Post Marketing Surveillance in Japan on Long Term Drug Use of JARDIANCE® Tablets in Patients With Type 2 Diabetes Mellitus
Conditions: Diabetes Mellitus, Type 2
Sponsor: Boehringer Ingelheim

ABCD
TITLE PAGE
Non-interventional Study Protocol
Document Number:
c02153926-02
BI Study Number:
1245.94
BI Investiational
Product(s):
Empagliflozin, BI 10773
Title:
Post Marketing Surveillance in Japan on Long Term Drug 
Use of JARDIANCE® Tablets in Patients with type 2
Diabetes Mellitus
Clinical Phase:
IV
Trial Clinical 
Monitor:
Phone: 
Fax:
Co-ordinating 
Investigator:
Not applicable
Status:
Final Protocol
Version and Date:
Version: 1  
Date: 10 APR 2015
Page 1 of 36
Proprietary confidential information
© 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission

Boehringer Ingelheim
Page 2 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
NON-INTERVENTIONAL STUDY PROTOCOL SYNOPSIS
Name of company/Marketing Authorisation 
Holder:
Tabulated
Study Protocol
Boehringer Ingelheim
Name of finished product:
JARDIANCE® Tablets
Name of active ingredient:
Empagliflozin
Protocol date:
Trial number:
Revision date:
10 APR 2015
1245.94
Title of study:
Post Marketing Surveillance in Japan on Long Term Drug Use of JARDIANCE® 
Tablets in Patients with type 2 Diabetes Mellitus
Co-ordinating 
Investigator :
Not applicable
Study site(s) :
1,300 in Japan
Clinical phase:
IV
Objectives:
To investigate the safety and efficacy of long-term daily use of JARDIANCE® Tablets
in Japanese patients with type 2 diabetes mellitus.
Methodology:
Non-interventional, prospective, observational
No. of patients: 
Total entered:
3,000 patients with the assessment of 3-year completed administration
each treatment:
Diagnosis:
Type 2 diabetes mellitus
Main criteria for 
inclusion:
Male and female Japanese patients with type 2 diabetes mellitus who have never 
been treated with JARDIANCE® Tablets before the enrolment.
Test product(s) :
JARDIANCE® Tablets
dose:
10 mg, 25 mg
mode of admin. :
Oral
Comparator product(s): Not applicable
dose:
Not applicable
mode of admin. :
Not applicable
Duration of treatment: 156 weeks

Boehringer Ingelheim
Page 3 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Name of company/Marketing Authorisation 
Holder:
Tabulated
Study Protocol
Boehringer Ingelheim
Name of finished product:
JARDIANCE® Tablets
Name of active ingredient:
Empagliflozin
Protocol date:
Trial number:
Revision date:
10 APR 2015
1245.94
Criteria for efficacy: 
Primary efficacy endpoint:
None
Secondary efficacy endpoint:
Change from baseline in HbA1c and FPG to the last- observation on treatment.
Criteria for safety:
Primary safety endpoint:
Incidence of adverse drug reactions (ADRs)
Statistical methods:
Descriptive statistics will be summarised for safety and efficacy. A mixed model 
repeated measures analysis will be performed for HbA1c over time.

Boehringer Ingelheim
Page 4 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
FLOW CHART
Screening
Treatment 
End of Trial
Observation period*
Before first 
administration of 
JARDIANCE® 
Tablets
12, 26, 40, 52, 64, 78, 
104, 130 W
156 W5
Registration
X1
Demographics
X
Administration of 
JARDIANCE® Tablets
X
X
Medical History/
Concomitant disease
X
Waist circumference
X
Blood pressure 
pulse rate and ECG
X
X
X
HbA1c and
fasting plasma glucose
X
X
X
Laboratory tests
X
X
X 
Physical examination 
(Body weight, height)
X
X2
X2
12-lead ECG
X
X
X
Pregnancy status3
X
X
X
Concomitant drug(s) and 
antidiabetic therapy4
X
X 
X
Adverse events
X 
X
W: Weeks
*: Time points during the observation period are approximate. Collected data should be 
reported as of the closest available visit.
1: Patients administered JARDIANCE® Tablets will be registered preferably within 14 days 
from the day of first administration．
2: Body weight only
3: Only for female patients
4: From 1 month before first administration of JARDIANCE® Tablets
5: Time point for 156 weeks should be more than 1092 days.
Electronic case report form (eCRF): At 12 weeks, 52 weeks, 104 weeks, 156 weeks or 
discontinuation and each time when an adverse event has occurred, data in corresponding 
observation period should be entered into eCRF and transmitted using the EDC system.

Boehringer Ingelheim
Page 5 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
TABLE OF CONTENTS
TITLE PAGE ...........................................................................................................................1
NON-INTERVENTIONAL STUDY PROTOCOL SYNOPSIS .........................................2
FLOW CHART........................................................................................................................4
TABLE OF CONTENTS ........................................................................................................5
ABBREVIATIONS..................................................................................................................8
1.
INTRODUCTION...............................................................................................10
1.1
MEDICAL BACKGROUND.............................................................................10
1.2
DRUG PROFILE................................................................................................10
2.
RATIONALE, OBJECTIVES, AND BENEFIT-RISK ASSESSMENT .......11
2.1
RATIONALE FOR PERFORMING THE STUDY ........................................11
2.2
STUDY OBJECTIVES.......................................................................................11
2.3
BENEFIT-RISK ASSESSMENT.......................................................................12
3.
DESCRIPTION OF DESIGN AND STUDY POPULATION........................13
3.1
OVERALL DESIGN AND PLAN.....................................................................13
3.1.1
Administrative structure of the study...............................................................13
3.2
DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)......................................................................................14
3.3
SELECTION OF POPULATION.....................................................................14
3.3.1
Main diagnosis for study entry ..........................................................................15
3.3.2
Inclusion criteria .................................................................................................16
3.3.3
Exclusion criteria ................................................................................................16
3.3.4
Removal of patients from therapy or assessments...........................................16
3.3.4.1
Removal from individual patients.........................................................................16
3.3.4.2
Discontinuation of the study by the sponsor.........................................................16
4.
TREATMENTS...................................................................................................17
4.1
PRESCRIBED TREATMENTS TO BE OBSERVED....................................17
4.1.1
Identity of test product(s) and comparator product(s)....................................17
4.1.2
Method of assigning patients to treatment groups...........................................17
4.1.3
Selection of doses in the study............................................................................17
4.1.4
Drug assignment and administration of doses for each patient......................17
4.2
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
TREATMENT.....................................................................................................17
4.2.1
Rescue medication, emergency procedures, and additional treatment(s) .....17
4.2.2
Restrictions ..........................................................................................................17
4.2.2.1
Restrictions regarding concomitant treatment ......................................................17
4.2.2.2
Restrictions on diet and life style..........................................................................17
4.3
TREATMENT COMPLIANCE........................................................................17
5.
VARIABLES AND THEIR ASSESSMENT ....................................................18

