Post Marketing Surveillance For General Drug Use To Assess The Safety And Efficacy Profile Of Viviant In Usual Practice.
Conditions: Osteoporosis
Sponsor: Pfizer

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016  
 
  
 
 
 
NON-INTERVENTIONAL (NI) DRUG STUDY PROTOCOL 
 
POST MARKETING SURVEILLANCE FOR GENERAL DRUG USE TO ASSESS 
THE SAFETY AND EFFICACY PROFILE OF VIVIANT IN USUAL PRACTICE 
 
Compound Number: 
PF-05208749 
Compound Name: 
Viviant Tablet 20 mg (Bazedoxifene Acetate) 
Study Number: 
B1781047 
Version and Date: 
Final                         23 Jul 2012 
Amendment 1          18 Jan 2013 
Amendment 2          04 Mar 2013 
Amendment 3          13 Aug 2013 
Amendment 4          28 Oct 2013 
Amendment 5          28 Nov 2013 
 Amendment 6         26 Mar 2015 
Amendment 7         22 Jun 2016 
 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016  
 
  
ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
BMD 
Bone Mineral Density 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Form 
CTX 
C-telopeptide of collagen cross links 
DVP 
Data Validation Plan 
DXA 
Dual energy X-ray Absorptiometry 
EIU 
Exposure in Utero 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
LSLV 
Last Subject Last Visit 
MFDS 
Ministry of Food and Drug Safety 
NTX 
N-telopeptide of collagen cross links 
PCD 
Primary Completion Date 
QUS 
Quantitative Ultrasound 
SAP 
Statistical Analysis Plan 
SRSD 
Single Reference Safety Document 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 3 of 39 
TABLE OF CONTENTS 
1. RATIONALE AND BACKGROUND ........................................................................................5 
2. RESEARCH QUESTION AND OBJECTIVES .........................................................................5 
3. RESEARCH METHODS ............................................................................................................5 
3.1. Study Design ...................................................................................................................5 
3.2. Study Population .............................................................................................................6 
3.2.1. Inclusion Criteria ................................................................................................6 
3.2.2. Exclusion Criteria ...............................................................................................7 
3.3. Data Sources ....................................................................................................................7 
3.4. Variables ..........................................................................................................................7 
3.5. Study Procedures .............................................................................................................8 
3.5.1. Study Duration ....................................................................................................8 
3.5.2. Study Treatment ..................................................................................................8 
3.5.3. Planned Numbers of Patients ..............................................................................8 
3.5.4. Endpoints ............................................................................................................8 
3.5.5. Investigating Matters ..........................................................................................9 
3.6. Power and Sample Size .................................................................................................17 
3.7. Data Collection and Data Management ........................................................................17 
3.7.1. Data Collection .................................................................................................17 
3.7.2. Data Management .............................................................................................19 
3.8. Data Analysis ................................................................................................................20 
3.8.1. Assessment Parameter ......................................................................................20 
3.8.2. Statistical Consideration ...................................................................................21 
3.8.3. Interim Analysis ................................................................................................21 
3.9. Quality Control ..............................................................................................................22 
3.9.1. Record Retention ..............................................................................................22 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 4 of 39 
3.10. Strengths of the Research Methods .............................................................................22 
3.11. Limitations of the Research Methods ..........................................................................22 
4. PROTECTION OF HUMAN SUBJECTS ................................................................................23 
4.1. Subject Information and Consent ..................................................................................23 
4.2. Subject Withdrawal .......................................................................................................23 
4.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ....................23 
4.4. Ethical Conduct of the Study ........................................................................................24 
5. ADVERSE EVENT REPORTING............................................................................................24 
5.1. REQUIREMENTS ........................................................................................................24 
5.1.1. Reporting period ...............................................................................................25 
5.1.2. Causality assessment ........................................................................................26 
5.2. DEFINITIONS OF SAFETY EVENTS .......................................................................26 
5.2.1. Adverse events ..................................................................................................26 
5.2.2. Serious adverse events ......................................................................................28 
5.2.3. Scenarios necessitating reporting to Pfizer Safety within 24 hours .................30 
6. COMMUNICATION OF ISSUES ............................................................................................33 
7. SINGLE REFERENCE SAFETY DOCUMENT ......................................................................34 
8. STUDY DISCLOSURE ............................................................................................................34 
9. LIST OF FIGURES ...................................................................................................................35 
10. REFERENCES ........................................................................................................................35 
APPENDIX 1. RESPONSIBLE PARTIES ...................................................................................36 
APPENDIX 2. AMENDMENTS...................................................................................................37 
APPENDIX 3. MILESTONES ......................................................................................................39 
 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 5 of 39 
1. RATIONALE AND BACKGROUND  
Viviant 20 mg was approved as a new medicine on 16 Nov 2011. As required for any new 
medicine approved by the Ministry of Food and Drug Safety (MFDS), safety and efficacy 
information of the medicine should be provided in the setting of routine practice during the 
re-examination period of  6 years from the approval date (16 Nov 2011 ~ 15 Nov 2017). 
The objective of the Re-examination system in Korea is to re-confirm the clinical usefulness 
of the product through collecting, reviewing, identifying and verifying the safety and efficacy 
information about the product in general practice (usually for a period of 6 years after the 
product is registered.). 
This survey is conducted for preparing application material for re-examination under the 
Pharmaceutical Affairs Laws and its Enforcement Regulation, and assessing the safety and 
efficacy profiles of Viviant 20 mg in usual practice according to the Re-examination 
Regulation for New Drugs. 
2. RESEARCH QUESTION AND OBJECTIVES 
This study is to observe safety and efficacy of Viviant 20 mg in the setting of routine practice. 
The objectives of this survey are: 
1) To examine the safety and efficacy profiles of Viviant 20 mg in Korean patients 
2) To identify factors that might have an influence on the safety and efficacy profiles of 
Viviant 20 mg in Korean patients. 
3. RESEARCH METHODS  
3.1. Study Design  
This study is an observational, non-interventional, multi-center study in which subjects will 
be treated as part of routine practice at Korean health care centers by accredited physicians. 
The study can be performed in primary, secondary or tertiary care medical center including 
the departments below where Viviant 20 mg is mainly prescribed for treatment and 
prevention of postmenopausal osteoporosis which is the indication for Viviant 20 mg. 
- Primary care medical center: Department of obstetrics and gynecology, endocrinology, 
orthopedics, family medicine and rehabilitation 
- Secondary care medical center: Department of obstetrics and gynecology, 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 6 of 39 
endocrinology, orthopedics, family medicine, rheumatology, neurosurgery and 
rehabilitation 
- Tertiary care medical center: Department of obstetrics and gynecology, endocrinology, 
orthopedics, neurosurgery and rheumatology  
Surveillance for long-term use: Patients who are treated with Viviant 20 mg for at least 6 
months (± 2 weeks) will be evaluated additionally if collected. The physician will be 
recommended to evaluate those subjects at 6 months (± 2 weeks) after the treatment. 
3.2. Study Population 
Subjects will be enrolled by continuous registration method. It means that the physician 
should enroll all postmenopausal women who are received Viviant 20 mg for the first time 
and agree to participate in this study by signing the ‘data privacy statement’ after contract is 
made with the physician or the institution. 
3.2.1. Inclusion Criteria 
Indication 
Treatment and prevention of postmenopausal osteoporosis in women 
A significant reduction in the incidence of vertebral fracture has been demonstrated, but 
efficacy on non-vertebral fracture has not been established. 
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study. 
1. Patients who is indicated in the current VIVIANT local label 
2. Evidence of a personally signed and dated data privacy statement indicating that the 
subject (or a legally acceptable representative) has been informed of all pertinent aspects 
of the study. 
Special patients with known hepatic disorder or renal disorder which was medically 
diagnosed or older (>= 65 years) will be evaluated if collected. 
The following subjects should be treated with caution. 
1. Patients with hypertriglyceridemia (This drug has not been studied in women with 
triglyceride levels > 300mg/dl (>3.4 mmol/L). It may increase serum triglyceride levels.) 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 7 of 39 
2. Patients with severe renal impairment. 
3. Patients with hepatic impairment (patients with hepatic impairment showed a 4.3-fold 
increase in area under the curve (AUC) compared with controls. Use in this population is 
not recommended.) 
3.2.2. Exclusion Criteria 
Patients meeting any of the following criteria will not be included in the study. 
1. Patients with hypersensitivity to the active substance or to any of the excipients. 
2. Patients with active or past history of venous thromboembolic events, including deep 
vein thrombosis, pulmonary embolism, and retinal vein thrombosis 
3. Pregnant women and women of child-bearing potential. 
4. Lactating women 
5. Patients with unexplained uterine bleeding. 
6. Patients with signs or symptoms of endometrial cancer (safety in this patient group has 
not been adequately studied). 
7. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase 
deficiency or glucose-galactose malabsorption should not take this medicinal product. 
3.3. Data Sources  
The followings are data sources for the study: 
1. Medical records 
2. Laboratory test results 
3. Subject interview 
3.4. Variables  
Variable 
Role 
Data source(s) 
Operational definition 
Demographic Characteristics 
Baseline characteristics 
Medical records 
 
