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Zafatec lock 100mg

Zafatec lock 50mg

Zafatec lock 25mg

Drug risk management plan for

Takeda Pharmaceutical Company Limited is solely responsible for the rights and content of the information

contained in this material, and the information cannot be used for any commercial purpose other than proper use.

Takeda Pharmaceutical Company Limited

 (Attachment style)

Zafatec lock 100mg Other related

Drug risk management plan (RMP) Overview

Zafatec lock 100 mg,

Brand name Active ingredient Toleragliptin succinate
same 50 mg,same 25 mg

Manufacturer and distributor Takeda Pharmaceutical Company Limited Medicinal effect classification 87396
Submission date Reiwa 3 Year 9 Month

1.1 Safety considerations

[Important identified risks] page [Significant potential risk] page [Important shortage information] page
Hypoglycemia 3 Skin disorders Four At the time of administration to patients with renal dysfunction
Ten
Acute pancreatitis FiveSafety
QT / QTc Event due to extension of interval At the time of administration to patients with hepatic dysfunction
Five Ten
arrhythmia Safety
Intestinal obstruction 6
Safety when administered to the elderly 11
Infection 7
Malignant tumor 8 Impact on cardiovascular risk 12
Related to overdose / overdose
8
Event to do

Pemphigoid 9
1.2 Effectiveness considerations
Effectiveness during long-term administration under actual conditions of use 12 page

↓ Activities for safety monitoring based on the above ↓ Activities for risk minimization based on the above

2. Overview of Pharmacovigilance Monitoring Plan page Four. Overview of risk minimization plan page
Normal drug safety monitoring activities 14 Normal risk minimization activities 17
Additional Pharmacovigilance Monitoring Activities Additional risk minimization activities

Zafatec Tablets Specific Use Results Survey "2 Long-term Patient Materials [Taking Zafatec Tablets
14
administration of type diabetes " (Patient medication precautions: hypoglycemia)
Zafatec lock 25 mg Specific drug use-results survey "Combined with And patients taking Zafatec tablets 17
high-grade renal dysfunction or end-stage renal failure 2 Mold 15 (Patient medication precautions: overdose / overdose

Survey on long-term use in diabetics " (Events related to)]

Materials for medical professionals [Clothing Zafatec tablets
3. Effectiveness study / test planning
page To patients who are used (Patient explanation material: Excessive
Overview 17
Events related to overdose / overdose)]
Zafatec Tablets Specific Use Results Survey "2 Long-term
16 Development and provision

administration of type diabetes "

Ingenuity in packaging form of this drug 18
The content of each item is RMP Please check the text of.
 (Attachment style)

Drug risk management plan

Reiwa 3 Year 9 Month 17 Day

President of Pharmaceuticals and Medical Devices Agency

Address: 4-chome, Doshomachi, Chuo-ku, Osaka 1 Turn 1 Name:

Takeda Pharmaceutical Company Limited

President and CEO Christophe Weber

Submit the title as follows.

Item overview

Date of approval 2015 Year 3 Month 26 Day Medications 87396

➀22700AMX00643000
Reexamination period 8 Year Service number ➁22700AMX00642000
➂30100AMX00217000
International birth date 2015 Year 3 Month 26 Day

➀ Zafatec lock 100 mg

Sales Sell ➁ Zafatec lock 50 mg
Name
➂ Zafatec lock 25 mg

Effective Toleragliptin succinate

➀ As toleragliptin 100 mg Film-coated lock containing

Content and dosage form ➁ As toleragliptin 50 mg Film-coated lock containing
➂ As toleragliptin 25 mg Film-coated lock containing

Dosage and administration Usually as toleragliptin in adults 100 mg of 1 In a week 1 Orally administer once.

Efficacy or effect 2 Type diabetes

Approval conditions Formulate a drug risk management plan and implement it appropriately.

Equipment Consideration 2019 Year 8 Month twenty one Zafatec lock on the day 25 mg Obtained manufacturing and marketing approval for the dosage form of.

1
 Change history

Last submission date

Reiwa 3 Year 6 Month 30 Day

Summary of changes:

1. "2. Zafatec Tablets in "Additional Pharmacovigilance Monitoring Activities" in "Overview of Pharmacovigilance Monitoring Plan" 25 mg Specific drug

use-results survey "Combined with severe renal dysfunction or end-stage renal failure 2 Long-term use in patients with type diabetesChanges in the

planned number of cases and the basis of the implementation plan.

2. "5.1 List of Pharmacovigilance Monitoring Plans ”Zafatec 25 mg Specific drug use-results survey "Combined with severe renal dysfunction or
end-stage renal failure 2 Number of cases that will be a milestone in "Survey on long-term use in patients with type diabetes" /Change the
target number of cases.

Reason for change:

Zafatec lock 25 mg Specific drug use-results survey "Combined with severe renal dysfunction or end-stage renal failure 2 Diabetes
mellitusAfter reexamining the feasibility of the "Survey on long-term use by humans", the planned number of cases was reviewed.

2
1. Overview of drug risk management plan

Zafatec Tablets (hereinafter referred to as this drug) is the first week of oral hypoglycemic drug 1 Since it is a single-dose product, in addition to the

following safety considerations, pay particular attention to the occurrence of unpredictable side effects, and take appropriate measures such as

conducting frequent side effect analysis.

1.1 Safety considerations

Significant identified risks

Hypoglycemia

Reasons for making it an important identified risk:

This drug is dipeptidyl peptidase-Four(Less than,DPP-4) Inhibits activity, glucagon-like peptide-1(Less than,GLP-1), Since
insulin secretion is promoted in a blood glucose-dependent manner by maintaining the blood concentration of), it is
considered unlikely to cause hypoglycemia. However, hypoglycemia is an important basic precaution in the treatment
of diabetes with oral hypoglycemic agents, and hypoglycemia may occur during administration of this drug, including
the effects of concomitant medications. Also, other similar drugsDPP-4 Severe hypoglycemia has been reported in
combination with inhibitors and sulfonylurea drugs ["Incretin ("GLP-1 With receptor agonists DPP-4 From the
Committee on Proper Use of Inhibitors) Recommendation" 2011 Year 9 Month 29 Day correction].