Boehringer Ingelheim
Page 6 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
5.1
EFFICACY..........................................................................................................18
5.1.1
Endpoint(s) of efficacy........................................................................................18
5.1.2
Assessment of efficacy.........................................................................................18
5.2
SAFETY...............................................................................................................18
5.2.1
Endpoint(s) of safety...........................................................................................18
5.2.2
Management and reporting of adverse events/adverse reactions...................19
5.2.2.1
Definitions of adverse events................................................................................19
5.3
ADVERSE EVENT AND SERIOUS ADVERSE EVENT COLLECTION 
AND REPORTING.............................................................................................20
5.3.1
Adverse event and serious adverse event collection.........................................20
5.3.2
Reporting to health authorities..........................................................................23
5.3.3
Assessment of safety laboratory parameters....................................................23
5.3.4
Electrocardiogram ..............................................................................................24
5.3.5
Assessment of other safety parameters .............................................................24
5.4
OTHER ................................................................................................................25
5.4.1
Other parameter .................................................................................................25
5.4.2
Other assessment.................................................................................................25
5.5
APPROPRIATENESS OF MEASUREMENTS..............................................25
6.
INVESTIGATIONAL PLAN.............................................................................26
6.1
VISIT SCHEDULE.............................................................................................26
6.2
DETAILS OF STUDY PROCEDURES AT SELECTED VISITS ................27
6.2.1
Screening and run-in period(s)..........................................................................27
6.2.2
Treatment period(s)............................................................................................28
6.2.3
End of trial and follow-up period......................................................................28
7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE......................................................................................................................29
7.1
STATISTICAL DESIGN - MODEL.................................................................29
7.2
NULL AND ALTERNATIVE HYPOTHESES ...............................................29
7.3
PLANNED ANALYSES.....................................................................................29
7.3.1
Primary analyses.................................................................................................29
7.3.2
Secondary analyses .............................................................................................29
7.3.3
Safety analyses.....................................................................................................30
7.3.4
Interim analyses ..................................................................................................30
7.4
HANDLING OF MISSING DATA ...................................................................30
7.5
RANDOMISATION ...........................................................................................30
7.6
DETERMINATION OF SAMPLE SIZE .........................................................30
8.
INFORMED CONSENT, DATA PROTECTION, STUDY RECORDS.......32
8.1
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT ...........................................................................................................32
8.2
DATA QUALITY ASSURANCE ......................................................................32
8.3
RECORDS...........................................................................................................32
8.3.1
Source documents ...............................................................................................32
8.3.2
Direct access to source data and documents.....................................................33

Boehringer Ingelheim
Page 7 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
8.4
STATEMENT OF CONFIDENTIALITY........................................................33
8.5
COMPLETION OF STUDY..............................................................................33
9.
REFERENCES....................................................................................................34
9.1
PUBLISHED REFERENCES............................................................................34
9.2
UNPUBLISHED REFERENCES......................................................................34
10.
APPENDICES.....................................................................................................35
11.
SUMMARY OF NON-INTERVENTIONAL STUDY PROTOCOL 
MODIFICATIONS.............................................................................................36

Boehringer Ingelheim
Page 8 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ABBREVIATIONS
ADR
Adverse drug reaction
AE
Adverse Event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AMY
Amylase
AST
Aspartate aminotransferase
BI
Boehringer Ingelheim
BICMQ
Boehringer Ingelheim customised MedDRA query
BMI
Body-mass index
BUN
Blood Urea Nitrogen
CK
Creatine Kinase
CRF
Case Report Form
DEDP
Drug Exposure During Pregnancy
ECG
Electrocardiogram
EDC
Electronic Data Capture
eGFR
Estimated Glomerular filtration Rate
FPG
Fasting plasma glucose
-GTP
Gamma-glutamyl-transferase
GPSP
Good Post-marketing Study Practice 
GVP
Good Vigilance Practice 
HDL
High Density Lipoprotein cholesterol
IRB
Institutional Review Board
J-PAL
Japanese Pharmaceutical Affairs Law
LDH
Lactic dehydrogenase
LDL
Low Density Lipoprotein cholesterol
LIP
Lipase
MedDRA
Medical Dictionary for Regulatory Activities
MHLW
Ministry of Health, Labour and Welfare
MMRM
Mixed model repeated measures
NGSP
National Glycohemoglobin Standardization Program
NYHA
New York Heart Association
MR
Medical Representative
PMDA
Pharmaceuticals and Medical Devices Agency
PMS
Post Marketing Surveillance 
REML
Restricted maximum likelihood
SAE
Serious Adverse Event
SGLT-2
Sodium-dependent glucose co-transporter-2
SMQ
Standardised MedDRA Queries
SOP
Standard Operating Procedure
T-BIL
Total Bilirubin
T-CHO
Total Cholesterol
TG
Triglycerides
UA
Uric Acid

Boehringer Ingelheim
Page 9 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ULN
Upper Limit of Normal range

