Clinical trial NCT04973228
Conditions: Seborrheic Dermatitis
Sponsor: Arcutis Biotherapeutics, Inc.
Start date: 2021-07-08; Completion date: 2022-04-06
Enrollment: 457 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase 3, double-blind, vehicle-controlled study assessed the safety and efficacy of roflumilast (ARQ-154) foam 0.3% applied once daily (qd) for 8 weeks by participants with seborrheic dermatitis.

Detailed description:

Arms: arm 1: Participants with seborrheic dermatitis apply roflumilast foam 0.3% once daily (QD) for 8 weeks. arm 2: Participants with seborrheic dermatitis apply vehicle foam QD for 8 weeks.
Interventions: intervention 1: Roflumilast Foam intervention 2: Vehicle Foam
Intervention descriptions: intervention 1: Roflumilast 0.3% foam for topical application intervention 2: Vehicle foam for topical application

Protocol documents:
Prot_000.pdf: 
Confidential 
Page 1 of 86 
Title Page 
ARQ-154-304 
A Phase 3, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled 
Study of the Safety and Efficacy of ARQ-154 Foam 0.3% Administered 
QD in Subjects with Seborrheic Dermatitis (STRATUM) 
Sponsor: 
Arcutis Biotherapeutics, Inc. 
3027 Townsgate Road, Suite 300 
Westlake Village, CA 91361 
Sponsor Representative: 
David Berk, MD 
Vice President, Clinical Development 
Tel.:  +1 805 418 5006 Ext. 711 
E-mail: dberk@arcutis.com
IND Number:  
142047 
Protocol Version: 
Amendment 2 
Date:  
05 May 2022 
GCP Statement 
This study is to be performed in full compliance with the protocol, International Conference on Harmonisation Good 
Clinical Practices (ICH GCP), and applicable regulatory requirements. All required study documentation will be 
archived as required by regulatory authorities. 
Confidentiality Statement 
This document contains confidential information. It contains proprietary information of Arcutis Biotherapeutics, Inc. 
Any viewing or disclosure of such information that is not authorized in writing by Arcutis Biotherapeutics, Inc. is 
strictly prohibited. Such information may be used solely for the purpose of reviewing or performing this study. 


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SITE INVESTIGATOR SIGNATURE PAGE 
ARQ-154-304 
A Phase 3, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and 
Efficacy of ARQ-154 Foam 0.3% Administered QD in Subjects with Seborrheic Dermatitis 
SPONSOR: 
Arcutis Biotherapeutics, Inc. 
3027 Townsgate Road, Suite 300 
Westlake Village, CA 91361 
ISSUE DATE: 
05 May 2022 
I have read this protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein, in accordance with the current International Conference on Harmonisation Good 
Clinical Practices (ICH GCPs) and applicable local and regional regulations. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Arcutis Biotherapeutics, Inc.. I will discuss the material with them to 
ensure that they are fully informed about ARQ-154 foam 0.3% and the study. 
I agree that I or my designee will completely inform all subjects in this study concerning the 
pertinent details and purpose of the study prior to their agreement to participate in the study in 
accordance with cGCPs and regulatory authority requirements. I will be responsible for 
maintaining each subject’s consent form in the study file and providing each subject with a 
signed copy of the consent form. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol. 
Investigational Site Name: 
Print Investigator Name: 
Investigator Signature: __________________________________  Date:  _______________ 


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SUMMARY OF CHANGES 
The following sections have been changed in Protocol Amendment 2 of the ARQ-154-304 
protocol: 
Section 
Summary of Changes 
Amendment 2 
4.5.2 Exclusion Criteria 
Exclusion 6: Clarified that Baseline/Screening C-SSRS (for 
adolescents and adults 12 years old and older) indicative of 
suicidal ideation or behavior, whether lifetime or 
recent/recurrent is exclusionary.  
6.3.2 Secondary Endpoint 
Updated  the multiple testing strategy for the secondary 
endpoints to include use of the Fallback Method. 
Appendix 1: Body and Scalp 
Diagram 
Updated scalp diagram. 
Editorial changes made throughout to improve accuracy or readability. 


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TABLE OF CONTENTS 
1.
PROTOCOL SUMMARY ..........................................................................................11 
1.1. 
Synopsis ......................................................................................................................11 
1.2. 
Study Schema .............................................................................................................17 
1.3. 
Schedule of Visits and Assessments ...........................................................................18 
2.
BACKGROUND AND RATIONALE .......................................................................20 
2.1. 
Introduction .................................................................................................................20 
2.2. 
Conclusions on Toxicity Findings ..............................................................................21 
2.3. 
Clinical Studies ...........................................................................................................22 
2.3.1. 
Seborrheic Dermatitis Phase 2a ..................................................................................22 
2.4. 
Rationale for Development .........................................................................................22 
2.4.1. 
Dose Selection ............................................................................................................23 
2.4.2. 
Risks and/or Benefits to Subjects ...............................................................................23 
3.
STUDY OBJECTIVES AND ENDPOINTS ..............................................................24 
3.1. 
Study Objectives .........................................................................................................24 
3.1.1. 
Primary Objective .......................................................................................................24 
3.2. 
Study Endpoints ..........................................................................................................24 
3.2.1. 
Primary Endpoint ........................................................................................................24 
3.2.2. 
Secondary Endpoints ..................................................................................................24 
4.
INVESTIGATIONAL PLAN .....................................................................................25 
4.1. 
Overall Study Design and Plan ...................................................................................25 
4.2. 
Number of Sites and Subjects .....................................................................................25 
4.3. 
Subject Participation ...................................................................................................25 
4.4. 
Subject Identification Number Assignment ................................................................25 
4.5. 
Selection of Study Population ....................................................................................25 
4.5.1. 
Inclusion Criteria ........................................................................................................25 
4.5.2. 
Exclusion Criteria .......................................................................................................26 
4.6. 
Randomization ............................................................................................................28 
4.7. 
Prohibitions and Concomitant Therapy ......................................................................28 
4.8. 
Treatment ....................................................................................................................30 
4.8.1. 
IP Supplies, Packaging, and Labeling ........................................................................30 


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4.8.2. 
Treatment Administration ...........................................................................................30 
4.8.3. 
Treatment Compliance ................................................................................................31 
4.8.4. 
Blinding ......................................................................................................................31 
4.8.5. 
Breaking Treatment Codes .........................................................................................32 
4.8.6. 
Removal of Subjects from Investigational Product ....................................................32 
4.8.7. 
Removal of Subjects from the Study ..........................................................................33 
5.
STUDY PROCEDURES ............................................................................................33 
5.1. 
Safety Assessments .....................................................................................................33 
5.1.1. 
Screening ....................................................................................................................33 
5.1.2. 
Contraception Requirements ......................................................................................34 
5.1.3. 
Baseline .......................................................................................................................35 
5.1.4. 
Physical Examination .................................................................................................35 
5.1.5. 
Vital Signs, Height and Weight ..................................................................................36 
5.1.6. 
Laboratory Tests .........................................................................................................36 
5.1.7. 
Patient Health Questionnaire Depression Scale (PHQ-8) ..........................................37 
5.1.8. 
Patient Health Questionnaire Depression Scale (Modified PHQ-A) ..........................37 
5.1.9. 
Children’s Depression Inventory 2 (Parent Report) ...................................................38 
5.1.10. 
Columbia-Suicide Severity Rating Scale (C-SSRS) ...................................................38 
5.1.11. 
Local Tolerability Assessment ...................................................................................39 
5.1.12. 
Pigmentation Assessment ...........................................................................................40 
5.1.13. 
Adverse Events ...........................................................................................................40 
5.2. 
Efficacy Evaluations ...................................................................................................40 
5.2.1. 
Investigator Global Assessment (IGA) .......................................................................40 
5.2.2. 
Overall Assessment of Erythema ................................................................................41 
5.2.3. 
Overall Assessment of Scaling ...................................................................................41 
5.2.4. 
Worst Itch-Numerical Rating Scale (WI-NRS) ..........................................................42 
5.2.5. 
Scalpdex ......................................................................................................................42 
5.2.6. 
Dermatology Life Quality Index (DLQI) and Children’s Dermatology Life 
Quality Index (CDLQI) ..............................................................................................42 
5.2.7. 
Body Surface Area (BSA) ..........................................................................................43 
5.3. 
Other Evaluations .......................................................................................................43 
5.3.1. 
Pharmacokinetics Assessment ....................................................................................43 


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5.3.2. 
Dermal Imaging ..........................................................................................................43 
5.4. 
Final Study Visit .........................................................................................................43 
5.5. 
Early Termination Visit ..............................................................................................43 
5.6. 
Unscheduled Visit .......................................................................................................44 
5.7. 
Adverse Events ...........................................................................................................44 
5.7.1. 
Adverse Event Definition ...........................................................................................44 
5.7.2. 
Serious Adverse Event ................................................................................................44 
5.7.3. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) .....................................46 
5.7.4. 
Safety Review with Subject ........................................................................................46 
5.7.5. 
Adverse Event Reporting ............................................................................................46 
5.8. 
Reporting Pregnancy ..................................................................................................48 
5.9. 
Treatment Stopping Rules ..........................................................................................48 
6.
DATA ANALYSIS ....................................................................................................49 
6.1. 
Statistical Methods ......................................................................................................49 
6.1.1. 
Determination of Sample Size ....................................................................................50 
6.1.2. 
Subjects to Analyze ....................................................................................................50 
6.1.3. 
Interim Analysis ..........................................................................................................50 
6.1.4. 
Background and Demographic Characteristics ..........................................................50 
6.1.5. 
Study Disposition........................................................................................................51 
6.1.6. 
Protocol Deviations and Eligibility Deviations ..........................................................51 
6.1.7. 
Investigational Product Application Compliance .......................................................51 
6.1.8. 
Pharmacokinetics Analysis .........................................................................................51 
6.2. 
Safety Analysis ...........................................................................................................51 
6.2.1. 
Adverse Events ...........................................................................................................51 
6.2.2. 
Clinical Laboratory Results ........................................................................................51 
6.2.3. 
Vital Signs ..................................................................................................................51 
6.2.4. 
Local Tolerance Assessments .....................................................................................52 
6.2.5. 
Medical History and Physical Examinations ..............................................................52 
6.3. 
Efficacy Evaluation ....................................................................................................52 
6.3.1. 
Primary Endpoint ........................................................................................................52 
6.3.2. 
Secondary Endpoint ....................................................................................................52 
7.
STUDY ADMINISTRATION ...................................................................................53 


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7.1. 
Ethics ..........................................................................................................................53 
7.1.1. 
Ethics Review Board ..................................................................................................53 
7.1.2. 
Ethical Conduct of the Study ......................................................................................53 
7.1.3. 
Subject Information and Consent/Assent ...................................................................53 
7.2. 
Study Completion and Termination ............................................................................54 
7.2.1. 
Study Completion .......................................................................................................54 
7.2.2. 
Study Termination ......................................................................................................54 
7.3. 
Study Monitoring ........................................................................................................54 
7.4. 
Data Quality Assurance ..............................................................................................55 
7.5. 
Data Handling and Record Keeping ...........................................................................55 
7.6. 
Protocol Amendments and Deviations .......................................................................55 
7.7. 
Confidentiality and Privacy ........................................................................................56 
7.8. 
Conflict of Interest ......................................................................................................56 
7.9. 
Report Format .............................................................................................................56 
7.10. 
Publication Policy .......................................................................................................56 
8.
REFERENCES ...........................................................................................................57 
9.
APPENDICES ............................................................................................................58 
APPENDIX 1. BODY & SCALP DIAGRAM ...........................................................................58 
APPENDIX 2. PATIENT HEALTH QUESTIONNAIRE DEPRESSION SCALE 
(PHQ-8) ......................................................................................................................60 
APPENDIX 3. MODIFIED PATIENT HEALTH QUESTIONNAIRE DEPRESSION 
SCALE (PHQ-A) ........................................................................................................61 
APPENDIX 4. CHILDREN’S DEPRESSION INVENTORY 2 (PARENT REPORT) ............62 
APPENDIX 5. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) 
BASELINE/SCREENING VERSION .......................................................................63 
APPENDIX 6. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) 
SINCE LAST VISIT VERSION ................................................................................66 
APPENDIX 7. SCALPDEX .......................................................................................................69 
APPENDIX 8. DERMATOLOGY LIFE QUALITY INDEX (DLQI) ......................................70 
APPENDIX 9. CHILDREN’S DERMATOLOGY LIFE QUALITY INDEX (CDLQI) ...........72 
APPENDIX 10. NIAID DMID TOXICITY TABLE .................................................................74 
APPENDIX 11. COVID-19 STUDY SITE GUIDANCE ..........................................................84 


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LIST OF TABLES 
Table 1: 
Excluded Medications and Treatments .......................................................................29 
Table 2: 
Laboratory Tests .........................................................................................................36 
LIST OF FIGURES 
Figure 1: 
Contraception Requirements for Female Subjects .....................................................35 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE 
Adverse Event 
AMP 
Adenosine Monophosphate 
BSA 
Body Surface Area 
Cmax 
Maximum Concentration 
CDI 
Children’s Depression Inventory 
CDLQI 
Children's Dermatology Life Quality Index 
COPD 
Chronic Obstructive Pulmonary Disease 
eCRF 
Case Report Form 
C-SSRS
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLQI 
Dermatology Life Quality Index 
ERB 
Ethics Review Board 
FDA 
U.S. Food and Drug Administration 
FOCBP 
Female of Childbearing Potential 
GCP 
Good Clinical Practices 
IB 
Investigational Brochure 
IC50 
Half Maximal Inhibitory Concentration 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ID 
Identification 
IGA 
Investigator Global Assessment 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
Kg 
Kilogram 
LED 
Light Emitting Device 
µg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 


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Abbreviation 
Definition 
Mg 
Milligram 
Min 
Minute 
mL 
Milliliter 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
Ng 
Nanogram 
NOAEL 
No Observed Adverse Effect Level 
NRS 
Numeric Rating Score 
P-450
Cytochrome P450 
PDE-4 
Phosphodiesterase 4 
PHQ-8 
Patient Health Questionnaire 
PHQ-A 
Modified Patient Health Questionnaire for Adolescents 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
QD 
Once Daily ("quaque die") 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
US 
United States 
WI-NRS 
Worst Itch Numeric Rating Score 


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1.
PROTOCOL SUMMARY
1.1. 
Synopsis
Name of Sponsor/Company: Arcutis Biotherapeutics, Inc. 
Protocol Number: 
ARQ-154-304 
Phase: 3 
IND: 142047 
Protocol Title: A Phase 3, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled Study 
of the Safety and Efficacy of ARQ-154 Foam 0.3% Administered QD in Subjects with 
Seborrheic Dermatitis 
Clinical Indication: Seborrheic Dermatitis 
Investigational Product: ARQ-154 foam investigational product (IP) will be supplied as 
ARQ-154 foam 0.3%.  The active ingredient in ARQ-154 foam is roflumilast, a 
phosphodiesterase 4 (PDE-4) inhibitor. Matching vehicle foam will contain only excipients of 
ARQ-154 foam. 
Subjects will be randomized 2:1 to receive ARQ-154 foam 0.3% or matching vehicle foam 
once daily (QD) applied to all areas of seborrheic dermatitis. Areas of application will be all 
areas affected including face, scalp, trunk, or intertriginous/genital regions, with a maximum 
BSA of 20%. Subjects should maintain treatment areas with IP for the duration of the study 
regardless of whether treatable areas of seborrheic dermatitis clear. New lesions that appear 
during the treatment period should also be treated. 
Study Design: This is a phase 3, randomized, parallel group, double blind, vehicle-controlled 
study in which ARQ-154 foam 0.3% or vehicle foam is applied QD for 8 weeks to subjects 
9 years of age and older with at least moderate seborrheic dermatitis affecting the scalp and/or 
rest of body. 
Primary Objective: The purpose of this study is to assess the safety and efficacy of ARQ-154 
foam 0.3% administered once daily (QD) vs vehicle foam for 8 weeks in subjects with 
seborrheic dermatitis.   
Study Sites: Approximately 50 sites in North America 
Number of Subjects (planned): 450 
Study Population: Subjects will be male and female children and adolescents (9-17 y/o) and 
adults (≥18 y/o). Subjects will have a minimum Investigator Global Assessment 
(IGA) = ‘Moderate’ (3) for study entry. Randomization will be stratified by study site and 
Baseline disease severity (IGA = 3 or IGA = 4). 


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Duration of Participation for Subjects: Screening (up to 4 weeks) + Treatment phase 
(8 weeks) for a total of up to approximately 12 weeks. 
Main Criteria for Inclusion: 
1. Participants legally competent to sign and give informed consent or
(for children/adolescents) assent with consent of a parent(s) or legal guardian, as
required by local law.
2. Males and females ages 9 years and older (inclusive) at the time of consent.
3. Clinical diagnosis of seborrheic dermatitis of at least 3 months duration at Screening as
determined by the Investigator. Stable disease for the past 4 weeks.
4. Seborrheic dermatitis up to 20% BSA involvement.  Involvement may be of the scalp
and/or face and/or trunk and/or intertriginous areas.
5. An Investigator Global Assessment (IGA) disease severity of at least Moderate (‘3’) at
Baseline.
6. Overall Assessment of Erythema and Overall Assessment of Scaling scores of at least
Moderate (‘2’) at Baseline.
7. Female subjects of childbearing potential (FOCBP) must have a negative serum
pregnancy test at Screening (Visit 1) and negative urine pregnancy test at Baseline
(Visit 2). In addition, sexually active FOCBP must agree to use at least one form of a
highly effective or a barrier method of contraception throughout the trial according to
Contraception Requirements for Female Subjects (see Figure 1).
8. Females of non-childbearing potential must either be premenarchal, post-menopausal
with spontaneous amenorrhea for at least 12 months (post-menopausal status should be
confirmed with FSH testing) or have undergone surgical sterilization according to
Contraception Requirements for Female Subjects (Figure 1).
9. Subjects in good health as judged by the Investigator, based on medical history,
physical examination, vital signs, serum chemistry labs, hematology values, and
urinalysis.
10. Subjects are considered reliable and capable of adhering to the Protocol and visit
schedule according to the Investigator judgment.


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Main Criteria for Exclusion: 
1. Subjects who cannot discontinue treatment with therapies for the treatment of
seborrheic dermatitis prior to the Baseline visit and during the study according to
Excluded Medications and Treatments (Table 1).
2. Planned excessive exposure to treated area(s) to either natural or artificial sunlight,
tanning bed, or other LED.
3. Subjects who cannot discontinue to use of strong systemic P-450 cytochrome inhibitors
e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole,
nefazodone, saquinavir, suboxone and telithromycin for two weeks prior to the
Baseline visit (Visit 2) and during the study.
4. Subjects with PHQ-8 (≥18 years old, inclusive) or modified PHQ-A (adolescents,
12 to 17 years old, inclusive) score ≥10 at Screening or Baseline visits.
5. Subjects (9-11 years old, inclusive) with a CDI-2 (parent report) raw score ≥17 for
females and ≥18 for males at Screening or Baseline visits.
6. History of severe depression, suicidal ideation or behavior, Baseline/Screening
C-SSRS (for adolescents and adults 12 years old and older) indicative of suicidal
ideation or behavior, whether lifetime or recent/recurrent.
7. Previous treatment with ARQ-151 or ARQ-154.
8. Subjects who have received oral roflumilast (Daliresp®, Daxas®), or apremilast
(Otezla®) within the past 4 weeks.
9. Known allergies or hypersensitivity to component(s) of the investigational product
which includes roflumilast, petrolatum, isopropyl palmitate, methylparaben,
propylparaben, diethylene glycol monoethyl ether, hexylene glycol, cetearyl alcohol,
dicetyl phosphate and ceteth-10 phosphate.
10. Known or suspected:
a.
Severe renal insufficiency as evidenced by calculated creatinine clearance
<30 mL/min
b. Moderate to severe hepatic disorders (Child-Pugh B or C)
11. Liver function test results excursions that exceed:
•
AST or ALT > 2x ULN
•
Total bilirubin:
−
1.5x ULN or
−
>ULN and ≤1.5x ULN and direct bilirubin is >35% of total bilirubin
•
ALP ≥ 2x ULN
12. Subjects with active pityriasis/tinea amiantacea.


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13. Subjects with a history or a major surgery within 4 weeks prior to Baseline (Visit 2) or
has a major surgery planned during the study.
14. Subjects with any serious medical condition or clinically significant laboratory
abnormality that would prevent study participation or place the subject at significant
risk, as determined by the Investigator.
15. Subjects with any condition on the treatment area which, in the opinion of the
Investigator, could confound efficacy measurements.
16. Subjects/caregivers unable to apply product to the scalp due to physical limitations if
the subject has current or history of seborrheic dermatitis involving the scalp.
17. Females who are pregnant, wishing to become pregnant during the study, or are
breast-feeding.
18. A clinically relevant history of abuse of alcohol or other drugs within 6 months prior to
Screening.
19. Current or history of cancer within 5 years from Screening with the exception of fully
treated skin basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in
situ of the cervix.
20. Subjects, parent(s)/legal guardian(s) of children/adolescent subjects who are unable to
communicate, read, or understand the local language.
21. Subjects who are family members of the clinical study site, or clinical study staff, or
Sponsor, or family members residing in the same household of enrolled subjects.
22. Any condition that in the Investigator’s assessment would preclude the subject from
participating in the study.
Key Assessments: Safety will be monitored through assessment of application site reaction, 
pigmentation, vital signs/weight, physical examinations, safety labs, and Adverse Events 
(AEs). Safety will also be monitored by C-SSRS, CDI-2 (children 9-11 y/o), and PHQ-8 
(in adults) or modified PHQ-A (adolescents 12-17 y/o) assessments. 
All AEs that occur after the first applications of IP through the end of the study should be 
collected. All SAEs should be collecting starting at Screening. 
Efficacy assessments will be evaluated utilizing: 
•
IGA
•
Overall Assessment of Erythema
•
Overall Assessment of Scaling
•
Worst Itch-Numeric Rating Scale (WI-NRS)
•
Scalpdex, DLQI/CDLQI, and BSA.