A double-blind comparative study conducted in Japan for this drug (CCT-001 Test and CCT-002 In the study), no hypoglycemia was
observed in the riociguat group. Long-term administration test (OCT-001 The frequency of side effects of hypoglycemia observed in
(Study) was as follows: long-term administration of a single long-term drug, long-term administration of a sulfonylurea drug, long-term
administration of a fast-acting insulin secretagogue, long-term administration of a biguanide drug, and thiazolidinedione. In each case
of long-term administration with drugs 0.4%(1/248 example),3.2%(5/158 example),
1.5%(1/67 example),1.4%(1/70 Example) and 1.4%(1/72 Example), and a long-term administration example with an α-
glucosidase inhibitor (example)0/65 Example) was not seen. The degree was all mild. In addition, no serious hypoglycemia was
reported. Complicated with severe renal dysfunction or end-stage renal disease2 Clinical trials in patients with type diabetes (
3003 In the test), this drug 25 mg of 12 Hypoglycemia observed in the weekly administration group was hypoglycemia 14.5%(
8/55 Example), unaware hypoglycemia 1.8%(1/55 Example), hypoglycemia in the placebo group 7.7%(4/52 Example), unaware
hypoglycemia 0%(0/52 It was an example. In addition, this drug25 mg of 12 In the weekly administration group, further 40 If
administration is continued for a week (total 52 Weekly administration), hypoglycemia 21.8%(12/55 Example), unaware
hypoglycemia 1.8%(1/55 It was an example. In the placebo group12 This drug will continue from a week later 25 mg of40
Hypoglycemia when administered weekly 14.6%(7/48 Example), unaware hypoglycemia 0%(0/48 It was an example. The degree
was all mild. In addition, no serious hypoglycemia was reported.

Clinical trial in combination with insulin preparation conducted in Japan (CCT-101 In the test), this drug and the insulin preparation were
used. 12 Hypoglycemia observed in the weekly combination group was hypoglycemia 10.3%(12/116 Example), unaware hypoglycemia
0%(0/116 Example), hypoglycemia in the insulin preparation alone group 8.9%(11/124 Example), unaware hypoglycemia 0.8%(1/124 It
was an example. In addition, in the group in which this drug and insulin preparation were used in combination, further40If you
continue to use it for a week (total 52 With weekly combination), hypoglycemia 19.0%(22/116 Example), unaware low blood sugar 0.9%(
1/116 It was an example. In addition, no serious hypoglycemia was reported.

Based on the above, although clinical studies have not shown a clear increase in the incidence of hypoglycemia due to this drug, there
have been reports of hypoglycemia, and this drug has been reported. OCT-001 Test and CCT-101 In the study as well, the incidence of
hypoglycemia tended to be high when sulfonylurea drugs or insulin preparations were used in combination, so this was regarded as an
important identified risk.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities

--- As additional pharmacovigilance monitoring activities, the following will be implemented.

1. Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type diabetes "

2. Zafatec lock 25 mg Specific drug use-results survey "Combined with severe renal dysfunction or end-stage renal failure2
Survey on long-term use in patients with type diabetes "

3
 [Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific
Use Results Survey "2 Type 2 diabetes long-term administration ”and Zafatec tablets specific drug use-results survey“ Complications
with severe renal dysfunction or end-stage renal failure 2 To collect and evaluate information such as the incidence, severity, and
case summary of hypoglycemia in the "Survey on long-term use in patients with type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
--- As a normal risk mitigation activity, the package insert "8. 8. Important basic notes ","9.1 Patients with complications /
history, etc. ”,“10.2 "Caution for combined use" and "11.1 Describe in the section "Serious side effects" and the drug
guide for patients to call attention.

--- As an additional risk mitigation activity, create and provide patient materials.
[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, as usual risk
miniaturization activities, information is provided to healthcare professionals by package inserts and information
to patients by patient-oriented drug guides. To prevent the onset of hypoglycemia and provide information on
how to deal with the onset of hypoglycemia by creating and providing materials for patients as an additional risk
reduction activity.

Significant potential risks

Skin disorders

Reasons for making it an important potential risk:

Others that are similar drugs DPP-4 In non-clinical studies of inhibitors, it has been reported that administration to monkeys resulted in
necrotic cutaneous symptoms depending on the dose and duration of administration. Also otherDPP-4 Inhibitors, mucocutaneous ocular
syndrome (including severe cases after manufacture and sale)Stevens-Johnson There are spontaneous reports of syndrome), erythema
multiforme, etc., and cautions regarding these are given in the precautions for use.

No alarming necrotic skin findings were found in this drug in nonclinical studies aimed primarily at confirming skin toxicity. In
addition, a double-blind comparative study conducted in Japan (CCT-001 test,CCT-002 Test and 3003 When the incidence of skin
disease-related adverse events * was examined in the study and the following, in addition, a domestic comparative study)
CCT-001 In the test, this drug 100 mg Group expression frequency [9.1%(5/55Example)] is the placebo group [0%(0/55 Although
it was slightly higher than [Example)], other group of this drug (Example)12.5 mggroup,25 mg group,50 mg group,200 mg
Group) is about the same,CCT-002 In the test, this drug 100 mg Frequency of occurrence in the group [4.0%(4/101 Example)] is a
placebo group [6.0%(3/50 Example)] was about the same.3003 In the test, this drug 25 mg of 12 Frequency of occurrence in the
weekly administration group [7.3%(4/55 Example)] is a placebo group [9.6%(5/52Example)] was about the same. Also other
DPP-4 There were no manifestations of serious events as reported with inhibitors.