Boehringer Ingelheim
Page 10 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
1.
INTRODUCTION
1.1
MEDICAL BACKGROUND
The estimated worldwide prevalence of diabetes in 2011was 366 million with an increase of 
50% expected within the next 20 years. Most of these patients have type 2 diabetes mellitus, 
which is characterised by insulin resistance and impaired insulin secretion. Diabetes is 
associated with microvascular complications and elevated cardiovascular risk. Treatment of 
type 2 diabetes usually involves lifestyle interventions such as diet and exercise, as well as 
the administration of oral or injectable antidiabetic drugs. Although initially effective, 
currently available oral antidiabetic agents often fail to maintain long-term glycaemic control 
or are associated with side effects that may limit their use. Hence, there is a need for new 
therapeutic options for patients with type 2 diabetes to provide sustained improvements in 
glycaemic control and to contribute to reducing cardiovascular risk factors such as 
overweight and hypertension.
The kidney has a role in the regulation of blood glucose levels and can therefore serve as a
target for new antidiabetic drugs. The sodium-dependent glucose co-transporter-2 (SGLT-2)
is mainly expressed in the renal proximal tubules and accounts for approximately 90% of
renal glucose reabsorption. Inhibition of SGLT-2 decreases the renal reabsorption of glucose, 
thereby promoting glucose excretion in the urine with a resulting reduction in blood glucose 
levels. Due to their insulin-independent mechanism of action, SGLT-2 inhibitors have a low 
risk of hypoglycaemia. Further benefits of SGLT-2 inhibition may include weight reduction 
due to the calorie loss associated with increased glucose excretion and a decrease in blood 
pressure that is possibly due to a mild diuretic effect.
1.2
DRUG PROFILE
Empagliflozin (internal code: BI 10773) is a novel, orally administered, potent, and selective
SGLT-2 inhibitor developed by Boehringer Ingelheim. Empagliflozin is proposed to be
registered for treatment of type 2 diabetes mellitus in conjunction with diet and exercise, as
monotherapy or as add on other oral antidiabetic treatments or insulin. Empagliflozin tablets
are to be administered once daily, with or without food. The recommended therapeutic dose
is 10 mg. If treatment efficacy is insufficient, the daily dose can be increased to 25 mg once 
daily while the patient’s condition is being carefully monitored.

Boehringer Ingelheim
Page 11 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
2.
RATIONALE, OBJECTIVES, AND BENEFIT-RISK 
ASSESSMENT
2.1
RATIONALE FOR PERFORMING THE STUDY
In Japan, post-approval execution of post marketing surveillance (PMS) is requested by the 
Japanese Pharmaceutical Affairs Law (J-PAL) in order to accumulate safety and efficacy data 
for re-examination. Re-examination period is defined by J-PAL. New integrant is 8 years for 
re-examination. Eight years after approval of a new substance, results of PMS need to be 
submitted as a part of re-examination dossier to the Japanese regulatory authority, the 
Ministry of Health, Labour and Welfare (MHLW). 
Collected data from PMS will be included in the Japanese periodic safety reports and 
submitted to MHLW on designated dates until the end of re-examination period.
The protocol may be revised because of new information or knowledge obtained in the course 
of conducting PMS. When a change of the approved label such as in dosage and 
administration or indications is made during the re-examination period of JARDIANCE® 
Tablets (except that for this change a re-examination period is newly designated by MHLW) 
and NBI finds it necessary to revise this protocol, handling each matter should be discussed 
and the protocol may be revised. If any issue or concern arises (e.g. suggestion of a potential 
for clinically significant adverse reaction, remarkable increase in incidence of an adverse 
reaction, or any issue or concern on safety or efficacy assessment made prior to the approval 
of JARDIANCE® Tablets) in the course of PMS, implementation of additional special 
surveillance or post-marketing clinical trial should be discussed to identify or confirm a cause 
or estimated cause of such issue. Special surveillance is defined by J-PAL. It means 
surveillance for long-term use or special patient population (elderly, renal/hepatic 
dysfunction etc.).
SGLT-2 inhibitor is a drug class with a new mode of action, and does not comprise sufficient 
Japanese safety data within the class. It's not that there is a particular safety issue concerning;
JARDIANCE®; however, further surveillance is needed to monitor possible increase in the 
incidence of malignant tumor which is potentially associated with drugs of the same class, as 
well as the effect on kidneys attributable to its mode of action by which a long-term use 
stimulates the urinary excretion of glucose, and also the effect on hepatic function and bone 
metabolism.
This long-term drug use surveillance is planned to collect and investigate primarily safety
data.  
2.2
STUDY OBJECTIVES
Study objectives are to investigate the safety and efficacy of long-term daily use of
JARDIANCE® Tablets in patients with type 2 diabetes mellitus.

Boehringer Ingelheim
Page 12 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
2.3
BENEFIT-RISK ASSESSMENT
In this non-interventional PMS, marketed products will be used. ADRs as risk of 
JARDIANCE® Tablets are listed in package insert.  

Boehringer Ingelheim
Page 13 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
3.
DESCRIPTION OF DESIGN AND STUDY POPULATION
3.1
OVERALL DESIGN AND PLAN
This PMS is a prospective study using a continuous investigation system. Patients with type 2
diabetes mellitus will be included in the surveillance. No specific criteria (e.g., demographics, 
baseline characteristics, concomitant drugs in use) are defined for patient enrolment.
Patients administered JARDIANCE® Tablets will be registered preferably within 14 days 
from the day of first administration. Patients will be observed for up to 156 weeks 
(approximately 36 months) after start of the treatment with JARDIANCE® Tablets or at 
premature discontinuation and dropout. Observations are made at the following time points: 
before first administration of JARDIANCE® Tablets (screening, this visit is defined as
baseline) and 12, 26, 40, 52, 64, 78, 104, 130 and 156 weeks after the start of treatment, or at 
discontinuation.
There are 4 separate eCRFs for 0-12 (Book 1), 13- 52 (Book 2), 53- 104 (Book 3) and 105-
156 weeks (Book 4).
At 12, 52, 104 and 156 weeks after the start of treatment or at discontinuation, data are to be 
transmitted immediately after entered into eCRF. In case of occurrence of any adverse events, 
data in corresponding observation period should be immediately entered into eCRF and 
transmitted.
3.1.1
Administrative structure of the study
Sponsor
Co-sponsor