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Pharmacokinetic Assessment: 
•
Pharmacokinetic samples (trough) will be collected for all subjects at the Week 4
and Week 8 visits.
Study Endpoints:  
The Primary Efficacy Endpoint will be: 
•
IGA success, defined as an IGA score of ‘clear’ or ‘almost clear’ plus a 2-point
improvement at Week 8
The Secondary Efficacy Endpoints will include: 
•
In subjects with a Baseline WI-NRS pruritus score of ≥4, achievement of a
≥4-point improvement from Baseline in WI-NRS pruritus score at Week 8
(“WI-NRS Success at Week 8”)
•
WI-NRS Success at Week 4
•
WI-NRS Success at Week 2
•
IGA Success at Week 4
•
Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 at Week 8
•
Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at
Week 8
•
Achievement of an IGA score of ‘clear’ at Week 8
•
IGA Success at Week 2
Additional exploratory endpoints will be included in the Statistical Analysis Plan (SAP).  
Statistical Methods: Approximately 450 subjects are planned for this study. 
Approximately 300 subjects will receive ARQ-154 foam 0.3% QD; approximately 
150 subjects will receive matching vehicle foam QD. 
The randomization scheme will be 2:1 (ARQ-154 foam 0.3% QD: matching vehicle QD) 
stratified by study site and Baseline IGA (IGA=3 vs IGA=4). 
This sample size provides >90% power to detect a 25% difference between treatment groups 
on IGA success at α=0.01 using a 2-sided Cochran-Mantel-Haenszel test stratified by the 
randomization factors. The results from a recent phase 2a study (ARQ-154-203) of ARQ-154 
compared to vehicle treatment were used to estimate the treatment difference. Specifically, in 
the phase 2a trial, 73.8% of subjects demonstrated IGA success in the ARQ-154 foam 0.3% 
group and 40.9% of subjects demonstrated IGA success in the vehicle group. 
The number of subjects to be enrolled will also provide sufficient power for the secondary 
endpoints. Additionally, the larger study size is included in order to provide 
additional/sufficient numbers of subjects on ARQ-154 treatment for a safety database. 


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Descriptive statistics will be presented for the subject disposition, demographics, baseline 
characteristics, treatment compliance, efficacy endpoints, and safety data collected in the 
clinical trial. This includes the number and percentage of subjects for binary 
endpoints/categorical data, and mean, SD, median, minimum, and maximum for continuous 
data. 
The primary endpoint of ‘IGA success at Week 8’ will be analyzed using a Cochran-Mantel-
Haenszel test stratified by the randomization factors of the study center and IGA score at 
Baseline (‘moderate’ vs. ‘severe’). The analysis will be performed on the Intention-to-Treat 
(ITT) population and missing data will be imputed using multiple imputations. 
Continuous secondary endpoints will be analyzed using Analysis of Covariance with treatment 
and stratification factors as independent variables. The ITT population will be used, and 
missing data will be imputed using multiple imputation. Binary secondary endpoints will be 
analyzed similarly to the primary endpoint. 
Secondary endpoints will only be tested statistically if the primary endpoint is considered 
statistically significant. To control for multiple comparisons among the secondary endpoints, 
the following multiplicity procedure will be used: 
Upon demonstration of statistical significance of the primary endpoint, the alpha level of 0.01 
will be split between testing of the WI-NRS success endpoints and other secondary efficacy 
endpoints. The testing over the WI-NRS success endpoints and the other secondary efficacy 
endpoints will be sequential, utilizing the Fallback Method for unused alpha. 
For the testing of WI-NRS success endpoints, an alpha level of 0.0033 will be used and will 
use a hierarchical method to first test WI-NRS success at Week 8, followed by WI-NRS at 
Week 4, followed by WI-NRS success at Week 2.  Should all three of these endpoints be 
statistically significant at the 0.0033 level, then this unused alpha will be carried to the other 
secondary endpoint group, which would then be tested at the .0033+.0067=0.01 level. 
An alpha level of 0.0067 (the remainder of the allotted 0.01) or the full 0.01 pending the 
results of the WI-NRS endpoint testing, will be used to hierarchically test IGA Success at 
Week 4, Scaling score of 0 at Week 8, Erythema score of 0 at Week 8, the percentage of 
subjects who attain IGA of 0 at Week 8, and IGA Success at Week 2.All subjects who are 
randomized and receive at least one confirmed dose of investigational product or vehicle foam 
will be included in the safety population. 
Efficacy analyses will be conducted in the ITT population. Sensitivity analyses may be 
conducted in the subset of the ITT population for whom the primary endpoint assessment was 
not missed due to COVID-19 disruption. 
Adverse events will be summarized by preferred term, system organ class, and treatment 
group for all AEs, serious AEs, related AEs, AEs leading to withdrawal from investigational 
product, and AEs leading to withdrawal from study. 


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1.2. 
Study Schema 
Screening (Visit 1) 
Baseline (Visit 2) 
Randomization and Treatment Day 0 
ARQ-154 
Foam 0.3% 
Vehicle 
Foam 
8-Week Treatment Period
(Visits 3, 4, & 5) 
A Phase 3, 8-Week, Parallel Group, Double Blind, 
Vehicle-Controlled Study of the Safety and Efficacy of ARQ-154 
Foam 0.3% Administered in Subjects with Seborrheic Dermatitis 
Approximately 450 children, adolescent and adult subjects with 
seborrheic dermatitis will be randomized 2:1 to receive either: 
•
ARQ-154 foam 0.3%, or
•
Vehicle foam


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1.3. 
Schedule of Visits and Assessments 
Study Procedure 
Screen 
Baseline 
Day 0 
Week 2 
Day 14 
Week 4 
Day 28 
Week 8a 
Day 56 
Visit 
1 
2 
3 
4 
5 
Visit Window 
-4 weeks
± 3 days 
± 5 days 
± 5 days 
Informed consent/assent 
X 
Medical/surgical history, demography 
X 
Physical examinationb 
X 
X 
X 
Fitzpatrick Skin Type 
X 
I/E criteria 
X 
X 
Randomization 
X 
Hematology, Chemistry, and Urinalysisc 
X 
X 
X 
X 
Vital signs, weight, heightd 
X 
X 
X 
X 
X 
IGA, Overall Assessment of Erythema, 
Overall Assessment of Scalinge  
X 
X 
X 
X 
X 
BSAf 
X 
X 
X 
X 
X 
DLQI/CDLQIg, Scalpdex 
X 
X 
X 
X 
X 
Daily WI-NRSh at home (non-clinic) 
Day -7 through Day 56 
Local Tolerability Assessmenti 
X 
X 
X 
Pigmentation Assessmentj 
X 
X 
X 
X 
X 
C-SSRS, CDI-2/PHQ-8/PHQ-Ak
X 
X 
X 
X 
Medical Photographyl 
X 
X 
X 
X 
Serum pregnancy testm 
X 
Urine pregnancy testn 
X 
X 
X 
PK samplingo 
X 
X 
IP application and subject/family trainingp 
X 
X 
Dispense investigational product kitq 
X 
X 
X 
Dispense / review dosing diary 
X 
X 
X 
X 
Weigh investigational productr 
X 
X 
X 
X 
Compliance calculations 
X 
X 
X 
Adverse event assessmentt 
X 
X 
X 
X 
Prior & Concomitant medications 
X 
X 
X 
X 
X 


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Footnotes from table above: 
a
Subjects that terminate early should return to the study site for the Week 8 assessments. 
b
Limited physical examination: skin (including assessment of Fitzpatrick Skin Type at Screening only), lungs, 
and heart only. 
c
To be collected at Screening, Baseline/Day 0, Week 4/Day28, and Week 8/Day 56. For subjects <18 years of 
age, if the Baseline/Day 0 visit occurs within 3 weeks of Screening, the Screening lab results may be utilized. 
d
Height will be collected at Baseline and Week 8. Weight will be collected at all study visits. Subject to void 
prior to weight. 
e
IGA will be a 5-point scale ranging from clear (0) to severe (4). IGA should be completed prior to other 
physician assessments and by the same Evaluator at each study visit. Overall Assessment of Erythema 
(0-3 scale) and Overall Assessment of Scaling (0-3 scale) will be completed. 
f
Total BSA affected by seborrheic dermatitis will be determined by the subject’s hand method, where the 
subject’s hand (including fingers) surface area is assumed to equal 1% of body surface area. 
g
The DLQI will be completed by subjects ≥17 years of age. The CDLQI will be completed for subjects 
9 to 16 years old, inclusive. 
h
WI-NRS will be completed by subjects daily at home starting 7 days prior to the Baseline/Day 0 visit to Day 56 
(Week 8) visit. Daily WI-NRS will be completed in the evening prior to IP application (except at Baseline and 
Week 2 when IP is applied at the clinic). 
i
Local tolerability assessments to be recorded prior to IP application for the Investigator assessment of skin 
irritation (Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s 
‘0-3’ burning/stinging assessment. Note for investigator tolerability assessments: reactions at the site of IP 
application, which may occur post-Baseline, should be differentiated from the preexisting inflammation 
associated with the subject’s seborrheic dermatitis. At Week 4 and Week 8, subjects will provide a recall 
assessment of burning/stinging experienced post IP application on the day prior to the clinic visit. 
j 
An assessment for hypopigmentation and hyperpigmentation will be performed by the Investigator at all visits. 
k 
Adolescents and adults will complete the C-SSRS (12 years of age and older). Adults will complete the PHQ-8. 
Adolescents (ages 12 to 17 inclusive) will complete the PHQ-A (PHQ-9 modified). Parents/caregivers will 
complete CDI-2 (parent report) for children 9-11 years of age, inclusive.  The CDI-2 will be completed 
throughout the study for subjects 9-11 years old at the time of assent.  
l
Medical photography will be obtained for target lesions by all study sites. All efforts will be made to de-identify
the subjects.
m
A serum pregnancy test will be administered to all females of child-bearing potential at the Screening visit only. 
Follicle Stimulating Hormone (FSH) testing will be performed at Screening (if indicated) to confirm post-
menopausal status. 
n
A urine pregnancy test will be performed at the Baseline, Weeks 4 and 8 to all females of child-bearing 
potential. A negative result is required for continued participation in the study, and results must be available at 
each visit prior to dispensing of investigational product. 
o
PK samples (trough) will be collected on Day 28 (Week 4) and Day 56 (Week 8). Ensure investigational
product is not applied in the area where PK will be drawn.
p
Subjects to apply assigned IP in the study site at every designated visit. 
q
Kits will be dispensed based on % BSA. See IP Handling Plan for details. 
r
Each IP canister in the Kit should we weighed and recorded at every visit. See IP Handling Plan for details. 
s
Compliance calculation is described in the IP Handling Plan. 
t
All AEs should be collected starting after the first application of the IP through the end of the study. All SAEs 
should be collected starting after the signing of the informed consent through 30 days after the last day of the IP 
application or the end of the study (whichever is later).  


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2.
BACKGROUND AND RATIONALE
2.1. 
Introduction
Roflumilast is a phosphodiesterase 4 (PDE-4) inhibitor approved globally to reduce the risk of 
exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) associated 
with chronic bronchitis.  Roflumilast and its active metabolite, roflumilast N-oxide, are high 
affinity selective inhibitors of PDE-4 (a major cyclic-3′,5′-adenosine monophosphate 
(cyclic AMP)-metabolizing enzyme), whose activity leads to accumulation of intracellular cyclic 
AMP.  There are four different subtypes of PDE-4: PDE-4a, PDE-4b, PDE-4c, and PDE-4d, each 
with several isoforms (splicing variants).  IC50 values of both roflumilast and roflumilast N-oxide 
for the different PDE-4 isoforms and subtypes are mostly sub-nanomolar and single digit 
nanomolar (Hatzelmann 2010).  The PDE-4 family of enzymes are the most prevalent 
phosphodiesterases in immune cells and inhibition of PDE-4 subtypes has been associated with 
anti-inflammatory effects in many biological systems. 
Roflumilast was initially developed as a 500 µg tablet for oral therapy in patients with COPD, 
and as such has been thoroughly evaluated in nonclinical studies.  The safety profile is 
well-established, and the results of those studies are relevant to the dermal roflumilast 
(ARQ-151 cream and ARQ-154 foam) development program.  Oral roflumilast (500 µg tablet) 
was approved by Health Canada as DAXAS® in December 2010 and by the US FDA as 
DALIRESP® in February 2011 for the treatment of COPD.  The study sponsor has conducted 
nonclinical studies in which roflumilast is applied dermally. 
The dermal nonclinical program for ARQ-151 cream followed current International Conference 
on Harmonisation (ICH) guidelines and includes a 13-week dermal toxicity study in minipigs, a 
13-week dermal toxicity study in mice, a 39-week dermal toxicity study in minipigs, a skin
sensitization study in guinea pigs, a phototoxicity study, an eye irritation study and a 104-week
carcinogenicity study in mice, the in life portion of which is complete.
Refer to the current ARQ-154 Investigator’s Brochure (IB) for the most current PDE-4 dermal 
and oral/systemic nonclinical and clinical information. 
Seborrheic dermatitis is a common, chronic inflammatory skin disease characterized by 
erythematous, scaly plaques, often with a yellowish, oily, moist, and/or greasy appearance, 
affecting areas of sebaceous gland abundance.  Frequently involved sites include the scalp 
(including retroauricular areas), eyebrows, ears, nasolabial folds, eyelids, trunk, and 
intertriginous areas.  There may be associated pruritus and/or pigmentary changes.  Seborrheic 
dermatitis affects about 2% of the adult population (Borda 2015, Dessinioti 2013) and occurs in 
the adolescent population as well.  Treatment of seborrheic dermatitis may vary by location on 
the body involved, eg, scalp or non-scalp and periocular or not.  For the scalp, anti-dandruff 
shampoos are often used such as anti-fungals, zinc products, selenium sulfide, salicylic acid, or 
tar.  Topical corticosteroid products may also be used.  Scalp lesions of seborrheic dermatitis can 
present a particular treatment challenge and form thick crusts which may not respond to topical 
steroids or antifungals.  On non-scalp regions such as the face, topical antifungals or low potency 
topical corticosteroids are typically used.  However, importantly, topical antifungals may 
demonstrate limited efficacy and topical steroids may demonstrate tachyphylaxis and cause 


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important adverse events, particularly on the face, such as telangiectasias, acne, atrophy, rosacea, 
and ocular complications.  Since seborrheic dermatitis is a chronic condition, treatment with 
topical steroids is particularly problematic due to the need for prolonged treatment duration, 
which may result in side effects.  Other medications which have been used for seborrheic 
dermatitis include topical sulfur/sulfonamide products, topical calcineurin inhibitors, and oral 
retinoids. 
Given the unmet need for new medical therapies for seborrheic dermatitis, and the precedent of 
topical anti-inflammatory agents as treatments for seborrheic dermatitis, the Sponsor pursued 
development of ARQ-154 foam for the treatment of seborrheic dermatitis.  Relative to topical 
formulations such as a cream or gel, the foam formulation in the present study is well suited for 
the treatment of the scalp, where seborrheic dermatitis may predominate and be most difficult to 
treat.  Foams have the ability to access skin lesions in hair-bearing areas and have commonly 
been used for treating scalp psoriasis (e.g., Olux® and Luxiq® foams) and seborrheic dermatitis 
(e.g., Extina® foam).  Results of the phase 2a study of ARQ-154 foam 0.3% in adults with 
seborrheic dermatitis suggest that ARQ-154 may be a highly efficacious and well-tolerated novel 
topical treatment. 
Arcutis is also developing a related cream formulation of roflumilast, ARQ-151 cream. A phase 
3 program of ARQ-151 cream 0.3% for plaque psoriasis recently completed, and phase 2 results 
of ARQ-151 cream 0.15% and 0.05% for atopic dermatitis are available. The composition of 
ARQ-154 topical roflumilast foam includes minimal qualitative or quantitative changes relative 
to the composition of ARQ-151 topical roflumilast cream.  Compared to ARQ-151, ARQ-154 
foam also involves addition of a propellant that is eliminated at delivery.  Since the composition 
of ARQ-154 foam is very close to the composition of ARQ-151 cream, Arcutis plans to rely on 
the nonclinical development program for ARQ-151 topical cream, as detailed below, in order to 
support the ARQ-154 foam development program. 
2.2. 
Conclusions on Toxicity Findings 
The safety profile of oral roflumilast is well-established.  An extensive systemic toxicity program 
that evaluated both roflumilast and its active N-oxide metabolite in multiple species via the oral 
route of administration was conducted to support registration of the 500 µg tablet for COPD. 
The previously conducted systemic toxicity program included studies to evaluate reproductive 
toxicity, genotoxicity and carcinogenicity, and the results of those studies are included in the 
labeling for oral roflumilast. 
To support the development of ARQ-151 topical cream a GLP-compliant dermal toxicity 
program is being conducted.  To date, no new risks have been identified through the dermal 
toxicity program.  In the 13-week dermal toxicity studies in minipigs and mice, and a 39-week 
dermal toxicity study in minipigs, no evidence of systemic toxicity was observed.  
Histopathological evaluation of skin in the minipig study included very slight to slight erythema 
at all treatment levels, and minor degrees of irritation such as hyperplasia.  The NOAEL in both 
studies was the 1% concentration of ARQ-151 (20 mg/kg), the highest dose administered and the 
maximum feasible concentration. 


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Across the dermal and systemic toxicology programs, the exposure to parent drug and N-oxide 
metabolite differs by route and species. While exposure to roflumilast and its active metabolite 
are likely to be higher following topical administration of ARQ-151 relative to oral 
administration, when the margins from the toxicity studies are considered as a whole, the 
NOAELs across routes and species provide assurance that the anticipated exposures with 
ARQ-151 cream will be safe. 
2.3. 
Clinical Studies 
2.3.1. 
Seborrheic Dermatitis Phase 2a 
ARQ-154-203 (NCT 04091646) was a Phase 2a, parallel group, double blind, vehicle-controlled 
study that evaluated ARQ-154 foam 0.3% for the treatment of seborrheic dermatitis involving 
the scalp, face, and/or body. ARQ-154 foam 0.3% or matching vehicle was applied once daily 
(QD) for eight weeks to adult subjects with a minimum Investigator Global Assessment (IGA) of 
moderate (IGA of 3 on a 5-point scale from 0 to 4). A total of 226 subjects were randomized at a 
ratio of 2:1 to receive ARQ-154 foam 0.3% or matching vehicle foam. All randomized subjects 
were included in both the safety and intent-to-treat (ITT) populations. 
The study demonstrated that ARQ-154 foam 0.3% was highly efficacious (including early 
timepoints), safe, and well-tolerated following once-daily topical application in subjects with 
moderate to severe seborrheic dermatitis. The study’s primary endpoint was IGA Success, 
defined as achievement of an IGA score of ‘clear’ or ‘almost clear’ PLUS a 2-grade 
improvement from Baseline at Week 8. This endpoint was met with IGA success in 73.8% of 
subjects in the ARQ-154 treatment group vs. 40.9% of vehicle-treated subjects (p<0.0001).  IGA 
success was greater with ARQ-154 than vehicle starting at the first post-baseline visit at Week 2 
(33.8% of ARQ-154 vs 14.5% of vehicle subjects, p=0.0029). Worst Itch-Numeric Rating Scale 
(WI-NRS) success at Week 8, defined as a ≥4-point improvement from Baseline was 64.6% for 
ARQ-154 vs. 33.3% for vehicle (p=0.0006), with statistical significance as early as Week 2 
(52.8% for ARQ-154 vs 22.8% for vehicle, p=0.0005). 
ARQ-154 foam 0.3% was safe and demonstrated excellent tolerability based on adverse event 
(AE) reporting and both investigator-rated and subject-rated local tolerability assessments.  No 
serious adverse events (SAEs) were reported, and only a few subjects reported treatment-related 
adverse events (TEAEs) (1.9% with ARQ-154 and 4.2% with vehicle) or discontinued study 
drug due to AEs (1.3% with ARQ‑154 and 2.8% with vehicle).  Most (>90%) TEAEs were grade 
1 or grade 2, i.e., mild or moderate.  Systemic exposure to roflumilast and roflumilast N-oxide in 
subjects with seborrheic dermatitis treated with ARQ-154 foam 0.3% appeared comparable to 
that of subjects with psoriasis treated with ARQ‑151 cream 0.3%, when adjusted for body 
surface area (BSA). 
2.4. 
Rationale for Development 
The development plan for ARQ-154 foam will leverage experience to date with ARQ-151 cream, 
which has been safe, well tolerated, and effective in multiple Phase 2 studies for the treatment of 
plaque psoriasis or atopic dermatitis.  Given the unmet need for new medical therapies for 
seborrheic dermatitis and the results of a phase 2a study of ARQ-154 foam 0.3% in seborrheic 


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dermatitis, the Sponsor is pursuing development of ARQ-154 foam 0.3% for the treatment of 
seborrheic dermatitis in this phase 3 study.  Relative to topical formulations such as a cream or 
gel, the foam formulation in the present study is expected to be well suited for the treatment of 
the scalp, where seborrheic dermatitis may predominate. 
2.4.1. 
Dose Selection 
ARQ-154 foam at 0.3% was selected for this study to match the dose of ARQ-154 foam from the 
phase 2a study ARQ-154-203. The 0.3% dose is also consistent with the dose of the related 
roflumilast cream formulation (ARQ-151 cream 0.3%) which is being evaluated in phase 3 for 
plaque psoriasis. The 0.3% dose for ARQ-151 cream was selected based on results of the phase 
2b study plaque psoriasis study ARQ-151-201, in which the 0.3% concentration demonstrated 
greater efficacy that the 0.15% concentration.  In that phase 2b study, there were no differences 
in the safety profiles of the two doses, supporting that it was not necessary to evaluate doses less 
than 0.3% in seborrheic dermatitis.  The Sponsor expects similar doses to be safe and effective in 
seborrheic dermatitis, as supported by the phase 2a seborrheic dermatitis study ARQ-154-203. 
Additionally, many cases of seborrheic dermatitis may be challenging to treat or refractory to 
standard treatment (particularly in patients with neurologic conditions, as included here) and the 
Sponsor is targeting greater efficacy than commonly used topical antifungals and low potency 
steroids, further supporting the choice to evaluate the 0.3% dose. 
Consistent with the close similarities between ARQ-151 and ARQ-154 formulations, study 
ARQ-154-203 demonstrated comparable pharmacokinetics with ARQ-154 foam as have been 
described with ARQ-151 cream.  Additionally, pharmacokinetics in seborrheic dermatitis 
appeared comparable to those seen in plaque psoriasis and atopic dermatitis. 
2.4.2. 
Risks and/or Benefits to Subjects 
Based on efficacy data from subjects randomized to active treatment group of the phase 2a study 
ARQ-154-203, including at Week 2, it is expected that subjects in the present study 
ARQ-154-304 will experience improvement in their seborrheic dermatitis.  Subjects randomized 
to the vehicle treatment group may also see some improvement as the formulation of ARQ-154 
may have a moisturizing effect. 
The safety monitoring practices employed in this protocol (i.e., physical examinations, vital 
signs/weight, local skin toleration assessments, hematology, serum chemistry, urinalysis, 
PHQ-8/PHQ-A/CDI-2, C-SSRS and AE questioning) are adequate to protect the subjects’ safety 
and should detect expected AEs.  The lack of nausea and vomiting seen in ARQ-151 cream and 
ARQ-154 foam studies to date may be related to the lack of ‘peak to trough’ Cmax variation, 
lower Cmax values than observed following oral administration, or bypassing of the 
gastrointestinal tract with topical administration. 
Oral roflumilast has now been used for almost a decade in the treatment of COPD exacerbations 
and its safety record has been well-documented.  The known adverse effects of oral treatment in 
the COPD population (nausea, diarrhea, weight loss, psychiatric AEs) are readily monitored as 
specific in this protocol. The current protocol is designed to detect these adverse events and 
others should they occur, and provides guidance for management, as necessary, to ensure patient 
safety.  Furthermore, the safety profiles of ARQ-151 and ARQ-154 at doses ranging from 


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0.15% to 0.5% in the preceding studies in seborrheic dermatitis and psoriasis suggests that 
ARQ-154 foam 0.3% will be similarly safe and well tolerated in the present study. 
3.
STUDY OBJECTIVES AND ENDPOINTS
3.1. 
Study Objectives 
3.1.1. 
Primary Objective 
The primary objective of this study is to assess the safety and efficacy of ARQ-154 foam 
0.3% administered once daily (QD) vs vehicle foam for 8 weeks in subjects with seborrheic 
dermatitis. 
3.2. 
Study Endpoints 
3.2.1. 
Primary Endpoint 
The primary efficacy endpoint in this study is success in Investigator Global Assessment (IGA) of 
disease severity, defined as an IGA score of ‘clear’ or ‘almost clear’ plus a 2-point improvement 
at Week 8. 
3.2.2. 
Secondary Endpoints 
The Secondary Efficacy Endpoints will include: 
•
In subjects with a Baseline WI-NRS pruritus score of ≥4, achievement of a ≥4-point
improvement from Baseline in WI-NRS pruritus score at Week 8 (“WI-NRS Success
at Week 8”)
•
WI-NRS Success at Week 4
•
WI-NRS Success at Week 2
•
IGA Success at Week 4
•
Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 at Week 8
•
Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at Week 8
•
Achievement of an IGA score of ‘clear’ at Week 8
•
IGA Success at Week 2
Additional exploratory endpoints will be included in the SAP. 


