Clinical trial NCT05372653
Conditions: Atopic Dermatitis (AD)
Sponsor: Otsuka Pharmaceutical Co., Ltd.
Start date: 2022-05-23; Completion date: 2023-11-29
Enrollment: 41 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
To investigate the efficacy of 0.3% OPA-15406 ointment when administered twice daily for 4 weeks in infants younger than 2 years of age with Atopic Dermatitis

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: OPA-15406
Intervention descriptions: intervention 1: 0.3% or 1% ointment, topical, twice daily, for 52 weeks

Protocol documents:
Prot_SAP_000.pdf: 
Clinical Study Report 271-102-00016 
16.1.9 Documentation of Statistical Methods 
Protocol 271-102-00016 
Statistical Analysis Plan 
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Version: 2.0 Date:  26/01/2024 
 
Otsuka Pharmaceutical Co., Ltd. 
 
 
Investigational Medicinal Product OPA-15406 (difamilast) 
 
 
 
 
 
Protocol No. 271-102-00016 
 
 
 
A Phase 3, Multicenter, Open-labeled, Uncontrolled Trial to Evaluate the Efficacy and 
Safety of OPA-15406 Ointment in Infants Younger Than 2 Years of Age With Atopic 
Dermatitis 
 
A Long-term Trial of OPA-15406 in Infants With Atopic Dermatitis (Phase 3 Trial) 
 
STATISTICAL ANALYSIS PLAN 
 
VERSION: 2.0 
DATE OF PLAN: 26 Jan 2024 
Protocol first version preparation date: 24 Feb 2022 
 
 
 
 
 
 
 
 
 
 
 
Confidential 
 


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Table of Contents 
Table of Contents ........................................................................................... 2 
List of Appendices.......................................................................................... 5 
List of Abbreviations and Definition of Terms ........................................... 6 
1 
Introduction .......................................................................................... 7 
2 
Trial Objectives ..................................................................................... 7 
3 
Trial Design ........................................................................................... 7 
3.1 
Type/Design of Trial ...........................................................................................7 
3.2 
Dosing Methods ..................................................................................................9 
3.2.1 
Dose, Regimen, and Treatment Period .............................................................9 
3.2.2 
Dose Modification of the Investigational Medicinal Product .........................10 
3.2.2.1 
Dose Increase ..............................................................................................10 
3.2.2.2 
Dose Reduction ...........................................................................................10 
3.2.2.3 
Interruption (Treatment Interruption) .........................................................10 
3.2.2.4 
Restarting IMP Administration After Interruption .....................................11 
3.3 
Trial Population .................................................................................................11 
3.4 
Handling of Time Points ...................................................................................11 
3.5 
Handling of Endpoints.......................................................................................13 
3.5.1 
IGA Response .................................................................................................13 
3.5.2 
EASI Response (EASI 75, EASI 90, EASI 50) ..............................................13 
4 
Sample Size .......................................................................................... 13 
5 
Datasets for Analysis .......................................................................... 13 
5.1 
Efficacy Analysis Set ........................................................................................13 
5.2 
Safety Analysis Set ............................................................................................13 
5.3 
Pharmacokinetic Analysis Set ...........................................................................14 
5.4 
Handling of Missing Data .................................................................................14 
6 
Primary and Secondary Endpoints ................................................... 14 
6.1 
Primary Endpoint (Primary Assessment Part)...................................................14 
6.2 
Secondary Endpoints .........................................................................................14 
6.2.1 
Efficacy Endpoint ...........................................................................................14 
6.2.2 
Safety Endpoints .............................................................................................14 


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6.2.3 
Pharmacokinetic Endpoint ..............................................................................14 
7 
Subject Disposition and Demographic and Other Baseline 
Characteristics .................................................................................... 14 
7.1 
Subject Disposition............................................................................................15 
7.2 
Demographic and Other Baseline Characteristics .............................................15 
7.3 
Assessment of Baseline Conditions ..................................................................15 
7.4 
Treatment Compliance ......................................................................................16 
7.5 
Prior and Concomitant Medications ..................................................................16 
7.6 
Protocol Deviations ...........................................................................................16 
8 
Efficacy Analyses ................................................................................ 16 
8.1 
Primary Efficacy Endpoint Analysis .................................................................17 
8.2 
Key Secondary Efficacy Endpoint Analyses .....................................................17 
8.3 
Secondary Efficacy Endpoint Analysis .............................................................17 
8.4 
Subgroup Analyses ............................................................................................18 
8.5 
Exploratory or Other Analyses ..........................................................................19 
9 
Safety Analysis .................................................................................... 21 
9.1 
Extent of Exposure to Investigational Medicinal Product .................................21 
9.2 
Adverse Events ..................................................................................................22 
9.2.1 
Subgroup Analyses of Adverse Events ...........................................................23 
9.2.2 
Analyses of Adverse Events by Drug Concentration .....................................23 
9.3 
Clinical Laboratory Data ...................................................................................23 
9.4 
Vital Signs and Body Weight ............................................................................24 
9.5 
Physical Examination ........................................................................................24 
9.6 
Electrocardiogram Data .....................................................................................24 
9.7 
Other Safety Variables ......................................................................................24 
10 
Pharmacokinetic Analysis .................................................................. 24 
10.1 
OPA-15406 Plasma Concentrations ..................................................................24 
10.2 
Handling of Data ...............................................................................................25 
11 
Pharmacodynamic Analysis .............................................................. 26 
12 
Pharmacogenomic Analysis ............................................................... 26 
13 
Interim Analysis .................................................................................. 26 
14 
Changes from Planned Analysis Plan ............................................... 27 


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15 
References ............................................................................................ 27 
16 
Amendment History ........................................................................... 27 
 


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List of Appendices 
Appendix 1 
Criteria for Potential Hy's Law ..................................................... 31 
Appendix 2 
List of Tables and Figures............................................................. 32 
Appendix 3 
List of Subject Data Listings......................................................... 50 
 


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List of Abbreviations and Definition of Terms 
 
Abbreviation 
Definition 
ALT (GPT) 
Alanine aminotransferase 
AST (GOT) 
Aspartate aminotransferase 
BSA 
Body surface area 
CTCAE 
Common terminology criteria for adverse events 
EASI 
Eczema Area and Severity Index 
IGA 
Investigator’s Global Assessment 
MedDRA 
Medical Dictionary for Regulatory Activities ICH 
OC 
Observed cases 
POEM 
Patient-Oriented Eczema Measure 
TEAE 
Treatment-emergent adverse event 
 


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1 
Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the detailed analysis 
methods of the planned statistical analyses to be included in the Clinical Study Report 
(CSR) for Trial 271-102-00016. 
2 
Trial Objectives 
The objectives and endpoints of the trial are shown below. 
Table 2-1 
Trial Objectives and Endpoints 
Objectives 
Endpoints 
Primary objective: To investigate the 
efficacy of 0.3% OPA-15406 ointment 
when administered twice daily for 4 
weeks in infants younger than 2 years of 
age with AD 
Efficacy endpoint: 
• 
Success rate in Investigator’s Global Assessment 
(IGA)  
(Percentage of subjects with an IGA score of 0 or 1 
with improvement by at least 2 grades) 
Secondary objectives: This trial will be 
conducted in infants younger than 2 years 
of age with AD 
• 
To investigate the safety of 0.3% 
OPA-15406 ointment when 
administered twice daily for 4 weeks 
• 
To investigate the efficacy and safety 
of 0.3% or 1% OPA-15406 ointment 
when administered twice daily for 52 
weeks 
• 
To investigate the pharmacokinetics 
of 0.3% or 1% OPA-15406 ointment 
when administered twice daily for 4 
weeks 
Efficacy endpoints: 
• 
Response rate in Eczema Area and Severity Index 
(EASI) 90 (improvement of ≥90% in EASI), EASI 75 
(improvement of ≥75% in EASI) and EASI 50 
(improvement of ≥50% in EASI) 
• 
Change from baseline in IGA score 
• 
Percent change from baseline in the total score of 
EASI and each clinical sign score 
• 
Change from baseline in the total score of Patient-
Oriented Eczema Measure (POEM) 
• 
Change from baseline in the total affected body 
surface area (BSA) (%) 
Safety endpoints: 
• 
Adverse events (AEs) 
• 
Vital signs, body weight 
• 
Clinical laboratory tests 
Pharmacokinetic endpoint: 
• 
Plasma concentration of OPA-15406 
 
3 
Trial Design 
3.1 
Type/Design of Trial 
This trial is a phase 3, multicenter, open-label, uncontrolled trial to evaluate the efficacy 
and safety of OPA-15406 ointment in infants younger than 2 years of age with atopic 
dermatitis. 


