Duphaston® Tablets 5 mg - A Survey on Efficacy and Safety in Patients With Endometriosis
Conditions: Endometriosis
Sponsor: Mylan Inc.

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TITLE PAGE 
MYLAN 
POST MARKETING OBSERVATIONAL STUDY 
PROTOCOL (DUPKST16002) 
A SURVEY ON EFFICACY AND SAFETY IN PATIENTS                             
WITH ENDOMETRIOSIS  
Product Name: 
Duphaston 
Type of Study: 
Observational 
Date: 
May 31, 2016 
CRO(s): (if applicable) 
Name  
Address 
Phone:   
Fax:   
Biometrics: (if applicable) 
Name  
Address 
Phone 
Fax 
Sponsor 
Mylan 
 
 
 
 
 
 
This study will be conducted in compliance with this protocol. 
Confidential Information 
No use or disclosure outside Mylan is permitted without prior written authorization from 
Mylan. 
 
 

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TABLE OF CONTENTS 
TITLE PAGE 
1 
TABLE OF CONTENTS 
2 
1 
INTRODUCTION 
3 
2 
RATIONALE 
3 
3 
STUDY OBJECTIVE 
3 
4 
INVESTIGATIONAL PLAN 
4 
4.1 
Selection of Study Population 
4 
4.1.1 
Inclusion Criteria 
4 
4.1.2 
Exclusion Criteria 
4 
4.2 
Number of Patients to be Enrolled 
5 
4.3 
Investigator Selection Criteria 
5 
4.4 
Study Duration 
5 
4.5 
Study Conduct 
6 
4.5.1 
Product Supply 
6 
4.5.2 
Description of Activities 
6 
5 
ADVERSE EVENTS 
9 
5.1 
Adverse Event Definition and Serious Adverse Event Categories 
9 
5.2 
Severity 
11 
5.3 
Relationship to Pharmaceutical Product 
11 
5.4 
Serious Adverse Event Collection Period 
11 
5.5 
Serious Adverse Event Reporting 
11 
6 
ETHICS AND QUALITY 
12 
7 
CASE REPORT FORMS 
13 
8 
DATA ANALYSIS PLANS 
17 
9 
FINAL REPORT AND PUBLICATIONS 
18 
10 
REFERENCES 
19 
 
 

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1 
INTRODUCTION 
Duphaston® Tablets have been used over a half century for the treatment of a wide range of 
indications in the field of gynecology and obstetrics, such as threatened miscarriage, habitual 
miscarriage, amenorrhea, irregular menstrual cycles (oligomenorrhea and hypermenorrhea), 
dysmenorrhea, dysfunctional uterine bleeding, infertility due to luteal insufficiency, endometriosis and 
so on, because the drug creates secretory endometrium similar to that by natural progesterone, exerts a 
potent effect to maintain pregnancy, forms a normal secretory endometrium, and has no effect to inhibit 
ovulation or elevate body temperature. As of April 30, 2010, Duphaston is approved overseas in 108 
countries worldwide for various indications related to progesterone deficiency. 
 
2 
RATIONALE 
In Japan, Duphaston® Tablets have appeared in 1965 for the treatment of endometriosis and been 
used at some medical institutions. However, after releasing of danazol in the early 1980’s and 
gonadotropin-releasing hormone (GnRH) agonists in the late 1980’s, pseudomenopause therapy 
became mainstream because of its high efficacy. However, pseudopregnancy therapy was recognized 
again due to adverse reactions associated with pseudomenopause therapy. After 2000, low-dose 
estrogen/progestin (LEP) combination drugs (as LEP products, ethinylestradiol/norethisterone 
combination drug and ethinylestradiol/drospirenone combination drug) and dienogest have been 
utilized as drugs that are safer and can be administered for a long time. In recent years, Duphaston® 
Tablets are increasing recognized again from the viewpoints of its efficacy and safety because the drug 
has no effect to inhibit ovulation or effect on basal body temperature, a diagnosis of ovulation and other 
conditions may be made by following up basal body temperature, and pregnancy may be achieved even 
during treatment with Duphaston1). As previously mentioned, Duphaston® Tablets are an old drug, and 
there are only few clinical data from Japanese patients; thus, its latest clinical efficacy and safety data 
are being demanded again mainly by obstetrician-gynecologists. 
 