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4.
INVESTIGATIONAL PLAN
4.1. 
Overall Study Design and Plan 
This is a phase 3, parallel group, double blind, vehicle-controlled study in which ARQ-154 foam 
0.3% or vehicle foam is applied QD x 8 weeks to subjects 9 years of age and older with at least 
moderate seborrheic dermatitis affecting the scalp and/or rest of body.  
4.2. 
Number of Sites and Subjects 
A total of up to approximately 450 subjects will be enrolled at approximately 50 study sites in 
North America. Additional countries or study sites may be added, as necessary. Subjects will be 
male and female children (9 - 11 y/o), adolescents (12 - 17 y/o) and adults (≥18 y/o). Subjects 
will have an IGA of disease severity of at least Moderate (‘3’) at Baseline. Subjects must have no 
more than 20% BSA of seborrheic dermatitis. All lesions on a subject will be treated including 
the scalp, face, trunk, and intertriginous areas. 
4.3. 
Subject Participation 
Subject participation involves a minimum of 5 clinic visits, including Screening, Baseline/Day 0, 
Week 2, Week 4, and Week 8. The interval between Screening and Baseline visits may take up 
to 4 weeks, the anticipated maximum duration of subject participation is 12 weeks. 
4.4. 
Subject Identification Number Assignment 
All subjects who sign an informed consent or assent (children/adolescents) form will be assigned 
a unique 5-digit subject identification (ID) number by the interactive web response system 
(IWRS). The first 2 digits correspond to the study site number (assigned by the Sponsor), the 
next 3 digits (starting with 800) correspond to the sequential order in which the subject is 
screened for the study (e.g., Subject ID <11800>: Site 11, subject number 800, as the first subject 
screened by that site). The subject ID will remain the same in the event the subject is rescreened. 
The study site is responsible for maintaining a current log of subject ID number assigned to each 
subject. The subject ID number will be used to identify the subject throughout the study and is 
required to be entered on all clinical study documentation (e.g., case report forms, labeling of 
clinical materials and sample containers, investigational product accountability logs, etc.). 
4.5. 
Selection of Study Population 
4.5.1. 
Inclusion Criteria 
Subjects must fulfill all the following inclusion criteria to be eligible for participation in the 
study: 
1. Participants legally competent to sign and give informed consent or
(for children/adolescents) assent with consent of a parent(s) or legal guardian, as required
by local law.
2. Males and females ages 9 years and older (inclusive) at the time of consent.


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3. Clinical diagnosis of seborrheic dermatitis of at least 3 months duration at Screening as
determined by the Investigator. Stable disease for the past 4 weeks.
4. Seborrheic dermatitis up to 20% BSA involvement.  Involvement may be of the scalp
and/or face and/or trunk and/or intertriginous areas.
5. An Investigator Global Assessment (IGA) disease severity of at least Moderate (‘3’) at
Baseline.
6. Overall Assessment of Erythema and Overall Assessment of Scaling scores of at least
Moderate (‘2’) at Baseline.
7. Female subjects of childbearing potential (FOCBP) must have a negative serum
pregnancy test at Screening (Visit 1) and negative urine pregnancy test at Baseline
(Visit 2). In addition, sexually active FOCBP must agree to use at least one form of
highly effective or a barrier method of contraception throughout the trial according to
Contraception Requirements for Female Subjects (see Figure 1).
8. Females of non-childbearing potential must either be premenarchal, post-menopausal
with spontaneous amenorrhea for at least 12 months (post-menopausal status should be
confirmed with FSH testing) or have undergone surgical sterilization according to
Contraception Requirements for Female Subjects (Figure 1).
9. Subjects in good health as judged by the Investigator, based on medical history, physical
examination, vital signs, serum chemistry labs, hematology values, and urinalysis.
10. Subjects are considered reliable and capable of adhering to the Protocol and visit
schedule according to the Investigator judgment.
4.5.2. 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria will be excluded from participation in 
the study: 
1. Subjects who cannot discontinue treatment with therapies for the treatment of seborrheic
dermatitis prior to the Baseline visit and during the study according to Excluded
Medications and Treatments (Table 1).
2. Planned excessive exposure to treated area(s) to either natural or artificial sunlight,
tanning bed, or other LED.
3. Subjects who cannot discontinue to use of strong systemic P-450 cytochrome inhibitors
e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole,
nefazodone, saquinavir, suboxone and telithromycin for two weeks prior to the Baseline
visit (Visit 2) and during the study.
4. Subjects with PHQ-8 (≥18 years old, inclusive) or modified PHQ-A
(adolescents, 12 to 17 years old, inclusive) score ≥10 at Screening or Baseline visits.
5. Subjects (9-11 years old, inclusive) with a CDI-2 (parent report) raw score ≥17 for
females and ≥18 for males at Screening or Baseline visits.


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6. History of severe depression, suicidal ideation or behavior, Baseline/Screening C-SSRS
(for adolescents and adults 12 years old and older) indicative of suicidal ideation or
behavior, whether lifetime or recent/recurrent.
7. Previous treatment with ARQ-151 or ARQ-154.
8. Subjects who have received oral roflumilast (Daliresp®, Daxas®), or apremilast (Otezla®)
within the past 4 weeks.
9. Known allergies or hypersensitivity to component(s) of the investigational product which
includes roflumilast, petrolatum, isopropyl palmitate, methylparaben, propylparaben,
diethylene glycol monoethyl ether, hexylene glycol, cetearyl alcohol, dicetyl phosphate
and ceteth-10 phosphate.
10. Known or suspected:
a.
Severe renal insufficiency as evidenced by calculated creatinine clearance
<30 mL/min
b. Moderate to severe hepatic disorders (Child-Pugh B or C)
11. Liver function test results that exceed:
•
AST or ALT > 2x ULN
•
Total bilirubin
−
1.5x ULN or
−
>ULN and ≤1.5x ULN and direct bilirubin is >35% of total bilirubin
•
ALP ≥ 2x ULN
12. Subjects with active pityriasis/tinea amiantacea.
13. Subjects with a history or a major surgery within 4 weeks prior to Baseline (Visit 2) or
has a major surgery planned during the study.
14. Subjects with any serious medical condition or clinically significant laboratory
abnormality that would prevent study participation or place the subject at significant risk,
as determined by the Investigator.
15. Subjects with any condition on the treatment area which, in the opinion of the
Investigator, could confound efficacy measurements.
16. Subjects/caregivers unable to apply product to the scalp due to physical limitations if the
subject has current or history of seborrheic dermatitis involving the scalp.
17. Females who are pregnant, wishing to become pregnant during the study, or are
breast-feeding.
18. A clinically relevant history of abuse of alcohol or other drugs within 6 months prior to
Screening.


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19. Current or history of cancer within 5 years from Screening with the exception of fully
treated skin basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in
situ of the cervix.
20. Subjects, parent(s)/legal guardian(s) of children/adolescent subjects who are unable to
communicate, read, or understand the local language.
21. Subjects who are family members of the clinical study site, or clinical study staff, or
Sponsor, or family members residing in the same household of enrolled subjects.
22. Any condition that in the Investigator’s assessment would preclude the subject from
participating in the study.
4.6. 
Randomization 
Randomization will take place at the Baseline (Day 0) visit after the Investigator confirms the 
subject to be fully eligible for participation as outlined in Section 4.5. Subjects will be randomly 
assigned to apply ARQ-154 foam 0.3% QD or vehicle foam QD. Assignment of ARQ-154 or 
vehicle will be made at a 2:1 ratio and stratified by study site and baseline disease severity 
(IGA = 3 or IGA = 4) according to a computer-generated randomization list. Kits containing 
canisters of IP will be assigned to each subject using the IWRS. A subject may receive more than 
one kit for the treatment period. The kits and canisters are blinded and each kit is numbered with 
a unique kit number.  
4.7. 
Prohibitions and Concomitant Therapy 
Prohibited medications and products are detailed in Table 1. 
Generally, the addition of new medications, including nonprescription medications, during the 
study is discouraged.  However, the short-term use of a medication may be authorized by the 
Investigator.  The Investigator must make the decision to authorize the use of any such a 
medication only after consideration of the clinical situation, the potential for masking symptoms 
of a more significant underlying event, and whether the use of the medication will compromise 
the outcome or validity of the clinical investigation.  If medication is required, the name, 
strength, frequency, duration of use, and reason for use will be recorded in source documents and 
transcribed to Case Report Forms.  Medications which have been used chronically by subjects, in 
particular statins and anti-hypertensives, are allowed for use during the study, except as 
prohibited in ‘Excluded Medications and Treatments’ (Table 1).  


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Table 1: 
Excluded Medications and Treatments 
Excluded Medications and Treatments 
Wash Out Period Prior to Baseline 
(Day 0) 
Etanercept 
4 weeks 
All other Biologics 
12 weeks or 5 half-lives, which is longer 
Systemic treatment with antifungal agents, corticosteroids, 
immunosuppressive therapies, retinoids, roflumilast, or 
Otezla® 
4 weeks 
Topical antifungals, corticosteroids, calcineurin inhibitors, 
sulfur-based treatments, medical devices, Eucrisa®, azelaic 
acid, or metronidazole 
2 weeks 
Medicated shampoos (e.g., coal tar, keratolytics including 
salicylic acid, antifungals, zinc pyrithione, selenium 
sulfide, corticosteroids, medical devices) 
2 weeks 
Topical medications used on the scalp for conditions 
besides seborrheic dermatitis, e.g., use of topical minoxidil 
for androgenetic alopecia 
2 weeks 
Phototherapy, tanning beds, other light emitting devices 
4 weeks 
Investigational drugs 
12 weeks (biologics) or 5 half-lives, 
whichever is longer; 
5 half-lives (orals); 
2 weeks (topical) 
Strong systemic P-450 cytochrome inhibitors 
(e.g., indinavir, nelfinavir, ritonavir, clarithromycin, 
itraconazole, ketoconazole, nefazodone, saquinavir, 
suboxone and telithromycin).  
2 weeks 
Intravenous administration of antibiotics or antiviral agents 
1 week 
Note: 
1.
Eye drop and nasal corticosteroid preparations are allowed.  Inhaled corticosteroid preparations are
allowed if used for a stable condition and at a stable dose for > 28 days before Screening and are
continued at the same dose throughout the study.
2.
Non-medicated emollients, moisturizers and sunscreens will be allowed once daily as normally used by
the subjects and applied at least 3 hours after application of investigational product to untreated areas
only.
3.
Only non-medicated shampoos are permitted. Medicated shampoos (e.g., coal tar, keratolytics including
salicylic acid, antifungals, zinc pyrithione, selenium sulfide, corticosteroids, medical devices) are
prohibited.  Subjects should not use other hair products for at least an hour before or after application of
investigational product.


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4.8. 
Treatment 
4.8.1. 
IP Supplies, Packaging, and Labeling 
The active ingredient in ARQ-154 foam is roflumilast, a phosphodiesterase 4 (PDE-4) inhibitor. 
Matching vehicle foam will contain only excipients of ARQ-154 foam. ARQ-154 foam 0.3% or 
vehicle foam will be provided in a canister containing approximately 60 grams of foam. Two 
canisters of IP will be packaged in each kit. The number of kits dispensed to a subject will be 
based on the BSA involvement. The kits and canisters will be labeled with a unique number to 
maintain blinding. 
The Sponsor will supply sufficient quantities of the IP (ARQ-154 foam 0.3%, and matching 
vehicle) to each site to allow for completion of this study. 
Records will be made of the receipt and dispensing of the investigational product supplied. At 
the conclusion of the study, any unused investigational product will be returned to the Sponsor or 
designee, or destroyed, as per Sponsor instructions. 
Refer to the most current version of the IP Handling Manual for details on the accountability, 
storage, and management of ARQ-154 and matching vehicle. 
4.8.2. 
Treatment Administration 
Initial treatment with the IP will occur on Day 0. At the randomization visit (Baseline), the study 
staff will demonstrate to the subject how to apply ARQ-154 foam 0.3% or vehicle foam using 
the first canister from the kit that is assigned to the subject at randomization. Study site staff will 
be trained to ensure a proper amount is dispensed from the foam can and applied to seborrheic 
dermatitis lesion(s) as a thin film and rubbed in thoroughly but gently, until the ‘white’ has 
disappeared. For scalp lesions, special attention should be given to ensuring adequate 
investigational product is applied to scalp skin and not rubbed off on hair. The subject will 
then practice dispensing a similar amount of investigational product and applying to seborrheic 
dermatitis lesion(s).  The study staff will confirm that the subject’s application technique is 
correct. 
Subjects will be instructed to apply IP QD in the evening (except at Baseline and Week 2, in 
which case IP will be applied at the study site) to areas of seborrheic dermatitis lesions identified 
by the Investigator at Baseline using a Body and Scalp Diagram (see Appendix 1). IP will be 
applied at least 20 minutes before going to bed. 
For Scalp Lesions: IP will be applied when the skin and hair on the scalp is dry.  Subjects should 
dispense IP on their fingers, then part hair where there are lesions and rub IP into scalp skin. As 
the IP is applied, the subject should move any hair away to ensure that sufficient foam is applied 
directly to the affected skin on the scalp. Subjects should not use other hair products for at least 
an hour before or after application. 
For Non-scalp Lesions: IP should be applied to affected areas as a thin layer and rubbed in 
thoroughly but gently until the foam has disappeared. 


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Subjects should not wash areas (or otherwise expose to water, e.g., swimming) where ARQ-154 
foam or vehicle has been applied until at least 4 hours after IP application and preferably not 
until the following morning. 
Subjects should continue to apply the IP to all treatment areas identified by the Investigator at 
Baseline using the Body and Scalp Diagram (see Appendix 1), even if that area has cleared 
during the treatment period. New lesions that develop during the study should be treated as well. 
Application will be to all areas affected including the face, scalp, trunk, and intertriginous areas. 
A Body and Scalp Diagram should be used to record existing and new areas of seborrheic 
dermatitis involvement that are subject to treatment.  
Parents/caregivers should wash their hands with soap and water after applying IP to a child. 
Parents/caregivers who are pregnant or women of childbearing potential who are trying to 
become pregnant, or who are breastfeeding, or planning to breastfeed during the study should 
avoid accidental exposure by either avoiding applying IP or by wearing gloves during its 
application. 
4.8.3. 
Treatment Compliance 
Weight of the IP applied will be measured for reporting purposes. Each IP canister will be 
weighed individually prior to dispensing at the Baseline visit or subsequent visits. IP canisters 
must be returned by subjects at each study visit (both empty and full) and will be weighed 
individually. Record IP canister weight in the source notes and in the eCRF. 
Subjects will complete a daily diary recording the date and time of each IP dose applied, any 
missed doses, and any relevant comments (e.g., potential AEs or reason for missed dose).  Site 
personnel will review the diary at each visit and use the information to question the subject 
regarding compliance and AEs and then record appropriate information in source documents and 
complete eCRFs. If a subject misses a scheduled dose, they should be instructed to return to the 
protocol IP administration schedule (i.e., if subject forgets a dose they should wait until that 
evening and apply as usual). 
A subject will be considered compliant with the dosing regimen if the subject applies at least 
80% of the expected applications during the entire IP application period (Baseline to Week 8) 
and does not miss more than 3 consecutive doses. 
Compliance will be assessed by review of the dosing diary. Re-training will be conducted at 
subsequent visits as needed, i.e., if the returned canister weighs substantially different than the 
expected weight, the diary shows less than 80% of expected use, or more than 3 consecutive 
doses are missed. 
Compliance will be documented in the source and eCRF. 
4.8.4. 
Blinding 
This is a double-blinded study, therefore neither the subjects nor the Investigator, clinical 
personnel, or Sponsor will be aware of which treatment an individual subject receives. 


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4.8.5. 
Breaking Treatment Codes 
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the Investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Refer to the current version of the ARQ-154-304 IWRS Plan for details on 
unblinding. Treatment assignment should, however, remain blinded unless the assignment 
knowledge is necessary to determine subject emergency medical care. The rationale for 
unblinding must be clearly explained in source documentation and on the eCRF, along with the 
date on which the treatment assignment was obtained. The Investigator is requested to contact 
the Medical Monitor promptly in the event of any treatment unblinding. 
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the Investigator, the subject will have the study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject. 
4.8.6. 
Removal of Subjects from Investigational Product 
A subject may discontinue from receiving the IP for any of the following reasons: 
•
Occurrence of any medical condition or circumstance that, in the opinion of the
Investigator, exposes the subject to substantial risk and/or does not allow the subject
to adhere to the requirements for IP administration as per the Protocol.
•
Occurrence of or considerable worsening of an AE (described in Section 5.7) that, in
the opinion of the Investigator in consultation with the Medical Monitor and Sponsor,
represents an unacceptable risk to the subject if he/she continues in the study.
The Investigator must follow the subject until the AE resolves or satisfactorily
stabilizes.
•
IP application must be discontinued immediately in the event of a female subject’s
pregnancy.
•
Subject’s decision to withdraw from receiving IP.
•
Weight loss of >5% from Baseline, if not dieting or intentionally trying to lose
weight, at the Investigator’s discretion and after consultation with the
Medical Monitor and Sponsor.
•
C-SSRS indicative of suicidal ideation
•
PHQ-8/PHQ-A score ≥15 if determined by Investigator in consultation with a mental
health professional.
•
CDI-2 raw score of ≥32 if determined by Investigator in consultation with a mental
health professional.
•
Requirement for use of prohibited concomitant medication (Table 1) after
consultation with the Sponsor and Medical Monitor.
•
Subjects repeated failure to comply with protocol requirements or study related
procedures.


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4.8.7. 
Removal of Subjects from the Study 
A subject may be removed from study participation for any of the following reasons: 
•
Subject’s decision to withdraw from the study.
•
Subject’s death.
•
Subject is lost to follow-up. A subject will be considered lost to follow-up after three
phone and three email attempts and documentation of a certified letter sent to the
subject’s address.
•
Termination of the study by the Sponsor, FDA, or other regulatory authorities.
5.
STUDY PROCEDURES
The Schedule of Visits and Assessments (Section 1.3) summarizes the clinical procedures to be 
performed at each visit. Individual clinical procedures are described in detail below. Additional 
evaluations/testing may be deemed necessary by the Investigator and/or the Sponsor for reasons 
related to subject safety. 
5.1. 
Safety Assessments 
This study assesses the safety and efficacy of ARQ-154 foam 0.3%. Safety will be determined by 
evaluating physical examinations, vital signs/weight, local tolerability assessments, 
pigmentation, clinical laboratory parameters, PHQ-8/PHQ-A/CDI-2, C-SSRS, and AEs as 
outlined in the Schedule of Visits and Assessments (Section 1.3). If deemed necessary, additional 
safety assessments will be performed at the discretion of the Investigator. 
5.1.1. 
Screening 
Before a subject’s participation in the clinical study, the Investigator is responsible for obtaining 
written informed consent from the subject or written assent from subjects (ages 9-17yrs) and 
consent from their parent(s) or legal guardian(s) after adequate explanation of the study design, 
anticipated benefits, and the potential risks. Informed consent must be obtained before 
completion of any non-standard of care study-specific procedures. Procedures that are part of 
standard of care are not considered study-specific and, therefore, may be performed prior to 
obtaining consent and used to confirm eligibility provided they occur within the time allowance 
outlined in the Schedule of Visits and Assessments (Section 1.3). A subject is considered a 
participant of the trial once the ICF or written assent for subjects ages 9-17yrs is completely 
signed. 
The following procedures/assessments will be performed at the Screening Visit (within 4 weeks 
after signing the ICF/assent): 
•
Review of medical and surgical history
•
Review of childbearing potential (female subjects) and contraceptive use
(Section 5.1.2)


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•
Collection of demographic data including age, sex, race, ethnicity
•
Limited physical examination of skin (including assessment of Fitzpatrick Skin Type
at Screening only), lungs, and heart
•
Vitals signs including temperature, heart rate, blood pressure
•
Collection of body weight (kg)
•
Laboratory tests: hematology, chemistry, urinalysis, serum pregnancy (for female
subjects of childbearing potential)
•
Seborrheic dermatitis assessments: IGA, BSA, Overall Assessment of Erythema,
Overall Assessment of Scaling, Pigmentation Assessment
•
Completion of DLQI/CDLQI, Scalpdex, C-SSRS, CDI-2/PHQ-8/PHQ-A
•
Collection of prior and concomitant medication
All screened subjects will receive a subject identification number (see Section 4.4) and be 
entered into the eCRF. Subjects that fail to meet the eligibility criteria will be designated as a 
screen failure and entered in the IWRS and eCRF as such. Subjects who are unable to enroll 
within the screening window will be rescreened.  
Subjects may be re-screened one time. The original assigned subject ID number will be used for 
re-screening. 
Subjects who consent but do not proceed with enrollment will be considered a screen failed 
subject. 
5.1.2. 
Contraception Requirements 
Females of childbearing potential (FOCBP) must have a negative serum pregnancy test at 
Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2). In addition, sexually 
active FOCBP must agree to use at least one form of a highly effective or barrier method of 
contraception throughout the trial according to Contraception Requirements for Female Subjects 
(Figure 1). 