Based on the above, there is no risk of skin disease-related adverse events occurring in this drug in either non-
clinical studies or clinical studies. However, otherDPP-4 Mucocutaneous ocular syndrome in inhibitors (Stevens-
Johnson Syndrome), erythema multiforme, etc. have been reported, and if a slight rash, etc. becomes severe, it
may affect the benefit / risk balance of this drug, so it was regarded as an important potential risk.

*: Adverse events related to skin diseases were defined as adverse events corresponding to "skin and subcutaneous tissue disorders" among the

adverse events classified by organs.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Regular Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use

Four
 Grade survey "2 To collect and evaluate information such as the incidence, severity, and case outline of skin disorders in "long-term
administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "11.2 Describe rash and pruritus in the section "Other
side effects" to call attention.

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, in order to provide
information to healthcare professionals in the package insert as a normal risk miniaturization activity.

Acute pancreatitis

Reasons for making it an important potential risk:

Pancreas contains this drug DPP-4 Inhibitors and GLP-1 Other sites of action of receptor agonists and similar drugs
DPP-4 Inhibitors and GLP-1 Acute pancreatitis has been reported as a receptor agonist after manufacturing and
marketing, and many of these drugs have been alerted in the precautions for use.

On the other hand, in a domestic comparative study of this drug, the incidence of acute pancreatitis-related adverse events * was similar
in all the drug group and the placebo group. Among the adverse events related to acute pancreatitisMedDRA Standard search formula (
Standardised MedDRA Queries:Less than,SMQ), There were no adverse events for which the causal relationship corresponding to the
narrow area of "acute pancreatitis" could not be ruled out. In addition, no findings related to the risk of developing acute pancreatitis
were found in nonclinical studies.

Based on the above, there is no risk of developing acute pancreatitis in any of the non-
clinical and clinical studies of this drug, but if acute pancreatitis develops, hospitalization
may be required. It is an important potential risk because it can affect the risk balance.

*: Acute pancreatitis-related adverse eventsSMQ Of all the basic words that correspond to the narrow area of "acute pancreatitis" and the basic

words that correspond to the wide area, it was defined as an adverse event related to clinical laboratory test values (blood and urine tests).

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 To collect and evaluate information such as the incidence, severity, and case outline of acute pancreatitis in "long-
term administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "11.1 Describe in the section "Serious side effects" and the
drug guide for patients to call attention.

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, we will provide information to
healthcare professionals through package inserts and information to patients through patient-oriented drug guides as normal risk
miniaturization activities. To do.

QT / QTc Arrhythmia associated with extended interval

Reasons for making it an important potential risk:

For healthy adults conducted overseas QT / QTc Evaluation test(CPH-005 In the study), the usual dose of this drug 2 Double 200
mg In the group QT / QTc Although there was no extension of the interval,800 mg In a groupQT / QTc There was an extension
of the interval. Domestic clinical trials including long-term administration conducted after that (CCT-002 Trial

Five
 Test,OCT-001 Test and OCT-002 Test) by accurate electrocardiogram measurement QT / QTc Risk assessment of interval extension and QT / QTc We

investigated arrhythmia-related adverse events * associated with extended intervals. resulting in,QT / QTc No extension of the interval was seen.QT /

QTc Loss of consciousness as an adverse event related to arrhythmia associated with extended intervals 1 An example occurred, but a causal

relationship with the study drug was ruled out.3003 Recognized in the examQT / QTc Adverse events related to arrhythmia associated with

prolonged intervals are treated with this drug. 25 mg of 12 In the weekly administration group 1.8%(1/55Example), in the placebo group 7.7%(4/52 It

was an example. Also, in non-clinical studiesQT / QTc There are no findings associated with the risk of developing proarrhythmias associated with

prolonged intervals.

Based on the above, this drug has been used in both non-clinical and clinical studies. QT / QTc There is no risk
of developing arrhythmia associated with prolonged intervals,QT / QTc Prolonged intervals may lead to
torsades de Pointe, ventricular tachycardia, etc., and affect the benefit-risk balance of this drug, so it was
regarded as an important potential risk.

*::QT / QTc Adverse event name (basic term) corresponding to arrhythmia-related adverse events associated with interval extension

Torsado pointoant, sudden death, cardiac death, sudden cardiac death, cardiac arrest, cardiopulmonary arrest, ventricular tachycardia, ventricular

tachycardia arrhythmia, ventricular arrhythmia, ventricular fibrillation, ventricular fibrillation, ventricular flutter, consciousness change , Fainting, loss of

consciousness, convulsive attack, epilepsy, electrocardiogram QT Extension,QT Prolonged syndrome, congenital QT Prolonged syndrome,

electrocardiogram QT Interval abnormalities, ECG repolarization abnormalities, ECG U Wave anomaly

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use Results

Survey "2 In "long-term administration of type diabetes"),QT / QTc To collect and evaluate information such as the occurrence status, severity,

and case summary of adverse arrhythmia-related events associated with the extension of the interval.

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "15.1 Information based on clinical use "and"17.3 Describe in
the "Other" section to call attention.

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, in order to provide
information to healthcare professionals in the package insert as a normal risk miniaturization activity.

Intestinal obstruction

Reasons for making it an important potential risk:

Others that are similar drugs DPP-4 It is an inhibitor, and there have been reports of intestinal obstruction after manufacturing and marketing, and cautions

have been given regarding the precautions for use of all drugs.

On the other hand, when the incidence of intestinal obstruction-related adverse events * was examined in a domestic comparative study
of this drug,CCT-001 Test drug 200 mg Gastrointestinal motility disorder in the group 1 Only cases were reported. Not found in the
placebo group. In addition, no findings related to the risk of developing intestinal obstruction were found in nonclinical studies.