3 
STUDY OBJECTIVE 
This survey is intended to collect efficacy and safety data of Duphaston® Tablets in patients with 
endometriosis under actual condition of its use and to obtain data for effectively and safely utilizing 
this drug. These evaluation and test results are assumed to provide useful information for assessing the 
contemporary significance of treatment with Duphaston® Tablets for endometriosis, ensuring the risk 
management (benefit-risk ratio) in patients treated with the drug and eventually examining disease 
control from the viewpoint of medical economy. 
 

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4 
INVESTIGATIONAL PLAN 
 
4.1 
Selection of Study Population 
 
4.1.1 
Inclusion Criteria 
The subjects of the survey will be patients with a diagnosis of “endometriosis,” an indication of 
Duphaston® Tablets, who meet the following inclusion criteria. 
(1) Women aged 20 to < 50 years 
(2) Subjects with a chocolate cyst of the ovary measuring  3 cm in diameter on transvaginal 
ultrasonography at patient enrollment 
(3) Subjects with a menstrual cycle of 25 to  38 days who ovulate and are confirmed to have normal 
menstruation at patient enrollment 
 
4.1.2 
Exclusion Criteria 
Subjects corresponding to those who are listed in the CONTRAINDICATIONS or PRECAUTIONS 
Sections for Duphaston® Tablets as well as patients meeting the following exclusion criteria will not 
be included in the subjects of the survey. 
(1) Subjects who used GnRH agonists within 6 months before patient enrollment 
(2) Subjects who utilized hormone preparations containing corpus luteum hormone or estrogen as an 
active ingredient, low-dose contraceptive pills, middle-dose contraceptive pills, testosterone 
derivatives, or herbal products indicated for endometriosis within 3 months before patient 
enrollment 
(3) Subjects who received surgical treatment for endometriosis such as transvaginal alcohol fixation, 
laparotomy or laparoscopic surgery within 2 months before patient enrollment 
(4) Subjects who are pregnant or may possibly be pregnant at patient enrollment 
(5) Subjects who are in breast feeding at patient enrollment 
(6) Subjects who are determined by the investigator/subinvestigator to be not suitable for the subjects 
of the survey because of other reasons 

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[CONTRAINDICATIONS] 
(1) Subjects with serious liver disorder or liver disease 
(2) Subjects with known hypersensitivity to the active substance or to any of the excipients 
(3) Subjects with known or suspected progestogen dependent neoplasms (e.g. meningioma) 
(4) Subjects with undiagnosed vaginal bleeding 
[PRECAUTIONS] 
Careful Administration 
(1) Subjects with a past or current history of heart or kidney disease 
(2) Subjects with liver disorder 
(3) Subjects with porphyria 
(4) Subjects with depression 
(5) Subjects with abnormal liver function values caused by acute or chronic liver disease 
(6) Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or 
glucosegalactose malabsorption 
 
4.2 
Number of Patients to be Enrolled 
Planned sample size of the survey: 65 patients 
Rationale for setting: 
Whether or not the size of chocolate cyst of the ovary reduced at the end of treatment from baseline 
will be evaluated using a sign test. When anticipated results would be a decrease-increase ratio of 7:3 
and 10% of all patients being unchanged, a sample size was calculated to be 58 patients. Assuming a 
dropout rate of 10%, a necessary sample size of the survey would be 65 patients. 
 
4.3 
Investigator Selection Criteria 
The survey will be conducted at approximately 12 sites including the department of gynecology and 
obstetrics, department of obstetrics, and department of gynecology. 