Basic Laboratory data 
Baseline characteristics 
Laboratory test results 
 
Concomitant medication  
Baseline characteristics 
Medical records and interview 
 
BMD and biochemical markers 
outcome 
Laboratory test results 
 
Efficacy result  
by the physician 
outcome 
Medical records and interview 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 8 of 39 
Adverse events 
outcome 
Medical records and interview 
 
 
Detailed instruction of variable will be included Statistical Analysis Plan (SAP) and CRF. 
  
3.5. Study Procedures 
3.5.1. Study Duration 
As specified in the product license given by the MFDS, this study will be conducted for 6 
years from the approval date of 16 Nov 2011 to 15 Nov 2017. 
3.5.2. Study Treatment 
The use and dosage recommendations for Viviant 20 mg will take place on the basis of the 
approved Local Product Document. The indication for Viviant 20 mg is treatment and 
prevention of postmenopausal osteoporosis in women. One tablet once daily, at any time of 
day, with or without food. 
3.5.3. Planned Numbers of Patients  
Planned number of patients: 3,000 patients 
The number of total subjects required for re-examination is at least 3,000 according to the 
Re-examination Regulation for New Drugs and Others. 
3.5.4. Endpoints 
3.5.4.1. Safety Endpoints 
The drug safety is evaluated through the following items: 
 
Serious adverse event 
 
Unexpected adverse drug reaction 
 
Identification of AE profile in usual practice 
 
Non-serious adverse event 
3.5.4.2. Efficacy Endpoint 
1. The drug efficacy is evaluated through the overall efficacy evaluation by the physician  
: Improved, No change, Worsened, Unevaluable 
2. Osteoporosis related fractures incident 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 9 of 39 
3. If  laboratory data will be collectable, 3 month (± 2 weeks) F/U data will be compared 
with the baseline data 
 
Any X-ray result by the physician.  
 
Any bone mineral density result: dual energy x-ray absorptiometry (DXA), quantitative 
ultrasound (QUS), etc 
 