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1) Screening period 
After obtaining informed consent from the subject’s legal guardian, the investigator 
or subinvestigator will perform the screening examination. The screening period is 
defined as the period between the day of screening examination and the day of 
baseline examination (2 - 30 days). 
2) IMP administration period 
The IMP administration period is defined as the period between the day of baseline 
examination and the end of Week 52 examination (or the end of withdrawal 
examination). The primary assessment part is defined as the period between the 
baseline examination and the Week 4 examination, and the long-term extension part 
is defined as the period between the Week 4 examination and the Week 52 
examination. Subjects who meet the inclusion and exclusion criteria at the baseline 
examination will be prescribed with the IMP. The IMP will be administered to the 
treatment area from the day of baseline examination twice daily for 52 weeks. If a 
subject discontinues the IMP administration between the day of baseline examination 
and the day of Week 52 examination, a withdrawal examination will be performed for 
that subject. 
3) Trial period 
The trial period for individual subjects is the period from the day of obtaining the 
written informed consent from the subject’s legal guardian to the day of the Week 52 
examination (or withdrawal examination). For subjects who missed the Week 52 
examination (or withdrawal examination), the day of discontinuation will be the day 
when the investigator or subinvestigator determined that the subject was to be 
withdrawn from the trial. It does not include the follow-up period for AEs. 


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Figure 3-1 
Trial Design Schematic 
 
3.2 
Dosing Methods 
3.2.1 
Dose, Regimen, and Treatment Period 
As the starting dose, 0.3% formulation will be administered twice daily (approximately 
12 hours apart between morning and night administrations) for 52 weeks. 
Primary Assessment Part (Baseline Through Week 4 Examination) 
• The 0.3% formulation will be administered twice daily for 4 weeks. 
• Even when the affected area is relieved, IMP administration should be continued 
there as the treatment area. 
 
Long-term Extension Part (Week 4 Examination through Week 52 Examination) 
• If subjects meet the dose increase criteria (see Section 3.2.2.1) at each 4-weekly 
assessment visit following the Week 4 examination, the 1% formulation will be used. 
• When subjects show an improvement in skin symptoms and use of the 1% 
formulation is considered unnecessary, the dosage can be reduced to the 0.3% 
formulation. As a general rule, formulation switching should be done after the 4-
weekly assessment (the formulation may be switched before the 4-weekly assessment 
if prompt dose reduction is required due to AEs or for other reasons). 
• If all skin symptoms have resolved, IMP administration may be suspended based on 
the judgment of the physician. If skin symptoms relapse after interruption, IMP 
administration will be restarted. 
同
意
取
得
ベ
 
ス
ラ
イ
ン
検
査
1
週
後
検
査
2
週
後
検
査
4
週
後
検
査・・・
 
週
後
検
査
スクリーニング期間（2～30日間）
治験薬投与期間（52週間）
【主要評価パート】
0.3%
OPA-15406軟膏
1日2回
【長期継続パート】*
0.3%又は1%
OPA-15406軟膏
1日2回
*長期継続パート（4週～52週後検査）
・4週ごとに来院し増量基準に従い1%製剤も使用可能
・1%製剤に初めて増量した被験者は1%製剤の投与開始後2週時に来院
52
Screening period (2 - 30 days) 
IMP administration period (52 weeks) 
[Primary assessment part] 
0.3% 
OPA-15406 ointment 
Twice daily 
[Long-term extension part]a 
0.3% or 1% 
OPA-15406 ointment 
Twice daily 
Informed consent
Baseline examination
Week 1 examination
Week 2 examination
Week 4 examination
Week 52 examination
aLong-term extension part (Week 4 - 52 examination) 
• Subjects are scheduled to visit every 4 weeks, and the use of 1% formulation is also acceptable in 
accordance with dose increase criteria. 
• Subjects whose dose is increased to 1% formulation for the first time are scheduled to visit 2 weeks 
after the start of 1% formulation administration. 


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The amount of IMP (g) per dose is 10 g/m2 BSA, which is calculated as follows. 
1) The subject’s BSA (m2) will be calculated based on height and body weight at 
each examination, using the following equation. 
 
BSA = body surface area; Ht = height; Wt = body weight 
 
2) The treatment area will be specified. 
3) The amount of IMP (g) per dose will be calculated as “subject’s BSA (m2)” × 
“treatment area (%)” × “10 g/m2.” 
Example: In case of a BSA of 0.7 m2 and an affected BSA of 32%: 0.7 m2 × 0.32 
× 10 g/m2 = 2.24 g 
The method of IMP administration is specified in the separate procedure for IMP 
administration. 
3.2.2 
Dose Modification of the Investigational Medicinal Product 
3.2.2.1 
Dose Increase 
For subjects receiving the 0.3% formulation with an IGA score of 2 or greater, the dose 
will be increased to the 1% formulation unless a concern about unacceptable tolerability 
is identified at a 4-weekly assessment (in the long-term extension part) including the 
Week 4 examination. Even for subjects with an IGA score of less than 2, the dose can be 
increased if judged necessary by the investigator or subinvestigator. Dose increase will be 
recorded together with the reason in the source documents and eCRF. 
3.2.2.2 
Dose Reduction 
For subjects receiving the 1% formulation, the dose can be reduced to the 0.3% 
formulation if judged necessary by the investigator or subinvestigator (eg, improvement 
in skin symptoms, occurrence of an AE) at a 4-weekly assessment after the Week 4 
examination (in the long-term extension part). Dose reduction will be recorded together 
with the reason in the source documents and eCRF. 
3.2.2.3 
Interruption (Treatment Interruption) 
IMP administration must not be suspended until the Week 4 examination. Interruption 
will be allowed if judged necessary by the investigator or subinvestigator (eg, resolution 
of skin symptoms, exacerbation of skin symptoms [which requires rescue medication], 
occurrence of an AE [excluding exacerbation of skin symptoms]) at a 4-weekly 


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assessment after the Week 4 examination (in the long-term extension part). Interruption 
will be recorded together with the reason in the source documents and eCRF. The 
investigator or subinvestigator should perform the specified examination/assessments 
during interruption, and decide on the necessity of restarting IMP administration. 
3.2.2.4 
Restarting IMP Administration After Interruption 
Following interruption, restarting IMP administration (exacerbation of skin symptoms, 
improvement of skin symptoms [in cases where IMP administration was suspended to 
allow rescue medication], improvement of an AE [excluding exacerbation of skin 
symptoms]) will be recorded together with the reason in the source documents and eCRF. 
3.3 
Trial Population 
Infants 3 months or older and younger than 2 years of age with AD and an IGA score of 2 
or 3. 
3.4 
Handling of Time Points 
The number of days from IMP administration to the endpoint measurement day will be 
calculated with the start day of IMP administration set as the starting point (Day 1). In 
determining the assessment time points for analyses, unscheduled data and withdrawal 
data, as well as scheduled visit data, will be included. However, unscheduled data 
obtained at 2 weeks after the start of 1% formulation administration and between 4 and 8 
weeks after the scheduled visit will be excluded from the determination of assessment 
time points in analysis. The acceptable windows for time points in the analysis of safety 
and efficacy endpoints will be as shown in Table 3.4-1. When there are multiple non-
missing measurement values in the acceptable window, the last data in the acceptable 
window will be adopted. Regarding efficacy and safety endpoints, the latest data among 
all the data obtained after the start of IMP administration will be adopted as the last time 
(Last Visit). 
The data nearest to the start day of IMP administration among predose data including 
screening data will be adopted as the baseline for analysis. 
Table 3.4-1 
Acceptable Windows for Time Points in Analysis 
Week 
Trial Day Interval 
Baseline 
1 
Week 1 
2 
10 
Week 2 
11 
21 
Week 4 
22 
42 
Week 8 
43 
70 
Week 12 
71 
98 
Week 16 
99 
126 


