No (unrelated, not related, unlikely to be related) – The time course between the administration of 
study drug and the occurrence or worsening of the AE rules out a causal relationship and another 
cause (concomitant drugs, therapies, complications, etc.) is suspected. 
Yes (possibly, probably, or definitely related) – The time course between the administration of 
study drug and the occurrence or worsening of the AE is consistent with a causal relationship and 
no other cause (concomitant drugs, therapies, complications, etc.) can be identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
The following factors should also be considered: 
 The temporal sequence from study drug administration- 
The event must occur after the study drug is given. The length of time from study drug exposure 
to the event should be evaluated in the clinical context of the event. 
 Underlying, concomitant, intercurrent diseases- 
Each report should be evaluated in the context of the natural history and course of the disease 
being treated and any other disease the patient may have. 
 Concomitant drug- 
The other drugs the patient is taking or the treatment the patient receives should be examined 
to determine whether any of them might be recognized to cause the event in question. 
 Known response pattern for this class of study drug- 
Clinical and/or preclinical data may indicate whether a particular response is likely to be a 
class effect. 

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knowledge of the occurrence. After the 30-day reporting window, any SAE that the Investigator 
considers related to study drug must be reported to the 
 or the 
Sponsor/designee. 
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, 
 personnel will be notified 
electronically by the EDC system and will retrieve the form. If the event meets serious criteria and 
it is not possible to access the EDC system, send an email to 
 at 
medpace-safetynotification@medpace.com or call the 
 SAE reporting line (phone 
number listed below), and fax/email the completed paper SAE form to 
 (contact 
information listed in Section 8.6) within 24 hours of awareness. When the EDC system becomes 
available, the SAE information must be entered as soon as possible of the system becoming 
available. 
Follow-Up Reports 
The Investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the patient 
dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation (e.g., 
patient discharge summary or autopsy reports) to 
 via fax or email. If it is 
not possible to access the EDC system, refer to the procedures outlined above for initial reporting 
of SAEs.  
8.4 
Pregnancy Reporting 
If a patient becomes pregnant from the time of initiation of study drug through the safety follow-up 
period defined in the protocol, the Investigator is to stop dosing with study drug immediately and 
the patient should be withdrawn from the study. ET procedures should be implemented at that 
time.  
A pregnancy is not considered to be an AE or SAE; however, it must be reported to 
 
 within 24 hours of knowledge of the event. 
 will then 
provide the Investigator/site the Exposure In Utero (EIU) form for completion. The 
Investigator/site must complete the EIU form and fax/email it back to 
 
within 24 hours of completion.  
If the female partner of a male patient becomes pregnant while the patient is receiving study drug 
or within the safety follow-up period defined in the protocol, the Investigator should notify 
 as described above.  
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the EIU form should be completed and faxed/emailed to 
 If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, neonatal 
death, or congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 

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K-877-ER-201, Study Protocol 
K-877-ER 
 
 
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8.5 
Expedited Reporting 
The Sponsor/designee will report all relevant information about Suspected Unexpected Serious 
Adverse Reactions (SUSARs) that are fatal or life-threatening as soon as possible to the Food and 
Drug Administration (FDA) and in any case no later than 7 days after knowledge by the 
Sponsor/designee of such a case. Relevant follow-up information will subsequently be 
communicated within an additional 8 days.  
All other SUSARs will be reported to the FDA as soon as possible but within a maximum of 
15 days of first knowledge by the Sponsor/designee.  
The Sponsor/designee will also inform all Investigators as required per local regulation. 
The requirements above refer to the requirements relating to investigational medicinal product. 
8.6 
Special Situation Reports 
Special situation reports include reports of overdose, misuse, abuse, medication error, and reports 
of adverse reactions associated with product complaints. 
 Overdose: Refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the maximum 
recommended dose according to the protocol. Clinical judgement should always be applied. 
In cases of a discrepancy in the drug accountability, overdose will be established only when 
it is clear that the patient has taken additional dose(s) or the Investigator has reason to suspect 
that the patient has taken additional dose(s).  
 Misuse: Refers to situations where the medicinal product is intentionally and inappropriately 
used in a way that is not in accordance with the protocol instructions or local prescribing 
information and may be accompanied by harmful physical and/or psychological effects.  
 Abuse: Is defined as persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 
 Medication error: Is any unintentional error in the prescribing, dispensing, or administration 
of a medicinal product by a healthcare professional, patient, or consumer, respectively. The 
administration or consumption of the unassigned treatment and administration of an expired 
product are always reportable as medication errors, cases of patients missing doses of 
investigational product are not considered reportable as medication errors. 
 Product complaint: Is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug or device after it is released for distribution. A special situations form 
will only be completed if a complaint is associated with an adverse drug reaction.  
All special situation events as described above must be reported on the Special Situations Report 
form and faxed/emailed to 
 (contact information listed below) within 
24 hours of knowledge of the event. All AEs associated with these Special Situation reports should 
be reported as AEs or SAEs as well as recorded on the AE eCRF and/or the SAE report form. 
Details of the symptoms and signs, clinical management, and outcome should be provided, when 
available. 