Based on the above, no risk of intestinal obstruction was observed in this drug in either non-clinical
studies or clinical studies. However, otherDPP-4 Significant potential risk as intestinal obstruction has
been reported as an inhibitor and hospitalization may be required if intestinal obstruction develops,
which may affect the benefit-risk balance of this drug. And said.

*: Intestinal obstruction-related adverse eventsSMQ It was defined as all the basic words corresponding to the narrow area of "obstruction of the

digestive tract" in.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

6
 [Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use Results

Survey "2 To collect and evaluate information such as the incidence, severity, and case outline of intestinal obstruction in "long-term

administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "11.1 Describe in the section "Serious side effects" and the
drug guide for patients to call attention.

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, we will provide information to
healthcare professionals through package inserts and information to patients through patient-oriented drug guides as normal risk
miniaturization activities. To do.

Infection

Reasons for making it an important potential risk:

in vitro In the experimentDPP-4 There are many reports on the effects of inhibition on the functioning of the
immune system (Scand. J. Immunol. 2001; 54: 249, Trends Immunol. 2008; 29: 295.). For infectious diseases,
existingDPP-4 Reported that the inhibitor increased the risk of development compared to the control group (
JAMA. 2007; 298 (2): 194) And reports that it did not rise (BMJ 2012; 344: e1369: 1).

No findings associated with the risk of developing infections have been found in nonclinical studies.

A double-blind comparative study of this drug conducted in Japan (CCT-001 Test and CCT-002 In the study), the incidence of adverse
events corresponding to "immune system disorders" and "infectious diseases and parasitosis" among the major organ classifications was
similar in all riociguat groups compared to the placebo group. Or it was a little low. on the other hand,3003 In the study, the adverse
events that correspond to "infectious diseases and parasitosis" among the major organ classifications are this drug. 25 mgof 12 In the
weekly administration group 30.9%(17/55 Example), in the placebo group 19.2%(10/52 It was an example.

Based on the above, there is no risk of developing an infectious disease in any of the non-clinical and clinical studies of this drug.DPP-4
Considering the effect of inhibition on the immune system and the possibility of increased risk of infectious diseases, it was considered as
an important potential risk.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As additional pharmacovigilance monitoring activities, the following will be implemented.

1. Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type diabetes "

2. Zafatec lock 25 mg Specific drug use-results survey "Combined with severe renal dysfunction or end-stage renal failure2 Survey
on long-term use in patients with type diabetes "

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 Type 2 diabetes long-term administration ”and Zafatec tablets specific drug use-results survey“ Complications with
severe renal dysfunction or end-stage renal failure 2 To collect and evaluate information such as the incidence, severity, and case
outline of infectious diseases in the "Survey on long-term use in patients with type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "11.2 Describe nasopharyngitis in the section "Other side
effects" to call attention.

[Reason for selection]

7
 Since it is considered necessary to provide information on proper use and promote understanding, in order to provide
information to healthcare professionals in the package insert as a normal risk miniaturization activity.

Malignant tumor

Reasons for making it an important potential risk:

Report that there is a causal relationship between incretin-related drugs and pancreatic cancer (Diabetes. 2013; 62 (7): 2595) Is
not related to the report (N Engl J Med. 2014; 370 (9): 794, Diabetes Obes and Metab. 2014; 16:48)DPP-4 There are many
unclear points about the effects on the whole body when the drug is inhibited for a long period of time, including information
on similar drugs overseas.

On the other hand, in the domestic comparative study, the incidence of adverse events corresponding to "benign, malignant
and unspecified neoplasms (including cysts and polyps)" among the major organ classifications was similar to that of the
placebo group. there were. In addition, no findings related to the risk of developing malignant tumors were found in
nonclinical studies.

Based on the above, no risk of developing malignant tumors was found in any of the non-clinical and clinical studies of this drug, but the causal

relationship between incretin-related drugs and pancreatic cancer DPP-4 Considering that there are many unclear points about the effect on the

whole body when the disease is inhibited for a long period of time, it is regarded as an important potential risk.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 To collect and evaluate information such as the incidence, severity, and case outline of malignant tumors in "long-
term administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
none
[Reason for selection]

At present, there is no noteworthy content of caution, and if new information is obtained, it will be considered.

Events related to overdose / overdose

Reasons for making it an important potential risk:

While the existing oral hypoglycemic drug is administered daily, the dosage and administration of this drug is
"usually as toleragliptin for adults. 100 mg of 1 In a week 1 Orally administer once. ".
Conducted overseas 2 No. 1 for diabetic patients 2 Phase-ranging study (006 In the test), this drug100 mg of 12 The
frequency of adverse events when administered daily for weeks was similar to that in the placebo group.

However, the week of this drug 1 The possibility of medication error cannot be ruled out due to the characteristics of multiple
doses, and given that events such as hypoglycemia may occur during overdose / overdose of this drug, events related to
overdose / overdose are important potentials. Risk.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 In order to collect detailed information and evaluate the obtained information individually for each case when an
overdose case is reported in "long-term administration of type diabetes").

8
 Details of risk reduction activities and reasons for their selection:

[Details]
--- As a normal risk mitigation activity, the package insert "7. Precautions related to usage and dosage "and"13.
Describe in the “Overdose” section and the Patient Drug Guide to call attention.

--- Additional risk mitigation activities include:

1. Creation and provision of materials for medical professionals and materials for patients

2. Ingenuity in packaging form of this drug

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, information activities for
healthcare professionals using package inserts and information activities for patients using drug guides for patients should
be carried out as normal risk miniaturization activities. In addition, as an additional risk reduction activity, we will create and
provide materials for healthcare professionals and patients to ensure thorough usage and dosage of this drug. In addition,
when packaging this drug, use a blister card to indicate when to take the drug and precautions for taking the drug to ensure
proper use.