Boehringer Ingelheim
Page 14 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Contract research organizations
Task: Registration centre and data management
Medical advisor
Task:
1. Providing medical advice and comments on the study results
2. Providing medical advice on risk minimisation
3. Reviewing the contents of publication for the study results
3.2
DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)
This is a non-interventional, observational study based on newly collected data under routine 
medical practice. There is no control group.
3.3
SELECTION OF POPULATION
Total number of entered patients is 3,000 patients with the assessment of 3-year completed 
administration.
No limitations are set up on background factors of patients and their concomitant drugs in use 
of actual medical practice. 
Estimated number of enrolled patients with renal dysfunction (45 mL/min/1.73m2<= eGFR 
<60 mL/min/1.73m2) is 100.
Grades for renal dysfunction are as follows.
Normal:
eGFR ≥90 mL/min/1.73m2
Mild:
eGFR ≥60 mL/min/1.73m2
and <90 mL/min/1.73m2
Moderate:
eGFR ≥30 mL/min/1.73m2
and <60 mL/min/1.73m2
Severe:
eGFR <30 mL/min/1.73m2
Estimated number of enrolled elderly patients (≥75 years) is 100.

Boehringer Ingelheim
Page 15 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Estimated number of enrolled patients with hepatic dysfunction is 100.
Patients with hepatic dysfunction: Investigator judgment is moderate or severe.
Investigator should judge the grade for hepatic dysfunction by using lab data category as 
described below and symptoms/concomitant diagnoses.
Normal:
Normal AST/ALT
Mild:
AST/ALT >ULN and <3x ULN
Moderate:
AST/ALT≥3xULN and <5x ULN + total Bil<= 2xULN
Severe:
AST/ALT≥5 xULN, or AST/ALT≥3xULN and <5x ULN + total Bil> 2xULN
ULN is taken from the corporate standard reference range (001-MCG-157_RD-01: Standard 
Ranges). 
Sites throughout entire country will be equally listed according the size of the hospitals or
general clinics at which JARDIANCE® Tablets are available for prescription.
Expected number of patients per site is 5-30 patients. Patients will be selected by using the 
continuous investigation system. The continuous investigation system is commonly used in 
Japanese PMS and accepted as a patient selection process by the PMDA. 
Continuous investigation system is a method of registration that the investigator enrols the 
patients who will start administration of marketed product into the PMS continuously 
(without exception) until the requested number of patients is reached.
Preferably, investigators will register patients within 14 days including the day on which the 
administration of JARDIANCE® Tablets is started. However, patients who are registered over 
15 days after starting administration of JARDIANCE® Tablets are also used for safety and 
efficacy analysis.
The registered patients: The patient registration date are entered into eCRF and transmitted
using the EDC system.
The entered patients: The patient are registered and observational data after taking 
JARDIANCE® Tablets are entered into eCRF and transmitted using the EDC system.
Investigators will confirm the continuous registration at the site at the end of the enrolment
period with the signed form. 
3.3.1
Main diagnosis for study entry
The PMS is performed in patients with type 2 diabetes mellitus.

Boehringer Ingelheim
Page 16 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
3.3.2
Inclusion criteria
Patients with type 2 diabetes mellitus who have never been treated with JARDIANCE® 
Tablets / Empagliflozin before enrollment will be included.
3.3.3
Exclusion criteria
None
3.3.4
Removal of patients from therapy or assessments
3.3.4.1
Removal from individual patients
Patients may voluntarily discontinue the treatment under study for any reason. Patients may 
also discontinue the PMS if the investigator judges that the patient is no longer able to 
participate for any medical reason (pregnancy, surgery, adverse events, or other disease).
3.3.4.2
Discontinuation of the study by the sponsor
NBI reserves the right to discontinue the PMS overall or at a particular PMS study site at any 
time for the following reasons:
1. Failure to meet expected enrolment overall goals or goals at a particular study site,
2. Emergence of any efficacy/safety information that could significantly affect continuation 
of the PMS,
3. Violation of Good Post-marketing Study Practice (GPSP) or the contract of a study site or 
investigator, thereby disturbing the appropriate conduct of the PMS.
The investigator / the PMS site will be reimbursed for reasonable expenses incurred as a 
result of PMS termination (except in case of the third reason).

Boehringer Ingelheim
Page 17 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
4.
TREATMENTS
4.1
PRESCRIBED TREATMENTS TO BE OBSERVED
4.1.1
Identity of test product(s) and comparator product(s)
In this non-interventional PMS, marketed products will be used. There will be no 
investigational products in this PMS. It is solely in the decision of the investigator to initiate 
JARDIANCE® Tablets.
4.1.2
Method of assigning patients to treatment groups
There is no randomisation, since this is an observational surveillance study.
4.1.3
Selection of doses in the study
The usual dose is 10 mg of a JARDIANCE® Tablet administered orally once daily. If 
treatment efficacy is insufficient, the daily dose can be increased to 25 mg once daily while 
the patient’s condition is being carefully monitored.
4.1.4
Drug assignment and administration of doses for each patient
The investigators indicate doses and timing based on the package insert.
4.2
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
TREATMENT
4.2.1
Rescue medication, emergency procedures, and additional treatment(s)
There are no special emergency procedures to be followed stipulated by the protocol. It is 
solely the responsibility of the investigator to initiate such measures according to local 
clinical practice.
4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
All the restrictions listed in the package insert are applied.
4.2.2.2
Restrictions on diet and life style
All the restrictions listed in the package insert are applied.
4.3
TREATMENT COMPLIANCE
The investigators advise patients to take the prescribed product correctly and verbally 
confirm compliance to treatment medications at every patient visit.