Biochemical markers of bone turnover: Deoxypyridinoline, N-telopeptide of collagen 
cross links (NTX), C-telopeptide of collagen cross links (CTX), osteocalcin, bone 
specific alkaline phosphatase, etc. 
3.5.5. Investigating Matters 
The physician is required to monitor any adverse events of all enrolled subjects during at 
least one follow up visit. Generally, this will be done during the subject's next visit. Efficacy 
will be evaluated at 3 months (± 2 weeks) after the initiation of Viviant treatment regardless 
of whether the treatment is ongoing or not at the time of evaluation. Safety, that is, the 
occurrence of adverse event, will be observed by 3 months (± 2 weeks) after the initiation of 
Viviant treatment if the treatment is continued for at least 3 months (± 2 weeks). If the 
treatment is discontinued earlier than 3 months (± 2 weeks), safety will be observed by one 
month after the discontinuation. If subject's next visit is not expected during the evaluation 
timeframe, the physician should contact subjects via phone to collect the information. The 
information collected during the follow up visit (including telephone contact) should be 
recorded in the subject's medical chart and Case Report Form (CRF). 
Any clinical and/or laboratory adverse events observed or reported from the time of  the 
subject’s first dosing in the observational period as per study design through and including 28 
calendar days after the last administration of the study drug within the observational period 
will be collected by the physician. 
Targeted investigational population 
- 
Targeted safety evaluation population: Patients who have had experience to be 
taken Viviant 20 mg at least one time and be completed follow up  
- 
Targeted efficacy evaluation population: Patients who are completed efficacy 
evaluation based on the protocol in the targeted safety evaluation population 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 10 of 39 
3.5.5.1. Basic Information 
- Name of Institution 
- Name of Physician 
- Department 
- Subject ID 
- Height/Weight: Record by cm / kg unit. 
- Month of Birth: Record the month of birth of the subject. 
- Confirmation of Data Privacy Statement:  If all agreement for using subject’s personal and 
medical information, signature and date are obtained from the subject or legally acceptable 
representative, then check the box of ‘yes’ and record the date of signature by the subject 
or legally acceptable representative. If not, check ‘no’ which means that case is excluded 
from this study. 
3.5.5.2. Diagnosis 
- Date of diagnosis for osteoporosis: Record the date of diagnosis for osteoporosis 
3.5.5.3. Medical History 
Select either ‘yes’ or ‘no’ for past/present disease. If ‘yes’ then write adequate full name of 
the disease down as Medical Terminology Dictionary indicates (written by Korean Medical 
Society) and select either ‘past disease’ or ‘present disease’ at each disease clause. 
Additionally, check either ‘yes’ or ‘no’ for ‘complication of osteoporosis’. 
- Past disease: Disease occurred past, but recovered before Viviant 20 mg administration 
- Present disease: Accompanied disease at the time of the first Viviant 20 mg administration 
- Complication of osteoporosis: Disease whose immediate cause is osteoporosis 
3.5.5.4. Concomitant Medication / Therapy 
The physician records the medication/therapy which has been administered/conducted 
continuously at the point of being enrolled in this study or administered/conducted newly 
after being enrolled. Check either ‘yes’ or ‘no’. If ‘yes’, record in detail. 
- Name of drug / Therapy name: Record generic name in case of single product and record 
trade name in case of combination product. Also, record name of concomitant therapy. 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 11 of 39 
- Daily total dosage / Frequency: Record the daily total dosage as unit. If not combination 
drug, avoid recording in tablets, capsules or vials. Record the frequency of concomitant 
therapy. 
- Duration of administration / Duration of therapy: Record the starting/ending date of the 
medicated drug and concomitant therapy (year/month/day). If the medication and therapy 
are being continued at the completion of the study, record the starting date only and check 
‘ongoing’. 
- Purpose of administration / Purpose of therapy: Record the purpose of administration or 
therapy. 
 
3.5.5.5. Administration Status and Evaluation of Viviant  
Record the following with regard to administrative status of Viviant 20 mg. 
- Duration of administration: Record the starting/ending date of Viviant 20 mg therapy 
(year/ month/day).  
- Date of Visit: Record the date of visit (year/ month/day). 
- Daily total dosage: Record the daily total dosage. 
- Laboratory test for Viviant treatment: Check either ‘yes’ or ‘no’. If ‘yes’, select among ‘X-
ray’, ‘bone mineral density’ or ‘biochemical marker of bone turnover’ and record the 
details in the section of laboratory test. 
- Phone contact: If the subject did not visit the physician’s site during the follow-up period, 
phone contact should be made to collect any relevant information. Check either ‘yes’ or 
‘no’. If ‘yes’, record the date of phone contact and the collected information. If ‘no’, 
record the reason of not being able to have a phone contact. 
- Osteoporosis related fracture: Check either ‘yes’ or ‘no’ for the question, ‘Has the subject 
experienced an osteoporosis related fracture after the initiation of Viviant 20 mg 
administration?’. If ‘yes’, record the details in the section of adverse event. 
3.5.5.6. Safety 
3.5.5.6.1. Adverse Event  
Every observed and reported adverse event, regardless of the causal relationship with the 
study drug, must be recorded on an adverse event section in case report forms. The query 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 12 of 39 
pattern of experience of adverse event to the subjects is as follow; 
“Have you had any health problem since last visit?” 
For adverse events repeating before and after administrating the study drug, record the first 
appearing date and the last disappearing date. Background information on Viviant 20 mg can 
be obtained from the current version of the local product document, which is the single 
reference safety document (SRSD) for information relating toViviant 20 mg. 
Check either ‘yes’ or ‘no’ in adverse event section. If ‘yes’, record in detail. 
- Adverse event: Record the term of adverse event. If possible, specify diagnosis, not 
individual symptoms. Record the term according to the term in the local product document 
or the Preferred Term in the WHO Preferred Terminology Standard (distributed by Korean 
Ministry of Health and Welfare). If there is no preferred term, look up the Medical 
Terminology written by Korean Medical Society. 
- Date of onset: Record the date of onset. Just record the year or year and month if an actual 
date is unknown. 
- Severity: Severity evaluation of adverse events must be done according to the following 
category. 
1. Mild- Not causing any significant problem to the subject  
Continuous medication of study drug is possible without dose adjustment.  
2. Moderate- Cause a problem that does not interfere significantly with usual activities or 
the clinical status 
Dose adjustment of study drug or other therapy is needed due to adverse 
event. 
3. Severe- Cause a problem that interferes significantly with usual activities or the clinical 
status  
Study drug should be stopped due to adverse event. 
If the severity of an adverse event changed, the adverse event must be entered separately. 
Record stop date of previous severity and onset date of new severity – along with 
completion of all other items. 
- Action: Check all relevant actions. 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 13 of 39 
1) Viviant:  Check the appropriate number for the adjustment of Viviant resulting from the 
adverse event. 
1. no action taken 2. dosage reduced 3. dosage increased 4. stopped temporarily  
5. permanently discontinued  6. not applicable 
2) Withdrawal:  Check either ‘yes’ or ‘no’ for the question, ‘Was the subject withdrawn 
from the study due to the adverse event?’ 
3) Others:  After the onset of adverse event, the physician should indicate other actions 
taken and record in detail. 
1. Treatment given (please specify in concomitant medication section) 
2. Others (please specify) 
3. No action taken 
- Seriousness: Check either ‘yes’ or ‘no’ for the question, ‘Is this case under the criteria of 
serious adverse event?’ If ‘yes’, record the appropriate number for the category of 
seriousness. 
A serious adverse event is any untoward medical occurrence in a subject administered a 
medicinal or nutritional product (including pediatric formulas) at any dose that: 
(1)  results in death; 
(2)  is life-threatening; 
(3)  requires inpatient hospitalization or prolongation of hospitalization; 
(4)  results in persistent or significant disability/incapacity(substantial disruption of the 
ability to conduct normal life functions); 
(5)  results in congenital anomaly/birth defect; 
(6) is an important medical event 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious.  The event may be suspected from 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 14 of 39 
clinical symptoms or laboratory findings indicating an infection in a subject exposed to a 
Pfizer product.  The terms “suspected transmission via product” and “transmission via 
product” are considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by PV personnel.  Such cases are also considered for reporting as 
product defects, if appropriate. 
In case of serious adverse event, the Drug Safety Unit of the Pfizer Pharmaceuticals Korea 
Ltd. is to be notified promptly by the physician (Telephone No. 02-317-2146 (working 
hours), 010-8771-7114 (24 hours) / Fax No. Toll-Free 0079814206-4512, Toll 02-317-2135 / 
E-mail: KOR.AEReporting@pfizer.com). The physician should complete the ‘Non 
Interventional Study Adverse Event Report Form’ and fax it within 24 hours of awareness of 
the adverse event. 
Record the followings at the end of the study or after the resolution of the adverse event. 
- Outcome: Select among ‘yes’, ‘unknown’, or ‘no-resolved’ as a reply to a question, ‘Is the 
adverse event still present?’ If the subject died without resolution of the AE, ‘yes’ should 
be checked. If ‘no-resolved’, record the resolved date. Just record the year or year and 
month if an actual date is unknown. 
- Causality of adverse event to the study drug: The causal relationship of adverse event to 
the study drug must be allocated by the physician according to the following criteria. 
(1) Certain 
- 
It follows a reasonable time sequence from administration of the drug (before 
and after the study medication). 
- 
It could not be explained by other drugs, chemical substance or accompanying 
diseases. 
- 
It has clinically reasonable reaction on cessation of the drug. 
- 
It has pharmacological or phenomenological reaction to re-administration of the 
drug, where necessary. 
(2) Probable/likely 
- 
It follows a reasonable time sequence from administration of the drug (before 
and after the study medication). 
- 
It could not be explained by other drugs, chemical substance or accompanying 
diseases. 
- 
It has clinically reasonable reaction on cessation of the drug. 
(No information on re-administration) 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 15 of 39 
(3) Possible 
- 
It follows a reasonable time sequence from administration of the drug. 
- 
It could also be explained by other drugs, chemical substance or accompanying 
diseases. 
- 
It lacks information or has unclear information on discontinuation of the drug. 
(4) Unlikely 
- 
It is not likely to have a reasonable causal relationship from administration of the 
drug. Rather, it seems to be temporary. 
- 
It could also be reasonably explained by other drugs, chemical substances or 
latent diseases. 
* Other causality of adverse event: If the adverse event is not related to the study 
drug, the physician should indicate the most appropriate cause from the followings 
and record in detail. 
1. Disease under the study 
2. Other disease (please specify) 
3. Concomitant treatment –drug or non-drug (please specify) 
4. Others (please specify) 
(5) Conditional/unclassified 
- 
It needs more data to make an appropriate assessment or its additional data are 
being reviewed. 
(6) Unaccessible/unclassifiable 
- 
Lack of sufficient information or conflicting information hampers accurate 
causality assessment or supplementation or confirmation. 
3.5.5.6.2. Laboratory Test   
Laboratory testing is not mandatory because this study is a non-interventional study. If the 
physician performed a laboratory test for diagnostics and monitoring in usual medical 
practice, the results can be collected. Check ‘not done’ if it is not performed. If ‘done’, record 
the following in detail. 
- 
Normal Range 
- 
Date of clinical laboratory test before administration 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 16 of 39 
- 
Date of clinical laboratory test during administration 
- 
Date of clinical laboratory test after administration 
- 
Result: Record the lab result of each test. 
- 
Remark 
Refer to [Section 5.1.4.] of the criteria for determining whether an abnormal objective test 
finding should be reported as an adverse event. If it meets the criteria, it has to be recorded in 
adverse event section of a case report form. 
 