Pemphigoid

Reasons for making it an important potential risk:

Pemphigoid, including severe cases, has been reported as a spontaneous report after manufacturing and marketing of this drug. It
has been reported in patients with pemphigoid as a history or complication, and in elderly patients who are known to frequently
develop pemphigoid, and its association with this drug has not been strongly suggested.

No pemphigoid-related adverse events * were reported in a domestic comparative study of this drug. In addition, no
findings related to the risk of developing Pemphigoid were found in non-clinical studies.

Based on the above, the risk of developing pemphigoid was not found in any of the non-clinical and clinical
studies of this drug, but the mechanism of pemphigoid development by this drug is unknown, but after
manufacturing and marketing. Contains this drug DPP-4 Pemphigoid has been reported as an inhibitor, and
in some cases, long-term treatment may be required, which may affect the benefit / risk balance of this drug,
so it is important. Potential risk.

*: Pemphigoid-related adverse eventsMedDRA It was defined as the basic terms "pemphigoid" and "pemphigoid ocular".

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 To collect and evaluate information such as the incidence, severity, and case outline of Pemphigoid in "long-term
administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "11.1 Describe in the section "Serious side effects" and the
drug guide for patients to call attention.

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, we will provide information to
healthcare professionals through package inserts and information to patients through patient-oriented drug guides as normal risk
miniaturization activities. To do.

9
 Important missing information

Safety when administered to patients with renal dysfunction

Reasons for making important missing information:

This drug is mainly excreted from the kidneys. Clinical pharmacology studies conducted overseas in healthy adults and patients with renal

dysfunction [101 Study (Patients with mild renal dysfunction 6 For example, patients with moderate renal dysfunction 6 For example, patients with

severe renal dysfunction 6 For example, patients with end-stage renal disease Five For example, as a result of examining the pharmacokinetics of this

drug in (single dose)], the higher the degree of renal dysfunction, the more the exposure dose of this drug (AUC) Increased, and in patients with

moderate renal dysfunction compared to healthy adults 2.06 Since it was confirmed to double, the dose in patients with moderate renal dysfunction

was changed to the usual dose (100 mg) Half amount (50 mg).

Domestic clinical trial [CCT-001 test(12 week),CCT-002 test(twenty four week),OCT-001 test(52 Weekly) and OCT-002 test(12 Weekly)
(Patients with mild renal dysfunction in the riociguat group of these studies:210For example, patients with moderate or higher renal
dysfunction:19 Example)], in order to evaluate the effect on the safety of patients with renal dysfunction, when a subpopulation analysis
was performed on the frequency of adverse events according to the degree of renal function, there was a clear tendency for the
frequency of adverse events to occur. I couldn't see it.

Complicated with severe renal dysfunction or end-stage renal disease 2 Clinical trials for patients with type
diabetes (3003 Trial: This drug 25 mg In administration), there were no new safety concerns.

However, regarding the safety of patients with moderate or higher renal dysfunction and patients with end-stage renal disease,
the number of patients who received this drug is small and information is insufficient, and it is widely used in patients with
various background factors in clinical practice. When used, it may affect the benefit / risk balance of this drug, so it was
considered as important shortage information.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As additional pharmacovigilance monitoring activities, the following will be implemented.

1. Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type diabetes "

2. Zafatec lock 25 mg Specific drug use-results survey "Combined with severe renal dysfunction or end-stage renal failure2
Survey on long-term use in patients with type diabetes "

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 Type 2 diabetes long-term administration ”and Zafatec tablets specific drug use-results survey“ Complications with
severe renal dysfunction or end-stage renal failure 2 In the "Survey on long-term use in patients with type diabetes"), when adverse
events were reported in patients with renal impairment, detailed information was collected and safety was obtained based on the
obtained information. To review and evaluate sex profiles.

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "7. Precautions related to usage and dosage ","9.2 "Patients with renal
dysfunction" and "16.6 Describe in the section "Patients with a specific background" and the drug guide for patients to call
attention.

[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, as usual risk miniaturization
activities, information is provided to healthcare professionals through package inserts and patients are provided with a drug guide for
patients. To provide information.

Safety when administered to patients with hepatic dysfunction

Reasons for making important missing information:

A clinical pharmacology study conducted overseas in healthy adults and patients with moderate hepatic dysfunction [102 Study (Patients
with moderate hepatic dysfunction 8 For example, a single dose)], as a result of examining the pharmacokinetics of this drug,AUC (0-inf)
as well as Cmax Was not significantly different compared to healthy adults.

Domestic clinical trial [CCT-001 test(12 week),CCT-002 test(twenty four week),OCT-001 test(52 week

Ten
 Between) and 3003 test(52 week/40 Weekly) (Number of subjects with hepatobiliary system disorders in the riociguat group of
these studies:420 Example)], in order to evaluate the effect on the safety of patients with hepatic dysfunction, a subpopulation
analysis was performed on the frequency of occurrence of harmful events according to the presence or absence of hepatic
dysfunction. No clear trend was seen.

However, although the pharmacokinetics of patients with severe hepatic dysfunction have not been investigated and
the safety studies in clinical trials are limited, it is widely used in patients with various background factors in clinical
practice. In this case, it may affect the benefit / risk balance of this drug, so it was considered as important shortage
information.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets
Specific Use Results Survey "2 To examine and evaluate the safety profile when this drug is used in patients with hepatic
dysfunction in "long-term administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
none
[Reason for selection]

At present, there is no noteworthy content of caution, and if new information is obtained, it will be considered.