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4.4 
Study Duration 
Planned survey period: 
June 2016 to October 2017 
Patient registration period: 
June 2016 to April 2017 
 
4.5 
Study Conduct 
 
4.5.1 
Product Supply 
This study does not provide the product to perform it under the medical service under health 
insurance actual situation. 
[DOSAGE AND ADMINISTRATION] 
Usually for adults, 5 to 15 mg (1 to 3 tablets) as dydrogesterone per day should be orally 
administered in 1 to 3 divided doses. For endometriosis, 5 to 20 mg (1 to 4 tablets) per day should be 
orally administered. 
<Recommended regimen> 
In this survey, the following regimen is recommended: 
Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the 
morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each 
menstrual cycle until 25th day. 
 
4.5.2 
Description of Activities 
(1) Request and contract for the survey 
The survey will be performed at medical institutions where Duphaston is used and supplied. Survey 
personnel of Mylan EPD G.K. will provide an investigator/subinvestigator at the applicable medical 
institution with an adequate explanation on the objectives, subjects and methods of the survey. If the 
investigator/subinvestigator accepted to take part in the survey, Survey personnel of Mylan EPD G.K. 
shall take procedures for a contract. The contract shall be concluded in writing between the head of the 
medical institution and the person requesting the survey in Mylan EPD G.K. 

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(2) Survey method 
This survey will be carried out using a central registration method and an electronic data capture 
(EDC) system. EDC system establishment and management are outsourced to Starsphere K.K. 
(3) Registration method 
(i) The investigator/subinvestigator will explain the details of the survey to a patient, obtain oral 
consent for participation in the survey from the patient, and record such a fact. The consent may 
be withdrawn at any time whether or not the survey has been undertaken. 
(ii) In order to secure data entries and protect access, the investigator/subinvestigator will enter the 
name of an individual user and password to log in, and then make “patient registration” in the 
EDC system. 
(iii) The patient should be registered within 14 days after the start of Duphaston treatment. 
(iv) Information listed in Table 1 should be entered in the EDC system to register the patient. 
(4) Cycle and observation period 
(i) One cycle will consist of one menstruation cycle. 
(ii) The observation period will be from the start of Duphaston treatment (cycle 1) to cycle 4. 
(5) Input of patient information 
The investigator/subinvestigator will enter information on all registered patients in the EDC system 
before the start of treatment, at the start of treatment (cycle 1), cycle 3 and after the completion of the 
observation period. If the treatment is discontinued, the investigator/subinvestigator will input 
information until the end day of treatment in the EDC system. 

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Table 1 List of Registration Items, Endpoints and Observation Time Points/Cycles 
 
Registration Form/Case Report Form 
Registration 
Form 
Case Report Form 
Observation time points/cycles 
At 
enrollment 
Before 
treatment 
initiation 
At 
treatment 
initiation 
(cycle 1) 
Cycle 2 
Cycle 3 
Cycle 4 
At the end of 
the observation 
period or at 
discontinuation 
Registration information 
 
 
 
 
 
 
 
(1) Subject identification No. 
 
 
 
 
 
 
 
(2) Subject initials 
 
 
 
 
 
 
 
(3) Birth date or age 
 
 
 
 
 
 
 
(4) Planned start date of treatment 
 
 
 
 
 
 
 
(5) Oral consent 
 
 
 
 
 
 
 
Patient background characteristics 
 
 
 
 
 
 
 
(1) Diagnosis 
 
 
 
 
 
 
 
(2) Body height and weight 
 
 
 
 
 
 
 
(3) Pregnancy and lactation status 
 
 
 
 
 
 
 
(4) Menstruation and ovulation status 
 
 
 
 
 
 
 
(5) Complications 
 
 
 
 
 
 
 
(6) Past history 
 
 
 
 
 
 
 
(7) History of allergy 
 
 
 
 
 
 
 
(8) Serious hepatopathy or liver 
disease 
 
 
 
 
 
 
 
(9) Heart or kidney disease 
 
 
 
 
 
 
 
(10) History of drug treatment 
 
 
 
 
 
 
 
(11) History of surgical treatment 
 
 
 
 
 
 
 
Treatment compliance, clinical 
course and efficacy 
 
 
 
 
 
 
 
(1) Observation date (date of 
confirmation) 
 
 
 
 
 
 
 
(2) Start date of treatment 
 
 
 
 
 
 
 