3.5.5.7. Final Evaluation 
- 
3-month (± 2 weeks) treatment: Check either ‘yes’ or ‘no’ for the question, ‘Has the 
subject been administered Viviant for at least 3 months (± 2 weeks)?’ If ‘no’, check 
among ‘adverse event’, ‘lack of efficacy’ or ‘other (please specify)’ for the reason. 
- 
Date of last safety observation: Record the date by when safety is observed. Safety, that 
is, the occurrence of adverse event, will be observed by 3 months (± 2 weeks) after the 
initiation of Viviant treatment if the treatment is continued for at least 3 months (± 2 
weeks). If the treatment is discontinued earlier than 3 months (± 2 weeks), safety will be 
observed by one month after the discontinuation. 
- 
Date of efficacy evaluation: Record the date of efficacy evaluation. Efficacy will be 
evaluated at 3 months (± 2 weeks) after the initiation of Viviant treatment regardless of 
whether the treatment is ongoing or not at the time of evaluation. 
- 
Efficacy evaluation: Select among ‘improved’, ‘no change’, ‘worsened’ or ‘unevaluable’. 
If ‘unevaluable’, check either ‘follow-up lost’ or ‘other (please specify)’ for the reason. 
Additionally, follow-up information will be collected for subjects treated with Viviant for the 
long term. 
- 
6-month (± 2 weeks) treatment and follow-up: Check either ‘yes’ or ‘no’ for the question, 
‘Has the subject been administered Viviant for at least 6 months (± 2 weeks)?’ If ‘yes’, 
check either ‘yes’ or ‘no’ for the question, ‘Was the follow-up made by 6 months (± 2 
weeks) after the initiation of Viviant treatment for the subject?’. If ‘yes’, record the date 
when the follow-up is completed. 
- 
Long-term efficacy evaluation: Select among ‘improved’, ‘no change’, ‘worsened’ or 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 17 of 39 
‘unevaluable’. If ‘unevaluable’, record the reason.  
- 
Safety observation: If the subject has been administered Viviant for more than 6 months 
(± 2 weeks), Perform the safety observation until 6 months (± 2 weeks) after the 1st 
Viviant treatment. 
3.6. Power and Sample Size  
Safety evaluation should be conducted for at least 3000 subjects in compliance with the 
MFDS regulation.  
3.7. Data Collection and Data Management  
3.7.1. Data Collection 
As used in this protocol, the term case report form (CRF) should be understood to refer to 
either a paper form or an electronic data record or both, depending on the data collection 
method used in this study (“eCRF” may be used to describe an electronic data record).  
A CRF should be completed for each included subject.  The completed original CRFs are the 
sole property of Pfizer and should not be made available in any form to third parties, except 
for authorized representatives of Pfizer or appropriate regulatory authorities, without written 
permission from Pfizer. 
Each study physician has ultimate responsibility for the collection and reporting of all 
clinical, safety and laboratory data entered on the CRFs and any other data collection forms 
(source documents) and ensuring that they are accurate, authentic / original, attributable, 
complete, consistent, legible, timely (contemporaneous), enduring and available when 
required.  The CRFs must be signed by the study physician or by an authorized staff member 
to attest that the data contained on the CRFs are correctly recorded.  Any corrections to 
entries made in the CRFs, source documents must be dated, initialed and explained (if 
necessary) and should not obscure the original entry.  For studies using electronic data 
capture systems, an audit trail of any corrections to original data entry must be ensured.  
In many cases, the source document is the subject medical chart.  In these cases, data 
collected on the CRFs must match the data in the chart.  
In some cases (e.g., subject interview), the CRF, or part of the CRF, may also serve as source 
documents.  In these cases, a document should be available at the physician’s site as well as 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 18 of 39 
at Pfizer and clearly identify those data that will be recorded in the CRF, and for which the 
CRF will stand as the source document. 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 19 of 39 
3.7.2. Data Management 
 