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Table 3.4-1 
Acceptable Windows for Time Points in Analysis 
Week 
Trial Day Interval 
Week 20 
127 
154 
Week 24 
155 
182 
Week 28 
183 
210 
Week 32 
211 
238 
Week 36 
239 
266 
Week 40 
267 
294 
Week 44 
295 
322 
Week 48 
323 
350 
Week 52 
351 
372 
 
For subjects receiving the 1% formulation, analysis time points with starting point of 
dose increase to the 1% formulation will also be defined in addition to the above-
described time points in analysis. For instance, when the dose is increased to 1% at 
Week 4, the record corresponding to Week 4 will be defined as that at the time of 
increase to 1%, and Week 2 After Dose Increase will be defined as the time point 
specified in the CRF (2 weeks after the start of 1% formulation administration). Week 4 
After Dose Increase and later are defined as shown in Table 3.4-2. 
Table 3.4-2 
Acceptable Windows for Time Points in 
Analysis Starting From the Time of Dose 
Increase 
Week 
Definition of time points 
Time of increase to 1% 
The time point on the same day as the day that 
the doctor first directed a dose increase 
Week 2 After Dose Increase 
2 weeks after the start of 1% formulation 
administration (the time point specified in the 
CRF) 
Week 4 After Dose Increase 
Analysis visits specified in Table 3.4-1 minus 
Week at increase to 1% 
Week 8 After Dose Increase 
Week 12 After Dose Increase 
Week 16 After Dose Increase 
Week 20 After Dose Increase 
Week 24 After Dose Increase 
Week 28 After Dose Increase 
Week 32 After Dose Increase 
Week 36 After Dose Increase 
Week 40 After Dose Increase 
Week 44 After Dose Increase 
Week 48 After Dose Increase 
 


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3.5 
Handling of Endpoints 
3.5.1 
IGA Response 
Response (improvement) is defined as an IGA score, which is the primary endpoint, of 0 
or 1 with improvement of at least 2 grades from baseline. Subjects without the above 
improvement will be handled as non-responders. In addition, subjects with missing IGA 
data will be handled as non-responders. 
3.5.2 
EASI Response (EASI 75, EASI 90, EASI 50) 
Response (improvement) in EASI 75 is defined as a decrease by ≥75% in the percent 
change from baseline in the total score of EASI. Subjects without the above improvement 
will be handled as non-responders. Response (improvement) in EASI 90 is defined as a 
decrease by ≥90% in the percent change from baseline in the total score of EASI. 
Subjects without the above improvement will be handled as non-responders. Response 
(improvement) in EASI 50 is defined as a decrease by ≥50% in the percent change from 
baseline in the total score of EASI. Subjects without the above improvement will be 
handled as non-responders. In addition, subjects with a missing total score of EASI will 
be handled as non-responders in EASI 75, EASI 90, and EASI 50. 
4 
Sample Size 
5 
Datasets for Analysis 
5.1 
Efficacy Analysis Set 
Consists of all subjects who have received the IMP at least once. 
5.2 
Safety Analysis Set 
Consists of all subjects who have received the IMP at least once. 


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5.3 
Pharmacokinetic Analysis Set 
Consists of all subjects who have received the IMP at least once and in whom a plasma 
drug concentration is determined for at least 1 time point after IMP administration. 
5.4 
Handling of Missing Data 
Missing data are not imputed. For IGA response, EASI 75, EASI 90, and EASI 50, 
subjects with missing IGA or EASI scores are handled as non-responders. 
6 
Primary and Secondary Endpoints 
6.1 
Primary Endpoint (Primary Assessment Part) 
• Success rate in IGA (percentage of subjects with an IGA score of 0 or 1 with 
improvement by at least 2 grades) 
 
6.2 
Secondary Endpoints 
6.2.1 
Efficacy Endpoint 
• Response rate in EASI 90 (improvement of ≥90% in EASI), EASI 75 (improvement 
of ≥75% in EASI) and EASI 50 (improvement of ≥50% in EASI) 
• Change from baseline in IGA score 
• Percent change from baseline in the total score of EASI and each clinical sign score 
• Change from baseline in the total score of POEM 
• Change from baseline in the total affected BSA (%) 
 
6.2.2 
Safety Endpoints 
• AEs 
• Vital signs, body weight 
• Clinical laboratory tests 
 
6.2.3 
Pharmacokinetic Endpoint 
• Plasma concentration of OPA-15406 
 
7 
Subject Disposition and Demographic and Other Baseline 
Characteristics 
Unless otherwise noted, the summarizations described below will be performed for each 
of the following treatment groups and for all subjects: subjects receiving only the 0.3% 
formulation even at 4 weeks postdose and later (hereinafter referred to as the 0.3% 


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formulation group) and subjects receiving the 1% formulation at least once at 4 weeks 
postdose or later (hereinafter, the 1% formulation [dose increase] group). 
7.1 
Subject Disposition 
The number of subjects for whom informed consent was obtained, the number of subjects 
receiving IMP administration, and the frequency distribution of completed or withdrawn 
subjects (the number and percentage of subjects, the same applies hereinafter) will be 
shown. The denominator of percentage is defined as subjects receiving IMP 
administration. For withdrawn subjects, the frequency distribution by withdrawal reason 
will be shown. The frequency distribution of subjects included in each analysis set will be 
shown. 
7.2 
Demographic and Other Baseline Characteristics 
In the efficacy analysis set, for age (month), sex, disease duration (month), body weight, 
height, body mass index (BMI), race, and AD severity, descriptive statistics or a 
frequency distribution will be shown depending on each characteristic. Descriptive 
statistics will be shown for age, disease duration, body weight, height, and BMI, and a 
frequency distribution will be shown for age group (<12 months, ≥12 months), sex, race, 
ethnicity, study country, and AD severity. By using MedDRA, medical 
histories/complication names will be coded by system organ class (SOC) and preferred 
term (PT). Medical histories/complication names will not be summarized but only listed. 
In deriving the disease duration, the data will not be imputed when date data is missing. 
The year and month data will be used for calculation when the day is missing. 
When “day, month, and year” are all available: (Administration start day, month, and 
year - AD onset day, month, and year + 1) / 30 
When only “month and year” are available: (Administration start year × 12 + 
Administration start month) - (AD onset year × 12 + AD onset month) + 1 
7.3 
Assessment of Baseline Conditions 
In the efficacy analysis set, a frequency distribution will be shown for IGA (2 or 3) at 
baseline, and descriptive statistics will be shown for the total EASI (Eczema Area and 
Severity Index) score at baseline. Affected area at baseline will be classified into the 
following categories, and a frequency distribution will be shown. 
Categories of affected area: ≥5% and <10%, ≥10% and <20%, ≥20% and <40%, and 
≥40% 


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7.4 
Treatment Compliance 
In the efficacy analysis set, compliance regarding administration frequency until 52 
weeks after baseline will be classified into the following categories, and the number and 
percentage of subjects will be calculated. In addition, the number and percentage of 
treated subjects will be calculated by week (Week 1, Week 2, Week 4, Week 8, Week 12, 
Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, 
Week 48, Week 52, and Any Exposure). Compliance regarding administration frequency 
will be calculated using the following equation. Treatment compliance with IMP (%) = 
(Actual administration frequency / directed administration frequency of the 0.3% or 1% 
formulation) × 100 
Categories of compliance regarding administration frequency: <50%, ≥50% and <60%, 
≥60% and <70%, ≥70% and <80%, ≥80% and <90%, ≥90% and <100%, ≥100% and 
<110%, ≥110% and <120%, and ≥120% 
In addition, frequency distribution will be shown for the reasons for dose increase, dose 
reduction, and treatment interruption. If there are multiple reasons, the first reason will be 
counted. 
7.5 
Prior and Concomitant Medications 
In the efficacy analysis set, the number and percentage of subjects receiving drugs will be 
calculated for drugs administered prior to the start day of IMP administration, drugs 
administered during the IMP administration period, and drugs administered after the end 
of IMP administration. Drugs will be coded by using the WHO Drug Dictionary and 
summarized by using ATC classification level 2 and Preferred names. Concomitant 
therapies will not be summarized but only listed. 
7.6 
Protocol Deviations 
The number and percentage of subjects with a significant deviation from the protocol will 
be shown. In addition, the number and percentage of subjects by significant deviation 
category will be shown for each site. 
8 
Efficacy Analyses 
The following analyses will be performed in the efficacy analysis set. In analyses of the 
primary endpoint, summarization will be performed for each of the following treatment 
groups: subjects secondly receiving only the 0.3% formulation even at 4 weeks postdose 
and later (hereinafter, the 0.3% formulation group) and subjects receiving the 1% 
formulation at least once at 4 weeks postdose or later (hereinafter, the 1% formulation 