Boehringer Ingelheim
Page 18 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
5.
VARIABLES AND THEIR ASSESSMENT
5.1
EFFICACY 
5.1.1
Endpoint(s) of efficacy
There is no primary endpoint for efficacy as the primary objective of a PMS is evaluating 
safety (See Section 5.2).
The secondary endpoint for this PMS is the change from baseline in HbA1c and FPG at the 
last observation during the observation period.
5.1.2
Assessment of efficacy
HbA1c:
The blood samples can be taken at any time and will be measured at the sites by using 
National Glycohemoglobin Standardization Program (NGSP). 
Fasting plasma glucose (FPG):
Fasting is defined as before breakfast and more than 10-hr past from previous JARDIANCE® 
Tablets administration. The blood samples should be taken before breakfast and before 
JARDIANCE® Tablets administration. The blood samples will be taken and measured at the 
sites. Plasma glucose will be reported in mg/dL.
5.2
SAFETY
5.2.1
Endpoint(s) of safety
Primary endpoint of this study is the number of patient with adverse drug reactions (ADRs)

Boehringer Ingelheim
Page 19 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
The other safety endpoint is the number of patient with serious adverse events (SAEs)
 
5.2.2
Management and reporting of adverse events/adverse reactions
5.2.2.1
Definitions of adverse events
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a medicinal product and which does not necessarily have a 
causal relationship with this treatment. An adverse event can therefore be any unfavorable
and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
Adverse drug reaction
An adverse drug reaction is defined as a response to a medicinal product which is noxious 
and unintended. Response in this context means that a causal relationship between a 
medicinal product and an adverse event is at least a reasonable possibility. Adverse reactions 
may arise from use of the product within or outside the terms of the marketing authorisation 
or from occupational exposure. Conditions of use outside the marketing authorization include 
off-label use, overdose, misuse, abuse and medication errors.
Serious adverse event
A serious adverse event is defined as any AE which
-
results in death, 
-
is life-threatening, 
-
requires in-patient hospitalization, or
-
prolongation of existing hospitalisation, 
-
results in persistent or significant disability or incapacity, or 
-
is a congenital anomaly/birth defect 
Life-threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death if more severe.
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalisation but might jeopardise the 
patient or might require intervention to prevent one of the other outcomes listed above.
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 hospitalisation or 
development of dependency or abuse. Any suspected transmission via a medicinal product of 
an infectious agent is also considered a serious adverse reaction.

Boehringer Ingelheim
Page 20 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
An AE which possibly leads to disability will be reported as an SAE. Every new occurrence 
of cancer or an exacerbation of an existing cancer will be reported as a SAE regardless of the 
duration between discontinuation of the drug and the occurrence of the cancer.
Adverse Event of Special Interest (AESI)
The term AESI relates to any specific AE that has been identified at the project level as being 
of particular concern for prospective safety monitoring and safety assessment within this 
study, e.g. the potential for AEs based on knowledge from other compounds in the same 
class. 
No AESIs have been defined for this study.
5.3
ADVERSE EVENT AND SERIOUS ADVERSE EVENT COLLECTION 
AND REPORTING
5.3.1
Adverse event and serious adverse event collection
The investigator shall maintain and keep detailed records of all AEs in their patient files. 
Collection of AEs
The study design is of non-interventional nature and the study is conducted within the 
conditions of the approved marketing authorisation. Sufficient data from controlled 
interventional trials are available to support the evidence on the safety and efficacy of the 
studied BI drug. For this reason the following AE collection and reporting requirements have 
been defined.
The following must be collected by the investigator in the (e)CRF from first intake of 
JARDIANCE® Tablets at baseline visit and within 7 days (inclusive) after the last intake:
-
all ADRs (serious and non-serious) as soon as possible, 
-
all AEs with fatal outcome in patients exposed to JARDIANCE® Tablets as soon as 
possible,   
All ADRs, including those persisting after study completion must be followed up until they 
are resolved, have been sufficiently characterized, or no further information can be obtained.
The investigator carefully assesses whether an AE constitutes an ADR using the information 
below.
Causal relationship of adverse event
The definition of an adverse reaction implies at least a reasonable possibility of a causal 
relationship between a suspected medicinal product and an adverse event. An adverse 
reaction, in contrast to an adverse event, is characterised by the fact that a causal relationship 
between a medicinal product and an occurrence is suspected. 

Boehringer Ingelheim
Page 21 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Medical judgment should be used to determine the relationship, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history. 
Possibility high:
There is a reasonable causal relationship between JARDIANCE® 
Tablets administered and the AE.
Possibility low:
It is probably/possibly that there is a reasonable causal relationship 
between JARDIANCE® Tablets administered and the AE.
Unknown:
Cannot be judged because information is insufficient or contradictory.
Unrelated:
There is no reasonable causal relationship between JARDIANCE® 
Tablets administered and the AE.
ADRs are defined that causal relationship is "Possibility high " or "Possibility low" or 
"Unknown".
Arguments that may suggest a reasonable causal relationship could be:
•
The event is consistent with the known pharmacology of the drug 
•
The event is known to be caused by or attributed to the drug class.
•
A plausible time to onset of the event relative to the time of drug 
exposure.
•
Evidence that the event is reproducible when the drug is re-
introduced
•
No medically sound alternative etiologies that could explain the 
event (e.g. preexisting or concomitant diseases, or co-medications).The 
event is typically drug-related and infrequent in the general 
population not exposed to drugs (e.g. Stevens-Johnson syndrome).
•
An indication of dose-response (i.e. greater effect size if the dose is 
increased, smaller effect size if dose is diminished).
Arguments that may suggest that there is no reasonable possibility of a causal
relationship could be:
•
No plausible time to onset of the event relative to the time of drug 
exposure is evident (e.g. pre-treatment cases, diagnosis of cancer or 
chronic disease within days/weeks of drug administration; an allergic 
reaction weeks after discontinuation of the drug concerned)
•
Continuation of the event despite the withdrawal of the medication, 
taking into account the pharmacological properties of the compound 
(e.g. after 5 half-lives).  Of note, this criterion may not be applicable to 
events whose time course is prolonged despite removing the original 
trigger.Additional arguments amongst those stated before, like 
alternative explanation (e.g. situations where other drugs or underlying 
diseases appear to provide a more likely explanation for the observed 
event than the drug concerned).