<Figure 1> Data Management Flow Chart 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 20 of 39 
3.7.2.1. Data Cleaning 
Data will be cleaned through the system and/or manual discrepancy check process as shown 
in the Figure 1. 
3.8. Data Analysis  
3.8.1.  Assessment Parameter 
3.8.1.1. Parameter on Cases 
- 
Descriptive analysis will be done pertaining to total collected cases, safety evaluable 
cases, efficacy evaluable cases, discontinuation cases and the cause for it. 
3.8.1.2. Parameter on Safety 
- 
Safety parameter will be evaluated. 
- 
Incidence of adverse event categorized according to physical organ and disease/symptom 
and  95% confidence interval will be presented. 
- 
Sub-analysis could be done by factors which are considered to affect safety. If necessary 
chi- square test (X2-test), Fisher’s exact test or Logistic Regression Analysis will be used 
for subgroup analysis. 
- 
Clinically significant abnormality from laboratory test (if any). If data are applicable, 
paired t-test, descriptive analysis and other statistical method will be used. 
3.8.1.3. Parameter on Efficacy 
- 
The four point scale: Improved, No Change, Worsened, Unevaluable will be 
descriptively summarized. Efficacy and 95% confidence interval of efficacy rate will be 
presented. Sub-analysis could be done by factors which are considered to affect efficacy. 
If necessary, Χ2-test, Fisher’s exact test or Logistic Regression Analysis will be used. 
- 
Osteoporosis related fractures incident. 
- 
If  laboratory data will be collectable, 3 month (± 2 weeks) F/U data will be compared 
with the baseline data 
 
Any X-ray result by the physician. 
 
Any bone mineral density result: dual energy x-ray absorptiometry(DXA), 
quantitative ultrasound(QUS), etc 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 21 of 39 
 
Biochemical markers of bone turnover: Deoxypyridinoline, N-telopeptide of 
collagen cross links(NTX), C-telopeptide of collagen cross links (CTX), 
osteocalcin, bone specific alkaline phosphatase, etc. 
3.8.2. Statistical Consideration 
Analysis will be performed for the pooled data from each physician collected during the re-
examination period. Evaluation of data will primarily consist of summary displays (e.g., 
descriptive statistics, tables, graphs). 
The primary interest of this study is any adverse event, unexpected adverse event, serious 
adverse event, each adverse drug reaction and the frequency of them reported during the re-
examination period. They will be presented with 95% confidence interval. Adverse events 
will be categorized according to physical organs/cases  will be separately summarized as 
‘overall adverse events and adverse drug reaction’, ‘serious adverse event and serious 
adverse drug reaction’ and ‘unexpected adverse and unexpected adverse drug reaction’.  
if necessary, the adverse event analysis and evaluation could be conducted for the subjects 
who are excluded from safety evaluation due to the off-label use. 
To identify any factor that affect safety and efficacy rate, subgroup analysis will be 
performed by the following factors: age, presence of concurrent diseases, presence of 
concomitant medication, etc. 
Total number of participating institutions, enrolled and retrieved cases, and the number of 
cases included in the analysis will be presented as summary tables. 
3.8.3. Interim Analysis  
As required by the MFDS regulations, the periodic report should be submitted to the MFDS 
every 6 months for the first two years and then annual report should be submitted to the 
MFDS for the third, fourth and fifth year. The final report should be submitted in the sixth 
year. Interim analysis will be performed in time for the report submission. 
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a Statistical Analysis Plan (SAP), which will be dated, filed and 
maintained by the sponsor. The SAP may modify the plans outlined in the protocol; any 
major modifications of primary endpoint definitions or their analyses would be reflected in a 
protocol amendment. 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 22 of 39 
3.9. Quality Control 
Detailed process for quality control will be documented in a Data Management Plan (DMP), 
which will be dated, filed and maintained by the sponsor. Validation procedure will be 
installed to eCRF based on the Data Validation Plan (DVP). Data will be cleaned through the 
system and/or manual discrepancy check process as shown in the Figure 1. 
3.9.1. Record Retention 
To enable evaluations and/or audits from regulatory authorities or Pfizer, the physician 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, e.g., CRFs and hospital records), all original signed data privacy 
statements, copies of all CRFs, serious adverse event forms, source documents, and detailed 
records of treatment disposition, and adequate documentation of relevant correspondence 
(e.g., letters, meeting minutes, telephone calls reports).  The records should be retained by the 
physician according to local regulations, or as specified in the Clinical Study Agreement, 
whichever is longer. 
If the physician becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
physician, another institution, or to an independent third party arranged by Pfizer.  The 
physician must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met. 
3.10. Strengths of the Research Methods 
 Large scale non interventional real world study for evaluating efficacy and safety of study drug 
 Subjects will be enrolled in a consecutive manner 
3.11. Limitations of the Research Methods 
 Regulatory required study for maintaining license and exclusivity. 
 SAP and number of subjects are ruled by PMS guideline of the MFDS, not specific disease 
and/or drug characteristics. 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 23 of 39 
4. PROTECTION OF HUMAN SUBJECTS 
4.1. Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws.  In case of data transfer, Pfizer will maintain high standards of 
confidentiality and protection of subject personal data. 
The data privacy statement must be in compliance with local regulatory requirements, and 
legal requirements. 
The data privacy statement used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC if applicable and Pfizer before 
use. 
The physician must ensure that each study subject, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation.  The physician, or a person designated by the physician, 
will obtain a signed data privacy statement from each subject or the subject’s legally 
acceptable representative before any study-specific activity is performed.  The physician will 
retain the original of each subject's signed data privacy statement. 
4.2. Subject Withdrawal 
Subjects may withdraw from the study at any time at their own or their legally acceptable 
representative’s request, or they may be withdrawn at any time at the discretion of the 
physician or sponsor for safety, behavioral, or administrative reasons.  In any circumstance, 
every effort should be made to document subject outcome, if possible.  The physician should 
inquire about the reason for withdrawal and follow-up with the subject regarding any 
unresolved adverse events. 
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent. 
4.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
It is the responsibility of the physician to have prospective approval of the study protocol, 
protocol amendments, and data privacy statements, and other relevant documents, if 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 24 of 39 
applicable, from the IRB/IEC.  All correspondence with the IRB/IEC should be retained in 
the Physician File.  Copies of IRB/IEC approvals should be forwarded to Pfizer.  
4.4. Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices 
described in Good Pharmacoepidemiology Practices (GPP) issued by the International 
Society for Pharmacoepidemiology (ISPE), the International Society for Pharmacoeconomics 
and Outcomes Research (ISPOR) guidances, Pharmaceutical Research and Manufacturers 
Association (PhRMA) guidelines and similar. 
5. ADVERSE EVENT REPORTING 
5.1. REQUIREMENTS 
The table below summarizes the requirements for recording safety events on the case report 
form and for reporting safety events on the non-interventional study (NIS) adverse event 
monitoring (AEM) Report Form to Pfizer Safety.  These requirements are delineated for 
three types of events: (1) serious adverse events (SAEs); (2) non-serious AEs (as applicable); 
and (3) scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation, and occupational 
exposure.  These events are defined in the section “Definitions of safety events”.   
 