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[dose increase] group). Unless otherwise noted, regardless of administration status 
(administration of the 0.3% formulation, administration of the 1% formulation, or 
treatment interruption), the data of the analysis time points specified in Table 3.4-1 will 
be summarized. 
8.1 
Primary Efficacy Endpoint Analysis 
Response (improvement) is defined as a postdose IGA score of 0 or 1 with improvement 
of at least 2 grades, and the primary endpoint is the success rate in IGA at Week 4. In all 
subjects of the efficacy analysis set, the number of subjects with an IGA response and 
success rate at 4 weeks after IMP treatment and their two-sided 95% confidence intervals 
(Clopper-Pearson method) will be calculated. The same analysis will be performed at 1 
week and 2 weeks postdose. Subjects with missing IGA data will be handled as non-
responders. The success rate at each assessment time point will be graphically shown. 
8.2 
Key Secondary Efficacy Endpoint Analyses 
In the same manner as the primary endpoint analysis in 8.1, the number of subjects with 
an IGA response and success rate at each assessment time point and their two-sided 95% 
confidence intervals (Clopper-Pearson method) will be calculated for each treatment 
group and all subjects. 
By using OC data, the number of subjects with an IGA response and success rate at each 
assessment time point and the last time (Last Visit) and their two-sided 95% confidence 
intervals (Clopper-Pearson method) will be calculated for each treatment group and all 
subjects. The success rate at each assessment time point will be graphically shown. 
The cumulative number and rate of subjects who improved at least once by each 
assessment time point with IGA response and their two-sided 95% confidence intervals 
(Clopper-Pearson method) will be calculated by treatment group and for all subjects. The 
success rate at each assessment time point will be graphically shown. 
EASI 75, EASI 90, and EASI 50 will be analyzed in the same manner as IGA response. 
8.3 
Secondary Efficacy Endpoint Analysis 
Regarding IGA score, total EASI score, EASI score of each symptom and each part, total 
POEM score, and total affected area (%), the descriptive statistics of actual measurements 
and changes from baseline at each assessment time point and the last time (Last Visit) 
will be calculated for each treatment group and all subjects. For the IGA score, total 
EASI score, EASI score of each symptom and each part, and total POEM score, the 
descriptive statistics will be calculated for percent change from baseline as well. For 


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changes in IGA from baseline, the time courses of changes in IGA score from baseline at 
each timepoint will be plotted with the mean and SD. As for total EASI score, the time 
courses of changes in total EASI score from baseline at each timepoint will be plotted 
with the mean and SD. 
Regarding IGA score, by using OC data, the shift table at each assessment time point and 
the last time (Last Visit) from baseline will be shown for each treatment group and all 
subjects. 
8.4 
Subgroup Analyses 
Regarding IGA response at 4 weeks after IMP administration in 8.1 and IGA response at 
the last time (Last Visit) in 8.2, the number of subjects with IGA response and success 
rate, and their two-sided 95% confidence intervals (Clopper-Pearson method) will be 
shown for each of the following subgroups. EASI 75, EASI 90, and EASI 50 will be 
analyzed in the same manner. The data at 52 weeks in 8.1 and 52 weeks (OC data) in 8.2 
will also be analyzed by age. 
Age: <12 months, ≥12 months 
Sex: male, female 
IGA score at baseline: 2 (mild), 3 (moderate) 
Severity of AD: mild, moderate, severe, most severe 
Total EASI score at baseline: <15, ≥15 
Affected area at baseline: <20%, ≥20% 
Presence of the use of anti-inflammatory drugs: present, absent 
Presence of the use of topical drugs other than anti-inflammatory drugs: present, absent 
By the modal dose: 0.3% OPA-15406 ointment, 1% OPA-15406 ointment 
Presence of dose increase set at 4 weeks postdose: no dose increase at 4 weeks postdose, 
dose increase at 4 weeks postdose 
By IGA score at 4 weeks postdose: 0, 1, 2, 3, 4 
In addition, the modal dose is defined as the most frequently administered concentration 
during the IMP administration period. However, when frequency is the same between 
concentrations, the last concentration administered will be adopted as the concentration 
of the modal dose. Subjects using anti-inflammatory drugs are defined as subjects who 
used prohibited concomitant topical drugs (steroids, tacrolimus, delgocitinib, 
guaiazulene, ibuprofen piconol, suprofen, and enoxolone) during the IMP administration 


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period in the cases of medical requirements such as the worsening of symptoms. In 
addition, subjects using topical drugs other than anti-inflammatory drugs are defined as 
subjects who used topical drugs other than prohibited concomitant anti-inflammatory 
drugs (steroids, tacrolimus, delgocitinib, guaiazulene, ibuprofen piconol, suprofen, and 
enoxolone) during the IMP administration period. 
Furthermore, subjects aged <12 months will be tabulated by the following categories. In 
the same manner as the age categories described above (<12 and ≥12 months), analysis 
will be performed at 4 and 52 weeks after IMP administration in 8.1, 52 weeks postdose 
in 8.2 (OC data), and the last time (Last Visit). 
Age: <6 months, ≥6 and <12 months 
8.5 
Exploratory or Other Analyses 


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9 
Safety Analysis 
In the safety analysis set, the following analyses will be performed. Unless otherwise 
noted, the summarizations described below will be performed for each of the following 
treatment groups and for all subjects: subjects receiving only the 0.3% formulation even 
at 4 weeks postdose and later (hereinafter referred to as the 0.3% formulation group) and 
subjects receiving the 1% formulation at least once at 4 weeks postdose or later 
(hereinafter, the 1% formulation [dose increase] group). 
9.1 
Extent of Exposure to Investigational Medicinal Product 
Descriptive statistics will be calculated for the number of days of administration (except 
for treatment interruption), total amount of IMP administration, and amount of 
administration per dose. The amount of administration is defined as the difference 
between the total weights of prescribed IMP and returned IMP. In addition, descriptive 
statistics will also be shown in the same manner for the amount with consideration of 
IMP concentration (0.3% OPA-15406 and 1% OPA-15406). In calculating the amount of 
treatment, the weight of the IMP with an unknown weight upon return will be calculated 
as 0 (zero) at return. 


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The sum of treatment duration and the descriptive statistics of treatment duration for 
0.3% OPA-15406, and the sum of treatment duration and the descriptive statistics of 
treatment duration for 1% OPA-15406 will be calculated. The same analysis will be 
performed for age categories (<12 months, ≥12 months). Furthermore, for subjects aged 
<12 months, the same analysis will be performed by the following categories: <6 months 
and ≥6 and <12 months. 
9.2 
Adverse Events 
By using MedDRA (Ver 26.1), adverse events will be coded by system organ class 
(SOC) and preferred term (PT). 
Regarding the following treatment-emergent AEs (TEAEs), the number and percentage 
of subjects with an onset will be calculated. If the same event occurred multiple times in 
the same subject, the most severe one will be used in analyses by severity, and the one 
with the earliest onset will be used in analyses by onset time. For skin and subcutaneous 
tissue disorders, analyses by the grade classification of the Common Terminology 
Criteria for Adverse Events (CTCAE) will also be performed. 
• TEAE 
• TEAEs by severity 
• TEAEs with an outcome of death 
• Serious TEAEs 
• TEAEs leading to discontinuation of the IMP 
• TEAEs leading to IMP treatment interruption 
• TEAEs leading to IMP dose reduction 
• TEAEs by CTCAE Grade (only for skin and subcutaneous tissue disorders) 
• TEAEs at treatment areas 
• TEAEs by onset time (≤4 weeks, >4 and ≤12 weeks, >12 and ≤24 weeks, >24 and 
≤36 weeks, >36 and ≤52 weeks, and >52 weeks) 
Adverse reactions (adverse events whose relationships with the IMP cannot be ruled out) 
will be analyzed in the same manner as TEAEs. 
Serious TEAEs, TEAEs leading to discontinuation of the IMP, TEAE leading to IMP 
treatment interruption, and TEAEs leading to IMP dose reduction will be summarized by 
severity and CTCAE Grade. 
For TEAEs that developed in ≥5% of any treatment group and non-serious TEAEs that 
developed in ≥5% of any treatment group, the number and percentage of subjects with an 
onset will be calculated. 