Boehringer Ingelheim
Page 22 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
•
Disappearance of the event even though the study drug treatment 
continues or remains unchanged.
Intensity of adverse event
The intensity of the AE should be judged based on the following:
Mild:
Awareness of sign(s) or symptom(s) which is/are easily tolerated
Moderate:
Enough discomfort to cause interference with usual activity
Severe:
Incapacitating or causing inability to work or to perform usual activities
Pregnancy:
In rare cases, pregnancy might occur in a study. Once a patient has been enrolled into the 
PMS, after having taken JARDIANCE® Tablets, the investigator must report any drug 
exposure during pregnancy which occurred in a female patient or in a partner to a male 
patient to the Sponsor by means of Part A of the Pregnancy Monitoring Form. The outcome 
of the pregnancy associated with the drug exposure during pregnancy must be followed up 
and reported by means of Part B of the Pregnancy Monitoring Form. 
In the absence of a reportable AE, only the Pregnancy Monitoring Form must be completed.
Expedited Reporting of AEs and Drug Exposure During Pregnancy
The following must be reported by the investigator to the Sponsor’s unique entry point from 
first intake of JARDIANCE® Tablets at baseline visit and within 7 days (inclusive) after last 
intake:
Type of Report
Timeline
All SADRs associated with the 
JARDIANCE® Tablets
As soon as possible
All AEs with fatal outcome in patients 
exposed to JARDIANCE® Tablets
As soon as possible
All non-serious ADRs associated with the 
JARDIANCE® Tablets
As soon as possible
All pregnancy monitoring forms
As soon as possible
The same timelines apply if follow-up information becomes available for the respective 
events. In specific occasions the Investigator could inform the Sponsor upfront via telephone. 
This does not replace the requirement to complete the appropriate (e)CRF. 

Boehringer Ingelheim
Page 23 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Information required
For each reportable adverse event, the investigator should provide the information requested 
on the appropriate (e)CRF pages.
Reporting of related Adverse Events associated with any other BI drug
The investigator is encouraged to report all adverse events related to any BI drug other than 
the JARDIANCE® Tablets according to the local regulatory requirements for spontaneous AE 
reporting at the investigator’s discretion by using the locally established routes and AE report 
forms. The term AE includes drug exposure during pregnancy, and, regardless of whether an 
AE occurred or not, any abuse, off-label use, misuse, medication error, occupational 
exposure, lack of effect, and unexpected benefit.
5.3.2
Reporting to health authorities
Adverse event reporting to regulatory agencies will be done by the MAH according to local 
and international regulatory requirements.
5.3.3
Assessment of safety laboratory parameters
The laboratory tests will be performed when required by investigator.
Safety laboratory assessment will be performed according to local practice and if available
the following parameters will be recorded in the eCRFs:

Boehringer Ingelheim
Page 24 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Haematology
Erythrocyte count (RBC), haemoglobin (Hb), haematocrit (Hct), 
Leukocyte counts (WBC) and platelet count.
Blood chemistry
HbA1c , Fasting plasma glucose, sodium (Na), potassium (K), chlorine 
(Cl), magnesium (Mg), calcium (Ca), phosphorus (P), creatinine (CRE), 
aspartate transaminase (AST, SGOT), alanine transaminase (ALT, 
SGPT), alkaline phosphatase (ALP), gamma-glutamyl-transferase (-
GTP), albumin , lactic dehydrogenase (LDH), total bilirubin (T-BIL), 
blood urea nitrogen (BUN), total cholesterol (T-CHO), HDL 
cholesterol (HDL), LDL cholesterol (LDL), Triglycerides (TG), 
Amylase (AMY), Lipase（LIP）, uric acid (UA), 25-OH vitamin D, 
iPTH, ketone and creatine kinase (CK).
Urinalysis
Glucose, protein, urobilinogen, sediment, albumin, ketone and 
creatinine. 
.
Enzymatic method:
eGFR（mL/min/1.73 m2）= 194×Creatinine（mg/dL）－1.094×Age－0.287
For female, ×0.739
Jaffe rate assay:
eGFR（mL/min/1.73 m2）= 175×Creatinine（mg/dL）－1.154×Age－0.203
For female, ×0.742
5.3.4
Electrocardiogram
If a resting 12-lead ECG will be performed by investigator’s order during the PMS and the 
investigator should review the ECG data and record the results (abnormal Yes or No) in the 
eCRF.
5.3.5
Assessment of other safety parameters
Vital signs
Vital signs (usually blood pressure and pulse after 2 minutes supine rest) will be recorded at 
the screening visit and at the closest time points specified in the Flow Chart.

Boehringer Ingelheim
Page 25 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
5.4
OTHER
5.4.1
Other parameter
Demographics and history
Demographics (gender, date of birth, indication, pregnancy status, height, body weight, waist
circumference, hypersensitivity factor, alcohol habit, pre-treatment drug, diagnosed date of 
type 2 diabetes mellitus, smoking history, start date of administration) 
Medical history (malignant tumor, cardiovascular/cerebrovascular disease (severity for 
cardiac failure for patients with past history of cardiac failure (NYHA classification)), urinary 
tract infection, genital infection, hypertension, osteoporosis, dyslipidaemia, 
goat/hyperuricaemia, others)
Concomitant disease (malignant tumor, cardiovascular/cerebrovascular disease (severity for 
cardiac failure for patients with past history of cardiac failure (NYHA classification)) , 
urinary tract infection, genital infection, osteoporosis, others), presence or absence of diabetic 
concomitant diagnosis (neuropathy/nephropathy/retinopathy), degree of renal/hepatic 
functions at baseline, history of antidiabetic treatment (drug therapy, diet therapy)
5.4.2
Other assessment
Concomitant drugs and antidiabetic therapies
Concomitant drugs and antidiabetic therapies present during PMS will be recorded in the 
CRF.
5.5
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this PMS are widely used measurements to monitor 
safety and efficacy aspects of treatment of type 2 diabetes mellitus.

Boehringer Ingelheim
Page 26 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
Screening and run-in period(s)
Before administration
The investigator will enter the following data of the patient into eCRF for registration. 
Preferably, registration should be executed within 14 days from the day of first administration
of JARDIANCE® Tablets.

Name of site, department and Investigator

Patient ID, date of birth, gender, start date of administration, indication and serum 
creatinine.
Treatment period(s)
Patients will receive continuous daily treatment until the criteria for stopping medication are 
met according to the package insert. 
During the treatment phase visits will be performed as planned if applicable and assessments 
will be documented within the nearest PMS visit.
End of trial and follow-up period
The visit at 156 weeks after starting JARDIANCE® Tablets treatment or the last visit before 
discontinuation will be the end of the PMS.