Safety event 
Recorded on the case report 
form  
Reported on the NIS AEM 
Report Form to Pfizer 
Safety within 24 hours of 
awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Scenarios involving exposure 
to a drug under study, 
including exposure during 
pregnancy, exposure during 
breast feeding, medication 
error, overdose, misuse, 
extravasation; lack of efficacy; 
and occupational exposure 
All (regardless of whether 
associated with an AE), 
except occupational 
exposure  
All (regardless of whether 
associated with an AE) 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 25 of 39 
For each AE, the investigator must pursue and obtain information adequate both to determine 
the outcome of the adverse event and to assess whether it meets the criteria for classification 
as a SAE (see section "Serious Adverse Events” below).  
Safety events listed in the table above must be reported to Pfizer within 24 hours of 
awareness of the event by the investigator regardless of whether the event is determined 
by the investigator to be related to a drug under study. In particular, if the SAE is fatal or 
life-threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available event information. This timeframe also applies to additional new (follow-up) 
information on previously forwarded safety event reports. In the rare situation that the 
investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the events. 
For safety events that are considered serious or that are identified in the far right column of 
the table above that are reportable to Pfizer within 24 hours of awareness, the investigator is 
obligated to pursue and to provide any additional information to Pfizer in accordance with 
this 24-hour timeframe. In addition, an investigator may be requested by Pfizer to obtain 
specific follow-up information in an expedited fashion.  This information is more detailed 
than that recorded on the case report form. In general, this will include a description of the 
adverse event in sufficient detail to allow for a complete medical assessment of the case and 
independent determination of possible causality.  Any information relevant to the event, such 
as concomitant medications and illnesses must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative.  
 
5.1.1. Reporting period  
For each patient, the safety event reporting period begins at the time of  the patient’s first 
dose of Viviant or the time of the patient’s informed consent if s/he is already exposed to 
Viviant, and lasts through the end of the observation period of the study, which must include 
at least 28 calendar days following the last administration of a drug under study; a report 
must be submitted to Pfizer Safety (or its designated representative) for any of the types of 
safety events listed in the table above occurring during this period.  If a patient was 
administered a drug under study on the last day of the observation period, then the reporting 
period should be extended for 28 calendar days following the end of observation. Most often, 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 26 of 39 
the date of informed consent is the same as the date of enrollment. In some situations, there 
may be a lag between the dates of informed consent and enrollment.  In these instances, if a 
patient provides informed consent but is never enrolled in the study (e.g., patient changes 
his/her mind about participation), the reporting period ends on the date of the decision to not 
enroll the patient.   
If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to Viviant, the SAE also must be reported to 
Pfizer Safety.  
 
5.1.2. Causality assessment 
The investigator is required to assess and record the causal relationship.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of 
each adverse event.  For AEs with a causal relationship to Viviant, follow-up by the 
investigator is required until the event and/or its sequelae resolve or stabilize at a level 
acceptable to the investigator, and Pfizer concurs with that assessment.   
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that Viviant caused or contributed to an adverse event. If the 
investigator’s final determination of causality is “unknown” and s/he cannot determine 
whether Viviant caused the event, the safety event must be reported within 24 hours.   
If the investigator cannot determine the etiology of the event but s/he determines that Viviant 
did not cause the event, this should be clearly documented on the case report form and the 
NIS AEM Report Form.  
 
5.2. DEFINITIONS OF SAFETY EVENTS 
5.2.1. Adverse events 
An AE is any untoward medical occurrence in a patient administered a medicinal product.  
The event need not necessarily have a causal relationship with the product treatment or usage. 
Examples of adverse events include but are not limited to:   

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 27 of 39 
 Abnormal test findings (see below for circumstances in which an abnormal test 
finding constitutes an adverse event); 
 Clinically significant symptoms and signs; 
 Changes in physical examination findings; 
 Hypersensitivity; 
 Progression/worsening of underlying disease; 
 Lack of efficacy;  
 Drug abuse;  
 Drug dependency. 
Additionally, for medicinal products, they may include the signs or symptoms resulting from: 
 Drug overdose; 
 Drug withdrawal; 
 Drug misuse;  
 Off-label use;  
 Drug interactions; 
 Extravasation; 
 Exposure during pregnancy; 
 Exposure during breast feeding; 
 Medication error; 
 Occupational exposure. 
Abnormal test findings 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 28 of 39 
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows:  
 Test result is associated with accompanying symptoms, and/or 
 Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
 Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or 
 Test result is considered to be an adverse event by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event. 
 