Safety when administered to the elderly

Reasons for making important missing information:

Domestic clinical trial [CCT-001 test(12 Weekly) and OCT-001 test(52 Weekly)] regarding the pharmacokinetics of this drug in non-elderly
patients (65 Under the age of) and the elderly (under the age of)65 As a result of comparing (aged and over), this drug AUC (0-168)as well
as Cmax Did not make a big difference.

Domestic clinical trial [CCT-001 test(12 week),CCT-002 test(twenty four week),OCT-001 test(52 week),OCT-002 test(12
Weekly) and 3003 test(52 week/40 Weekly) (in the riociguat group of these studies 65 Number of subjects over the age
of:416 Example, out 75 Subjects over the age of:69 Example)], non-elderly people (65 Under the age of) and the elderly
(under the age of)65 A subpopulation analysis was performed to evaluate the effect on safety of (aged and older), and
there was no constant tendency in the frequency of adverse events among the elderly.

However,75 Regarding the safety of elderly people over the age of this drug, the number of patients who received this drug is
small and there is insufficient information, and when it is widely used in patients with various background factors in clinical
practice, this drug is used. This is important information lacking because it may affect the benefit / risk balance of the patient.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets
Specific Use Results Survey "2 To examine and evaluate the safety profile when this drug is used in elderly people in "long-
term administration of type diabetes mellitus").

Details of risk reduction activities and reasons for their selection:

[Details]
As a normal risk mitigation activity, the package insert "9.8 In the section "Elderly" and the drug guide for patients

11
 Describe and call attention.
[Reason for selection]

Since it is considered necessary to provide information on proper use and promote understanding, we will provide information to
healthcare professionals through package inserts and information to patients through patient-oriented drug guides as normal risk
miniaturization activities. To do.

Impact on cardiovascular risk

Reasons for making important missing information:

When the frequency of cardiovascular adverse events * was examined in a domestic comparative study of this drug,CCT-001
test (12 Weekly) 50 mg Group expression frequency [5.9%(3/51 Example)] is the placebo group [0%(0/55 Although it was slightly
higher than [Example)], other group of this drug (Example)12.5 mg group:54 example,25 mg group:52 example,100 mggroup:
55 example,200 mg group:54 For example), it is about the same.CCT-002 test(twenty four Weekly) 100 mgGroup expression
frequency [5.9%(6/101 Example)] is a placebo group [8.0%(4/50 Example)] was about the same.3003In the test, this drug 25 mg
of 12 Frequency of occurrence in the weekly administration group [3.6%(2/55 Example)] is a placebo group [1.9%(1/52 Example)]
was about the same. Vital signs, electrocardiography and lipid metabolism markers, as well as the frequency of adverse events
associated with them, were similar to those in the placebo group.

Based on the above, no cardiovascular risk has been observed with this drug at this time, but cardiovascular risk is generally
high in diabetic patients, and cardiovascular risk is an important consideration in the treatment of diabetes with oral
hypoglycemic agents. Since there is a lack of information in long-term use cases, it was regarded as important missing
information.

*: Cardiovascular adverse eventsSMQ It was defined as all the basic terms that correspond to a wide range of "myocardial infarction" or

"central nervous system bleeding and cerebrovascular disease" in.

Contents of Pharmacovigilance Monitoring Activities and Reasons for Selection:

[Details]
--- Normal drug safety monitoring activities
--- As an additional drug safety monitoring activity, Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type
diabetes "is carried out.

[Reason for selection]

Ordinary Pharmacovigilance Monitoring Activities and Additional Pharmacovigilance Monitoring Activities (Zafatec Tablets Specific Use
Results Survey "2 To collect and evaluate information such as the incidence, severity, and outline of cases of cardiovascular adverse
events in "long-term administration of type diabetes").

Details of risk reduction activities and reasons for their selection:

[Details]
none
[Reason for selection]

At present, there is no noteworthy content of caution, and if new information is obtained, it will be considered.

1.2 Effectiveness considerations

Effectiveness during long-term administration under actual conditions of use

Reasons for consideration regarding effectiveness:

Under the actual usage of daily medical care 2 To investigate the efficacy of this drug during long-term administration in patients with type diabetes.

The data obtained by the time of initial approval regarding the efficacy of this drug during long-term administration are as follows.3 Phase single

long-term administration or combined long-term administration study (OCT-001 test)[680 Examples (single administration example, sulfonylurea

drug combination example, fast-acting insulin secretagogue combination example, α-glucosidase inhibitor combination example, biguanide drug

combination example, thiazolidine system combination example, respectively 248 example,158 example,67 example,65 example,70 Example and 72

example),52 Weekly] only.

A clinical trial in combination with an insulin drug conducted as a post-marketing clinical trial (CCT-101 Test)52 Weekly
combination example 116 For example, insulin preparation alone group (12 Combined use of this drug (weekly)40 Weekly)

12
 Group 124 Efficacy data are available for long-term administration of the example.

In addition, it is complicated by severe renal dysfunction or end-stage renal failure. 2 Clinical trials for patients with type diabetes (3003Test)25 mg of

52 Weekly administration example 55 example,40 Weekly administration example 48 Efficacy data are available for long-term administration of the

example.

Name of efficacy study / study:

Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type diabetes "

Outline of survey / test purpose, content and method, and reason for selection:

It also collects information on efficacy in specific drug use-results surveys. Detail is"2. See "Summary of Pharmacovigilance
Monitoring Plan" section.

13
2. Overview of Pharmacovigilance Monitoring Plan

Normal drug safety monitoring activities

Overview of regular pharmacovigilance monitoring activities:

Collect, evaluate, and analyze voluntary reports, literature / academic information, and information on foreign measures, and consider and
implement safety measures based on the results.