Boehringer Ingelheim
Page 27 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
6.2
DETAILS OF STUDY PROCEDURES AT SELECTED VISITS
6.2.1
Screening and run-in period(s)
Screening Visit 
Screening Visit is before the first administration of JARDIANCE® Tablets
Demographics
Gender, birth date, indication, pregnancy status, height, body 
weight, BMI (derived from weight and height), waist
circumference, smoking history, duration of type 2 diabetes 
mellitus, grade of hepatic dysfunction and hypersensitivity 
factor.
Medical history / Concomitant 
disease
Document medical history and concomitant disease
Pre-treatment drug
Document start and stop date of each pre-treatment drug
Vital signs
Blood pressure and pulse rate.
ECG
Resting 12-lead ECG will be performed if applicable.
Laboratory tests
Haematology, Biochemistry, Urinalysis (see section 5.3.3 for 
minimum assessments).
Concomitant drugs and 
antidiabetic therapies
Document indication, start and stop date of each concomitant 
drugs and antidiabetic therapies.
Administration
Document dose and start date.

Boehringer Ingelheim
Page 28 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
6.2.2
Treatment period(s)
Treatment period(s)
12, 26, 40, 52, 64, 78, 104 and 130 weeks after the start of treatment
When stop the treatment, please complete the EOT visit instead.
Vital signs
Blood pressure and pulse rate.
Body weight
Document body weight
Pregnancy status
Document when pregnancy is discovered.
ECG
Resting 12-lead ECG will be performed if applicable.
Laboratory tests
Haematology, Biochemistry, Urinalysis (see section 5.3.3 for 
minimum assessments).
Concomitant drugs and 
antidiabetic therapies
Document indication, start and stop date of each concomitant 
drugs and antidiabetic therapies.
Administration
Document dose, start and stop date and reason of termination.
Adverse events
Document details of any new AEs and obtain any new 
information about AEs ongoing at the last visit. 
 
  
6.2.3
End of trial and follow-up period
End of trial
EOT
Complete this visit at 156 weeks after the start of treatment or at discontinuation.
Vital signs
Blood pressure and pulse rate.
Body weight
Document body weight
Pregnancy status
Document when pregnancy is discovered.
ECG
Resting 12-lead ECG will be performed if applicable.
Laboratory tests
Haematology, Biochemistry, Urinalysis (see section 5.3.3 for 
minimum assessments).
Concomitant drugs and 
antidiabetic therapies
Document indication, start and stop date of each concomitant 
drugs and antidiabetic therapies.
Administration
Document dose, start and stop date and reason of termination.
Adverse events
Document details of any new AEs and obtain any new 
information about AEs ongoing at the last visit. 
 
  

Boehringer Ingelheim
Page 29 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
7.1
STATISTICAL DESIGN - MODEL
This is a non-interventional, prospective and observational study to investigate the safety and 
efficacy of long-term use of JARDIANCE® Tablets in patients with type 2 diabetes mellitus.
7.2
NULL AND ALTERNATIVE HYPOTHESES
The analyses in this PMS are descriptive and exploratory by nature. No formal hypotheses 
tests will be made.
7.3
PLANNED ANALYSES
The safety evaluation will be performed on the “safety set” that will include all patients who 
have received treatment of JARDIANCE® Tablet at least one time except those who are 
found to have no observation after enrolment, invalid registration, or invalid contract with the 
site. The efficacy evaluation will be performed on the “efficacy set”, a subset of the safety set, 
which will include all patients in the “safety set” except those who have no available efficacy 
data and/or who do not suffer from type 2 diabetes mellitus.
7.3.1
Primary analyses
In this PMS, the primary endpoint is the number of patient with ADRs. The details are given 
in Section 7.3.3
7.3.2
Secondary analyses
For change from baseline in HbA1c and FPG, descriptive statistics will be calculated with 
95% confidence interval for the mean change from baseline.
A mixed model repeated measures analysis using all the available longitudinal observations
during the observation period after the first administration of JARDIANCE® Tablets will be
performed. Within-patient variability from all time points is assumed to have a particular 
variance-covariance structure, which is “compound symmetry.” Least square means will be
computed at every time point and their respective standard error and 95% confidence interval
estimate account for the estimated covariance parameters.

Boehringer Ingelheim
Page 30 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
7.3.3
Safety analyses
The analysis and reporting of adverse events will concentrate on treatment-emergent adverse
events. To this end, all adverse events occurring between first drug intakes until 7 days after
last treatment administration will be considered ‘treatment-emergent’. Adverse events that
start before first drug intake and deteriorate under treatment will also be considered as
‘treatment-emergent’.
AEs will be coded using lowest level terms of the Medical Dictionary for Drug Regulatory 
Activities (MedDRA). AEs occurring in routine medical practice will be evaluated. The 
relationship of an AE to JARDIANCE® Tablets will be assessed by the investigator and the 
sponsor. An ADR is defined as an AE if either the investigator or the sponsor (or both) assess 
the causal relationship of JARDIANCE® Tablets either as “Possibility high”, “Possibility low” 
or “Unknown”.
The frequency of ADRs will be tabulated by system organ class and preferred term according 
to the current MedDRA version. The frequency of SAE will also be tabulated likewise.
The incidence of ADRs stratified based on patient demographics will also be investigated.
7.3.4
Interim analyses
Interim analyses will be performed periodically for the purpose of creating safety update 
reports to the local authority as well as for publications.
7.4
HANDLING OF MISSING DATA
The REML based MMRM analysis will handle missing data for continuous efficacy 
endpoints for patients who discontinue the study treatment prematurely or whom 
corresponding assessments / measurements are not documented / available.
7.5
RANDOMISATION
No randomisation of patients for treatment is performed, since this is an observational study.
7.6
DETERMINATION OF SAMPLE SIZE
According to the request from the Japanese authority, this PMS will target to include 3,000 
patients who complete a 3-year JARDIANCE® observation period. There is no target number 
of enrolment. For the 3,000 completer patients, an ADR with a true incidence of at least 
0.10% (or 0.16%) will occur in at least one patient with a probability of 95% (or 99%).
In addition, according to the request from the Japanese authority, this PMS will target to 
include elderly patients, patients with renal dysfunction and hepatic dysfunction. The sample 
size for this patient subset was determined based on the following:
Elderly patients (≥75 years)