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In addition, TEAEs will be summarized in regard to the following items. 
• TEAEs except for events that developed during the treatment interruption period 
• TEAEs that developed by 4 weeks after IMP administration (only for all subjects) 
• TEAEs that developed by 8 weeks after IMP administration 
• TEAEs that developed in the treatment area 
• TEAEs that developed in the treatment area by 4 weeks after IMP administration 
 
9.2.1 
Subgroup Analyses of Adverse Events 
The summary of adverse events and summary of adverse events (treatment area) will be 
tabulated by the following subgroups. TEAEs (by SOC and PT) and TEAEs by severity 
(by SOC and PT) will also be summarized by event. Adverse reactions will also be 
summarized in the same manner. 
• Sex (male, female) 
• Age (<12 months, ≥12 months) 
• Presence of the use of anti-inflammatory drugs 
• Presence of the use of topical drugs other than anti-inflammatory drugs 
For the summary of adverse events that developed by 4 weeks after IMP administration 
and the adverse events (treatment area) that developed by 4 weeks after IMP 
administration, subgroup analysis will be performed by sex and age. 
Furthermore, subjects aged <12 months will be tabulated by the following categories. 
Age: <6 months, ≥6 and <12 months 
9.2.2 
Analyses of Adverse Events by Drug Concentration 
Regarding the following TEAEs, the summary of adverse events and summary of adverse 
events (treatment area) will be tabulated. TEAEs (by SOC and PT) and TEAEs by 
severity (by SOC and PT) will also be summarized by event. Adverse reactions will also 
be summarized in the same manner. 
• TEAEs that developed at administration of 0.3% OPA-15406 
• TEAEs that developed at administration of 1% OPA-15406 
 
9.3 
Clinical Laboratory Data 
Regarding the actual measurements and changes from baseline at each assessment time 
point and the last time (LOCF) for the OC data of laboratory parameters (except for urine 
qualitative test), the descriptive statistics will be calculated for each treatment group and 
all subjects. For the urine qualitative test of laboratory tests, the shift table at each 


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assessment time point from baseline will be prepared for each treatment group and all 
subjects. For the tests other than urine qualitative test, the shift table before and after 
administration in which values are classified into normal, high level, and low level on the 
basis of the reference value will be prepared for each treatment group and all subjects. 
The number and percentage of subjects who meet the criteria of the abnormality of 
hepatic functions (Hy’s Law) (Appendix 1) will be calculated for each treatment group 
and all subjects. In addition, the listing of the abnormality of hepatic functions will also 
be prepared. All the postdose data will be included in the judgment. 
9.4 
Vital Signs and Body Weight 
Regarding body weight, body temperature, blood pressure (systolic/diastolic), and pulse 
rate, the descriptive statistics of the actual measurements and changes from baseline at 
each assessment time point and the last time (LOCF) based on the OC data will be 
calculated for each treatment group and all subjects. 
9.5 
Physical Examination 
Data will not be summarized. 
9.6 
Electrocardiogram Data 
Not applicable. 
9.7 
Other Safety Variables 
Not applicable. 
10 
Pharmacokinetic Analysis 
In the pharmacokinetic analysis set, descriptive statistics will be calculated as shown 
below. 
10.1 
OPA-15406 Plasma Concentrations 


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10.2 
Handling of Data 
• For the acceptable windows for assessment time points, the acceptable windows 
for assessment time points for analysis described in Table 10.2-1, rather than the 
time points specified in section 1.3 of the protocol, will be used. 


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• 
• 
• 
• Plasma OPA-15406 concentration will be noted with 3 significant digits. 
• 
• The number of digits for descriptive statistics are defined as shown in 
Table 10.2-2. 
 
Table 10.2-2 
Number of Digits for Descriptive Statistics 
Descriptive statistics to be 
calculated 
Number of digits 
Number of subjects analyzed 
Integer 
Number of subjects summarized 
Integer 
Arithmetic mean 
Numerical values will be rounded off at the (n + 1) place so that their 
number of digits (n) will be the same as that of values in individual 
subjects in the target data. 
Standard deviation 
Median 
Minimum 
Numerical values will be displayed, as they are, in the same number 
of digits (n) as that of values in individual subjects in the target data. 
Maximum 
Coefficient of variation 
Numerical values will be rounded off to the first decimal place. 
 
11 
Pharmacodynamic Analysis 
Not applicable. 
12 
Pharmacogenomic Analysis 
Not applicable. 
13 
Interim Analysis 


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14 
Changes from Planned Analysis Plan 
Not applicable. 
15 
References 
Not applicable. 
16 
Amendment History 


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Appendix 1 
Criteria for Potential Hy's Law 
The potential Hy’s Law Cases are defined as subjects with the following criteria:  ALT > 
= 3xULN (OR SCREENING VALUE) OR AST > = 3xULN (OR SCREENING 
VALUE) AND BILIRUBIN > = 2xULN (OR SCREENING VALUE) 
 


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Appendix 2 
List of Tables and Figures 
CT-1 Subject Disposition 
CT-2 Reasons for Discontinuation 
CT-3 Demographic Characteristics 
CT-4.1 Concomitant Medications:  Medications Taken Prior to Start of Study Therapy 
CT-4.2 Concomitant Medications:  Medications Taken During Study Therapy 
CT-4.3 Concomitant Medications:  Medications Taken After Study Therapy 
CT-5.1.1 Analysis of Responder Rate for Overall IGA Score at Week 4 
CT-5.1.2 Analysis of Responder Rate for Overall IGA Score by Visit 
CT-5.1.3 Analysis of Responder Rate for Overall IGA Score by Visit - OC 
CT-5.1.4 Analysis of Responder Rate for Overall IGA Score by Visit - Cumulative 
CT-5.2.1 Analysis of 75% Over Responder Rate for Overall EASI Score at Week 4 
CT-5.2.2 Analysis of 75% Over Responder Rate for Overall EASI Score by Visit 
CT-5.2.3 Analysis of 75% Over Responder Rate for Overall EASI Score by Visit - OC 
CT-5.2.4 Analysis of 75% Over Responder Rate for Overall EASI Score by Visit - 
Cumulative 
CT-5.3.1 Analysis of 90% Over Responder Rate for Overall EASI Score at Week 4 
CT-5.3.2 Analysis of 90% Over Responder Rate for Overall EASI Score by Visit 
CT-5.3.3 Analysis of 90% Over Responder Rate for Overall EASI Score by Visit - OC 
CT-5.3.4 Analysis of 90% Over Responder Rate for Overall EASI Score by Visit - 
Cumulative 
CT-5.4.1 Analysis of 50% Over Responder Rate for Overall EASI Score at Week 4 
CT-5.4.2 Analysis of 50% Over Responder Rate for Overall EASI Score by Visit 
CT-5.4.3 Analysis of 50% Over Responder Rate for Overall EASI Score by Visit - OC 
CT-5.4.4 Analysis of 50% Over Responder Rate for Overall EASI Score by Visit - 
Cumulative 
CT-5.5.1 Shift Tables of Overall IGA Score - OC 
CT-5.6.1 Analysis of Baseline and Change from Baseline in Overall IGA Score 


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CT-5.6.2 Analysis of Baseline and Percent Change from Baseline in Overall IGA Score 
CT-5.7.1 Analysis of Baseline and Change from Baseline in Overall EASI Score 
CT-5.7.2 Analysis of Baseline and Percent Change from Baseline in Overall EASI Score 
CT-5.7.3 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
Erythema 
CT-5.7.4 Analysis of Baseline and Percent Change from Baseline in Overall EASI Score, 
Erythema 
CT-5.7.5 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
Induration/Papulation 
CT-5.7.6 Analysis of Baseline and Percent Change from Baseline in Overall EASI Score, 
Induration/Papulation 
CT-5.7.7 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
Excoriation 
CT-5.7.8 Analysis of Baseline and Percent Change from Baseline in Overall EASI Score, 
Excoriation 
CT-5.7.9 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
Lichenification 
CT-5.7.10 Analysis of Baseline and Percent Change from Baseline in Overall EASI 
Score, Lichenification 
CT-5.7.11 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
HEAD/NECK 
CT-5.7.12 Analysis of Baseline and Percent Change from Baseline in Overall EASI 
Score, HEAD/NECK 
CT-5.7.13 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
UPPER LIMBS 
CT-5.7.14 Analysis of Baseline and Percent Change from Baseline in Overall EASI 
Score, UPPER LIMBS 
CT-5.7.15 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
TRUNK 
CT-5.7.16 Analysis of Baseline and Percent Change from Baseline in Overall EASI 
Score, TRUNK 