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Figure 1: 
Contraception Requirements for Female Subjects 
5.1.3. 
Baseline 
Each subject will undergo Baseline assessments outline in the Schedule of Visits and 
Assessments (Section 1.3). For subjects <18years, if the Baseline (Day 0) visit occurs within 
3 weeks of Screening, the Screening lab results may be utilized.  
Randomization and IP kit assignment will take place, via IWRS, after the subject has been found 
to be fully eligible for participation. A subject will be considered enrolled into the study upon 
randomization. 
5.1.4. 
Physical Examination 
Physical examinations will be performed according to the Schedule of Visits and Assessments 
(Section 1.3). The physical exam will be limited to skin (including assessment of Fitzpatrick skin 
type at Screening only), lungs, and heart only.  
Fitzpatrick skin phototype assessment will be rated as follows: 
I.
Always burns easily; never tans (sensitive)
II.
Always burns easily; tans minimally (sensitive)
III.
Burns moderately; tans gradually (light brown) (normal)
IV.
Burns minimally; always tans well (moderate brown) (normal)
V.
Rarely burns; tans profusely (dark brown) (insensitive)
VI.
Never burns; deeply pigmented (insensitive)


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5.1.5. 
Vital Signs, Height and Weight 
Vital signs will be performed according to the Schedule of Visits and Assessments (Section 1.3). 
Blood pressure, heart rate, and temperature will be measured while the subject is sitting/resting 
for at least 5 minutes. 
Height will be collected at Baseline and Week 8. 
Subjects should void prior to weight being taken and remove any objects of significant weight 
(i.e., jackets, outerwear, shoes, cell phones, wallet, key chains, etc.). A 5% unintentional weight 
loss from Baseline should be reported to the medical monitor. 
5.1.6. 
Laboratory Tests 
All tests listed in Table 2 will be performed according to the Schedule of Visits and Assessments 
(Section 1.3) unless otherwise noted. For subjects <18 years old, Screening safety lab results 
collected within 3 weeks of the Baseline visit may be utilized as the Baseline safety lab 
assessment. No food restrictions are required for the collection of specimens. In addition, 
laboratory safety tests may be performed at unscheduled time points, if deemed necessary by the 
Investigator. Laboratory samples will be sent to the central lab. Refer to the most current Central 
Laboratory Manual for collection, processing, shipping, and report receipt instructions. 
Table 2: 
Laboratory Tests 
Hematology 
Serum Chemistry 
•
Hemoglobin
•
Hematocrit
•
Total and differential leukocyte count
•
Red blood cell count with indices and morphology
•
Platelet count
•
Blood Urea Nitrogen
•
Bilirubin (total and direct)
•
Alkaline phosphatase
•
Aspartate aminotransferase
•
Alanine aminotransferase
•
Albumin
•
Sodium
•
Potassium
•
Chloride
•
Glucose
•
Creatinine
Urinalysis 
Additional Tests 
•
pH
•
Specific gravity
•
Protein*
•
Glucose
•
Ketones
•
Bilirubin
•
Blood*
•
Nitrite*
•
Urobilinogen
•
Leukocyte esterase*
•
Urine pregnancy test
(for females of childbearing potential only)
•
Serum pregnancy test (hCG) **
•
FSH test (post-menopausal females only)
•
Pharmacokinetic (PK) assessments
*If urinalysis is positive for protein, blood, nitrite, and/or leukocyte esterase, a microscopic examination
(for red blood cells, white blood cells, bacteria, casts, and epithelial cells) will be performed.
**At Screening for FOCBP only 


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5.1.7. 
Patient Health Questionnaire Depression Scale (PHQ-8) 
The PHQ-8 Assessment (see Appendix 2) will be completed by adult subjects according to the 
Schedule of Visits and Assessments (Section 1.3). 
PHQ-8 score is the sum of the responses for the 8 questions. 
Five severity categories of depression are defined as follows: 
•
None – Minimal depression (0 to 4)
•
Mild depression (5 to 9)
•
Moderate depression (10 to 14)
•
Moderately severe depression (15 to 19)
•
Severe depression (20 to 24)
A subject with a PHQ-8 score of 10-14 should be referred to a mental health professional for 
evaluation, regardless of the reason for their change in score. 
A subject with with a PHQ-8 score of ≥15 should be immediately referred to a mental healthcare 
professional and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the IP.  
5.1.8. 
Patient Health Questionnaire Depression Scale (Modified PHQ-A) 
The Modified PHQ-A Assessment (Appendix 3) will be completed by adolescent subjects 
(12-17 years old, inclusive) according to the Schedule of Visits and Assessments (Section 1.3). 
Modified PHQ-A score is the sum of the responses for the 8 questions. 
Five severity categories of depression are defined as follows: 
•
None - Minimal depression (0 to 4)
•
Mild depression (5 to 9)
•
Moderate depression (10 to 14)
•
Moderately severe depression (15 to 19)
•
Severe depression (20 to 24)
A subject with a modified PHQ-A score of 10-14 should be referred to a mental health 
professional for evaluation, regardless of the reason for their change in score.  
A subject with a modified PHQ-A score ≥15 should be immediately referred to a mental health 
professional, and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the IP.  


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5.1.9. 
Children’s Depression Inventory 2 (Parent Report) 
The CDI-2 Assessment will be performed according to the Schedule of Assessments 
(Section 1.3) for subjects 9-11 years old, inclusive. Subjects 9-11 years old at the time of assent 
will complete the CDI-2 throughout the study. 
The CDI-2 quantifies depressive symptomatology using reports from children/adolescents, 
teachers, and parents or caregivers. It is recommended for use in initial evaluation and is 
appropriate when there is a need for an assessment and robust description of a child’s depressive 
symptoms. 
This study will use the CDI Parent Report Form. An example of the Parent Repot Form is 
presented in Appendix 4. 
A subject with a CDI-2 raw total score of ≥21 for females and ≥22 for males should be referred 
to a mental health professional for evaluation. 
A subject with a CDI-2 raw total score of ≥32 should be referred to a mental health professional, 
and Investigators in consultation with the mental health professional should consider interruption 
or discontinuation of the investigational product.  
5.1.10. 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
C-SSRS Assessments will be performed according to the Schedule of Visits and Assessments
(Section 1.3) for subjects 12 years old and older.
The administration schedule of the C-SSRS will be: 
•
The Baseline-Screening version (Appendix 5) will be used at Screening to provide a
pre-treatment assessment baseline.
•
On all subsequent visits, the Since Last Visit version (Appendix 6) will be used.
•
A score greater than 0 at the Screening or Baseline visit in suicidal ideation may
indicate the need for mental health intervention. The Investigator should not enroll
the subject in the study.
•
Any score greater than 0 in the suicidal ideation score may indicate the need for
mental health intervention. The Investigator should give consideration for the subject
to discontinue from the IP and prompt referral to a mental health professional and/or
possibly the emergency room. The Medical Monitor should be contacted.
The C-SSRS administrator will be trained via C-SSRS training video. A training certificate for 
the administrator(s) will be on file in the trial master file at the site. 
The Investigator must review the completed C-SSRS. A qualified mental health care provider 
must be available, immediately if needed, to refer the subject for further evaluation. 


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5.1.11. 
Local Tolerability Assessment 
The Investigator Local Tolerability Assessment will be performed according to the Schedule of 
Visits and Assessments (Section 1.3).  
Application site reactions will be graded at each timepoint. Irritation reactions are graded using 
the scale detailed in the following section (Berger 1982). Reactions at the site of product 
application, which may occur post-Baseline, should be differentiated from the preexisting 
inflammation associated with the subject’s seborrheic dermatitis. 
For the Baseline visit, when IP is applied in the clinic, the Investigator assessments will be 
conducted by the Investigator prior to IP application. 
Dermal Response 
0 = no evidence of irritation 
1 = minimal erythema, barely perceptible 
2 = definite erythema, readily visible; minimal edema or minimal papular response 
3 = erythema and papules 
4 = definite erythema  
5 = erythema, edema and papules 
6 = vesicular eruption 
7 = strong reaction spreading beyond application site 
Other Effects 
A = slight glazed appearance 
B = marked glazing 
C = glazing with peeling and cracking 
D = glazing with fissures 
E = film of dried serous exudates 
F = small petechial erosions and/or scabs 
G = no other effects 
The Subject Local Tolerability Assessment will be performed according to the Schedule of Visits 
and Assessments (Section 1.3). 
This assessment will be administered by the site 10 to 15 minutes after IP application in the 
clinic at Baseline and recall assessments at Weeks 4 and 8. 
Grade 
Sensation Following Investigational Product Application 
0 (none) 
No sensation 
1 (mild) 
Slight warm, tingling sensation; not really bothersome 
2 (moderate) 
Definite warm, tingling sensation that is somewhat bothersome 
3 (severe) 
Hot, tingling/stinging sensation that has caused definite discomfort 


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5.1.12. 
Pigmentation Assessment 
The Investigator will assess for pigmentation in areas affected previously and/or currently by 
seborrheic dermatitis according to the Schedule of Visits and Assessments (Section 1.3). 
Hypopigmentation and hyperpigmentation will be scored individually using a 0 – 3 scale: ‘0’ for 
none, ‘1’ for mild, ‘2’ for moderate, and ‘3’ for severe. 
5.1.13. 
Adverse Events 
Adverse events (AEs) will be collected and assessed throughout the study according to the 
Schedule of Visits and Assessments (Section 1.3). The Investigator is responsible for ensuring 
that all adverse events observed by the clinical staff or reported by the subject that occur after the 
first application of investigational product through the end of the study are recorded in the 
subject’s medical record and the eCRF. 
The Investigator is responsible for ensuring that all serious adverse events observed by the 
clinical staff or reported by the subject that occur after signing of the informed consent through 
30 days after the last day of the application of the investigational product or the end of study 
(whichever is later) are recorded in the subject’s medical record and are submitted per SAE 
reporting requirements (Section 5.7.2). 
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s) 
will be evaluated by the PI and treated and/or followed up for up to 30 days after end of 
treatment or until the symptoms or value(s) return to the subject’s baseline value, or acceptable 
levels, as judged by the Investigator. 
Refer to Section 5.7 for further details on Adverse Events. 
5.2. 
Efficacy Evaluations 
Investigators will be trained in the administration of rating scales. A training certificate is issued 
upon successful completion of the training and will be valid for 12 months, unless compliance 
issues are identified that warrant retraining. 
5.2.1. 
Investigator Global Assessment (IGA) 
Investigator’s Global Assessments (‘whole body’ and ‘intertriginous area’) will be performed at 
according to the Schedule of Visits and Assessments (Section 1.3). The IGA should be 
completed prior to any other physician assessments. 
The IGA is a static evaluation of qualitative overall seborrheic dermatitis severity. This global 
assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4). 
Each grade is defined by a distinct and clinically relevant morphologic description that 
minimizes inter-observer variability. 
Every effort must be made for the same Evaluator to complete the IGA for the subject at 
every study visit, particularly for Baseline and Week 8. 


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Investigator Global Assessment of Disease (IGA) 
Score 
Description 
0 
Clear: No erythema, no scaling (hypo-hyperpigmentation can be present) 
1 
Almost clear: Slight erythema and/or trace (barely perceptible) amounts of scaling 
2 
Mild: Pink to red color and/or slight scaling 
3 
Moderate: Distinct erythema (redness) and/or clearly visible scaling 
4 
Severe: Severe erythema (intense, fiery red) and/or severe scaling (coarse, thick scales 
with flaking onto clothes or skin) 
5.2.2. 
Overall Assessment of Erythema 
Overall Assessment of Erythema will be performed according to the Schedule of Visits and 
Assessments (Section 1.3). 
Overall Assessment of Erythema is a static qualitative evaluation, involving an ordinal scale with 
4 severity grades (reported only in integers of 0 to 3).  Each grade is defined by a distinct and 
clinically relevant morphologic description that minimizes inter-observer variability.  
Every effort must be made for the same Evaluator to complete the Overall Assessment of 
Erythema for the subject at every study visit, particularly for Baseline and Week 8. 
Overall Assessment of Erythema 
Symptom 
Score 
Description 
Erythema 
0 
None: No evidence of erythema 
1 
Mild: Barely perceptible erythema which is faint or patchy 
2 
Moderate: Distinct erythema, 
3 
Severe: Intense (fiery red) erythema 
5.2.3. 
Overall Assessment of Scaling 
Overall Assessment of Erythema will be performed according to the Schedule of Visits and 
Assessments (Section 1.3). 
Overall Assessment of Scaling are static qualitative evaluations, involving an ordinal scale with 
4 severity grades (reported only in integers of 0 to 3).  Each grade is defined by a distinct and 
clinically relevant morphologic description that minimizes inter-observer variability.  
Every effort must be made for the same Evaluator to complete the Overall Assessment of 
Scaling for the subject at every study visit, particularly for Baseline and Week 8. 


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Overall Assessment of Scaling 
Symptom 
Score 
Description 
Scaling 
0 
None: No scaling evident on lesions 
1 
Mild: Barely detectable, scattered, small flaking scales 
2 
Moderate: Scales clearly visible and prominent 
3 
Severe: Coarse, thick scales, with flaking into clothes or skin 
5.2.4. 
Worst Itch-Numerical Rating Scale (WI-NRS) 
Given that itch is an important symptom of seborrheic dermatitis, a WI-NRS assessment is 
included in the present study.  A responder analysis will be performed to evaluate achievement 
of a 4-point reduction of WI-NRS, which has been described as optimal for demonstrating a level 
of clinically meaningful improvement in itch severity in other skin conditions, including other 
forms of eczema (Yosipovitch 2019) and psoriasis (Kimball 2016). 
WI-NRS Assessment will be performed by subjects daily at home according to the Schedule of 
Visits and Assessments (Section 1.3) starting 7 days prior to the scheduled Baseline/Day 0 visit 
up to the Week 8/Day 56 visit. Subjects will be provided with a diary to record their daily 
WI-NRS assessments. 
The WI-NRS has been developed as a simple, single item to assess the patient-reported severity 
of this symptom at its highest intensity during the previous 24-hour period. (Naegeli 2015). The 
WI-NRS will be determined by asking the subject’s assessment of worst itch over the past 
24 hours. The scale is from ‘0 to 10’ (“no itch” to “worst imaginable itch”).  
5.2.5. 
Scalpdex 
The Scalpdex (Appendix 7) will be performed by subjects according to the Schedule of Visits 
and Assessments (Section 1.3). 
5.2.6. 
Dermatology Life Quality Index (DLQI) and Children’s Dermatology Life 
Quality Index (CDLQI) 
The DLQI (ages 17+ years) and CDLQI (ages 9-16 years, inclusive) will be performed according 
to the Schedule of Visits and Assessments (Section 1.3). The DLQI/CDLQI is a simple, 
self-administered and user-friendly validated questionnaire. The DLQI/CDLQI is designed to 
measure the health-related quality of life of patients suffering from a skin disease. The 
DLQI/CDLQI consists of 10 questions concerning patients’ perception of the impact of skin 
diseases on different aspects of their health-related quality of life over the last week.  


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The DLQI (Appendix 8) will be completed by subjects ages 17 years and older. The CDLQI 
(Appendix 9) will be completed by caregivers of subjects ages 9-16 years. 
5.2.7. 
Body Surface Area (BSA) 
BSA assessments will be performed according to the Schedule of Visits and Assessments 
(Section 1.3).  
The BSA affected by seborrheic dermatitis will be determined by the subject’s hand method, 
where the subject’s hand (including fingers) surface area is assumed to equal 1% of body surface 
area. 
5.3. 
Other Evaluations 
5.3.1. 
Pharmacokinetics Assessment 
Pharmacokinetic (PK) samples will be collected according to the Schedule of Visits and 
Assessments (Section 1.3) for all subjects.  
•
PK will be evaluated through trough sampling at Week 4 and Week 8.
PK samples will be collected while the subject is having serum chemistries drawn, when 
applicable. Ensure the IP is not applied in the area where PK will be drawn. 
5.3.2. 
Dermal Imaging 
Medical photography as supportive evidence of clinical outcome will be conducted by all sites 
using Canfield equipment. Photos will be obtained according to the Schedule of Visits and 
Assessments (Section 1.3). Photography should be focused on single lesions or specific body 
sections (e.g., arm). Body or half body photos should only be taken if necessary. For subjects 
with seborrheic dermatitis lesions on the face, scalp, and/or body, effort should be made to 
prioritize obtaining a photograph of the facial lesion(s). All efforts will be made to de-identify 
the subjects. Subjects who are unwilling to participate in the medical photography will be 
allowed to opt out of this procedure and documented on the informed consent. Refer to the 
current Photography Manual for instructions regarding photography. 
5.4. 
Final Study Visit 
The approximate final study visit will occur at Week 8 (Day 56). The procedures performed 
during this visit are described in the Schedule of Visits and Assessments (Section 1.3). A 5-day 
scheduling window is allowed for this visit. Adverse events will be recorded as reported by the 
participant or and followed to resolution (as necessary) as outlined in Section 5.7. 
5.5. 
Early Termination Visit 
If a subject is withdrawn from the study, an early termination visit will be scheduled. This visit 
should include the procedures and assessments that would be performed at the Week 8 visit 
(Day 56). Subjects who withdraw consent from study participation, will not be required to 
perform an early termination visit. 


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5.6. 
Unscheduled Visit 
Unscheduled visits may be necessary to repeat testing following abnormal laboratory results, for 
follow-up of AEs, or for any other reason, as warranted in the judgement of the Investigator. 
The following information will be collected for all subjects: 
•
Concomitant medications/procedures
•
AEs
5.7. 
Adverse Events
5.7.1. 
Adverse Event Definition
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational product, whether or not related to the investigational 
product. 
The definition of AEs includes worsening of a pre-existing medical condition.  Worsening 
indicates that the pre-existing medical condition has increased in severity, frequency, and/or 
duration or has an association with a worse outcome.  When recording such events, provide 
descriptions that the pre-existing condition has changed (e.g., worsening hypertension for a 
subject with pre-existing hypertension).  A pre-existing condition that has not worsened during 
the study or involves an intervention, such as elective cosmetic surgery or a medical procedure 
while on study, is not considered an AE. 
Progression of treatment indication including new or worsening of anticipated clinical signs or 
symptoms, which are collected as clinical efficacy variables and assessed as unequivocally 
associated with the disease progression and /or lack of efficacy, should NOT be reported as 
adverse events unless the disease progression is greater than anticipated in the natural course of 
the disease.  
In general, abnormal laboratory findings without clinical significance (based on the 
investigator’s judgment) are not to be recorded as AEs.  However, abnormal laboratory findings 
that result in new or worsening clinical sequelae, or that require therapy or adjustment in current 
therapy, are considered AEs.  Where applicable, clinical sequelae (not the laboratory 
abnormality) are to be recorded as the AE. 
5.7.2. 
Serious Adverse Event 
The definitions and reporting requirements of the Food and Drug Administration (FDA)/ICH 
Guidelines for Clinical Safety Data Management, Definitions and Standards for Expedited 
Reporting, Topic E2A will be adhered to.  Mandatory reporting of all serious unexpected adverse 
drug reactions (SUSARs) to Health Canada [as per C.05.014 (1) of the FDR] will be adhered. If 
any AEs are serious, as defined by ICH Guidelines for Clinical Safety, required procedures will 
be followed. 


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As SAE is defined as any AE that, in the view of either the PI or Sponsor, meets at least 1 of the 
following serious criteria: 
•
Fatal
•
Life-threatening (places the subject at immediate risk of death)
•
Requires inpatient hospitalization or prolongation of existing hospitalization
•
Results in a persistent or significant incapacity/disability
•
Congenital anomaly/birth defect
•
Other important medical events that, based upon appropriate medical judgment, may
jeopardize the subject and may require medical or surgical intervention to prevent one
of the outcomes listed in the above definition
Hospitalization does not include the following: 
•
Rehabilitation facilities, hospice facilities or respite care (e.g., caregiver relief)
•
Nursing homes or skilled nursing facilities
•
Emergency department visits
•
Same day surgeries (as outpatient/same day/ambulatory procedures)
•
<24 hour admissions for observation or evaluation
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is 
not in itself an SAE.  Examples include: 
•
Admission for treatment of a preexisting condition that did not worsen
•
Hospitalizations for cosmetic elective surgery, social, and/or convenience admissions
•
Pre-planned treatments or surgical procedures should be noted in the baseline
documentation for the individual subject
•
Diagnostic and therapeutic procedures, such as surgery, should not be reported as
AEs; however, the medical condition for which the procedure was performed should
be reported if it occurs during the reporting period and meets the definition of an AE.
For example, an acute appendicitis that begins during the AE reporting period should
be reported as an AE, and the resulting appendectomy should be recorded as
treatment of the AE.
Unexpected is defined as an AE that is not listed in the IB or is not listed at the specificity or 
severity that has been observed; or is not consistent with the risk information described in the 
general investigational plan or study documentation.  


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5.7.3. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
SUSAR is defined as a serious adverse reaction, the nature or severity of which is not consistent 
with the known study treatment information. A serious event or reaction is not defined as a 
SUSAR when: ‘it is serious but expected’ or it does not fit the definition of an SAE, whether 
expected or not. 
5.7.4. 
Safety Review with Subject 
At each subsequent clinic visit after the Screening visit, subjects will be queried with an 
open-ended question such as: ‘How have you been feeling since your last visit?’  Additionally, 
the study staff will review subject diaries and, if it appears that a potential AE was recorded, 
study staff will query the subject and determine if an AE occurred. 
5.7.5. 
Adverse Event Reporting 
The Investigator is responsible for recording all adverse events, observed by the clinic staff, or 
reported by the subject that occur after the first application of investigational product through the 
end of the study are recorded in the subject’s medical record and the eCRF.  Serious adverse 
events observed by the clinic staff or reported by the subject after signing the informed consent 
form will be recorded.  
All adverse events that meet the criteria for “serious” (i.e., SAEs) will be reported to the Sponsor 
via fax or e-mail to ArcutisPV@EVERSANA.com within 24 hours of becoming aware of the 
event, whether or not the serious events are deemed drug-related.  
All serious event reporting will adhere to ICH E6: Guideline for Good Clinical Practice and ICH 
E2A: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.  
The Institutional Review Board (IRB) will be notified of the Alert Reports as per FDA, ICH and 
the IRB’s policies and procedures. 
The Sponsor, or delegate, will be responsible for reporting SAEs to health authorities per local 
reporting requirements. The Investigator will be responsible for reporting events to their 
respective IRBs/ Ethics Review Board (ERB) in accordance with the IRB/ERB requirements. 
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s) 
will be evaluated by the PI and treated and/or followed for up to one month after end of 
treatment until the symptoms or value(s) return to the subject’s baseline value, or acceptable 
levels, as judged by the Investigator. Where appropriate, medical test(s) and/or examination(s) 
will be performed to document resolution of event(s).  
The Investigator will review each adverse event and assess its relationship to Investigational 
Product (unrelated, unlikely, possibly, probably, likely). Each sign or symptom reported will be 
graded on the NIH NCI CTCAE toxicity grading scale 5-point severity scale (Grade 1, 2, 3, 4 
and 5). The date and time of onset, time relationship to drug dosing, duration, and outcome) of 
each event will be noted. 
The relationship of each AE to the Investigational Product will be assessed using the following 
definitions: 


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Unrelated 
•
The AE must clearly be caused by the subject’s clinical state, or the study
procedure/conditions.
•
Definitely not related to drug.
•
Temporal sequence of an AE onset relative to administration of drug not reasonable.
•
Another obvious cause of an AE.
Unlikely 
•
Time sequence is unreasonable.
•
There is another more likely cause for an AE.
Possibly 
•
Corresponds to what is known about the drug.
•
Time sequence is reasonable.
•
Could have been due to another equally, likely cause.
Probably 
•
Is a known effect of the drug.
•
Time sequence from taking drug is reasonable.
•
Ceases on stopping the drug.
•
Cannot be reasonably explained by the known characteristics of the subject’s
clinical state.
Likely 
•
Is a known effect of the drug (e.g., listed in Physicians' Desk Reference,
Compendium of Pharmaceuticals and Specialties, IB).
•
Time sequence from taking drug is reasonable.
•
Event stops upon stopping drug, event returns upon restarting drug.
The following CTCAE toxicity grading scale 5-point severity scale definitions for rating 
maximum severity will be used: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living.* 
Grade 3 
Severe or medically significant but not immediately life-threatening; Hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily 
living.** 
Note: An experience may be severe but may not be serious, e.g., severe headache). 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
Note: A semi-colon indicates ‘or’ within the description of the grade. 
*
Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using the
telephone, managing money, etc.
** Self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
AEs will be coded using the most current MedDRA® version available at the start of the study. 