Boehringer Ingelheim
Page 31 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Elderly patients were observed in 14.6% of the patients with type 2 diabetes mellitus based 
on the National Health and Nutrition Examination Survey (2007) [R13-5199]; it is estimated 
that approximately 400 ~ 500 elderly patients will be included in the 3,000 completer patients.
Based on this assumption, more than 100 elderly patients are highly likely to be enrolled in 
this PMS.
Renal dysfunction
The patients with renal dysfunction (eGFR 45~60 mL/min/1.73m2) were observed in 14.8% 
of the patients with type 2 diabetes mellitus in based on the historical cohort study with type 
2 diabetes [R13-5102]; it is estimated that approximately 400 ~ 500 patients with renal
dysfunction will be included in the 3,000 completer patients.
Based on this assumption, 100 patients with renal dysfunction are highly likely to be enrolled
in this PMS.
Hepatic dysfunction
Based on the result that hepatic function disorder was observed in 13.7% of the patients in the 
surveillance on the long-term use of Amaryl ®Tablets, an agent for type 2 diabetes [R11-
4205], it is estimated that approximately 350 ~ 450 patients with hepatic dysfunction will be 
included in the 3,000 completer patients.
Based on this assumption, 100 patients with hepatic dysfunction are highly likely to be 
enrolled in this PMS.
If the number of completer patients with 3-year JARDIANCE® observation period or specific 
diseases is less than expected by monitoring received CRF data, registration period or total 
number of enrolled patients may be extended.

Boehringer Ingelheim
Page 32 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
8.
INFORMED CONSENT, DATA PROTECTION, STUDY
RECORDS
The PMS will be carried out in routine clinical practice without any intervention involving
the patients, and there is no restriction on daily clinical practice. Principles are specified in 
accordance with the Japanese GPSP regulations (Ministry of Health and Welfare Ordinance 
No.1711, December 12, 2004), Japanese Good Vigilance Practice (GVP) regulations 
(Ministry of Health and Welfare Ordinance No.1315, October 22, 2004) and relevant BI 
Standard Operating Procedures (SOPs). Standard medical care (prophylactic, diagnostic and 
therapeutic procedures) remains the responsibility of the patient’s treating physician.
The rights of the investigator and of the sponsor with regard to publication of the results of 
this PMS are described in the contract. As a general rule, no PMS results should be published 
prior to finalisation of the Study Report.
8.1
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT
The review by IRB is not mandatory for conducting PMS in Japanese GPSP, due to the fact 
that required PMS by MHLW is an observational study using market products involved in
normal therapeutic procedures without any interventional procedure.
The same applies for the implementation of changes introduced by amendments. The sponsor 
will enter into a contract with a representative, e.g. head of hospital, in accordance with 
GPSP.
Written informed consent prior to patient participation in the trial is not regulatory or legal 
requirements in accordance with GPSP.
8.2
DATA QUALITY ASSURANCE
This PMS is to be conducted in accordance with both the in-house PMS SOP and working 
instructions which are in compliance with GPSP.
8.3
RECORDS
Case Report Forms (CRFs) for individual patients will be provided by the sponsor via an 
Electronic Data Capture (EDC) system.
8.3.1
Source documents
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data entered in the eCRFs that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may need 

Boehringer Ingelheim
Page 33 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
to request previous medical records or transfer records, depending on the trial; also current 
medical records must be available.
For eCRFs, all of the following data must be derived from source documents.
•
Patient identification (gender, date of birth)
•
Patient participation in the PMS (substance, patient number)
•
Dates of Patient’s visits, including dispensing of medication
•
Medical history (including indication and concomitant diseases, if applicable)
•
Medication history
•
Adverse events and outcome events (onset date, end date, treatment for AEs)
•
Serious adverse events (onset date, and end date)
•
Laboratory results
8.3.2
Direct access to source data and documents
The investigator / institution will permit PMS-related regulatory inspection, providing direct 
access to all related source data / documents. All source documents, including progress notes 
and copies of laboratory and medical test results, must be available at all times for inspection 
by health authorities (e.g. PMDA). The accuracy of the data will be verified by reviewing the 
documents described in Section 8.3.1
8.4
STATEMENT OF CONFIDENTIALITY
Individual patient medical information obtained as a result of this PMS is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers.
Data generated as a result of the PMS needs to be available on request by the regulatory 
authorities.
8.5
COMPLETION OF STUDY
Completion of the PMS will be notified to PMDA when the re-examination document is 
applied to in accordance with J-PAL and GPSP.

Boehringer Ingelheim
Page 34 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.
REFERENCES 
9.1
PUBLISHED REFERENCES
R13-5199
National Health and Nutrition Examination Survey (2007)
R13-5102
Wada T, et al: Clinical and Experimental Nephrology, Published online: 2014 
Aug; 18(4):613-20.
R11-4205  Pharmacovigilance  sanofi-aventis K.K.. Special Surveillance of Amaryl® 
Tablets (in Long-term Use) –Special Surveillance of Glimepiride (Amaryl® 
Tablets 1mg and 3mg Tablets)
9.2
UNPUBLISHED REFERENCES

Boehringer Ingelheim
Page 35 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
10.
APPENDICES
Not applicable.

Boehringer Ingelheim
Page 36 of 36
Non-interventional Study Protocol
1245.94
Observational plan
c02153926-02
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
11.
SUMMARY OF NON-INTERVENTIONAL STUDY 
PROTOCOL MODIFICATIONS
Summary of Modifications Sheet (SOMS)
Number of Protocol modification
Date of Protocol modification
BI Trial number
BI Product(s)
Title of protocol
To be implemented only after 
approval of the 
IRB/IEC/Competent Authorities
To be implemented immediately 
in order to eliminate hazard –
IRB / IEC / Competent Authority 
to be notified of change with 
request for approval
Can be implemented without 
IRB/IEC/ Competent Authority 
approval as changes involve 
logistical or administrative 
aspects only
Section to be changed
Description of change
Rationale for change