(3) Compliance with Duphaston 
treatment 
 
 
 
 
 
 
 
(4) Measurement of ovarian 
chocolate cyst 
 
 
 
 
 
 
 
(5) Severity of dysmenorrhea 
 
 
 
 
 
 
 
(6) Use of analgesics 
 
 
 
 
 
 
 
(7) VAS for dysmenorrhea 
 
 
 
 
 
 
 
(8) Concomitant 
medications/therapies 
 
 
 
 
 
 
 
(9) Date of withdrawal/dropout and 
its reason 
 
 
 
 
 
 
 
Laboratory tests 
 
 
 
 
 
 
 
(1) Serum CA125 
 
 
 
 
 
 
 
(2) Others 
 
 
 
 
 
 
Adverse events 
 
 
 
 
 
 
 
Adverse events 
 
 
 
 
 
 
 
One cycle will consist of one menstruation cycle. 
Each endpoint will be observed in cycles marked with a symbol. Observation results should be entered in the EDC system. 
: Endpoint  
: Investigate information on the next observation day, and enter it. 
: Perform the test during a non-menstruation period. 
: Enter information if observed. 
 
 

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5 
ADVERSE EVENTS 
 
5.1 
Adverse Event Definition and Serious Adverse Event Categories 
An adverse event (AE) is defined as any untoward medical occurrence in a patient administered a 
medicinal product, which does not necessarily have a causal relationship with this treatment.  An 
adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not the event is considered causally related to the use of the product. 
Adverse reactions are defined as a response to a medicinal product which is noxious and 
unintended. A 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 authorization or from occupational exposure. 
Conditions of use outside the marketing authorization include off-label use, overdose, misuse, abuse 
and medication errors.  
Other pharmacovigilance relevant information is defined by the following. 
 Intrauterine exposure (         weeks of gestation) 
 Lactational exposure 
 Overdose 
 Misuse 
 Abuse 
 Medication error 
 Unexpected treatment effect 
 Ineffectiveness 
 Suspected pathogen infection to the drug 
 Off-label use 
 Occupational exposure 
 
 

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If an adverse event meets any of the following criteria, it is considered a serious adverse event 
(SAE): 
Death of Subject: 
An event that results in the death of a subject. 
Life-Threatening: 
An event 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. 
Hospitalization: 
An event that results in an admission to the hospital 
for any length of time.  This does not include an 
emergency room visit or admission to an outpatient 
facility. 
Prolongation of Hospitalization: An event that occurs while the study subject is 
hospitalized and prolongs the subject's hospital stay. 
Congenital Anomaly: 
An anomaly detected at or after birth, or any anomaly 
that results in fetal loss. 
Persistent or Significant  
  Disability/Incapacity: 
An event that results in a condition that substantially 
interferes with the activities of daily living of a study 
subject.  Disability is not intended to include 
experiences of relatively minor medical significance 
such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained 
ankle). 
Important Medical Event  
  Requiring Medical or Surgical  
  Intervention to Prevent  
  Serious Outcome: 
An important medical event that may not be 
immediately life-threatening or result in death or 
hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or 
surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, 
hospitalization, prolongation of hospitalization, 
congenital anomaly, or persistent or significant 
disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an 
important medical event.  Examples of such events 
include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
 

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5.2 
Severity 
The physician will use the following definitions to rate the severity for any adverse event being 
collected as an endpoint/data point in the study and for all serious adverse events. 
Mild: 
The adverse event is transient and easily tolerated by the subject. 
Moderate: 
The adverse event causes the subject discomfort and interrupts the 
subject's usual activities. 
Severe: 
The adverse event causes considerable interference with the subject's 
usual activities and may be incapacitating or life threatening. 
 
5.3 
Relationship to Pharmaceutical Product 
The investigator will use the following definitions to assess the relationship of the adverse event to 
the use of study drug: 
Reasonable 
Possibility 
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event. 
No Reasonable 
Possibility 
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event. 
 