Additional Pharmacovigilance Monitoring Activities

Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type diabetes "

[Safety considerations]
Hypoglycemia, skin disorders, acute pancreatitis,QT / QTc Arrhythmia associated with prolonged interval, intestinal obstruction, infection, malignant

tumor, events related to overdose / overdose, pemphigoid, safety at the time of administration to patients with renal dysfunction, at the time of

administration to patients with hepatic dysfunction Safety, safety when administered to the elderly, impact on cardiovascular risk

【Purpose】

Under the actual usage of daily medical care 2 The safety and efficacy of this drug during long-term administration to patients with type diabetes will

be investigated.

[Implementation plan]

Investigation period:2016 Year Five Mon ~2021 Year Ten Month 31 Day Patient registration

period:2016 Year Five Mon ~2018 Year Ten Month 31 Scheduled number of cases per day:

3,000 example

Implementation method: Implemented by the central registration method. The observation period is36 Months

[Basis for implementation plan]

2 Diabetes mellitus drugs are likely to be used for a long period of time under the actual usage of daily medical care. Therefore, in order
to examine the safety and efficacy of long-term administration of this drug under the actual conditions of daily medical use, an
observation period3 Scheduled number of cases per year 3,000 Set as an example.3,000 By accumulating examples0.1%Side effects that
occur with the above frequency 95%It is possible to detect with the probability of.

In addition, it is currently being implemented DPP-4 Among the specific drug use-results surveys for Nessina tablets, which are
inhibitors, "single administration / α-GI "Combination", "Thiazolidine-based drug combination", "Sulfonylurea-based drug combination",
"Biguanide-based drug combination" 2015 Year Four Month 15 Cases subject to safety evaluation as of the date 6,734 For example, the
elderly are 52.5%, Patients with renal dysfunction 54.4%, For patients with liver dysfunction 17.8%Met. The planned number of cases in
this survey3,000 By setting as an example, about as an elderly person 1,600 For example, as a patient with renal dysfunction 1,600 For
example, as a patient with liver dysfunction 500 Expected to collect examples. This setting is not based on statistical grounds.

[Time and grounds for the milestone]

During regular safety reports: To conduct a comprehensive review of safety information.

At the time of interim tabulation: Observation period of all cases 1 After a year has passed, an interim report will be prepared and an interim report will be prepared.

hand over.
At the time of final tabulation after the completion of the survey: The final tabulation is carried out when the observation period of all cases is completed and the data is fixed.

Then, prepare and submit the final report.

[Additional measures that may be implemented based on the results of the drug safety monitoring activities and their start
Criteria for determining

At the turning point, the drug risk management plan will be reviewed based on the following contents.

--- When new findings are found regarding safety considerations, the necessity of changing the risk reduction plan such
as revision of the package insert will be examined.

--- Consider the necessity of formulating a risk reduction plan and adding / changing the contents of drug safety monitoring activities,
including the existence of new safety considerations.

14
Zafatec lock 25 mg Specific drug use-results survey "Combined with severe renal dysfunction or end-stage renal failure 2 Survey on long-term
use in people with type diabetes "

[Safety considerations]
Safety when administered to patients with hypoglycemia, infectious diseases, and renal dysfunction

[Purpose]

Complicated with severe renal dysfunction or end-stage renal failure under the actual usage of daily medical care 2 This drug for patients with type

diabetes 25 mg Consider the safety of the product during long-term use.

[Implementation plan]

Investigation period:2020 Year 3 Mon ~2023 Year 1 Month 31 Day Patient

registration period:2020 Year 3 Mon ~2021 Year 9 Month 30 Scheduled number

of cases per day:85example

Implementation method: Implemented by the central registration method. The observation period is12 For months.

[Basis for implementation plan]

Do not have severe renal dysfunction 2 Specific drug use-results survey for patients with type diabetes "2 Long-term administration of
type diabetes mellitus is underway.

1 Day 1 Of multiple doses DPP-4 In the inhibitor Nessina tablets (alogliptin benzoate),2 Cases subject to
safety evaluation collected from specific drug use-results surveys of patients with type diabetes 7,628
For example, severe renal dysfunction (eGFR<30 mL / min / 1.73m2) 113 It was an example.
Complicated with severe renal dysfunction 2 This drug for patients with type diabetes under the actual conditions of daily medical use 25
mg In order to examine the safety of long-term administration, the frequency of adverse drug reactions and the specific use outcome
survey in this study2 Compare and evaluate the frequency of side effects in "long-term administration of type diabetes". In addition,
safety information will be collected and evaluated for the same number of cases with severe renal dysfunction accumulated in the specific
drug use-results survey of Nessina tablets. In these evaluations, cases of hypoglycemia, which is an important identified risk of this drug,
and infectious diseases, which are an important potential risk, are present or not, and if they occur, the time of onset and severity.
Evaluate the overview.

Considering the number of patients with severe renal dysfunction and feasibility accumulated in the specific drug use-results survey of
Nessina tablets as the planned number of cases required for the above examination. 85 For example, the observation period 12 A
monthly specific drug use-results survey was planned.

[Time and grounds for the milestone]

During regular safety reports: To conduct a comprehensive review of safety information.

Survey completed 8 Months later (at the time of report preparation): After fixing the data of all registered cases, aggregate the data and prepare the report.

Create and submit.

[Additional measures that may be implemented based on the results of the drug safety monitoring activities and their start
Criteria for determining

At the turning point, we will review the drug risk management plan including the following contents.

--- Risks such as revision of package inserts when new findings are found regarding safety considerations
Consider whether or not the miniaturization plan needs to be changed.

--- We will consider whether or not it is necessary to change the plan contents of this survey, including the existence of new safety considerations.

15
3. Outline of efficacy survey / test plan

Zafatec Tablets Specific Use Results Survey "2 Long-term administration of type diabetes "

[Considerations regarding effectiveness]

Efficacy at long-term administration

Administration of this drug 36 Up to a month later HbA1c The inspection value and the amount of change of the above are totaled. In addition,

the test values and changes in fasting blood sugar, fasting insulin, etc. are totaled.