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CT-5.7.17 Analysis of Baseline and Change from Baseline in Overall EASI Score, 
LOWER LIMBS 
CT-5.7.18 Analysis of Baseline and Percent Change from Baseline in Overall EASI 
Score, LOWER LIMBS 
CT-5.8.1 Analysis of Baseline and Change from Baseline in POEM Score 
CT-5.8.2 Analysis of Baseline and Percent Change from Baseline in POEM Score 
CT-5.9 Analysis of Baseline and Change from Baseline in Overall Percentage Affected 
Body Surface Area 
CT-6.1.1 Subgroup Analysis of Responder Rate for Overall IGA Score by Age 
CT-6.1.2 Subgroup Analysis of Responder Rate for Overall IGA Score by Sex 
CT-6.1.3 Subgroup Analysis of Responder Rate for Overall IGA Score by IGA Score at 
Baseline 
CT-6.1.4 Subgroup Analysis of Responder Rate for Overall IGA Score by Severity of 
Atopic Dermatitis 
CT-6.1.5 Subgroup Analysis of Responder Rate for Overall IGA Score by Total EASI 
Score at Baseline (<15, 15<=) 
CT-6.1.6 Subgroup Analysis of Responder Rate for Overall IGA Score by Affected Body 
Surface Area 
CT-6.1.7 Subgroup Analysis of Responder Rate for Overall IGA Score by Topical Anti-
Inflammatory Agents 
CT-6.1.8 Subgroup Analysis of Responder Rate for Overall IGA Score by Topical 
Medications Excluding Anti-Inflammatory Agents 
CT-6.1.9 Subgroup Analysis of Responder Rate for Overall IGA Score by Modal Dose 
CT-6.1.10 Subgroup Analysis of Responder Rate for Overall IGA Score by IMP Increase 
from Week 4 
CT-6.1.11 Subgroup Analysis of Responder Rate for Overall IGA Score by IGA Score at 
Week 4 
CT-6.1.12 Subgroup Analysis of Responder Rate for Overall IGA Score by Age 
(Subjects Under 12 Months of Age) 
CT-6.2.1 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Age 


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CT-6.2.2 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Sex 
CT-6.2.3 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
IGA Score at Baseline 
CT-6.2.4 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Severity of Atopic Dermatitis 
CT-6.2.5 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Total EASI Score at Baseline (<15, 15<=) 
CT-6.2.6 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Affected Body Surface Area 
CT-6.2.7 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Topical Anti-Inflammatory Agents 
CT-6.2.8 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Topical Medications Excluding Anti-Inflammatory Agents 
CT-6.2.9 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Modal Dose 
CT-6.2.10 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
IMP Increase from Week 4 
CT-6.2.11 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
IGA Score at Week 4 
CT-6.2.12 Subgroup Analysis of 75% Over Responder Rate for Overall EASI Score by 
Age (Subjects Under 12 Months of Age) 
CT-6.3.1 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Age 
CT-6.3.2 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Sex 
CT-6.3.3 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
IGA Score at Baseline 
CT-6.3.4 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Severity of Atopic Dermatitis 
CT-6.3.5 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Total EASI Score at Baseline (<15, 15<=) 


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CT-6.3.6 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Affected Body Surface Area 
CT-6.3.7 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Topical Anti-Inflammatory Agents 
CT-6.3.8 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Topical Medications Excluding Anti-Inflammatory Agents 
CT-6.3.9 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Modal Dose 
CT-6.3.10 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
IMP Increase from Week 4 
CT-6.3.11 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
IGA Score at Week 4 
CT-6.3.12 Subgroup Analysis of 90% Over Responder Rate for Overall EASI Score by 
Age (Subjects Under 12 Months of Age) 
CT-6.4.1 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Age 
CT-6.4.2 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Sex 
CT-6.4.3 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
IGA Score at Baseline 
CT-6.4.4 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Severity of Atopic Dermatitis 
CT-6.4.5 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Total EASI Score at Baseline (<15, 15<=) 
CT-6.4.6 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Affected Body Surface Area 
CT-6.4.7 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Topical Anti-Inflammatory Agents 
CT-6.4.8 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Topical Medications Excluding Anti-Inflammatory Agents 
CT-6.4.9 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Modal Dose 


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CT-6.4.10 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
IMP Increase from Week 4 
CT-6.4.11 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
IGA Score at Week 4 
CT-6.4.12 Subgroup Analysis of 50% Over Responder Rate for Overall EASI Score by 
Age (Subjects Under 12 Months of Age) 


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CT-7.1 Summary of Treatment Compliance for Number of Administrations 
CT-7.2 Extent of Exposure to Trial Medication 
CT-7.3.1 Summary of Reason for Dose Increased 
CT-7.3.2 Summary of Reason for Dose Reduced 
CT-7.3.3 Summary of Reason for Treatment Interrupted 
CT-7.4 Summary of Treatment Period 
CT-7.5 Summary of Exposure to Trial Medication 
CT-7.6.1 Summary of Total Exposure to Trial Medication 
CT-7.6.2 Summary of Total Exposure to Trial Medication by Age 
CT-7.6.3 Summary of Total Exposure to Trial Medication by Age (Subjects Under 12 
Months of Age) 
CT-8.1.1.1 Adverse Events 
CT-8.1.1.2 Adverse Events - Sex:  Male 
CT-8.1.1.3 Adverse Events - Sex:  Female 
CT-8.1.1.4 Adverse Events - Age:  Less Than 12 Months 
CT-8.1.1.5 Adverse Events - Age:  Greater Than or Equal to 12 Months 
CT-8.1.1.6 Adverse Events - With Topical Anti-Inflammatory Agents 
CT-8.1.1.7 Adverse Events - Without Topical Anti-Inflammatory Agents 


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CT-8.1.1.8 Adverse Events - With Topical Medications Excluding Anti-Inflammatory 
Agents 
CT-8.1.1.9 Adverse Events - Without Topical Medications Excluding Anti-Inflammatory 
Agents 
CT-8.1.1.10 Adverse Events - Onset Timing of Administration of 0.3% OPA-15406 
CT-8.1.1.11 Adverse Events - Onset Timing of Administration of 1% OPA-15406 
CT-8.1.1.12 Adverse Events - Age:  Less Than 6 Months (Subjects Under 12 Months of 
Age) 
CT-8.1.1.13 Adverse Events - Age:  Greater Than or Equal to 6 Months (Subjects Under 
12 Months of Age) 
CT-8.1.2.1 Adverse Events (Between Baseline and Week 4) 
CT-8.1.2.2 Adverse Events (Between Baseline and Week 4) - Sex:  Male 
CT-8.1.2.3 Adverse Events (Between Baseline and Week 4) - Sex:  Female 
CT-8.1.2.4 Adverse Events (Between Baseline and Week 4) - Age:  Less Than 12 
Months 
CT-8.1.2.5 Adverse Events (Between Baseline and Week 4) - Age:  Greater Than or 
Equal to 12 Months 
CT-8.1.2.6 Adverse Events (Between Baseline and Week 4) - Age:  Less Than 6 Months 
(Subjects Under 12 Months of Age) 
CT-8.1.2.7 Adverse Events (Between Baseline and Week 4) - Age:  Greater Than or 
Equal to 6 Months (Subjects Under 12 Months of Age) 
CT-8.1.3 Adverse Events (Between Baseline and Week 8) 
CT-8.2.1.1 Adverse Events According to Application Site 
CT-8.2.1.2 Adverse Events According to Application Site - Sex:  Male 
CT-8.2.1.3 Adverse Events According to Application Site - Sex:  Female 
CT-8.2.1.4 Adverse Events According to Application Site - Age:  Less Than 12 Months 
CT-8.2.1.5 Adverse Events According to Application Site - Age:  Greater Than or Equal 
to 12 Months 
CT-8.2.1.6 Adverse Events According to Application Site - With Topical Anti-
Inflammatory Agents 