5.2.2. Serious adverse events 
A serious adverse event is any untoward medical occurrence in a patient administered a 
medicinal or nutritional product (including pediatric formulas) at any dose that: 
 Results in death; 
 Is life-threatening; 
 Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events); 
 Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
 Results in congenital anomaly/birth defect. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious. 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 29 of 39 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious.  The event may be suspected from 
clinical symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited cases 
by PV personnel.  Such cases are also considered for reporting as product defects, if 
appropriate. 
 
Hospitalization 
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (e.g., from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, an event leading to an emergency room visit should be assessed for medical 
importance.  
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. 
For example, the following reports of hospitalization without a medical AE are not to be 
reported.  
 
Social admission (e.g., patient has no place to sleep) 
 
Administrative admission (e.g., for yearly exam) 
 
Optional admission not associated with a precipitating medical AE (e.g., for 
elective cosmetic surgery) 
 
Hospitalization for observation without a medical AE 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 30 of 39 
 
Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with a worsening of the pre-existing condition 
(e.g., for work-up of persistent pre-treatment lab abnormality) 
 
Protocol-specified admission during clinical study (e.g., for a procedure 
required by the study protocol) 
 
5.2.3. Scenarios necessitating reporting to Pfizer Safety within 24 hours  
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, extravasation, lack of efficacy, and occupational exposure are 
described below. 
Exposure during pregnancy 
An exposure during pregnancy (EDP) occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been  
exposed to (e.g., environmental) Viviant, or the female becomes, or is found to be, 
pregnant after discontinuing and/or being exposed to Viviant (maternal exposure). 
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (e.g., a nurse reports that she is pregnant and 
has been exposed to chemotherapeutic products). 
2. A male has been exposed, either due to treatment or environmental exposure to 
Viviant prior to or around the time of conception and/or is exposed during the partner 
pregnancy (paternal exposure). 
As a general rule, prospective and retrospective exposure during pregnancy reports from any 
source are reportable irrespective of the presence of an associated AE and  the procedures for 
SAE reporting should be followed. 
If a study participant or study participant’s partner becomes, or is found to be, pregnant 
during the study participant’s treatment with Viviant, this information must be submitted to 
Pfizer, irrespective of whether an adverse event has occurred using the NIS AEM Report 
Form and the EDP Supplemental Form.  

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 31 of 39 
In addition, the information regarding environmental exposure to Viviant in a pregnant 
woman (e.g., a subject reports that she is pregnant and has been exposed to a cytotoxic 
product by inhalation or spillage) must be submitted using the NIS AEM Report Form and 
the EDP supplemental form. This must be done irrespective of whether an AE has occurred.   
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-
up is conducted to obtain information on EDP outcome for all EDP reports with pregnancy 
outcome unknown.  A pregnancy is followed until completion or until pregnancy termination 
(e.g., induced abortion) and Pfizer is notified of the outcome.  This information is provided 
as a follow up to the initial EDP report.  In the case of a live birth, the structural integrity of 
the neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) 
for termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed. 
Additional information about pregnancy outcomes that are reported as SAEs follows:  
 Spontaneous abortion includes miscarriage and missed abortion; 
 Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to investigational product 
Additional information regarding the exposure during pregnancy may be requested.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on 
preterm infants to identify developmental delays).   

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 32 of 39 
In the case of paternal exposure, the study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner.  It must be documented that the 
study participant was given this letter to provide to his partner. 
 
Exposure during breastfeeding 
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated AE. An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (e.g., vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an AE associated with such a 
drug’s administration, the AE is reported together with the exposure during breastfeeding. 
 
Medication error 
A medication error is any unintentional error in the prescribing, dispensing or administration 
of a medicinal product  that may cause or lead to inappropriate medication use or patient 
harm while in the control of the health care professional, patient, or consumer.  Such events 
may be related to professional practice, health care products, procedures, and systems 
including: prescribing; order communication; product labeling, packaging, and nomenclature; 
compounding; dispensing; distribution; administration; education; monitoring; and use.   
Medication errors include: 
 Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or 
prescription on the part of the healthcare provider or the patient/consumer); 
 Confusion with regard to invented name (e.g., trade name, brand name). 
The investigator must submit the following medication errors to Pfizer, irrespective of the 
presence of an associated AE/SAE : 
 Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE. 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 33 of 39 
 Medication errors that do not involve a patient directly (e.g., potential medication 
errors or near misses).  When a medication error does not involve patient exposure to 
the product the following minimum criteria constitute a medication error report: 
− 
An identifiable reporter; 
− 
A suspect product; 
− 
The event medication error. 
 
Overdose, Misuse, Extravasation 
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product  
are reported to Pfizer by the investigator, irrespective of the presence of an associated 
AE/SAE.  
 
Lack of Efficacy 
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE or the indication for use of the Pfizer 
product. 
 
Occupational Exposure 
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE. 
  
6. Communication of Issues 
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable 
Competent Authority in any area of the world, or if the physician is aware of any new 
information which might influence the evaluation of the benefits and risks of Viviant 20 mg, 
Pfizer should be informed immediately.   