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5.8. 
Reporting Pregnancy 
During study participation, all subjects should be instructed to contact the Investigator 
immediately if they suspect they might be pregnant (e.g., missed or late menstrual period).  If 
pregnancy is confirmed, Investigational Product must be discontinued immediately, the subject 
should be referred to an obstetrician experienced in reproductive toxicity for evaluation and 
counseling, and the subject should be followed until conclusion of the pregnancy. 
The Investigator is responsible for reporting all available pregnancy information on the 
pregnancy report to ArcutisPV@EVERSANA.com within 24 hours of becoming aware of the 
event, although pregnancy itself is not considered an AE.  Follow-up information detailing the 
outcome of the pregnancy and the health of the newborn should be reported as it becomes 
available. In addition, any pregnancy resulting in a congenital abnormality or birth defect of the 
newborn, or neonatal death occurring within 30 days of the birth must be reported as a SAE, 
regardless of causality. 
Partner pregnancies of a male subject do not need to be reported. 
5.9. 
Treatment Stopping Rules 
If a subject has non-cutaneous adverse events of concern, clinically significant laboratory values 
or any condition that the investigator determines could possibly be related to the investigational 
product, the Investigator should immediately contact the Medical Monitor to discuss if the 
subject should be discontinued from treatment with investigational product. 
Treatment for any individual subject will be discontinued if the subject experiences: 
•
A SAE or a clinically significant non-serious AE which in the opinion of the Principal
Investigator or Medical Monitor warrants discontinuation from the study for that
subject’s well-being
•
A treatment-emergent severe (Grade 3) laboratory abnormality (confirmed by repeat
sample; see Appendix 10 for more information).
A subject with a PHQ-8/PHQ-A score ≥15 should receive immediate referral to a mental health 
care professional, and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the investigational product. 
•
Subjects with a PHQ-8 or modified PHQ-A score of 10-14 should be referred to a
mental health professional for evaluation, regardless of the reason for their change in
score.
A subject with a CDI-2 raw total score ≥32 should be referred to a mental health professional, 
and Investigators in consultation with the mental health professional should consider interruption 
or discontinuation of the investigational product.  
•
Subjects with a CDI-2 raw score ≥21 for females and ≥22 for males should be
referred to a mental health professional for evaluation.


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A subject that is experiencing suicidal ideation and behavior should be referred immediately to a 
qualified mental health care provider and consideration given to discontinuation from IP. 
As noted above, IP must be discontinued immediately in the event of a female subject’s 
pregnancy. 
IP Treatment should be interrupted: 
•
If a subject develops an application site reaction with the clinical appearance of an
‘irritation reaction’, and with a severity of a Dermal Response Score of 5
(erythema, edema, and papules) or greater on the scale of Berger and Bowman,
treatment should be interrupted for up to one week and may then be resumed if the
reaction has, in the opinion of the Investigator, adequately resolved.
IP Treatment should be discontinued: 
•
If the reaction reoccurs. IP should be discontinued permanently, and the subject
followed until the reaction resolves.
For cases of suspected allergic contact dermatitis, the medical monitor and sponsor should be 
notified and there should be discussion about performing patch testing to further evaluate. Patch 
testing is encouraged in such cases. 
In the event of a medical emergency where unblinding is required to provide medical care to the 
subject, refer to the most current IWRS Plan and Breaking Treatment Codes (Section 4.8.5). 
Contact the Medical Monitor and the Sponsor promptly. 
6.
DATA ANALYSIS
Data will be handled and processed according to the Contract Research Organization’s (CRO) 
Standard Operating Procedures, which are written based on the principles of GCP. 
6.1. 
Statistical Methods 
The methodology presented below is a summary of the more detailed analysis plan that will be 
presented in the Statistical Analysis Plan (SAP).  The SAP will be finalized before the database 
is locked and unblinded.  Any changes to the methods described in the final SAP will be 
described and justified in the clinical study report. 
All statistical processing will be performed using SAS® (Version 9.4 or later) unless otherwise 
stated. 
Descriptive statistics will be used to provide an overview of the efficacy, safety and 
pharmacokinetic results.  For categorical parameters, the number and percentage of subjects in 
each category will be presented. The denominator for percentage will be based on the number of 
subjects appropriate for the purpose of analysis.  For continuous parameters, descriptive statistics 
will include n (number of subjects), mean, standard deviation (SD), median, minimum, 
and maximum. 


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6.1.1. 
Determination of Sample Size 
A sample size of approximately 450 subjects is planned for the study. 
The randomization scheme will be 2:1 (ARQ-154 foam 0.3% QD: matching vehicle QD). 
Randomization will be stratified by site and baseline disease severity (IGA = 3 or IGA = 4).  
Approximately 300 subjects will receive ARQ-154 foam 0.3% QD; approximately 150 subjects 
will receive vehicle foam QD. 
A sample size of 450 subjects will provide at least 90% power to detect a 25% difference 
between treatment groups on IGA success at α=0.01 using a 2-sided Cochran-Mantel-Haenszel 
test stratified by the randomization factors. The results from a recent Phase 2a study 
(ARQ-154-203) of ARQ-154 compared to vehicle treatment were used to estimate treatment 
difference. Specifically, in the Phase 2a trial, 73.8% of subjects demonstrated IGA success in the 
ARQ-154 0.3% group and 40.9% of subjects demonstrated IGA success in the vehicle group. 
The number of subjects to be enrolled will also provide sufficient power for the secondary 
endpoints. Additionally, the larger study size is included in order to provide additional/sufficient 
numbers of subjects on ARQ-154 treatment for a safety database. 
6.1.2. 
Subjects to Analyze 
The analysis populations are defined as follows: 
•
Safety population will include all subjects who are randomized and receive at least
one confirmed dose of IP or vehicle foam. This population will be used for all safety
analyses.
•
Efficacy analyses will be conducted in the Intent-to-Treat (ITT) population.
Sensitivity analyses may be conducted in the subset of the ITT population for whom
the primary endpoint assessment was not missed due to COVID-19 disruption
•
The Intention-to-Treat (ITT) population will include all randomized subjects. This
population will be the primary analysis population for the analysis of efficacy
endpoints.
•
The pruritus population is a subset of the ITT population and include subjects with
WI-NRS pruritus score ≥4 at Baseline. This population will be used for the analysis
of achievement of a 4-point reduction in WI-NRS pruritus score as compared to
Baseline.
6.1.3. 
Interim Analysis 
No interim analyses are planned. 
6.1.4. 
Background and Demographic Characteristics 
Descriptive statistics will be presented for the subject disposition, demographics, Baseline 
characteristics, treatment compliance, efficacy endpoints and safety data collected in the clinical 
trial. This includes the number and percentage of subjects for binary endpoints/categorical data, 
and mean, SD, median, Minimum, and maximum for continuous data.  


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6.1.5. 
Study Disposition 
Number of subjects randomized, receiving IP, completing study, and withdrawing prematurely 
(with reason for withdrawal) will be summarized by treatment group. 
6.1.6. 
Protocol Deviations and Eligibility Deviations 
The number of subjects with important protocol deviations and/or eligibility deviations will be 
summarized in categories by treatment group. 
6.1.7. 
Investigational Product Application Compliance 
The number of IP applications by each subject based on diary data will be summarized using 
descriptive statistics.  
The amount of IP used by each subject based on can weight will be summarized by treatment 
using descriptive statistics. 
IP dose compliance will be calculated based on number of applications divided by the expected 
number (amount) of IP applications for each subject.  Compliance will be summarized 
descriptively by treatment group.  Amount of IP (weight) used will also be summarized. 
6.1.8. 
Pharmacokinetics Analysis 
The PK population will include all subjects receiving the active drug with sufficient plasma 
concentrations of roflumilast to define a profile, as determined by the pharmacokineticist.  This 
population will be used for analyses of PK parameters. 
6.2. 
Safety Analysis 
Descriptive statistics will be calculated for quantitative safety data and frequency counts will be 
compiled for classification of qualitative safety data. The safety population will be used for these 
analyses. 
6.2.1. 
Adverse Events 
Adverse events (AEs) will be summarized by preferred term, system organ class, and treatment 
group for all AEs, serious AEs, related AEs, AEs leading to withdrawal from investigational 
product, and AEs leading to withdrawal from study. 
6.2.2. 
Clinical Laboratory Results 
Shifts in clinical laboratory parameters from Baseline to worst post-Baseline grade will be 
provided. 
6.2.3. 
Vital Signs 
The subject incidence rate of >5% weight loss or gain on study will be provide, as well as 
whether weight loss was explained or unexplained. 


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6.2.4. 
Local Tolerance Assessments 
For both the Investigator’s and Subject’s assessment of the numeric application site reaction, 
scores will be summarized individually by using number and percentage of subjects by visit, as 
well as mean/median scores. 
6.2.5. 
Medical History and Physical Examinations 
Medical history for all subjects will be presented in a by-subject listing. 
Clinically significant changes observed during physical examination will be captured as adverse 
events and included in AE tabulations. 
6.3. 
Efficacy Evaluation 
Efficacy analyses will be conducted in the Intent-to-Treat (ITT) population.  Sensitivity analyses 
may be conducted in the subset of the ITT population for whom the primary endpoint assessment 
was not missed due to COVID-19 disruption. 
6.3.1. 
Primary Endpoint 
The primary endpoint of ‘IGA success at Week 8’ will be analyzed using a Cochran-Mantel-
Haenszel test stratified by the randomization factors of the study center and IGA score at 
baseline (‘moderate’ v. ‘severe’). The analysis will be performed on the Intention-to-Treat (ITT) 
population and missing data will be imputed using multiple imputation. 
6.3.2. 
Secondary Endpoint 
Continuous secondary endpoints will be analyzed using Analysis of Covariance with treatment 
and stratification factors as independent variables.  The ITT population will be used and missing 
data will be imputed using multiple imputation.  Binary secondary endpoints will be analyzed 
similarly to the primary endpoint. 
Secondary endpoints will only be tested statistically if the primary endpoint is considered 
statistically significant.  To control for multiple comparisons among the secondary endpoints, the 
following multiplicity procedure will be used. 
Upon demonstration of statistical significance of the primary endpoint, the alpha level of 0.01 
will be unequally split between testing of the WI-NRS success endpoints and the other secondary 
efficacy endpoints. The testing over the WI-NRS success endpoints and the other secondary 
efficacy endpoints will be sequential, utilizing the Fallback Method for unused alpha. 
For the testing of WI-NRS success endpoints, an alpha level of 0.0033 will be used and will use 
a hierarchical method to first test WI-NRS success at Week 8, followed by WI-NRS at Week 4, 
followed by WI-NRS success at Week 2.  Should all three of these endpoints be statistically 
significant at the 0.0033 level, then this unused alpha will be carried to the other secondary 
endpoint group, which would then be tested at the .0033+.0067=0.01 level. 
An alpha level of 0.0067 (the remainder of the allotted 0.01) or the full 0.01, pending the results 
of the WI-NRS endpoint testing, will be used to hierarchically test IGA Success at Week 4, 


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Scaling score of 0 at Week 8, Erythema score of 0 at Week 8, the percentage of subjects who 
attain IGA of 0 at Week 8, and IGA Success at Week 2. 
7.
STUDY ADMINISTRATION
7.1. 
Ethics 
7.1.1. 
Ethics Review Board 
Before screening of subjects into the study, the current protocol, ICF, and any accompanying 
material to be provided to the subjects will be reviewed and approved by an appropriate 
IRB/ERB, as required by FDA (21 CFR § 56) or Health Canada and ICH GCP regulations.  A 
letter documenting the IRB approval must be received by the Sponsor before the initiation of the 
study at a clinical site. Amendments to the protocol will be subject to the same requirements as 
the original protocol. 
The Investigator, Sponsor, or designee will submit a progress report at least once yearly to the 
IRB. However, the frequency of these reports will depend on IRB requirements. As soon as 
possible after completion or termination of the study, the Investigator will submit a final report to 
the IRB per the IRB requirements, and in compliance with FDA and ICH GCP guidelines. 
The Investigator, Sponsor, or designee shall promptly notify the IRB of any SAEs, SUSARs, or 
any other information that may affect the safe use of the IP during the study, per the IRB local 
requirements, and in compliance with FDA regulations and ICH GCP guidelines. 
7.1.2. 
Ethical Conduct of the Study 
This research will be conducted in accordance with the protocol, the principles of the 
Tri-Council Policy Statement, the ethical principles set forth in the Declaration of Helsinki, and 
the ICH harmonized tripartite guideline regarding E6 (R2), December 2016. 
7.1.3. 
Subject Information and Consent/Assent 
The Investigator is responsible for obtaining written informed consent or assent 
(for children/adolescents) from everyone participating in this study after adequate explanation 
(in non-technical terms) of the aims, methods, objectives, and potential hazards of the study and 
before undertaking any study-related procedures. The investigator must use the most current IRB 
or ERB-approved consent/assent forms for documenting written informed consent and assent 
(for children/adolescents). Subjects will be assured that they may withdraw from the study at any 
time without jeopardizing their medical care. Each informed consent (or assent as applicable) 
will be read, appropriately signed, and dated by the subject or the subject’s legally authorized 
representative and the person conducting the consent discussion, and by an impartial witness if 
required by the IRB/ERB local requirements. 
Subjects will be given a copy of their ICF/assent. 


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7.2. 
Study Completion and Termination 
7.2.1. 
Study Completion 
The study is considered completed with the last visit of the last subject participating in the study. 
The final data from the investigational site will be sent to the Sponsor (or designee) after 
completion of the final subject visit at that site, in the time frame specified in the Clinical Trial 
Agreement. 
7.2.2. 
Study Termination 
The Sponsor reserves the right to close the investigational site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Investigational sites will be closed upon 
study completion. An investigational site is considered closed when all required documents and 
study supplies have been collected and a site closure visit has been performed. The Investigator 
may initiate site closure at any time, provided there is reasonable cause and sufficient notice is 
given in advance of the intended termination. 
Reasons for the early closure of an investigational site by the Sponsor or Investigator may 
include but are not limited to: 
•
Failure of the Investigator to comply with the protocol, the Sponsor’s procedures, or
GCP guidelines.
•
Inadequate recruitment of subjects by the Investigator.
•
Discontinuation of further drug development.
7.3. 
Study Monitoring
Prior to the initiation of the clinical investigation, Sponsor representatives or designees may visit 
the clinical site where the investigation is to be conducted.  Sponsor representatives or designees 
shall ensure that the Investigator understands the investigational status of the investigational 
product, all requirements of the investigation to be undertaken, and all of his/her responsibilities 
as an Investigator.  Sponsor representatives or designees will also visit the clinical site at 
appropriate intervals as required to ensure compliance with the protocol and to verify the 
accuracy and completeness of data reported on the eCRFs.  The Study Director or designees shall 
be available for consultation with the Investigator and serve as liaisons between the clinical site 
and the Sponsor. 
The Sponsor or authorized designees may inspect all documents and records required to be 
maintained by the Investigator, including but not limited to medical records (office, clinic, or 
hospital) and investigational product dispensation logs for the subjects in this clinical 
investigation.  The Investigator must permit access to such records.  The Investigator must 
obtain, as part of informed consent, permission for an authorized representative of the Sponsor, 
or regulatory authorities, to review, in confidence, any records identifying subjects. 


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7.4. 
Data Quality Assurance 
To ensure the collection of adequate, consistent, complete, and reliable data during this clinical 
investigation, Sponsor representatives or designees may conduct audits of participating sites at 
appropriate intervals throughout the study.  The results of these periodic site audits may be 
subject to review by independent auditors at completion of the clinical investigation. 
All clinical data will undergo a quality control check prior to clinical database lock. Edit checks 
are performed for appropriate databases as a validation routine to check for missing data, data 
inconsistencies, data ranges etc. Corrections are made prior to database lock. 
7.5. 
Data Handling and Record Keeping 
During the clinical study, the Investigator will maintain adequate source records, including 
medical records, records detailing the progress of the study for each subject, laboratory reports, 
signed informed consent forms, IP disposition records, correspondence with the IRB or IEC and 
Study Monitor/Sponsor, AE reports, and information regarding subject discontinuation and 
completion of the clinical investigation. 
All required study data will be recorded on eCRFs. Any change of data will be recorded on the 
audit trail and a reason for the change will be entered. 
The Principal Investigator must retain all documentation relating to the study for a period of at 
least 2 years after the last marketing application approval or, if not approved, 2 years following 
the discontinuance of the test article for investigation.  If this requirement differs from any local 
regulations, the local regulations will take precedence unless the local retention policy is less 
than 2 years. 
7.6. 
Protocol Amendments and Deviations 
No change or amendment to this protocol may be made by the Investigator or Sponsor after the 
protocol has been agreed to and signed by all parties unless such change(s) or amendment(s) has 
(have) been agreed upon by the investigator and Sponsor.  Any change agreed upon will be 
recorded in writing, and the written amendment will be signed by the Investigator and Sponsor.  
Institutional review board approval is required prior to the implementation of an amendment, 
unless overriding safety reasons warrant immediate action, in which case the IRB(s)/IEC(s) will 
be promptly notified. 
No deviation from the protocol will be made except to protect the life or physical well-being of a 
subject in an emergency.  Except in such emergencies, prior approval of the Sponsor, and the 
IRB/IEC, is required before deviations from the planned protocol.  All protocol deviations that 
occur during the study will be documented and reported to Sponsor and to the IRB(s)/IEC(s), if 
applicable, according to regulations.  Further details about the documentation, evaluation, and 
follow-up of protocol deviations are detailed in this study’s clinical monitoring plan. 
No waivers to inclusion/exclusion criteria will be granted; subjects need to meet all criteria, 
exactly as specified, to be enrolled.  Additionally, prospective deviations from the protocol or 
investigational plan are not permitted except to protect the life or physical well-being of a subject 
in an emergency.  Deviations that occur unintentionally or are the result of action by the subject 


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must be documented and reported to the IRB(s), if applicable, according to regulations.  Further 
details about the documentation, evaluation, and follow-up of protocol deviations are detailed in 
this study’s clinical monitoring plan. 
7.7. 
Confidentiality and Privacy 
The Investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as date of birth) will be recorded on any form 
or biological sample submitted to the Sponsor. 
The Investigator agrees that all information received from Arcutis Biotherapeutics Inc., including 
but not limited to the IB, this protocol, eCRF, the IP, and any other study information, remain the 
sole and exclusive property of Arcutis Biotherapeutics Inc. during the conduct of the study and 
thereafter. This information is not to be disclosed to any third party (except employees or agents 
directly involved in the conduct of the study or as required by law) without prior written consent 
from Arcutis Biotherapeutics Inc. The Investigator further agrees to take all reasonable 
precautions to prevent the disclosure by any employee or agent of the study site to any third 
party or otherwise into the public domain. 
7.8. 
Conflict of Interest 
All study Investigators will provide documentation of their financial interest or arrangements 
with Arcutis Biotherapeutics Inc., or proprietary interests in the investigational drug under study. 
This documentation must be provided prior to the Investigator’s participation in the study. Any 
change to the Investigator’s financial interest during the study and up to one year after study 
completion will be reported to the Sponsor. All Investigators with reported conflict of interest 
will be required to have such conflicts managed in a way that is appropriate to their participation 
in the design and conduct of this study. 
7.9. 
Report Format 
According to the ICH Harmonized Tripartite Guideline (Organization of the Common Technical 
Document for the Registration of Pharmaceuticals for Human Use M4 and the ICH M2 Expert 
Working Group), the final report will be written according to the ICH E3 Guideline 
(Structure and Content of Clinical Study Reports). 
7.10. 
Publication Policy 
The Sponsor is supportive of publishing clinical trial findings.  Any form of publication that is 
derived from this study must be submitted to Arcutis Biotherapeutics Inc. for review and 
approval. The process of coordinating publication efforts is detailed in the Clinical Trial 
Agreement. 


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8.
REFERENCES
Berger RS, Bowman JP. A reappraisal of the 21-day Cumulative Irritation Test in man. 
J. Toxicol Ot & Ocular Toxicol. 1982:1(2);109-115.
Borda LJ, Wikramanayake TC. Seborrheic Dermatitis and Dandruff: A Comprehensive Review. 
J Clin Investigat Dermatol. 2015;3(2):10. 
DALIRESP (roflumilast) tablets [package insert]. AstraZeneca Pharmaceuticals LP, Wilmington, 
DE USA; 2018. 
DAXAS (roflumilast) film-coated tablets [product monograph]. AstraZeneca Canada, Inc., 
Mississauga, Ontario Canada; 2017. 
Dessinioti C, Katsambas A. Seborrheic dermatitis: Etiology, risk factors, and treatments: 
Facts and controversies. Clinics in Dermatology. 2013;31:343-351. 
EUCRISA™ (crisaborole) ointment, 2%, for topical use [package insert]. Pfizer Laboratories 
Div. Pfizer Inc, NY, USA; 2017. 
Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast – 
a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary 
disease. Pulm Pharmacol Ther. 2010;23:235–256. 
Investigator’s Brochure, Edition 4.0, 22 January 2021. 
Kimball AB, Naegeli AN, Edson-Heredia E, et. Psychometric properties of the Itch Numeric 
Rating Scale in patients with moderate-to-severe plaque psoriasis. Br. J. Dermatol. 
2016;175(1):157-162. doi:10.1111/bjd.1446. 
Naegeli AN, Flood E, Tucker J, et al. The Worst Itch Numeric Rating Scale for patients with 
moderate to severe plaque psoriasis or psoriatic arthritis. Int J Dermatol. 2015;54(6):715–22. 
OTEZLA® (apremilast) tablets, for oral use [package insert].  Celgene Corporation, Summit, 
NJ USA; 2017. 
Yosipovitch G, et al. Peak Pruritis Numerical Rating Scale: psychometric validation and 
responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol.  
2019;181(4):761-769. doi:10.1111/bjd.17744. 


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9.
APPENDICES
APPENDIX 1. BODY & SCALP DIAGRAM 
Site personnel to mark treatable areas identified by the Investigator. 
Reminder: Application will be all areas affected including scalp, face, trunk and/or 
intertriginous/genital regions. Subject should continue to apply even if area(s) clears and treat 
new lesions. 