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CT-8.2.1.7 Adverse Events According to Application Site - Without Topical Anti-
Inflammatory Agents 
CT-8.2.1.8 Adverse Events According to Application Site - With Topical Medications 
Excluding Anti-Inflammatory Agents 
CT-8.2.1.9 Adverse Events According to Application Site - Without Topical Medications 
Excluding Anti-Inflammatory Agents 
CT-8.2.1.10 Adverse Events According to Application Site - Onset Timing of 
Administration of 0.3% OPA-15406 
CT-8.2.1.11 Adverse Events According to Application Site - Onset Timing of 
Administration of 1% OPA-15406 
CT-8.2.1.12 Adverse Events According to Application Site - Age:  Less Than 6 Months 
(Subjects Under 12 Months of Age) 
CT-8.2.1.13 Adverse Events According to Application Site - Age:  Greater Than or Equal 
to 6 Months (Subjects Under 12 Months of Age) 
CT-8.2.2.1 Adverse Events According to Application Site (Between Baseline and Week 
4) 
CT-8.2.2.2 Adverse Events According to Application Site (Between Baseline and Week 
4) - Sex:  Male 
CT-8.2.2.3 Adverse Events According to Application Site (Between Baseline and Week 
4) - Sex:  Female 
CT-8.2.2.4 Adverse Events According to Application Site (Between Baseline and Week 
4) - Age:  Less Than 12 Months 
CT-8.2.2.5 Adverse Events According to Application Site (Between Baseline and Week 
4) - Age:  Greater Than or Equal to 12 Months 
CT-8.2.2.6 Adverse Events According to Application Site (Between Baseline and Week 
4) - Age:  Less Than 6 Months (Subjects Under 12 Months of Age) 
CT-8.2.2.7 Adverse Events According to Application Site (Between Baseline and Week 
4) - Age:  Greater Than or Equal to 6 Months (Subjects Under 12 Months of Age) 
CT-8.3.1 Adverse Events Occurring on Treatment 
CT-8.4.1.1 Treatment-emergent Adverse Events on Treatment by System Organ Class, 
Preferred Term and Period of Onset 


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CT-8.4.1.2 Drug-related Treatment-emergent Adverse Events on Treatment by System 
Organ Class, Preferred Term and Period of Onset 
CT-8.4.1.3 Treatment-emergent Adverse Events on Treatment by System Organ Class, 
Preferred Term and Period of Onset (CTD Format) 
CT-8.5.1.1.1 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term 
CT-8.5.1.1.2 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Sex:  Male 
CT-8.5.1.1.3 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Sex:  Female 
CT-8.5.1.1.4 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Age:  Less Than 12 Months 
CT-8.5.1.1.5 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Age:  Greater Than or Equal to 12 Months 
CT-8.5.1.1.6 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - With Topical Anti-Inflammatory Agents 
CT-8.5.1.1.7 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Without Topical Anti-Inflammatory Agents 
CT-8.5.1.1.8 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - With Topical Medications Excluding Anti-Inflammatory Agents 
CT-8.5.1.1.9 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Without Topical Medications Excluding Anti-Inflammatory Agents 
CT-8.5.1.1.10 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Onset Timing of Administration of 0.3% OPA-15406 
CT-8.5.1.1.11 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Onset Timing of Administration of 1% OPA-15406 
CT-8.5.1.1.12 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Age:  Less Than 6 Months (Subjects Under 12 Months of Age) 
CT-8.5.1.1.13 Incidence of Treatment-emergent Adverse Events by System Organ Class 
and Preferred Term - Age:  Greater Than or Equal to 6 Months (Subjects Under 12 
Months of Age) 


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CT-8.5.2.1.1 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity 
CT-8.5.2.1.2 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Sex:  Male 
CT-8.5.2.1.3 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Sex:  Female 
CT-8.5.2.1.4 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Age:  Less Than 12 Months 
CT-8.5.2.1.5 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Age:  Greater Than or Equal to 12 Months 
CT-8.5.2.1.6 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - With Topical Anti-Inflammatory Agents 
CT-8.5.2.1.7 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Without Topical Anti-Inflammatory Agents 
CT-8.5.2.1.8 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - With Topical Medications Excluding Anti-Inflammatory 
Agents 
CT-8.5.2.1.9 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Without Topical Medications Excluding Anti-
Inflammatory Agents 
CT-8.5.2.1.10 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Onset Timing of Administration of 0.3% OPA-15406 
CT-8.5.2.1.11 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Onset Timing of Administration of 1% OPA-15406 
CT-8.5.2.1.12 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Age:  Less Than 6 Months (Subjects Under 12 Months of 
Age) 
CT-8.5.2.1.13 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and Severity - Age:  Greater Than or Equal to 6 Months (Subjects Under 
12 Months of Age) 
CT-8.5.3.1 Incidence of Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term and CTCAE Grade 


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CT-8.6.1.1.1 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term 
CT-8.6.1.1.2 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Sex:  Male 
CT-8.6.1.1.3 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Sex:  Female 
CT-8.6.1.1.4 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Age:  Less Than 12 Months 
CT-8.6.1.1.5 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Age:  Greater Than or Equal to 12 Months 
CT-8.6.1.1.6 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - With Topical Anti-Inflammatory Agents 
CT-8.6.1.1.7 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Without Topical Anti-Inflammatory Agents 
CT-8.6.1.1.8 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - With Topical Medications Excluding Anti-
Inflammatory Agents 
CT-8.6.1.1.9 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Without Topical Medications Excluding Anti-
Inflammatory Agents 
CT-8.6.1.1.10 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Onset Timing of Administration of 0.3% OPA-15406 
CT-8.6.1.1.11 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Onset Timing of Administration of 1% OPA-15406 
CT-8.6.1.1.12 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Age:  Less Than 6 Months (Subjects Under 12 Months 
of Age) 
CT-8.6.1.1.13 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term - Age:  Greater Than or Equal to 6 Months (Subjects 
Under 12 Months of Age) 
CT-8.6.2.1.1 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity 


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CT-8.6.2.1.2 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Sex:  Male 
CT-8.6.2.1.3 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Sex:  Female 
CT-8.6.2.1.4 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Age:  Less Than 12 Months 
CT-8.6.2.1.5 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Age:  Greater Than or Equal to 12 Months 
CT-8.6.2.1.6 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - With Topical Anti-Inflammatory Agents 
CT-8.6.2.1.7 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Without Topical Anti-Inflammatory Agents 
CT-8.6.2.1.8 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - With Topical Medications Excluding Anti-
Inflammatory Agents 
CT-8.6.2.1.9 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Without Topical Medications Excluding 
Anti-Inflammatory Agents 
CT-8.6.2.1.10 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Onset Timing of Administration of 0.3% 
OPA-15406 
CT-8.6.2.1.11 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Onset Timing of Administration of 1% OPA-
15406 
CT-8.6.2.1.12 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Age:  Less Than 6 Months (Subjects Under 
12 Months of Age) 
CT-8.6.2.1.13 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and Severity - Age:  Greater Than or Equal to 6 Months 
(Subjects Under 12 Months of Age) 
CT-8.6.3.1 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class, Preferred Term and CTCAE Grade 