If an investigator's opinion of no reasonable possibility of being related to study drug is given, an 
alternate etiology must be provided by the investigator for the adverse event. 
5.4 
All Adverse Events ( including Serious Adverse Event ) and Other 
Pharmacovigilance Relevant Information Collection Period 
All adverse events and other pharmacovigilance relevant information during the survey will be 
collected during a period from the start of Duphaston treatment to the end of the observation period 
or discontinuation. All adverse events and other pharmacovigilance relevant information entered in 
the EDC system. 
5.5 
All Adverse Events ( including Serious Adverse Event ) and Other 
Pharmacovigilance Relevant Information Reporting 
If all adverse events and other pharmacovigilance relevant information occurred, the investigator 
should enter in the EDC system. And the investigator has to report the form “notification of Adverse 
events” to the Affiliate Safety Representatives within 24 hours of becoming aware.    
 
 

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Affiliate Safety Representatives: 
Safety Management Implementation Manager: Takao Miki 
Address: 3-5-27 Mita, Minato-ku, Tokyo 108-6306 
Tel: 03-4588-4492; Fax: 03-4588-4494 
 
6 
ETHICS AND QUALITY 
(1) Ethics committee 
    This survey will be approved by the ethics committee of the medical institution. 
(2) Registration of the Survey 
This survey will be registered in the Clinical Trials.gov.  
(3) Protocol revision 
If new evidence is obtained during the period of the survey, the necessity for revising the protocol 
should be examined and, as necessary, revised. Also, when approval for partial changes in the dosage 
and administration or indications (excluding the case where a new reexamination period is designated) 
is received, the necessity for revising the protocol should be examined and, as necessary, revised. 
(4) Measures when problems or questions arise 
In the below mentioned cases, in order to detect or evaluate these factors and to demonstrate 
estimates made from the results of evaluation, the implementation of a new special drug use-results 
survey and/or postmarketing clinical study should be considered: 
(i) When significant safety concerns such as the onset of serious and unknown ADRs are 
suggested 
(ii) When the incidence of ADRs clearly increased 
(iii) When any safety and efficacy problems as compared with pre-approval study results are 
identified 
(5) Handling of information 
(i) Information obtained from the survey shall be carefully managed based on the Personal 
Information Protection Law as paying full consideration to the sources of information and 
the privacy of patients. 

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(ii) Cases of ADRs reported which are notified to the Ministry of Health, Labour and Welfare 
may be disclosed as reported cases on the “Pharmaceuticals and Medical Devices Agency 
Homepage” of the Pharmaceuticals and Medical Devices Agency. 
(6) Others 
(i) Mylan EPD G.K. will pay expenses (expenses for the survey, management costs and overhead 
costs) for conducting the survey. 
(ii) No person except for the investigators/subinvestigators may be involved in information 
obtained through the implementation of the survey because the EDC system will be used. 
(iii) Data management and statistical analysis activities in the survey will be outsourced to third-
party agencies specified in the Section “10. Name and Address of the Person to Whom the 
Activities Are Outsources, and Scope of the Outsourced Activities.” 
(iv) The conflict of interest in the survey will be properly managed to maintain fairness. 
 
7 
CASE REPORT FORMS 
The following items (see Table 1) will be investigated and entered in the EDC system. 
(1) Patient background characteristics 
(i) Diagnosis, (ii) body height and weight, (iii) pregnancy and lactation status, (iv) menstruation 
and ovulation status, (v) complications, (vi) past history, (vii) history of allergy, (viii) serious 
hepatopathy or liver disease, (ix) heart or kidney disease, (x) history of drug treatment, (xi) 
history of surgical treatment 
(2) Treatment compliance, clinical course and efficacy 
(i) 
Observation date 
 Observation days will be before the start of treatment, at the start of treatment 
(cycle 1), cycle 3 and at the completion of the observation period or at 
discontinuation. 
(ii) Start date of treatment 
(iii) Compliance with Duphaston treatment 
 Verification of continuation 