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 The iStock design is a trademark of iStockphoto LP 


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APPENDIX 2. PATIENT HEALTH QUESTIONNAIRE DEPRESSION 
SCALE (PHQ-8) 


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APPENDIX 3. MODIFIED PATIENT HEALTH QUESTIONNAIRE 
DEPRESSION SCALE (PHQ-A) 


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APPENDIX 4. CHILDREN’S DEPRESSION INVENTORY 2 
(PARENT REPORT) 


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APPENDIX 5. COLUMBIA-SUICIDE SEVERITY RATING SCALE 
(C-SSRS) BASELINE/SCREENING VERSION 


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APPENDIX 6. COLUMBIA-SUICIDE SEVERITY RATING SCALE 
(C-SSRS) SINCE LAST VISIT VERSION 


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APPENDIX 7. SCALPDEX 


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APPENDIX 8. DERMATOLOGY LIFE QUALITY INDEX (DLQI) 


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APPENDIX 9. CHILDREN’S DERMATOLOGY LIFE QUALITY INDEX 
(CDLQI) 


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APPENDIX 10. NIAID DMID TOXICITY TABLE 
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, DIVISION OF 
MICROBIOLOGY AND INFECTIOUS DISEASES (DMID) Toxicity Table for Use in 
Trials Enrolling Healthy Adults (2014) Modified 
ABBREVIATIONS USED IN THE FOLLOWING TABLES: 
Abbreviation/Term 
Definition/Explanation 
Abbreviation/Term 
Definition/Explanation 
ALT 
alanine aminotransferase 
LO 
Low 
aPTT 
activated partial thromboplastin 
time 
mEq 
Milliequivalent 
AST 
aspartate aminotransferase 
mmHg 
millimeter of mercury 
AV block 
atrioventricular block 
Ms 
Millisecond 
bpm 
beats per minute 
N 
Normal 
BUN 
blood urea nitrogen 
PT 
prothrombin time 
CK 
creatine kinase 
PTT 
partial thromboplastin time 
CPK 
creatine phosphokinase 
QTc 
QT-interval corrected for 
heart rate 
FEV1 
forced expiratory volume in 
1 second 
QTcB 
Bazett’s corrected QT 
interval 
g 
Gram 
QTcF 
Fridericia’s corrected QT 
interval 
HI 
High 
RBC 
red blood cell 
HPF 
high power field 
Rx 
Therapy 
IU 
international unit 
S 
Second 
IV 
Intravenous 
U 
Unit 
K/CUMM 
x103/mm3 
ULN 
upper limit of normal 
LLN 
lower limit of normal 


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ESTIMATING SEVERITY GRADE 
For abnormalities NOT found elsewhere in the Toxicity Tables use the scale below to estimate 
grade of severity: 
GRADE 1 
Mild: 
Transient or mild discomfort (<48 hours); no medical 
intervention/therapy required 
GRADE 2 
Moderate: 
Mild to moderate limitation in activity - some assistance 
may be needed; no or minimal medical intervention/therapy 
required 
GRADE 3 
Severe: 
Marked limitation in activity, some assistance usually 
required; medical intervention/therapy required 
hospitalizations possible. 
LABORATORY RANGES 
Where discrepancies in the ULN and LLN of laboratory ranges occur between those included in 
this document and those of the laboratory that performs the assays, the values provided by the 
laboratory will be used for assignment of severity grade. 


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CLINICAL ADVERSE EVENTS 
Cardiovascular 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Arrhythmia 
Asymptomatic, transient signs, no 
Rx required  
Recurrent/persistent; 
symptomatic Rx required 
Hemorrhage, blood loss 
Estimated blood loss ≤100 mL 
Estimated blood loss >100 mL, no 
transfusion required 
Transfusion required 
QTcF (Fridericia’s 
correction)1 or QTcB 
(Bazett’s correction) 
Asymptomatic, QTc interval 
450-479 ms, OR
Increase in interval<30 ms above 
baseline 
Asymptomatic, QTc interval 
480-499 ms, OR
Increase in interval 30-59 ms 
above baseline 
Asymptomatic, QTc interval 
≥500 ms, OR  
Increase in interval ≥60 ms 
above baseline 
PR interval (prolonged) 
PR interval 0.20-0.25 s 
PR interval >0.25 s 
Type II 2nd degree AV block 
OR Ventricular pause >3.0 s 
Respiratory 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Cough 
Transient-no treatment 
Persistent cough 
Interferes with daily activities 
Bronchospasm, acute 
Transient wheeze; no treatment 
Requires treatment; normalizes 
with bronchodilator and  
FEV1 < 80% predicted before 
bronchodilator  
Minimal normalization with 
bronchodilator andFEV1 <80% 
predicted after bronchodilator 
Dyspnea 
Does not interfere with usual and 
social activities 
Interferes with usual and social 
activities, no treatment 
Prevents daily and usual social 
activity or requires treatment 
1 Inclusion dependent upon protocol requirements 


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Respiratory 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Nasal discharge (rhinitis 
infective per CTCAE 4.0) 
- 
Localized; local intervention 
indicated (e.g. topical antibiotic, 
antifungal, or antiviral) 
- 
Pharyngitis (CTCAE 4.0) 
- 
Localized; local intervention 
indicated (e.g. topical antibiotic, 
antifungal, or antiviral) 
IV antibiotic, antifungal, or 
antiviral intervention indicated; 
radiologic or operative 
intervention indicated 
Pneumonitis (rales or rhonchi) 
(CTCAE 4.0) 
Asymptomatic; clinical or 
diagnostic observations only; 
intervention not indicated 
Symptomatic; medical intervention 
indicated; limiting instrumental 
ADL 
Severe symptoms; limiting 
self-care ADL; oxygen indicated 
Lung infection (CTCAE 4.0) 
- 
Moderate symptoms; oral 
intervention indicated 
(e.g. antibiotic, antifungal, 
antiviral) 
IV antibiotic, antifungal, or 
antiviral intervention indicated; 
radiologic, endoscopic, or 
operative intervention indicated 
Gastrointestinal 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Nausea  
No interference with activity 
Some interference with activity 
Prevents daily activities 
Vomiting  
No interference with activity or 
1-2 episodes/24 hours 
Some interference with activity or 
>2 episodes/24 hours 
Prevents daily activity or 
requires IV hydration 
Diarrhea  
2-3 loose or watery stools or  
<400 g/24 hours 
4-5 loose or watery stools or  
400-800 g/24 hours 
6 or more loose or watery stools 
or >800 g/24 hours or requires 
IV hydration 
 
 
 


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Urinary Tract 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Urinary tract infection  
(CTCAE 4.0) 
- 
Localized; local intervention 
indicated (e.g. oral or topical 
antibiotic, antifungal, antiviral) 
IV antibiotic, antifungal, or antiviral 
intervention indicated; radiologic or 
operative intervention indicated 
Reactogenicity 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Local reactions 
Pain 
Does not interfere with activity 
Repeated use of non-narcotic pain 
reliever >24 hours or interferes 
with activity 
Any use of narcotic pain reliever or 
prevents daily activity 
Tenderness 
Discomfort only to touch 
Discomfort with movement 
Significant discomfort at rest 
Erythema/redness 2 
2.5-5 cm 
5.1-10 cm 
>10 cm 
Induration/swelling 3 
2.5-5 cm and does not interfere 
with activity 
5.1-10 cm or interferes with 
activity 
>10 cm or prevents daily activity 
Systemic reactions 
Allergic reaction  
Pruritus without rash  
Localized urticaria  
Generalized urticaria; angioedema 
or anaphylaxis  
Headache  
No interference with activity 
Repeated use of non-narcotic pain 
reliever >24 hours or some 
interference with activity 
Significant; any use of narcotic pain 
reliever or prevents daily activity 
Fatigue  
No interference with activity 
Some interference with activity 
Significant; prevents daily activity 
 
2 In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a continuous variable. 
3 Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 


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Reactogenicity 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Myalgia 
No interference with activity 
Some interference with activity 
Significant; prevents daily activity 
All Other Conditions 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Illness or clinical adverse 
event (as defined according to 
applicable regulations) 
No interference with activity 
Some interference with activity not 
requiring medical intervention 
Prevents daily activity and requires 
medical intervention 
LABORATORY AND VITAL SIGNS TOXICITY GRADING (Some laboratory values have been modified to be consistent 
with the normal ranges of the ACM laboratory used in the present study) 
Blood, Serum, or Plasma Chemistries a 
LO/HI/N b 
Mild 
(Grade 1) c 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Sodium (mEq/L or mmol/L) 
LO 
131-<LLN 
130 
<130 
HI 
>ULN-148
149-150
>150
Potassium (mEq/L or mmol/L) 
LO 
<LLN-3.2 
<3.2-3.1 
<3.1 
HI 
>ULN-5.6
>5.6-5.7
>5.7
Glucose (mg/dL) 
LO mmol/L 
<LLN-3.0 
<3.0-2.2 
<2.2 
HI mmol/L 
>ULN-8.9
>8.9-13.9
>13.9
Blood urea nitrogen 
HI mmol/L 
>8.9-17.8
>17.8-35.5
>35.5
Creatinine 
N 
115-151 (µmol/L)
152-177 (µmol/L)
> 177 (µmol/L)


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Blood, Serum, or Plasma Chemistries a 
LO/HI/N b 
Mild 
(Grade 1) c 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Calcium (CTCAE 4.0) 
LO mmol/L 
<LLN-2.0 
<2.0-1.75 
<1.75 
HI mmol/L 
>ULN-2.9
>2.9-3.1
>3.1
Magnesium (CTCAE 4.0) 
LO mmol/L 
<LLN-0.5 
<0.5-0.4 
<0.4 
Phosphorous (CTCAE 4.0) 
LO mmol/L 
<LLN-0.8 
<0.8-0.6 
<0.6 
Creatine kinase (CPK or CK) (CTCAE 4.0) 
HI 
>ULN-2.5xULN
>2.5xULN-5xULN
>5xULN
Albumin 
LO g/L 
<30-28 
<28-25 
<25 
Total protein 
LO g/L 
<LLN-52 
<52-50 
<50 
Alkaline phosphatase (U/L) (CTCAE 4.0) 
HI 
>ULN-2.5xULN
>2.5xULN-5xULN
>5xULN
AST (U/L) (CTCAE 4.0) 
HI 
>ULN-3xULN
>3xULN-5xULN
>5xULN
ALT (U/L) (CTCAE 4.0) 
HI 
>ULN-3xULN
>3xULN-5xULN
>5xULN
Bilirubin, serum total (mmol/L) (CTCAE 4.0) 
HI mmol/L 
>ULN-1.5xULN
>1.5xULN-3xULN
>3xULN
Bilirubin, serum total (mg/dL) when ALT ≥105 
(Hy’s law) 
HI 
1.3-1.5 
1.6-2.0 
>2.0
Bilirubin, serum direct (mmol/L) (CTCAE 4.0) 
HI mmol/L 
>ULN-1.5xULN
>1.5xULN-3xULN
>3xULN
Amylase (U/L) (CTCAE 4.0) 
HI 
>ULN-1.5xULN
>1.5xULN-2xULN
>2xULN
Lipase (U/L) (CTCAE 4.0) 
HI 
>ULN-1.5xULN
>1.5xULN-2xULN
>2xULN


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Blood, Serum, or Plasma Chemistries a 
LO/HI/N b 
Mild 
(Grade 1) c 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Uric acid (mg/dL/mmol/L) (CTCAE 4.0) 
HI 
>ULN – 10 mg/dL
(0.59 mmol/L)
without physiologic
consequences
- 
>ULN – 10 mg/dL
(0.59 mmol/L) with
physiologic
consequences
a Depending upon the laboratory used, references ranges, eligibility ranges and grading may be split out by sex and/or age. 
b Low, High, Not Graded (N). 
c If initial boundary of grade 1 has gap from reference range or eligibility range, calculations based on the New England Journal of Medicine (NEJM) reference 
ranges. 


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Hematology 
LO/HI/N a 
Mild 
(Grade 1) b 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Hemoglobin (women) (g/dL) 
Hemoglobin (men) (g/dL) 
LO 
10.8-11.3 
9.2-10.7 
<9.2 
LO 
12.0-12.5 
10.0-11.9 
<10.0 
White blood cell count (K/CUMM) 
HI 
11.00-15.00 
15.00-20.00 
>20.00
LO 
2.50-3.50 
1.50-2.49 
<1.50 
Lymphocytes (K/CUMM) 
LO 
0.76-0.90 
0.50-0.75 
<0.5 
Neutrophils (K/CUMM) 
LO 
1.50-1.95  
1.00-1.49 
<1.00 
Eosinophils (K/CUMM) 
HI 
0.58-0.74  
0.75-1.50 
>1.50
Platelets (K/CUMM) 
LO 
120-130
100-120
<100 
Coagulation 
Prothrombin time (PT, seconds) 
HI 
> ULN-14.4
14.5-15.7 
>15.7
Partial thromboplastin time 
(PTT or aPTT, seconds) 
HI 
>ULN-42.1
42.2-50.0 
>50.0
Fibrinogen (mg/dL) (CTCAE 4.0) 
HI 
>ULN-500
501-600
>600
LO 
<LLN-0.75xLLN 
<0.75xLLN-
0.5xLLN 
<0.5xLLN 
Urine 
Protein (dipstick) 
HI 
1+ 
2+ 
>2+
Glucose (dipstick) 
HI 
1+ 
2+ 
>2+
Blood (microscopic) - red blood cells per high 
power field (RBC/HPF) 
HI 
5-10 for males
9-10 for females
11-50
>50 and/or gross
blood
a Low, High, Not Graded. 
b If initial boundary of grade 1 has gap from reference range or eligibility range, calculations based on the New England Journal of Medicine (NEJM) reference 
ranges. 


Protocol ARQ-154-304 
Arcutis Biotherapeutics, Inc. 
Amendment 1  
Confidential 
Page 83 of 86 
Vital Signs 
LO/HI/N a 
Mild 
(Grade 1) b 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Fever (°C) c 
HI 
38.0-38.4 
38.5-38.9 
>38.9
Fever (°F) 
HI 
100.4-101.1 
101.2-102.0 
>102.1
Tachycardia - beats per minute 
HI 
101-115
116-130
>130 or ventricular
dysrhythmias
Bradycardia - beats per minute 
LO 
40-45
35-40
<35 
Hypertension (systolic) - mm Hg d 
HI 
141-150
151-160
>160
Hypertension (diastolic) - mm Hg 
HI 
91-95
96-100
>100
Hypotension (systolic) - mm Hg 
LO 
85-89
80-84
<80 
Tachypnea - breaths per minute 
HI 
23-25
26-30
>30
a Low, High, Not Graded. 
b If initial boundary of grade 1 has gap from reference range or eligibility range, calculations based on the New England Journal of Medicine (NEJM) reference 
ranges. 
c Oral temperature; no recent hot or cold beverages or smoking. A protocol should select either °C or °F for inclusion. 
d Assuming subject is awake, resting, and supine; for adverse events, 3 measurements on the same arm with concordant results 


Protocol ARQ-154-304 
Arcutis Biotherapeutics, Inc. 
Amendment 1  
 
 
Confidential 
Page 84 of 86 
 
 
  
 
APPENDIX 11. COVID-19 STUDY SITE GUIDANCE 
 
BACKGROUND 
As the impact of coronavirus disease 2019 (COVID-19) continues to develop, Premier Research 
Inc. and Arcutis Biotherapeutics Inc. have collated the following guidelines in response for study 
sites participating in the ARQ-154-304. While it is ideal for subjects to perform all 
protocol-specific assessments at the study site, both Premier and Arcutis are focused on 
prioritizing subject safety and data integrity. Therefore, the following guidelines will identify 
challenges and mitigation strategies while operating clinical trials remotely. 
REMOTE DATA COLLECTION 
In the event subjects are unable to complete protocol-specific assessments onsite, study sites may 
collect data from subjects remotely via telephone and/or by traditional mail or email. The method 
used for data collection must be clearly documented in the source. Whenever possible, sites 
should adhere to the protocol visit window for remote data collection. Screening and Baseline 
(Day 0) visits/assessments must be performed in the clinic and must NOT be completed 
remotely. If necessary, these visits can be delayed ensuring they are conducted in the clinic and 
not remotely. 
Data collection by phone may be performed. Subjects are contacted via telephone and site staff 
will collect data verbally for all critical data points applicable. Subject responses should be 
recorded in the site source documents. Data collected remotely should be entered into the EDC 
system (iMedidata Rave). 
Data collection by mail or email may also be performed for applicable assessments. Site staff 
will contact subjects via traditional mail or email to collect data using paper versions of study 
questionnaires. C-SSRS cannot be collected by mail/email as this requires subject interview by 
site staff. 
Investigator assessments and subject questionnaires normally completed during on-site visits 
should be completed on the appropriate paper source documents and entered in the EDC. The 
following subject assessments/questionnaires are approved to be collected via 
telemedicine/remotely: 
• C-SSRS 
• PHQ-8/PHQ-A/CDI-2 
• DLQI/CDLQI 
• Scalpdex 
• Subject Local Tolerability 
• Adverse Events 
• Concomitant medication 


Protocol ARQ-154-304 
Arcutis Biotherapeutics, Inc. 
Amendment 1  
Confidential 
Page 85 of 86 
The following Investigator assessments cannot be completed via telemedicine/remotely: 
•
IGA
•
BSA
•
Investigator Local Tolerability
•
Pigmentation Assessment
•
Overall Assessment of Erythema
•
Overall Assessment of Scaling
•
Subject Weight
GUIDELINES FOR REMOTE DATA COLLECTION 
1. Highest priorities: the subject safety and preserving integrity of data are critical.
2. Study visits and procedures must be followed per protocol whenever possible. Any
specific changes in study conduct that deviate from the protocol should be communicated
to the IRB and Sponsor (via reporting to your site assigned CRA). All protocol deviations
which occurred as a result of COVID-19 disruptions (e.g., visits out of window, missed
assessments, etc.) should be differentiated from other PDs. It is prudent to receive IRB
guidance or approval if a deviation is known to occur in advance (i.e., extending IP
application or changing assessment windows, etc.).
3. If, despite all efforts, a planned clinic visit is absolutely not possible due to a COVID-19
related issue (e.g., site has closed, subject prohibited from coming to clinic, etc.),
sponsor’s strong preference is a delayed clinic visit. If the subject can come to clinic
within a reasonable amount of time considering the protocol allowed visit window. If a
delayed clinic visit cannot be completed within 14 days of the protocol specified visit
window, please contact the Medical Monitor for additional guidance.
4. It is critical to ensure subjects have enough IP in the event timely clinic visit(s) is/are not
possible. It is also critical to ensure subjects are instructed to continue to apply IP per
protocol for the duration of their participation in the study. Subjects should also be
reminded to complete their daily diaries and IP compliance should be assessed via phone
if clinic visits are not possible or are delayed.
5. It is critical for preserving data integrity to make every effort possible to have a subject
return to clinic for the Week 8 visit. For visits conducted in the clinic, it is critical to
ensure Rater consistency for all efficacy assessments (e.g., IGA, etc.). If absolutely
necessary, it is preferred to have several missed visits and a delayed Week 8 visit versus
having an Early Termination and no Week 8 visit. If it is not possible for a subject to
return on-site within window for the Week 8 visit, sites should:
a.
Ensure the subject has signed the most current IRB approved ICF.
b. Contact subjects to discuss continue administration of IP and continue to complete
their dosing diaries per regular IP administration instructions.


Protocol ARQ-154-304 
Arcutis Biotherapeutics, Inc. 
Amendment 1  
Confidential 
Page 86 of 86 
c.
Subjects are approved to continue applying IP post Week 8 as long as the following
have been discussed with the subject:
−
Site should confirm the subject has adequate IP to continue dosing and if not ask
the subject to return to the site to pick up additional IP or refer to the current IP
Handling Plan for instructions on shipment of IP from site to subject.
−
Confirm the subject has no AEs that would warrant discontinuation of the IP.
−
Site should discuss any new or ongoing conmed(s) and determine if the use of any
warrant having the subject stop IP application or not.
−
For any female subject of childbearing potential that site should discuss and
confirm the subject has continued her methods of ensuring pregnancy does not
occur. Any deviation from these methods should be discussed further and the site
should determine if IP should be halted or contact the medical monitor or Arcutis
if they have any questions.  A pregnancy test can be performed at the next onsite
visit (this is applicable to prior visits being missed due to COVID-19 as well).
−
Subjects are approved to continue dosing for up to 14 days past their Week 8 visit.
After this, sites should reach out to the Medical Monitor and/or Arcutis directly
for approval to have subjects continue dosing.
−
All the above discussions must be documented in the source.
d. If available, home health nurse visits could be considered for collection of Vital Signs
and Clinical Labs.
e.
In the event a subject is quarantined, has symptoms, or is confirmed positive for
COVID-19, it is the Sponsor’s opinion that IP can continue, assuming no other
contraindications.

SAP_001.pdf: 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022                |    AD-PR-109.02  Effective date: 17-Aug-2020       Page 1 of 56 
   Statistical Analysis Plan 
Sponsor: 
Arcutis Biotherapeutics, Inc. 
Protocol Title: 
A Phase 3, 8-Week, Parallel Group, Double Blind, 
Vehicle-Controlled Study of the Safety and Efficacy of 
ARQ-154 Foam 0.3% Administered QD in Subjects with 
Seborrheic Dermatitis (STRATUM) 
Protocol Number: 
ARQ-154-304 
Premier Research PCN: 
ARCU214357 
Document Version: 
Final 3.0 
Document Date:  
22-Sep-2022 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 2 of 56 
APPROVALS 
Role 
Signatures 
Biostatistician 
Premier Research 
Print Name:  
 
 
 
Sign Name: 
Peer Reviewer 
Premier Research 
Print Name:  
 
 
 
Sign Name: 
Arcutis 
Biotherapeutics, Inc. 
Representative 
Print Name:  
 
 
 
Sign Name: 
Arcutis 
Biotherapeutics, Inc. 
Representative 
Print Name:  
 
 
 
Sign Name: 
 
 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 3 of 56 
DOCUMENT HISTORY 
Final V1.0 
19-Apr-2022 – Initial version. 
Final V2.0 
13-May-2022 – update to multiple endpoint 
testing strategy for secondary endpoints to 
reflect amendment 2 of the protocol, 
clarification that Scalpdex analyses will 
include only subjects with scalp involvement; 
minor update to calculation of compliance. 
Final V3.0 
22-Sep-2022 – Post-database lock and post-
unblinding update to SAP as per FDA to 
amend the primary estimand and multiple 
imputation procedure based on 
recommendations from FDA during pre-NDA 
meeting held 9/14/2022. 
 