16
Four. Overview of risk minimization plan

Normal risk minimization activities

Overview of normal risk mitigation activities:

Information and alerts will be provided through the package insert and the drug guide for patients.

Additional risk minimization activities

Materials for patients [Patients taking Zafatec tablets (patient medication precautions: hypoglycemia) and patients
taking Zafatec tablets (patient medication precautions: events related to overdose / overdose) ] Creation and
provision

[Safety considerations]
Events related to hypoglycemia, overdose / overdose

【Purpose】

--- Hypoglycemia
Promote patients' understanding of hypoglycemia, prevent the onset of hypoglycemia, and provide
information on what to do when it does occur.

--- Events related to overdose / overdose

Promote the patient's understanding of the dosage and administration and precautions related to the dosage and administration, and

prevent overdose.

[Specific method]
Provide and explain to healthcare professionals at the time of delivery, and request the use and distribution of medication to

patients. [Further measures that may be adopted based on the planned milestone and the results of implementation]

At the time of regular safety reports, check the distribution status of materials and the reporting status of hypoglycemia and overdose. If it is judged

from this result that further strengthening of risk reduction activities is necessary, we will consider revising materials, changing the implementation

method such as distribution method, and creating additional materials.

Scheduled reporting time: At the time of regular safety reporting

Preparation and provision of materials for healthcare professionals [to patients taking Zafatec tablets (patient explanation
materials: events related to overdose / overdose)]

[Safety considerations]
Events related to overdose / overdose
【Purpose】

By informing healthcare professionals about the dosage and administration and precautions related to the dosage and administration, the patient's understanding

will be promoted and overdose will be prevented.

[Specific method]
It is requested that the patient be provided and explained to the medical staff at the time of delivery, and presented and explained at the time of medication instruction to the

patient.

[Further measures that may be adopted based on the planned milestone and the results of implementation]

At the time of regular safety reports, check the distribution status of materials and the reporting status of overdose. From this result, the risk

If it is judged that further strengthening of miniaturization activities is necessary, consider revising materials, changing the implementation method such as

distribution method, and creating additional materials.

Scheduled reporting time: At the time of regular safety reporting

17
Ingenuity in packaging form of this drug

[Safety considerations]
Events related to overdose / overdose
【Purpose】

By using a blister card as the packaging form for this drug, the timing of taking the drug and precautions for taking the drug will be
displayed to ensure proper use.

[Specific method]
At the time of delivery, we will provide and explain to the medical staff along with the above materials for patients and medical staff, and request that

they be used when instructing patients to take medication.

[Further measures that may be adopted based on the planned milestone and the results of implementation]

Confirm the reporting status of overdose at the time of regular safety reports. If it is judged from this result that further strengthening of
risk reduction activities is necessary, revision of the packaging form, etc. will be considered.

Scheduled reporting time: At the time of regular safety reporting

18
Five. List of Pharmacovigilance Monitoring Plans, Efficacy Survey / Test Plans and Risk Minimization Plans

5.1 List of Pharmacovigilance Monitoring Plans

Normal drug safety monitoring activities

Collect, evaluate, and analyze voluntary reports, literature / academic information, and information on foreign measures, and consider and
implement safety measures based on the results.

Additional Pharmacovigilance Monitoring Activities

Additional Pharmacovigilance Monitoring Cases that become milestones It will be a turning point Of the report
Implementation status
Number / target number of cases
Name of activity Scheduled time Scheduled creation date

Immediately after marketing survey Not applicable Sales start 6 Months end Created (created2016 Year 1

rear Monthly submission)

Zafatec lock specific use Target number of cases Regular safety report In progress

Grade survey "2 Diabetes mellitus 3,000 example

Time
Periodic administration "
At the time of interim aggregation Created (created2021 Year 6

Monthly submission)

At the time of final aggregation Cheap after the final tabulation

At the time of regular report

Submit to

Combination with insulin preparation Target number of cases When the analysis result is known end Created (created2018 Year 1

Clinical trial 250 example

Monthly submission)

Zafatec lock 25 mg Special Target number of cases Regular safety report In progress

Regular use result survey "advanced kidney

85example
Time
Dysfunction or end-stage renal disease
Survey completed 8 Months Survey completed 8 Months later
To merge 2 Diabetes mellitus
After (report writing (Report preparation
Regarding long-term use by people
Time) Time)
Research"

5.2. List of efficacy study / test plans

Survey / trial on effectiveness Cases that become milestones It will be a turning point Of the report
Implementation status
Test name Number / target number of cases
Scheduled time Scheduled creation date

Zafatec lock specific use Target number of cases At the time of final aggregation In progress Cheap after the final tabulation

Grade survey "2 Diabetes mellitus 3,000 example

At the time of regular report

Periodic administration " Submit to

Combination with insulin preparation Target number of cases When the analysis result is known end Created (created2018 Year 1

Clinical trial 250 example

Monthly submission)

19
5.3 5.3 List of risk minimization plans

Normal risk minimization activities

Information and alerts will be provided through the package insert and the drug guide for patients.

Additional risk minimization activities

Name of additional risk minimization activity Time to be a turning point Implementation status

Providing information through a survey immediately after marketing Sales start 6 Months later end
Materials for patients [Patients taking Zafatec tablets (patient At the time of regular safety report In progress

medication precautions: hypoglycemia) and patients taking

Zafatec tablets (patient medication precautions: events
related to overdose / overdose)] Creation and provision of

Preparation and provision of materials for healthcare At the time of regular safety report In progress

professionals [to patients taking Zafatec tablets (patient

explanation materials: events related to overdose / overdose)]

Ingenuity in packaging form of this drug At the time of regular safety report In progress

20