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K-877-ER 
 
 
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10 
DATA MANAGEMENT AND RECORD KEEPING 
10.1 
Data Management 
10.1.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the Clinical Research Associates 
(CRAs) during monitoring visits. The CRAs will verify data recorded in the EDC system with 
source documents. All corrections or changes made to any study data must be appropriately tracked 
in an audit trail in the EDC system. An eCRF will be considered complete when all missing, 
incorrect, and/or inconsistent data has been accounted for. 
10.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
10.1.3 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure user name and password in order to enter, review, or correct 
study data. These procedures must comply with Title 21 of the Code of Federal Regulations 
(21 CFR Part 11) and other appropriate international regulations. All passwords will be strictly 
confidential. 
10.1.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
 Medical Dictionary for Regulatory Activities (latest) for medical history and AEs; and 
 World Health Organization Drug Dictionary for prior and concomitant medications. 
10.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 

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10.2 
Record Keeping 
Records of patients, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data are defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records.  
10.3 
End of Study 
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last patient in the study.  
 

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11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL  
11.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study subjects 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, 
and that the clinical study data are credible. 
11.2 
Institutional Review Board 
The Institutional Review Board (IRB) will review all appropriate study documentation in order to 
safeguard the rights, safety, and well-being of patients. The study will only be conducted at sites 
where IRB approval has been obtained. The protocol, IB, ICF, advertisements (if applicable), 
written information given to the patients, safety updates, annual progress reports, and any revisions 
to these documents will be provided to the IRB by the Investigator. 
Federal regulations and International Council for Harmonisation (ICH) GCP Guidelines require 
that approval be obtained from an IRB prior to participation of patients in research studies. Prior 
to study onset, the protocol, any protocol amendments, ICFs, advertisements to be used for patient 
recruitment, and any other written information regarding this study to be provided to a patient or 
patient’s legal guardian must be approved by the IRB. 
No drug will be released to the clinical site for dosing until written IRB authorization has been 
received by the Sponsor. 
11.3 
Informed Consent 
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB prior to its use and must be in compliance with all FDA 
regulations/ICH GCP guidelines, local regulatory requirements, and legal requirements.  
The Investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
patient has been informed of his/her rights to privacy. The Investigator will obtain written informed 
consent from each patient before any study-specific activity is performed and must document in 
the source documentation that consent was obtained prior to enrollment in the study. The original 
signed copy of the ICF must be maintained by the Investigator and is subject to inspection by a 
representative of the Sponsor, their representatives, auditors, the IRB and/or regulatory agencies. 
A copy of the signed ICF will be given to the patient. 
11.4 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, FDA/ICH GCP, and applicable regulatory requirements, and 
that valid data are entered into the eCRFs. 
To achieve this objective, the CRA’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well-organized and easily retrievable data. Before 
the enrollment of any patient in this study, the Sponsor or their designee will review with the 

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Investigator and site personnel the following documents: protocol, IB, eCRFs and procedures for 
their completion, informed consent process, and the procedure for reporting SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, and 
logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and his/her staff will be expected to cooperate with the monitor and 
provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the clinical site by signature and date on the study-specific monitoring log. 
11.5 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Patients or their legal 
representatives may request their medical information be given to their personal physician or other 
appropriate medical personnel responsible for their welfare. 
Patient medical information obtained during the study is confidential and disclosure to third parties 
other than those noted above is prohibited. 
11.6 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating patients (sufficient information to link 
records, e.g., eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE 
forms, source documents, and detailed records of treatment disposition. The records must be 
retained by the Investigator according to specifications in the FDA regulations/ICH GCP 
guidelines, local regulations, or as specified in the Clinical Study Agreement, whichever is longer. 
The Investigator must obtain written permission from the Sponsor before disposing of any records, 
even if retention requirements have been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor must 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor.  
11.7 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 

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11.8 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR Part 54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 
 

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12 
STUDY ADMINISTRATIVE INFORMATION 
12.1 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by 
 or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB, unless immediate implementation of the change is necessary for patient safety. In this case, 
the situation must be documented and reported to the IRB and the Sponsor within 5 working days. 

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13 
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