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 Presence or absence of treatment interruption and the number of days of treatment 
interruption per cycle (approximate) 
 Presence or absence of missed doses and the number of days with missed doses 
(approximate) 
(iv) Measurement of ovarian chocolate cyst 
 An ovarian chocolate cyst will be measured when a patient makes visits before the 
start of treatment, immediately after the end of cycle 3 and at the completion of the 
observation period or at discontinuation. 
 In measurement of ovarian chocolate cyst, on a section visualizing the maximum 
diameter, two radial directions, namely the maximum diameter (D1) and maximum 
diameter (D2) orthogonal to D1, will be measured. Measured values (cm) will be 
rounded off to one decimal place and inputted. 
 A chocolate cyst of the ovary will be deemed as a spheroid, and its volume will be 
calculated using the following formula: [(D1 + D2) × 1/2]3 × 0.52 (π = 3.1). The 
volume will be rounded off to one decimal place. 
 If there are two or more chocolate cysts of the ovary, similarly, two radial 
directions (D1 and D2) of each cyst will be measured and entered. Also, each of 
their volumes will be calculated in the same manner. 
 When the directions of measurements before the start of treatment, cycle 3 and at 
the completion of the observation period or at treatment discontinuation vary 
because of reasons such as a chocolate cyst of the ovary cannot be clearly 
identified, the reason will be entered in the column for comments. 
 For a chocolate cyst of the ovary newly confirmed during the treatment period, 
whether it is a cyst that has not been accidentally measured before treatment 
initiation or a new cyst will be inputted in the column for comments. 
 For a chocolate cyst of the ovary that becomes difficult to identify during the 
treatment period, such a fact and its number will be entered in the column for 
comments. 
(v) Severity of dysmenorrhea (dysmenorrhea severity score) 
 The severity of dysmenorrhea will be assessed in accordance with Table 2, and a 
score will be entered. A dysmenorrhea score2) will be calculated using a total of 
the recorded score and a score for the use of analgesics. 

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(vi) Use of analgesics (including over-the-counter drugs) for the treatment of dysmenorrhea 
(score for the use of analgesics) 
 The use of analgesics will be assessed in accordance with Table 3, and a score will 
be entered. A dysmenorrhea score will be calculated using a total of the recorded 
score and a dysmenorrhea severity score. 
(vii) Visual analogue scale (VAS) for dysmenorrhea 
 The VAS for dysmenorrhea will be assessed in accordance with Table 4. A length 
(cm) from the left end of the line (0) will be measured. 
Measured values (cm) will be rounded off to one decimal place and inputted. 
 
Table 2 Severity of dysmenorrhea 
Severity of 
dysmenorrhea 
Contents 
Score 
None 
None 
0 
Mild 
Rarely interfering with work (study and house work) 
1 
Moderate 
Interfering with work (study and house work) requiring lying 
down to rest 
2 
Severe 
Being confined to bed for  1 day, being unable to work (study 
and house work) 
3 
Table 3 Use of analgesics 
Use of 
analgesics 
Contents 
Score 
None 
None 
0 
Mild 
An analgesic was used for a day during the last (or current) 
menstruation period. 
1 
Moderate 
An analgesic was used for 2 days during the last (or current) 
menstruation period. 
2 
Severe 
An analgesic was used for  3 days during the last (or current) 
menstruation period. 
3 
Table 4 VAS for dysmenorrhea 
 
 
No pain 
Worst pain 
imaginable 
(Example) 
↓ 

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(viii) Concomitant medications/therapies (If “yes,” the name of a drug, daily dose, route of 
administration, reason for administration, start date of administration, end date of 
administration, name of concomitant therapy, reason for implementing concomitant 
therapy, start date of concomitant therapy, and end date of concomitant therapy will be 
inputted.) 
(ix) Date of withdrawal/dropout and its reason 
(3) Laboratory tests 
(i) 
Serum CA125 
 The test will be performed during a non-menstruation period, and the date of 
observation and test result will be entered. 
(ii) Others 
 If “yes” for other test items, observed details will be inputted. 
(4) Adverse events and other pharmacovigilance relevant information 
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory 
value), symptom, or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the drug. If an AE is noted, a follow-up investigation will be performed until it 
resolves whenever possible. AE information during the survey will be collected during a period from 
the start of Duphaston treatment to the end of the observation period or discontinuation. 
 