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 34 of 39 
In addition, the physician will inform Pfizer immediately of any urgent safety measures taken 
by the physician to protect the study subjects against any immediate hazard, and of any 
serious breaches of this NI study protocol that the physician becomes aware of. 
7. Single Reference Safety Document 
Background information on Viviant 20 mg can be obtained from the current version of the 
local product document, which is the single reference safety document (SRSD) for 
information relating to Viviant 20 mg in this study. 
8. STUDY DISCLOSURE 
Pfizer fulfils its commitment to publicly disclose the results of studies through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov). Pfizer registers study 
protocols and posts Basic Results on ClincialTrials.gov for Pfizer-sponsored interventional 
studies that evaluate the safety and/or efficacy of a Pfizer product and for Pfizer sponsored 
NI studies, regardless of design or data source, that evaluate the safety and efficacy of a 
Pfizer product. 
The results are posted in a tabular format called Basic Results and the posting timelines are: 
 Newly FDA approved products: 
Basic Results must be submitted within 30 calendar days of the FDA marketing 
approval for studies whose PCD occurred prior to 1 anniversary year or more from 
the date of marketing approval. 
 FDA-previously approved products: 
Basic Results are due within 1 anniversary year of the PCD and/or LSLV. 
When PCD and LSLV are not the same date, Basic Results are posted 1 anniversary 
year from the PCD and the record is updated 1 anniversary year from LSLV. PCD 
cannot occur after LSLV. 
 Discontinued products: 
Basic Results are due within 1 anniversary year of the decision to discontinue the 
product for all indications if there are no plans to out license the product or within 2 
anniversary years if out licensing plans are not completed. 
 Marketed outside of the United States (US) only: 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 35 of 39 
Basic Results are due within1 anniversary year of the ex-US approval or for already 
approved products, within 1 anniversary year of LSLV. 
For products marketed in the US and ex-US, the US timelines are followed. 
Primary Completion Date (PCD)  is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical trial concluded according to the pre-specified protocol, was terminated 
or ongoing. 
9. LIST OF FIGURES 
<Figure 1> Data Management Flow Chart 
10. REFERENCES 
1. 골다공증 진단 및 치료 지침 2008 (대한골대사학회 지침 위원회)  
2. 2002  Lancet the treatment of postmenopausal osteoporosis. Lancet. 2002 Jun 
8;359(9322):2018-26 
3. Safety and tolerablility of bazedoxifene in postmenopausal women with 
osteoporosis : results of 5-year, randomized, placebo-controlled phase 3 trial. 2011 
Feb;22(2):567-76. Epub 2010 Jun 10. 
4. Future long-term trials of postmenopausal hormone replacement therapy - what is 
possible and what is the optimal protocol and regimen? Climacteric. 2012 
Jun;15(3):288-93 
5. Sustained efficacy and safety of bazedoxifene in preventing fractures in 
postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-
controlled study.  Osteoporos Int (2012) 23:351–363 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 36 of 39 
APPENDIX 1. RESPONSIBLE PARTIES 
Protocol Contact 
Name, degree(s) 
Title 
Affiliation 
Address 
, MD 
Sr. Medical Manager 
Pfizer Pharmaceuticals 
Korea Ltd 
Pfizer Tower, 1-11, 
Hoehyun-Dong 3-Ga, 
Jung-Gu, Seoul, Korea 
 
Country Coordinating Physicians 
NA 
PPD

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 37 of 39 
APPENDIX 2. AMENDMENTS 
 
Current amendment: 7 
Amendment 
number 
Date 
Rationale for amendment 
Protocol section(s) changed 
1 
18 Jan 2013 
Clarification of the type of study sites 
3.1. Study Design 
Clarification of inclusion criteria 
3.2.1. Inclusion Criteria 
Addition of number of subjects 
3.5.3. Planned Numbers of Patients 
Clarification of efficacy evaluation 
time point 
3.5.5. Investigating Matters 
Addition of medical history item 
3.5.5.3. Medical History 
Addition of statistical analyses method 
3.8.1.2. Parameter on Safety 
Addition of statistical analyses method 
3.8.1.3. Parameter on Efficacy 
2 
04 Mar 2013 
Clarification of the analysis set 
3.5.5. Investigating Matters 
3 
13 Aug 2013 
Correction of the follow-up period for 
long-term surveillance 
3.1. Study Design 
Clarification of safety observation and 
efficacy evaluation time point 
3.5.5. Investigating Matters 
Clarification of medical history item 
3.5.5.3. Medical History 
Addition of concomitant therapy 
3.5.5.4. Concomitant Medication / 
Therapy 
Clarification of evaluation item (incl. 
long-term surveillance) 
3.5.5.5. Administration Status and 
Evaluation of Viviant 
3.5.5.7. Final Evaluation 
Addition of ‘not applicable’ for the 
action taken for an AE 
3.5.5.6.1. Adverse Event 
Reflection of the data management 
related process applicable to an eCRF 
study 
3.7.2. Data management 
3.7.2.1 Data Cleaning 
3.9. Quality control 
Reflection of the current disclosure 
requirements 
6. Study Disclosure 
Other administrative, non-substantive, 
stylistic changes were made. 
Not specified 
4 
28 Oct 2013 
Reflection of SOP amendment 
5.1.3. Definition of an Adverse 
Event 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 38 of 39 
5 
28 Nov 2013 
Addition of the details of study sites 
3.1. Study Design 
Addition of daily total dosage 
3.5.5.5. Administration Status and 
Evaluation of Viviant 
Clarification of the term used. 
3.5.5.6.1. Adverse Event 
Addition of the safety evaluation date 
and details for long term evaluation 
3.5.5.7. Final Evaluation 
Clarification of the sample size 
3.6. Power and Sample Size 
Clarification of the analysis method 
3.8.1.2. Parameter on Safety 
Clarification of the analysis method 
3.8.1.3. Parameter on Efficacy 
Clarification of the analysis method 
3.8.2. Statistical Consideration 
Clarification of the term used. 
5.1.2. Reporting Period 
Clarification of the term used. 
5.1.5. Serious Adverse Events 
Clarification of the term used. 
5.1.8. Exposure during Pregnancy 
6 
26Mar2015 
Reflection of SOP amendment 
5. Adverse Event Reporting 
Content numbering updated.  
(Content is same as Amend #5.) 
6. Communication of Issues 
Content numbering updated.  
(Content is same as Amend #5.) 
7. 
Single 
Reference 
Safety 
Document 
Content numbering updated.  
(Content is same as Amend #5.) 
8. Study Disclosure 
Content numbering updated.  
(Content is same as Amend #5.) 
9. List Of Figures 
Content numbering updated.  
(Content is same as Amend #5.) 
10. References 
7 
22Jun2016 
Korean term of “Adverse Event” is 
changed in accordance with updated 
MFDS Re-Examination guideline. 
Not specified  but overall protocol.  
Revision of subject’s personal data 
collection; Month of Birth 
3.5.5.1 Basic Information 
Revision 
of 
 
24 
hours 
contact 
information; Drug Safety Unit of the 
Pfizer Pharmaceuticals Korea Ltd. 
3.5.5.6.1 Adverse Event 
Change of Protocol Contact 
Appendix 1. 
Responsible Parties 
 
 

<Viviant Tablet 20 mg> 
<B1781047>  NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 22 Jun 2016 
 
Template Version 02/Jul/2012 
 
 
Page 39 of 39 
APPENDIX 3. MILESTONES  
Milestone 
Planned date 
Start of data collection 
Oct 2013 
End of data collection 
15 Nov 2017 
Interim reports 
15 Jul 2012 
15 Jan 2013 
15 Jul 2013 
15 Jan 2014 
15 Jan 2015 
15 Jan 2016 
15 Jan 2017 
Final study report 
15 Feb 2018