 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 4 of 56 
TABLE OF CONTENTS 
1. 
OVERVIEW ....................................................................................................................... 9 
2. 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 10 
2.1. 
Study Objectives ......................................................................................................... 10 
2.1.1. Primary Objective ....................................................................................................... 10 
2.2. 
Study Endpoints .......................................................................................................... 10 
2.2.1. Efficacy Endpoints ...................................................................................................... 10 
2.2.2. Safety Endpoints ......................................................................................................... 11 
3. 
OVERALL STUDY DESIGN AND PLAN ..................................................................... 12 
3.1. 
Overall Design ............................................................................................................ 12 
3.2. 
Sample Size and Power ............................................................................................... 12 
3.3. 
Study Population ......................................................................................................... 12 
3.4. 
Treatments Administered ............................................................................................ 12 
3.5. 
Method of Assigning Subjects to Treatment Groups .................................................. 13 
3.6. 
Blinding and Unblinding............................................................................................. 13 
3.7. 
Schedule of Events ...................................................................................................... 13 
4. 
STATISTICAL ANALYSIS AND REPORTING ........................................................... 16 
4.1. 
Introduction ................................................................................................................. 16 
4.2. 
Interim Analysis and Data Monitoring ....................................................................... 16 
5. 
ANALYSIS POPULATIONS .......................................................................................... 16 
6. 
GENERAL ISSUES FOR STATISTICAL ANALYSIS .................................................. 17 
6.1. 
Statistical Definitions and Algorithms ........................................................................ 17 
6.1.1. Baseline ....................................................................................................................... 17 
6.1.2. Adjustments for Covariates......................................................................................... 18 
6.1.3. Multiple Comparisons ................................................................................................. 18 
6.1.4. Handling of Dropouts or Missing Data ....................................................................... 20 
6.1.5. Analysis Visit Windows ............................................................................................. 23 
Table 3 Analysis Windows for Calculation of Average Weekly WI-NRS: ........................... 23 
6.1.6. Pooling of Sites ........................................................................................................... 24 
6.1.7. Derived Variables ....................................................................................................... 24 
6.1.8. Data Adjustments/Handling/Conventions .................................................................. 27 
6.2. 
Special Handling for COVID-19 Disruptions ............................................................. 28 
7. 
STUDY PATIENTS/SUBJECTS AND DEMOGRAPHICS ........................................... 29 
7.1. 
Disposition of Patients/Subjects and Withdrawals ..................................................... 29 
7.2. 
Protocol Deviations ..................................................................................................... 29 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 5 of 56 
7.3. 
Demographics and Baseline Characteristics ............................................................... 30 
7.4. 
Exposure and Compliance .......................................................................................... 30 
8. 
EFFICACY ANALYSIS .................................................................................................. 31 
8.1. 
Primary Efficacy Analysis .......................................................................................... 31 
8.1.1. IGA Success ................................................................................................................ 31 
8.1.2. Hypothesis Testing...................................................................................................... 33 
8.1.3. Sensitivity and Supplemental Analyses of the Primary Efficacy Endpoint ................ 33 
8.1.4. Impact of Site on the Primary Efficacy Endpoint ....................................................... 34 
8.2. 
Secondary Efficacy Analysis ...................................................................................... 34 
8.2.1. Investigator Global Assessment (IGA) ....................................................................... 34 
8.2.2. Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score ................................... 35 
8.2.3. Other Efficacy Endpoints ............................................................................................ 35 
8.2.4. Overall Assessment of Erythema ................................................................................ 36 
8.2.5. Overall Assessment of Scaling ................................................................................... 36 
8.3. 
Other Efficacy Analysis .............................................................................................. 38 
8.4. 
Subgroup Analyses of Efficacy Variables .................................................................. 40 
9. 
SAFETY AND TOLERABILITY ANALYSIS ............................................................... 40 
9.1. 
Adverse Events ........................................................................................................... 40 
9.1.1. Adverse Events Leading to Discontinuation ............................................................... 41 
9.1.2. Deaths and Serious Adverse Events ........................................................................... 41 
9.2. 
Local Tolerability Assessments .................................................................................. 41 
9.3. 
Clinical Laboratory Evaluations ................................................................................. 42 
9.4. 
Vital Signs ................................................................................................................... 42 
9.5. 
PHQ-8 and Modified PHQ-A ..................................................................................... 42 
9.6. 
CDI-2 .......................................................................................................................... 43 
9.7. 
C-SSRS ....................................................................................................................... 43 
9.8. 
Physical Examination.................................................................................................. 43 
9.9. 
Concomitant Medication ............................................................................................. 44 
9.10. Pigmentation Assessment ........................................................................................... 44 
10. 
CHANGES FROM PLANNED ANALYSIS ................................................................... 44 
10.1. Version 2.0 .................................................................................................................. 44 
10.2. Version 3.0 .................................................................................................................. 44 
11. 
OTHER PLANNED ANALYSIS ..................................................................................... 45 
11.1. Pharmacokinetic Analysis ........................................................................................... 45 
12. 
CHANGES TO ANALYSIS PLANNED IN THE PROTOCOL ..................................... 45 
12.1. Definition of PK Population ....................................................................................... 45 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 6 of 56 
13. 
REFERENCES ................................................................................................................. 45 
14. 
TABLES, LISTINGS AND FIGURES ............................................................................ 47 
14.1. Planned Table Descriptions ........................................................................................ 47 
14.2. Planned Figure descriptions ........................................................................................ 53 
14.3. Planned Listing Descriptions ...................................................................................... 54 
15. 
TABLES, LISTINGS AND FIGURES SHELLS ............................................................. 56 
15.1. Standard Layout for all Tables, Listings and Figures ................................................. 56 
 
 
 
 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 7 of 56 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
ATC 
anatomical therapeutic chemical 
BLQ 
below limit of quantification 
BMI 
body mass index 
CDLQI 
children’s dermatology life quality index 
CI 
confidence interval 
CMH 
Cochran Mantel Haenszel 
COVID-19 
Novel coronavirus disease 
CRF 
case report form 
CS 
clinically significant 
CSR 
clinical study report 
DBL 
database lock 
DBP 
diastolic blood pressure 
DLT 
dose limiting toxicity 
DLQI 
dermatology life quality index 
DSMB  
data safety monitoring board 
DSUR 
development safety update report 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European medicines agency 
FDA 
food and drug administration 
GCP 
good clinical practice 
HR 
heart rate 
IB 
investigator’s brochure 
IGA 
investigator global assessment 
IP 
investigational product 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 8 of 56 
Abbreviation 
Definition 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent-to-treat 
LLOQ 
lower limit of quantification 
MedDRA 
medical dictionary for regulatory activities 
MI 
multiple imputation 
MTD 
maximum tolerated dose 
NA 
not applicable 
NCS 
non-clinically significant 
PD 
protocol deviation 
PHQ 
patient health questionnaire 
PK 
Pharmacokinetic 
PP 
per-protocol 
RR 
respiratory rate or relative rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
standard error 
SOC 
system organ class 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
WHO-DD 
world health organization drug dictionary 
WI-NRS 
worst itch – numeric rating scale 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 9 of 56 
1. 
OVERVIEW 
This statistical analysis plan (SAP) describes the planned analysis and reporting for Arcutis 
Biotherapeutics, Inc. protocol number ARQ-154-304 (A Phase 3, 8-Week, Parallel Group, 
Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-154 Foam 0.3% 
Administered QD in Subjects with Seborrheic Dermatitis), dated 05-May-2022 Amendment 2. 
Version 1 of the ARQ-154-SAP was approved on 19-Apr-2022 and was included as background 
for a Type C meeting submitted to FDA on the same date.  FDA’s written response to Arcutis 
questions was received on 3-Jun-2022.  In the interim, Protocol Amendment 2 and SAP Version 
2.0 (13-May-2022) were created to update the multiple testing strategy for secondary endpoints. 
The database was locked on 17-May-2022 and unblinded on 19-May-2022.  Results have since 
been presented at a medical conference (Blauvelt A., et al.).  On 9-Sep-2022, FDA provided the 
following advice in preliminary feedback prior to a pre-NDA meeting held on 14-Sep-2022. 
For the primary estimand, you proposed a treatment policy strategy to handle all intercurrent 
events, including treatment discontinuation due to adverse event or lack of efficacy. For 
intercurrent events of treatment discontinuation due to adverse events or lack of efficacy, we 
recommend a composite strategy policy where subjects will be defined as non-responders, 
as we consider this to be the appropriate approach for handling such events. Your proposal 
to handle intercurrent events of treatment discontinuation using the treatment policy strategy 
can be used as part of a supportive estimand. 
The purpose of this version of the SAP is to document the change to the primary estimand and 
related multiple imputation strategies. The revised estimand will be the focus of the Clinical 
Study Report and NDA.  Key results based on the original estimand defined in SAP versions 1 
and 2 will be provided as supplemental information for the primary and secondary endpoints 
covered by the multiple testing strategy. 
 
Reference materials for this statistical plan include the protocol and the accompanying sample 
data collection documents. Operational aspects related to collection and timing of planned 
clinical assessments are not repeated in this SAP unless relevant to the planned analysis. 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials (ICH 1998). All work planned and reported for this SAP will follow internationally 
accepted guidelines, published by the American Statistical Association (ASA 2018) and the 
Royal Statistical Society (RSS 2014), for statistical practice. 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 10 of 56 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc 
or unplanned, exploratory analysis performed will be clearly identified as such in the final CSR. 
The statistical plan described hereafter is an a priori plan. It will be approved before any 
unblinded inferential or descriptive analysis of data pertaining to Arcutis Biotherapeutics, Inc.’s 
study ARQ-154-304. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. Primary Objective 
The primary objective of this study is to assess the safety and efficacy of ARQ-154 foam 0.3% 
administered once daily (QD) vs vehicle foam for 8 weeks in subjects with seborrheic dermatitis. 
2.2. 
Study Endpoints 
2.2.1. Efficacy Endpoints 
2.2.1.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint of this study is success in Investigator Global Assessment (IGA) 
of disease severity, defined as IGA score of ‘clear’ or ‘almost clear’ plus at least 2-point 
improvement at Week 8.  
2.2.1.2. 
Secondary Efficacy Endpoint(s) 
The secondary efficacy endpoints of this study include the following:  
• In subjects with an average weekly Baseline Worst Itch Numeric Rating Scale (WI-NRS) 
pruritus score of ≥ 4, achievement of at least 4-point from baseline in WI-NRS pruritus 
score at Week 8 (“WI-NRS Success at Week 8”) 
• WI-NRS Success at Week 4 
• WI-NRS Success at Week 2 
• IGA Success at Week 4 
• IGA Success at Week 2 
• Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 at Week 8 
• Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at Week 8 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 11 of 56 
• Achievement of an IGA score of ‘clear’ at Week 8 
2.2.1.3. 
Other Secondary Efficacy Endpoint(s) 
Other secondary efficacy endpoints of this study include the following:  
• Change and percent change in Scalpdex total score from baseline at Weeks 2, 4, and 8. 
• Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at Weeks 2, 
and 4. 
• Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 at Weeks 2, and 
4. 
• Change and percent change from baseline in Dermatology Life Quality Index (DLQI), 
Children’s DLQI (CDLQI) at Weeks 2, 4, and 8. 
• Change and percent change from baseline in body surface area (BSA) affected at 
Weeks 2, 4, and 8. 
• Change and percent change from baseline in Overall Assessment of Erythema score at 
Weeks 2, 4, and 8. 
• Change and percent change from baseline in Overall Assessment of Scaling score at 
Weeks 2, 4, and 8. 
• Achievement of an IGA score of ‘clear’ at Week 4. 
• Achievement of an IGA score of ‘clear’ at Week 2. 
• Achievement of daily WI-NRS score of 0 or 1. 
• Change and percent change from average weekly baseline in WI-NRS  
2.2.2. Safety Endpoints 
The safety endpoints of this study include the following: 
• Adverse events 
• Local tolerability assessments 
• Clinical laboratory parameters 
• Vital signs/weight 
• Patient Health Questionnaire (PHQ-8) 
• Modified PHQ-Adolescents (PHQ-A) 
• Children’s Depression Inventory 2 (CDI-2) 
• Columbia-Suicide Severity Rating Scale (C-SSRS) 
• Physical examinations 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 12 of 56 
• Pigmentation Assessment 
3. 
OVERALL STUDY DESIGN AND PLAN 
3.1. 
Overall Design 
This is an 8-week, parallel group, double blind, vehicle-controlled study for the treatment of 
subjects with seborrheic dermatitis. This study will include both male and female subjects 9 
years and older having an IGA score of at least “Moderate” (3). Approximately 450 subjects will 
be enrolled. Subjects should not have more than 20% body surface area (BSA) of seborrheic 
dermatitis. After having met all inclusion criteria, and none of the exclusion criteria, subjects will be 
randomized in a 2:1 ratio to ARQ-154 foam 0.3% QD (Roflumilast foam 0.3%) or Vehicle foam QD 
on Baseline Day 0 which will be applied to areas of lesions of seborrheic dermatitis. The interval 
between Screening and Baseline Day 0 could be up to 4 weeks followed by 8 weeks of treatment 
phase. The total duration of the study is anticipated to be around 12 weeks. Subjects will have to 
apply the study drug once a day in the evening, except for on Day 0 and Week 2, the study drug is 
applied at the study site. Subjects have to record the date and time each dose has been applied, any 
missed doses, and any additional comments.  
3.2. 
Sample Size and Power 
A sample size of approximately 450 subjects is planned for the study. Approximately 
300 subjects will receive ARQ-154 foam 0.3%; approximately 150 subjects will receive vehicle 
foam. This will provide at least 90% power to detect a 25% difference between treatment groups 
on IGA success at α=0.01 assuming the proportion of IGA success at vehicle arm was 40% (odds 
ratio of 2.79 for Roflumilast vs. vehicle). The number of subjects to be enrolled will also provide 
sufficient power for the secondary endpoints. Additionally, the larger study size is included in 
order to provide additional/sufficient number of subjects on ARQ-154 treatment for a safety 
database. 
3.3. 
Study Population 
Study population consists of male and female subjects of age 9 years or older with no more than 
20% BSA of seborrheic dermatitis. Subjects should have a minimum IGA of ‘Moderate’ (3) at 
baseline.  
3.4. 
Treatments Administered 
Subjects who meet the eligibility criteria will be randomized to 1 of the 2 following treatment 
groups in a 2:1 ratio (active:vehicle): 
• ARQ-154 foam 0.3% QD (Roflumilast foam 0.3%)   
• Matching vehicle foam QD 


 
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3.5. 
Method of Assigning Subjects to Treatment Groups 
Randomization will take place at the Baseline visit after the Investigator confirms that the subject 
meets all eligibility criteria listed in the protocol. Subjects will be randomly assigned to apply 
ARQ-154 foam 0.3% QD or vehicle QD by an interactive response technology system (IRT). 
Assignment of treatment arm will be made in a 2:1 ratio stratified by study site and baseline 
disease severity (IGA = 3 or IGA = 4). Kits containing tubes of investigational product will be 
assigned to each subject by the IRT system. A subject may receive more than one kit for the 
treatment period. The kits and tubes will be labeled with a unique number, in a blinded manner. 
3.6. 
Blinding and Unblinding 
This is a double-blind study, therefore neither the subjects nor the Investigator, clinical 
personnel, or sponsor will be aware of which treatment an individual receives. In the event of a 
medical emergency where breaking the blind is required to provide medical care to the subject, 
the Investigator may obtain the treatment assignment directly from the IRT system for that 
subject. Refer to the current version of the IRT plan for details on unblinding. Treatment 
assignments should, however, remain blinded unless assignment knowledge is necessary to 
determine subject emergency medical care. The rationale for unblinding must be clearly 
explained in source documentation and on the CRF, along with the date on which the treatment 
assignment was obtained. The Investigator is requested to contact the Sponsor promptly in the 
event of any treatment unblinding.  
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the Investigator, the subject will have the study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject. 
3.7. 
Schedule of Events 
A detailed schedule of events for the study is provided in Table 1. 
Table 1: 
Schedule of Events 
Study Procedure 
Screen 
Baseline 
Day 0 
Week 2 
Day 14 
Week 4 
Day 28 
Week 8a 
Day 56 
Visit 
1 
2 
3 
4 
5 
Visit Window 
-4 weeks 
± 3 days 
± 5 days 
± 5 days 
Informed consent/assent 
X 
Medical/surgical history, demography 
X 
Physical examinationb 
X 
X 
X 
Fitzpatrick Skin Type 
X 


 
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I/E criteria 
X 
X 
Randomization 
X 
Hematology, Chemistry, and Urinalysisc 
X 
X 
X 
X 
Vital signs, weight, heightd 
X 
X 
X 
X 
X 
IGA, Overall Assessment of Erythema, 
Overall Assessment of Scalinge 
X 
X 
X 
X 
X 
BSAf 
X 
X 
X 
X 
X 
DLQI/CDLQIg, Scalpdex 
X 
X 
X 
X 
X 
Daily WI-NRSh at home (non-clinic) 
Day -7 through Day 56 
Local Tolerability Assessmenti 
X 
X 
X 
Pigmentation Assessmentj 
X 
X 
X 
X 
X 
C-SSRS, CDI-2/PHQ-8/PHQ-Ak 
X 
X 
X 
X 
Medical Photographyl 
X 
X 
X 
X 
Serum pregnancy testm 
X 
Urine pregnancy testn 
X 
X 
X 
PK samplingo 
X 
X 
IP application and subject/family trainingp 
X 
X 
Dispense investigational product kitq 
X 
X 
X 
Dispense / review dosing diary 
X 
X 
X 
X 
Weigh investigational productr 
X 
X 
X 
X 
Compliance calculations 
X 
X 
X 
Adverse event assessmentt 
X 
X 
X 
X 
Prior & Concomitant medications 
X 
X 
X 
X 
X 


 
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Footnotes from table above: 
a Subjects that terminate early should return to the study site for the Week 8 assessments. 
b Limited physical examination: skin (including assessment of Fitzpatrick Skin Type at Screening only), 
lungs, and heart only. 
c To be collected at Screening, Baseline/Day 0, Week 4/Day28, and Week 8/Day 56. For subjects 
<18 years of age, if the Baseline/Day 0 visit occurs within 3 weeks of Screening, the Screening lab 
results may be utilized. 
d Height will be collected at Baseline and Week 8. Weight will be collected at all study visits. Subject 
to void prior to weight. 
e IGA will be a 5-point scale ranging from clear (0) to severe (4). IGA should be completed prior to 
other physician assessments and by the same Evaluator at each study visit. Overall Assessment of 
Erythema (0-3 scale) and Overall Assessment of Scaling (0-3 scale) will be completed. 
f    Total BSA affected by seborrheic dermatitis will be determined by the subject’s hand method, 
where the subject’s hand (including fingers) surface area is assumed to equal 1% of body surface 
area. 
g The DLQI will be completed by subjects ≥17 years of age. The CDLQI will be completed for subjects 
9 to 16 years old, inclusive. 
h WI-NRS will be completed by subjects daily at home starting 7 days prior to the Baseline/Day 0 visit to 
Day 56 (Week 8) visit. Daily WI-NRS will be completed in the evening prior to IP application (except at 
Baseline and Week 2 when IP is applied at the clinic). 
i Local tolerability assessments to be recorded prior to IP application for the Investigator assessment of 
skin irritation (Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the 
subject’s ‘0- 3’ burning/stinging assessment. Note for investigator tolerability assessments: reactions at 
the site of IP application, which may occur post-Baseline, should be differentiated from the preexisting 
inflammation associated with the subject’s seborrheic dermatitis. At Week 4 and Week 8, subjects will 
provide a recall assessment of burning/stinging experienced post IP application on the day prior to the 
clinic visit. 
j An assessment for hypopigmentation and hyperpigmentation will be performed by the Investigator at all 
clinic visits. 
k Adolescents and adults will complete the C-SSRS (12 years of age and older). Adults will complete the 
PHQ-8. Adolescents (ages 12 to 17 inclusive) will complete the PHQ-A (PHQ-9 modified). 
Parents/caregivers will complete CDI-2 (parent report) for children 9-11 years of age, inclusive. The CDI-
2 will be completed throughout the study for subjects 9-11 years old at the time of assent. 
l Medical photography will be obtained for target lesions. All efforts will be made to de-identify the 
subjects.  Subjects unwilling to participate in the medical photography will be allowed to opt out of this 
procedure. 
m A serum pregnancy test will be administered to all females of child-bearing potential at the Screening visit 
only. 
n A urine pregnancy test will be performed at the Baseline, Weeks 2, 4, and 8 to all females of 
child-bearing potential. A negative result is required for continued participation in the study, and results 
must be available at each visit prior to dispensing of investigational product. 
o PK samples (trough) will be collected on Day 28 (Week 4), and Day 56 (Week 8). Ensure 
investigational product is not applied in the area where PK will be drawn. 
p Subjects to apply assigned IP in the study site at every designated visit. 
q Kits will be dispensed based on % BSA. See IP Handling Plan for details. 
r Each IP canister in the Kit should we weighed and recorded at every visit. See IP Handling Plan for details. 