If an AE (including an abnormal laboratory value) occurred, the following information should be 
entered: 
 AE term 
 Date of onset of AE 
 Severity 
 Seriousness 
 Serious/non-serious 
 Outcome 
 Date of outcome 
 Causal relationship with Duphaston 
 Action for Duphaston 
 If an abnormal change in a laboratory value is noted, the applicable laboratory 
value 
 

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If other pharmacovigilance relevant information occurred, it should be entered.                        
Other pharmacovigilance relevant information is defined by the following. 
 Intrauterine exposure (         weeks of gestation) 
 Lactational exposure 
 Overdose 
   Misuse 
 Abuse 
 Medication error 
 Unexpected treatment effect 
 Ineffectiveness 
 Suspected pathogen infection to the drug 
 Off-label use 
 Occupational exposure 
 
8 
DATA ANALYSIS PLANS 
 
8.1       In principle, the following items will be summarized and analyzed  
(1) Matters concerning the disposition of patients 
 Number of patients enrolled and number of patients whose case report forms (CRFs) are 
completed 
 Numbers of patients analyzed for safety and efficacy 
 Number of patients excluded from analysis and reasons for exclusion 
 Date of withdrawal/dropout and their reasons 
(2) Matters concerning safety 
 Occurrence of AEs (e.g., types, severity and incidence of AEs) 
 Occurrence of adverse drug reactions (ADRs) (e.g., types, severity and incidence of ADRs)  
(3) Matters concerning efficacy 
 Change in the volume of ovarian chocolate cyst (If there are two or more cysts, a total volume) 

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 Change over time in dysmenorrhea score (total of a dysmenorrhea severity score and a score for 
the use of analgesics) 
 Change over time in VAS for dysmenorrhea 
 Change in serum CA125 
8.2       Analysis Methods  
Statistical analyses are outsourced to Densuke Systems Co., Ltd. 
Appropriate statistical procedures will be used according to the characteristics of the endpoint set. 
 
9 
FINAL REPORT AND PUBLICATIONS 
Information collected from this survey will be used to notify information on proper use. In addition, 
collected information will be examined by a committee composed of the representatives of the 
investigators/subinvestigators and presented in papers or at academic conferences regardless of the 
details of information collected. 
[Members composing the case review committee] 
(1) Name: Jo Kitawaki 
Affiliation: Professor, Department of Obstetrics and Gynecology, Kyoto Prefectural University of 
Medicine 
(2) Name: Mikio Momoeda 
Affiliation: Chief Director, Department of Integrated Women’s Health, St. Luke’s International 
Hospital 
(3) Name: Kaori Koga 
Affiliation: Associate Professor, Department of Obstetrics and Gynecology, Graduate School of 
Medicine and Faculty of Medicine, the University of Tokyo 
 

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10 
REFERENCES 
1) Mikio Momoeda. Treatment of dysmenorrhea associated with endometriosis (Chapter 8). 
Illustrated Series for Informed Consent. Iyaku Journal; 2015. p. 41-51. 
2) Harada T, Momoeda M, Taketani Y, et al.: Low-dose oral contraceptive pill for dysmenorrhea 
associated with endometriosis: A placebo-controlled, double-blind, randomized trial. Fertil Steril 
2008; 90: 1583-8. 

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MYLAN 
CLINICAL STUDY PROTOCOL (DUPKST16002) 
A SURVEY ON EFFICACY AND SAFETY IN PATIENTS                             
WITH ENDOMETRIOSIS 
 
 
APPROVED BY: 
 
Takumi Kanzo 
 
 
Protocol Author - Print Approver Name/Title Here 
 
Date 
Jun Kato 
 
 
Study-Designated Physician - Print Approver Name/Title Here 
 
Date 
Atsushi Imamura   
 
 
Statistics - Print Approver Name/Title Here 
 
Date 
Dima Martini 
 
 
Project Director - Print Approver Name/Title Here 
 
Date 
Eiko Soehlke 
 
 
PASS – Print Approver Name/Title Here 
 
Date