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CT-8.7.1.1 Incidence of Deaths due to Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term 
CT-8.8.1.1 Incidence of Serious Treatment-emergent Adverse Events by System Organ 
Class and Preferred Term 
CT-8.8.2.1 Incidence of Serious Treatment-emergent Adverse Events by System Organ 
Class, Preferred Term and Severity 
CT-8.8.3.1 Incidence of Serious Treatment-emergent Adverse Events by System Organ 
Class, Preferred Term and CTCAE Grade 
CT-8.9.1.1 Incidence of Treatment-emergent Adverse Events Resulting in 
Discontinuation from Study by System Organ Class and Preferred Term 
CT-8.9.2.1 Incidence of Treatment-emergent Adverse Events Resulting in 
Discontinuation from Study by System Organ Class, Preferred Term and Severity 
CT-8.9.3.1 Incidence of Treatment-emergent Adverse Events Resulting in 
Discontinuation from Study by System Organ Class, Preferred Term and CTCAE Grade 
CT-8.10.1.1 Incidence of Treatment-emergent Adverse Events Resulting in Reduction of 
IMP by System Organ Class and Preferred Term 
CT-8.10.2.1 Incidence of Treatment-emergent Adverse Events Resulting in Reduction of 
IMP by System Organ Class, Preferred Term and Severity 
CT-8.10.3.1 Incidence of Treatment-emergent Adverse Events Resulting in Reduction of 
IMP by System Organ Class, Preferred Term and CTCAE Grade 
CT-8.11.1.1 Incidence of Treatment-emergent Adverse Events Resulting in Interruption 
of IMP by System Organ Class and Preferred Term 
CT-8.11.2.1 Incidence of Treatment-emergent Adverse Events Resulting in Interruption 
of IMP by System Organ Class, Preferred Term and Severity 
CT-8.11.3.1 Incidence of Treatment-emergent Adverse Events Resulting in Interruption 
of IMP by System Organ Class, Preferred Term and CTCAE Grade 
CT-8.12.1 Incidence of Treatment-emergent Adverse Events Greater Than or Equal to 
5% in Any Group by System Organ Class and Preferred Term 
CT-8.13.1 Incidence of Non-Serious Treatment-emergent Adverse Events Greater Than 
or Equal to 5% in Any Group by System Organ Class and Preferred Term 
CT-8.14.1 Incidence of Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term According to Application Site 


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CT-8.15.1 Incidence of Drug-related Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term According to Application Site 
CT-9.1 Listing of Deaths 
CT-9.2 Listing of Serious Adverse Events 
CT-9.3 Listing of Study Drug Discontinuations Due to Adverse Events 
CT-9.4 Incidence of Potential Hy's Law Cases 
CT-9.5 Listing of Potential Hy's Law Cases - by Subject 
CT-10.1.1 Mean Change From Baseline in Laboratory Test Values:  Serum Chemistry 
CT-10.1.2 Mean Change From Baseline in Laboratory Test Values:  Hematology 
CT-10.2.1 Shift Tables of Clinical Laboratory Test Results:  Serum Chemistry 
CT-10.2.2 Shift Tables of Clinical Laboratory Test Results:  Hematology 
CT-10.2.3 Shift Tables of Clinical Laboratory Test Results:  Urinalysis 
CT-11.1 Mean Change From Baseline in Vital Sign Parameters 
 
CF-1.1 Incidence of Responder Rate for Overall IGA Score at Week 4 
CF-1.2.1 Incidence of Responder Rate for Overall IGA Score by Visit - OC 
CF-1.2.2 Incidence of Responder Rate for Overall IGA Score by Visit - Cumulative 
CF-2.1 Incidence of 75% Over Response Rate for Overall EASI Score at Week 4 
CF-2.2.1 Incidence of 75% Over Response Rate for Overall EASI Score by Visit - OC 
CF-2.2.2 Incidence of 75% Over Response Rate for Overall EASI Score by Visit - 
Cumulative 
CF-3.1 Incidence of 90% Over Response Rate for Overall EASI Score at Week 4 
CF-3.2.1 Incidence of 90% Over Response Rate for Overall EASI Score by Visit - OC 
CF-3.2.2 Incidence of 90% Over Response Rate for Overall EASI Score by Visit - 
Cumulative 
CF-4.1 Incidence of 50% Over Response Rate for Overall EASI Score at Week 4 
CF-4.2.1 Incidence of 50% Over Response Rate for Overall EASI Score by Visit - OC 
CF-4.2.2 Incidence of 50% Over Response Rate for Overall EASI Score by Visit - 
Cumulative 


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CF-5.1 Means of Change from Baseline in Overall IGA Score by Visit 
CF-6.1 Means of Change from Baseline in Overall EASI Score by Visit 
CF-6.2 Means of Percent Change from Baseline in Overall EASI Score by Visit 
PKT-1.1 Individual and Summary of OPA-15406 Plasma Concentrations Following 
Multiple Topical Administrations of 0.3% OPA-15406 Ointment to Pediatric Patients 
With Atopic Dermatitis 
PKT-1.2 Individual and Summary of OPA-15406 Plasma Concentrations Following 
Multiple Topical Administrations of 1% OPA-15406 Ointment to Pediatric Patients With 
Atopic Dermatitis 
PKT-2.1 Individual and Summary of OPA-15406 Plasma Concentrations Normalized by 
Dose Derived From Treated Body Surface Area Following Multiple Topical 
Administrations of 0.3% OPA-15406 Ointment to Pediatric Patients With Atopic 
Dermatitis 
PKT-2.2 Individual and Summary of OPA-15406 Plasma Concentrations Normalized by 
Dose Derived From Treated Body Surface Area Following Multiple Topical 
Administrations of 1% OPA-15406 Ointment to Pediatric Patients With Atopic 
Dermatitis 
PKF-1 Mean OPA-15406 Plasma Concentrations Following Multiple Topical 
Administrations of OPA-15406 Ointment to Pediatric Patient With Atopic Dermatitis 


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PKF-2 Mean OPA-15406 Plasma Concentrations Normalized by Dose Derived From 
Treated Body Surface Area Following Multiple Topical Administrations of OPA-15406 
Ointment to Pediatric Patients With Atopic Dermatitis 


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Appendix 3 
List of Subject Data Listings 
PDATA-1 Inclusion and Exclusion Criteria Not Met 
PDATA-2 Subject Disposition 
PDATA-3.1 Medical History 
PDATA-3.2 History of Atopic Dermatitis 
PDATA-4.1 Concomitant Medications:  Medications Taken Prior to Start of Study 
Therapy 
PDATA-4.2 Concomitant Medications:  Medications Taken During Study Therapy 
PDATA-4.3 Concomitant Medications:  Medications Taken After Study Therapy 
PDATA-4.4 Concomitant Medications:  Therapy 
PDATA-5.1 Exposure to Trial Medication 
PDATA-5.2 Listing of Trial Medication by Subject 
PDATA-6 Physical Examination 
PDATA-7 Vital Signs 
PDATA-8 Blood Sampling for Pharmacokinetics 
PDATA-9 Screening Failures 
PDATA-10 Protocol Deviations (Major) - CRF 
PDATA-11 Eczema Area and Severity Index 
PDATA-12 Overall Investigator's Global Assessment of Disease Severity 
PDATA-13 Patient-Oriented Eczema Measure 
PDATA-14 Affected Body Surface Area 
PDATA-15 Treatment Area 
PDATA-16 Patch Application and Removal 
PDATA-17 Treatment Tracking 
DREAS-1 Discontinued Subjects and Reasons for Discontinuations 
DEMOG-1 Demographic Characteristics 
DEMOG-2 Informed Consent 
AE-1 Adverse Events 


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SMED-1 Actual Exposure to Study Medication 
SMED-2 Investigational Medicinal Product Compliance for Number of Administrations 
EFF-1 Change from Baseline in IGA Score and Response with Overall IGA Score 
EFF-2 Change from Baseline in Total EASI Score 
EFF-3 Change from Baseline in EASI Score, Erythema 
EFF-4 Change from Baseline in EASI Score, Induration/Papulation 
EFF-5 Change from Baseline in EASI Score, Excoriation 
EFF-6 Change from Baseline in EASI Score, Lichenification 
EFF-7 Change from Baseline in EASI Score, HEAD/NECK 
EFF-8 Change from Baseline in EASI Score, UPPER LIMBS 
EFF-9 Change from Baseline in EASI Score, TRUNK 
EFF-10 Change from Baseline in EASI Score, LOWER LIMBS 
EFF-11 Change from Baseline in Overall Percentage Affected Body Surface Area 
EFF-12 Change from Baseline in POEM Score 
EFF-13 Efficacy Outcome 
LAB-1 Laboratory Test Results:  Serum Chemistry 
LAB-2 Laboratory Test Results:  Hematology 
LAB-3 Laboratory Test Results:  Urinalysis 
PDEV-1 Summary of Subjects with Major Protocol Deviations by Type of Deviation 
SUBEX-1 Subjects Excluded From Analysis Set