 
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s Compliance calculation is described in the IP Handling Plan. 
t All AEs should be collected starting after the first application of the IP through the end of the study. All 
SAEs should be collected starting after the signing of the informed consent through 30 days after the last 
day of the IP application or the end of the study (whichever is later). 
4. 
STATISTICAL ANALYSIS AND REPORTING 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations primarily use SAS (release 9.4 or higher). If the use of other software is 
warranted, the final statistical methodology report will detail what software was used for what 
purposes. 
Continuous (quantitative) variable summaries will include the number of subjects (n) with 
non-missing values, mean, standard deviation (SD), median, Q1, Q3, minimum, and maximum.  
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular category or each possible value. In general, the denominator 
for the percentage calculation will be based upon the total number of subjects in the study 
population for each treatment group unless otherwise specified.  
The minimum and maximum will be reported with the same degree of precision (ie, the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
reported to 1 degree of precision more than the observed data and measures of spread (SD) will 
be reported to 2 degrees of precision more than the observed data. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
Unless otherwise indicated in section 6.1.3, all statistical tests will be conducted at the 0.01 
significance level using 2-tailed tests, and p-values will be reported. Corresponding 95% and 
99% confidence intervals (CIs) will be presented for statistical tests. 
ARQ-154 0.3% foam will be described as “Roflumilast foam 0.3%” throughout the tables, 
figures, and listings. 
4.2. 
Interim Analysis and Data Monitoring 
No interim analyses are planned. 
5. 
ANALYSIS POPULATIONS 
The following analysis populations are planned for this study:  


 
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• Intent-To-Treat Population (ITT): The ITT population includes all randomized 
subjects. This population will be used as primary analysis population of efficacy 
endpoints along with disposition. 
• Per-protocol Population (PP): The PP population will be a subset of the subjects in the 
ITT population, who are at least 80% compliant with study medication application, have 
IGA assessment at week 8, and show no “important deviations” from the study protocol 
that would affect the interpretation of efficacy.  “Important deviations” will result from a 
blinded review at the end of the study and the team will determine the important 
deviations that can impact on efficacy.   
• Modified Intent-to-Treat Population (mITT): The mITT population includes all 
randomized subjects with the exception of subjects who missed the week 8 IGA 
assessment specifically due to COVID-19 disruption. This population will be used for 
sensitivity of the primary endpoint. 
• Pruritus Population in ITT (PRU4-ITT): This PRU population is a subset of the ITT 
population and includes subjects with average weekly WI-NRS pruritus score ≥4 at 
Baseline. This population will be used for the analysis of achievement of at least 4-point 
improvement in average weekly WI-NRS pruritus score as compared to Baseline. 
• Safety Population (SAF): The Safety Population includes all subjects who are 
randomized and receive at least one confirmed dose of investigational product (IP). 
This population will be used for all safety analyses. 
• Pharmacokinetic Population (PK): The PK population will include all subjects who 
received at least one confirmed dose of investigational product (IP) and provided at least 
one PK sample. This population will be used for summary of PK concentration results.  
6. 
GENERAL ISSUES FOR STATISTICAL ANALYSIS 
6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
Baseline is defined as Study Day 1. In general, the last observation recorded before the first dose 
of study drug will be used as the baseline for all calculations of change from baseline. For 
assessments where time was recorded, the last observation recorded before the first application 
of study drug will be used as the baseline observation for all calculations of change from 
baseline. If the last non-missing assessment is performed on the same date as the first study 
treatment administration and time is not available, it is assumed that the assessment took place 
prior to IP application, per study site training, and the assessment will be considered as baseline, 
except for adverse events (AEs) and medications starting on the first study treatment dose 


 
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administration date which will be considered post baseline. 
Average weekly baseline WI-NRS is defined as the average of all non-missing scores reported 
during the last 7 days prior to treatment if at least 4 of 7 evaluable daily WI-NRS questionnaires 
are available. Daily baseline WI-NRS is defined as the last non-missing assessment prior to the 
first study treatment. 
For subject tolerability assessments, baseline is derived as the last non-missing measurement 
taken on the day of first application of study drug. 
6.1.2. Adjustments for Covariates 
Covariates for this study include pooled site group (see Section 6.1.6) and IGA severity at 
baseline (moderate, or severe). Subgroup analyses may be generated for the baseline covariates. 
6.1.3. Multiple Comparisons 
Secondary endpoints will only be tested if the primary endpoint is considered statistically 
significant at the α=0.01 level. To control for multiple comparisons among the secondary 
endpoints, the following multiplicity procedure will be used: 
Upon demonstration of statistical significance of the primary endpoint, the alpha level of 0.01 will be 
unequally split between to families of testing – one family for the WI-NRS success endpoints and 
another family for the other secondary efficacy endpoints. The testing over the WI-NRS success 
endpoints and the other secondary efficacy endpoints will be sequential, utilizing the Fallback 
Method for unused alpha.  
For the testing of WI-NRS success endpoints, an alpha level of 0.0033 will be used and will use a 
hierarchical method to first test WI-NRS success at Week 8, followed by WI-NRS at Week 4, 
followed by WI-NRS success at Week 2. Should all three of these endpoints be statistically 
significant at the 0.0033 level, then this unused alpha will be carried to the other secondary endpoint 
family, which would then be tested at the .0033+.0067=0.01 level.  If any of the WI-NRS family do 
not reach statistical significance, the testing stop at that point in the WI-NRS family, but will 
continue in the other family, at the 0.0067 level. 
In the other secondary endpoint family, an alpha level of 0.0067 (the remainder of the allotted 0.01) 
or the full 0.01, pending the results of the WI-NRS endpoint testing, will be used to hierarchically 
test: 1) IGA Success at Week 4, 2) Scaling score of 0 at Week 8, 3) Erythema score of 0 at Week 8, 
4) the percentage of subjects who attain IGA of 0 at Week 8, and lastly, 5) IGA Success at Week 2. 
This is illustrated in Figure 1. 
Figure 1: 
Primary and Secondary Endpoint Testing 
 


 
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α = 0.01
IGA Success
@Week 8
If this is met, partition α as follows
α = 0.0033 (sequential testing)
WI-NRS Success @ Week 8
WI-NRS Success @ Week 4
WI-NRS Success @ Week 2
α = 0.0067 or α = 0.01  (sequential 
testing)
IGA Success @ Week 4
Scaling Score of 0 @ Week 8
Erythema Score of 0  @ Week 8
IGA score of 0 @ Week 8
IGA Success @ Week 2


 
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6.1.4. Handling of Dropouts or Missing Data 
6.1.4.1. 
Imputation of Missing Data 
6.1.4.1.1 
Imputation for the primary estimand  
Any subject who prematurely withdraws from the study will have their last available data 
assigned to an analysis window as described in Section 6.1.5.  To comply with the definition of 
the primary estimand (Section 8.1.1), data collected on or after the date of last dose for subjects 
who discontinue due to lack of efficacy or adverse event will be removed from the source data 
used for multiple imputation process. WI-NRS weekly averages will be removed from the source 
data used for multiple imputation if the day of last dose falls within the day interval used for the 
weekly average as defined in Section 6.1.5. This procedure will ensure that the data collected 
after intercurrent events are not used in the imputation process.  
For the primary efficacy endpoint of IGA score, the primary analysis will impute missing values 
using a regression-based multiple imputation model.  
This is a three-step process.  
1. The first step is to understand the pattern of missingness. In order to perform the multiple 
imputation, a monotone missing pattern must be achieved. For example, if there exist 
values for baseline and Week 8 visits, but missing values for the Week 2 or 4 visits, 
Markov-Chain Monte-Carlo (MCMC) method will be used to impute the small amount of 
missing data that may be missing at the intermediate visits that is required to make the 
missing data pattern monotone before applying the multiple imputation algorithm. This 
method uses a non-informative Jeffreys prior to derive the posterior mode from the 
expectation-maximization (EM) algorithm as the starting values for the MCMC method. 
This MCMC method will use seed of 81054655. The IGA score will be treated as a 
continuous variable for this step. To avoid values that could not be observed in practice, 
imputed values will be constrained to be integers in the range of 0 to 4. Total of 10 
imputations are done in the MCMC step. 
2. Once the monotone pattern is achieved, the next step is to implement the imputation 
algorithm. For this, the Predictive Mean Matching method (PMM) will be used. This 
method is particularly helpful if the normality assumption is violated. For subjects with 
complete data up to a particular visit, a PMM model will be fit that includes the outcome 
at that visit as the dependent variable and as independent variables, treatment group, and 
pooled site using a seed of 13698136. This process will be repeated 15 times, resulting in 
a total of 150 complete analysis datasets. The seed may be changed after unblinding in 
case of any issues with the imputation process, and it will be documented in the CSR if 
any change is required.  For subjects who discontinue due to lack of efficacy or adverse 


 
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event, data from analysis visits that occurred or would have occurred after discontinuation 
will be replaced with the baseline value.  As a result, these subjects will be defined as 
non-responders for all analyses at these specific analysis visits.   
3. For each completed dataset, compute the necessary derived variables. The dichotomous 
success rate (IGA score of ‘clear’ or ‘almost clear’ plus at least 2-point improvement) 
will be derived. The results obtained will be analyzed using the Cochran-Mantel-
Haenszel (CMH) analysis for each of the complete analysis data sets stratified by 
baseline IGA score and pooled site as described in Section 6.1.6. The results will be 
combined into one multiple imputation inference (odds ratio, associated confidence 
interval and p-value) using PROC MIANALYZE as illustrated (Ratitch 2013). 
This approach to imputation should be superior to other strategies such as carrying forward the 
last available observation, which may yield unrealistic imputed values. Also, the use of multiple 
imputation avoids the problem of artificially increasing power through data imputation 
associated with single-imputation methods because it accounts for the uncertainty associated 
with the imputation. The multiple imputation is performed for ITT population only. The analysis 
for the mITT Population will use the MI datasets already created for the ITT population 
(i.e., no new MI datasets will be generated). 
Similar multiple imputation procedure will be implemented for tested secondary endpoints as 
primary endpoint. Other missing data will not be imputed, with the exception of incomplete dates 
as described in Section 6.1.8. For responder analysis, only observed data will be used. Only 
observed data will be summarized using descriptive statistics. 
The SAS pseudo code for the multiple imputation process is listed below: 
Step 1: 
proc mi data=example seed=81054655 nimpute=10 round=1 out=example_1; 
   mcmc impute=monotone; 
   var <baseline score> ………… <visit8 score>; 
run; 
Step 2: 
proc mi data=example_1 seed=13698136 nimpute=15 out=example_2; 
   by <Step 1 imputation number>;   
   class <treatment> <site>; 
   monotone regpmm(<baseline score> ………… <visit8 score>); 
   var <treatment> <pooled site> <baseline score> ………… <visit8 score>; 
run; 
 
Step 3: This step involves running CMH test stratified by pooled site and baseline IGA score on 
each completed dataset and combining the results using proc mianalyze. 


 
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Proc freq data=example noprint; 
   by <imputationnumber> <visit> ; 
   tables <pooled site>*<BL IGA>*<treatment>*<outcome>/ cmh alpha=0.01 
COMMONRISKDIFF(TEST=MH cl=mh); 
   output out=example_stat cmh; 
run; 
In order to apply PROC MIANALYZE, normalizing transformations must be applied to odds 
ratio. P-Values are obtained using Wilson Hilferty transformation as illustrated  
(Ratitch 2013). 
6.1.4.1.2 
Imputation for supplemental estimand 
Based on the feedback from FDA, the originally pre-specified primary analysis estimand will 
remain unchanged, but will be re-labeled as a supplemental estimand and will handle all 
intercurrent events using a “Treatment Policy Strategy” (Section 8.1.1).  Imputation for the 
supplemental estimand will be similar to the process described above for the primary estimand; 
however, subjects who discontinue due to lack of efficacy or adverse event will be treated the 
same as those who did not discontinue for one of those reasons.  All observed data for these 
subjects will be included in the imputation process subject to the analysis visit window strategy 
described in Section 6.1.5.  
6.1.4.2. 
Tipping Point Analysis 
The sensitivity analysis for the primary endpoint will be performed by using a specified sequence 
of shift parameters. The range of shift parameters to be included in this analysis are 0 to 2 by 0.5 
for active and -2 to 0 by 0.5 for Vehicle. Once the approximate point of the shift is determined, the 
analysis will be rerun using an expanded range around the approximate tipping point, to determine 
the tipping point with greater precision (i.e., to 2 decimal places, by 0.01). Thus, the value at which 
the results of the primary analysis are shifted from significant (i.e., α ≤ 0.01) to non-significant 
(i.e., α > 0.01) will be determined.  
Steps 1 and 3 of the analysis will be the same as for the multiple imputation analysis as described 
in Section 6.1.4.1.16.1.4.1. However, Step 2 of the analysis is where the shift parameters will be 
applied. Pseudo-code for Step 2 is as follows: 
proc mi data=example_1 seed=13698136 nimpute=15  out=example_2; 
    by <Step 1 imputation number>;   
    class <treatment> <site>; 
    monotone regpmm(<baseline score> ………… <visit8 score>); 
    var <treatment> <site> <baseline score> ………… <visit8 score>; 
    mnar adjust( <visit2 score> / shift=YY adjustobs=(treatment =‘Roflumilast 
Foam 0.3%’));  
    mnar adjust( <visit4 score> / shift=YY adjustobs=(treatment = 
‘Roflumilast Foam 0.3%’)); 


 
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    mnar adjust( <visit8 score> / shift=YY adjustobs=(treatment = 
‘Roflumilast Foam 0.3%’)); 
    mnar adjust(<visit2 score> / shift=ZZ adjustobs=(treatment=‘Vehicle 
Foam’));  
    mnar adjust(<visit4 score> / shift=ZZ adjustobs=(treatment=‘Vehicle 
Foam’)); 
    mnar adjust(<visit8 score> / shift=ZZ adjustobs=(treatment=‘Vehicle 
Foam’)); 
 
run; 
YY and ZZ will encompass all combinations of the range of shift parameters as 
pre-specified above. 
Imputed values for subjects who discontinue due to lack of efficacy or adverse event will be 
handled as described in Step 2 of Section 6.1.4.1.1 to ensure that these subjects are analyzed as 
non-responders at all visits on or after discontinuation of treatment. 
6.1.5. Analysis Visit Windows 
Visits will be analyzed as scheduled. Unscheduled, early termination visits, and/or repeated 
measurements will only be included if a scheduled measurement is not available, and the early 
termination or unscheduled/repeated measurement falls within the analysis visit windows as 
described in Table 2. Unscheduled/repeated measurements will be listed. 
Table 2: 
Analysis Visit Windows 
Visit  
Name 
Visit  
Number  
Target  
Start Day 
Lower  
Limit 
Upper  
Limit 
Week 2 
3 
14 
2 
22 
Week 4 
4 
28 
23 
42 
Week 8 
5 
56 
43 
   
Table 3 Analysis Windows for Calculation of Average Weekly WI-NRS: 
Study Days for Calculation of average 
weekly WI-NRS 
Week (Derived) 
(-7, 1)* 
Baseline 
(2, 7) 
Week 1 
(8, 14) 
Week 2 
(15, 21) 
Week 3 


 
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Study Days for Calculation of average 
weekly WI-NRS 
Week (Derived) 
(22, 28) 
Week 4 
(29, 35) 
Week 5 
(36, 42) 
Week 6 
(43, 49) 
Week 7 
(50, 56)  
Week 8 
* Day 1 WI-NRS score will be used to calculate the “Baseline” only when it is collected before the application of 
the first study drug. 
6.1.6. Pooling of Sites 
Sites will be pooled for statistical analysis as follows. For analysis, sites should have a minimum 
of 10 randomized subjects (ITT population), with at least one subject in each treatment group. 
The smallest sites within each country will be grouped sequentially in order of smallest to 
largest, restricting to those sites that did not meet the minimum enrollment of 10, until each 
pooled site has a minimum of 10 subjects with at least 1 subject in each treatment group in each 
strata combination. 
 
As sensitivity analysis of different pooling strategy, sites that have randomized less than 50% of 
the number of randomized subjects at the site with the largest number of randomized subjects, 
those sites will be pooled within each country. The sensitivity analysis of pooling strategy will be 
applied for the primary endpoint only. 
6.1.7. Derived Variables 
• Average weekly baseline WI-NRS is defined as the average of all non-missing scores 
reported during the last 7 days prior to treatment if at least 4 of 7 evaluable daily WI-
NRS questionnaires are available. Daily baseline WI-NRS is defined as the last non-
missing assessment prior to the first study treatment. 
• IGA success = IGA of “Clear” or “Almost Clear” plus at least 2-point improvement from 
baseline. 
• Study day is calculated as:  
o observation date – first dose date + 1 if record is collected on or after first dose 
date  
o observation date – first dose date if record is collected prior to first dose date. 


 
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• Compliance = number of applications divided by the expected number of IP 
applications for each subject. Number of expected study treatment applications will be 
calculated as the sum of number of investigational product applications and number of 
doses missed. Compliance will be calculated using drug accountability data over the 
entire treatment period for each subject, up to treatment completion or discontinuation. 
o Number of expected IP applications = last treatment or missed dose date – 
first treatment date + 1. 
o Number of IP applications = number of expected IP applications – number of days 
with missed IP applications as collected in the CRF. 
o Number of Days on IP = last treatment date – first treatment date + 1. 
• Total Weight of IP Applied (g) = dispensed can weight – returned can weight. 
• Average Daily Weight of IP Applied (g/day) = total weight of IP applied/number of 
days on IP.  
• BMI (kg/m2) = (weight in kg)/[(height in cm/100)2]. For Week 2, and 4, baseline height 
will be used to derive BMI. For Week 8, Week 8 height will be used to derive BMI since 
height is not collected at all visits. 
• BMI Categories: 
o Underweight: 
BMI < 18.5 
o Normal: 
18.5 ≤ BMI ≤ 24.9 
o Overweight: 
25.0 ≤ BMI ≤ 29.9 
o Obese: 
BMI ≥ 30.0   
• Age Categories: 
o 9 – 17 years  
o 18 – 64 years 
o ≥ 65 years 
• Duration (months) since diagnosis of seborrheic dermatitis is derived as: 
o (Randomization date – diagnosis date)/30.4375 
o If day of diagnosis is not available, assume that diagnosis occurred on the 1st of 
the month.   
• WI-NRS 4-point Reduction = achievement of at least 4-point reduction in average 
weekly WI-NRS pruritus score at Weeks 2, 4, and 8 compared to baseline, calculated 
only for subjects with a pruritus score of ≥ 4 at baseline (PRU4-ITT population). 


 
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• Average Weekly WI-NRS Pruritus Score will be calculated in a 7-day period, see table 
3 for the analysis window. A minimum of 4 days of observations are needed to calculate 
average weekly WI-NRS.  
• DLQI Score = sum of the 10 questions (individual questions scored as Very much=3, 
A lot=2, A little=1, Not at all=0, Not relevant=0, Question 7: Yes=3, No=0, with Not 
relevant recoded to 0; range for score 0 to 30). If 1 item is missing, it is scored as 0 for 
that item. If 2 or more items are missing, the score should not be calculated. 
• CDLQI Score = sum of the 10 questions (individual questions scored as Very much=3, 
Quite a lot=2, Only a little=1, Not at all=0; Question 7: if the last week was school time, 
the question was scored as Very much=3, Quite a lot=2, Only a little=1, Not at all=0, 
with Prevented school recoded to 3, and if the last week was vacation, the standard 
responses apply; range for score 0 to 30). If 1 item is missing, that item is scored as 0. If 
2 or more items are missing, the score should not be calculated. 
• PHQ-8 = sum of the 8 questions (individual questions scored as Not at all=0, Several 
days=1, More than half the days=2, and Nearly every day=3; range for score 0 to 24). If 
more than 1 item is missing the score should not be calculated.  If 1 item is missing the 
score is calculated as (sum of answered items*8)/number of answered items. 
• Modified PHQ-A = sum of the 8 questions (individual questions scored as Not at all=0, 
Several days=1, More than half the days=2, and Nearly every day=3; range for score 
0 to 24). If more than 1 item is missing the score should not be calculated.  If 1 item is 
missing the score is calculated as (sum of answered items*8)/number of answered items. 
• CDI-2 = total score is calculated as a sum of the 17 questions (individual questions 
scored as much or most of the time=3, often=2, some of the time=1, Not at all=0; 
range for score 0 to 51). 
o CDI-2 emotional problem scale is a sum of 9 questions (Q1, Q3-6, Q8, Q10 -12) 
o CDI-2 function problem scale is a sum of 8 questions (Q2, Q7, Q9, Q13-17) 
• Scalpdex Score Transformation = Scalpdex is rated on a 1 to 5 scale which will be 
transformed to 0 to 100 Scale where 1=0; 2=25; 3=50; 4=75; 5=100. This transformed 
score is used to calculate scale scores. 
o Emotions Scale = average of (Q2, Q4, Q5, Q6, Q7, Q9, Q10, Q11, Q12, Q14, Q16, 
Q17, Q19, Q20, Q22) after transforming to 0 to 100 scale as mentioned above. Q 
refers to question number. Q19 will be reverse scored i.e., 1=100; 2=75; 3=50; 4=25; 
5=0. 
o Symptoms Scale = average of (Q1, Q3, Q8) after transforming to 0 to 100 scale as 
mentioned above. Q refers to question number. 


 
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o Functioning Scale = average of (Q13, Q15, Q18, Q21, Q23) after transforming to 0 
to 100 scale as mentioned above. Q refers to question number. 
• 
Scalpdex Total Score = calculated as mean of all the 23 scalpdex questions using the 
transformed scale of 0 to 100. Q19 will be reverse scored i.e., 1=100; 2=75; 3=50; 4=25; 
5=0 while calculating the mean. Q refers to question number. 
• Change from Baseline = value at current time point – value at baseline.  
• TEAE = any AE with onset date/time after the first application of IP.  
• C-SSRS Suicidal Ideation = A “yes” answer at any time during treatment to any one of 
the five suicidal ideation questions (Categories 1-5: Wish to be Dead, Non-specific 
Active Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without 
Intent to Act, Active Suicidal Ideation with Some Intent to Act, without Specific Plan 
Active Suicidal Ideation with Specific Plan and Intent). 
• C-SSRS Suicidal Behavior = A “yes” answer at any time during treatment to any one of 
the five suicidal behavior questions (Categories 6-10: Preparatory Acts or Behavior, 
Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), Completed Suicide). 
• Trunk Involvement = “Yes” if a subject has coverage area (trunk) greater than 0% as 
captured in the BSA page.  
6.1.8. Data Adjustments/Handling/Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings. 
All p-values will be displayed in four decimals and rounded using standard scientific notation 
(eg, 0.XXXX). If a p-value is less than 0.0001 occurs, it will be shown in tables as < 0.0001. 
Similarly, if a p-value is greater than 0.9999, occurs it will be shown in tables as > 0.9999. 
Adverse events will be coded using the MedDRA version 24.1 or above. 
Medications will be coded using the World Health Organization Drug Dictionary Enhanced 
(WHO-DDE) Global B3 version September 2021. 
A treatment-related AE is any AE with a relationship to the study drug of possibly, probably, 
likely, or missing. 
For partial AE and medication start dates: 
• If the year is unknown, then do not impute the date but assign a missing value. 
• If the year is known, but the month or month and day is unknown, then: 
o If the year matches the year of first dose date and the end date (if present) is after first 
dose date, then impute as the month and day of the first dose date. 


 
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o Otherwise, assign 01 January. 
• If the year and month are known, but the day is unknown, then: 
o If the month and year match the month and year of the first dose date, then impute as 
the day of the first dose date. 
o Otherwise, assign 01. 
For partial AE and medication end dates: 
• If the year is unknown, then do not impute the date but assign as missing value. 
• If the year is known, but the month or month and day is unknown, then: 
o If the year matches the year of the last date of the study (date of last contact if subject 
lost to follow-up; date of completion or early termination otherwise), then impute as 
the month and day of the last date of the study. 
o Otherwise, assign 31 December. 
• If the year and month are known, but the day is unknown, then: 
o If the month and year match the month and year of the last date of the study, then 
impute as the day of the last date of the study. 
o Otherwise, assign the last day of the month. 
6.2. 
Special Handling for COVID-19 Disruptions 
In some cases, study visits will have to be delayed/not performed as a result of COVID-19 
disruptions (e.g., sites were closed, or subjects were under stay-at-home orders). Where possible, 
study sites may collect post-baseline data from subjects remotely by telemedicine, traditional 
mail, and/or email; this will be clearly documented in the source. If possible, sites should adhere 
to the protocol visit window for remote data collection. 
Investigator assessments and subject questionnaires normally completed directly during on-site 
visits should be completed on the appropriate paper source documents. The following 
assessments/questionnaires are approved to be collected via telemedicine/remotely: 
• WI-NRS 
• DLQI/CDLQI 
• Scalpdex 
• C-SSRS  
• PHQ-8/PHQ-A/CDI-2 
• Subject Local Tolerability 
The following assessments cannot be completed via telemedicine/remotely: 


 
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• IGA 
• BSA 
• Investigator Local Tolerability 
• Overall Assessment of Erythema 
• Overall Assessment of Scaling 
• Pigmentation Assessment 
• Subject Weight 
Study visits and procedures must be followed per protocol whenever possible. Any specific 
changes in study conduct that deviate from the protocol should be communicated to the 
institutional review board and Sponsor. All protocol deviations which occurred as a result of 
COVID-19 disruptions (e.g., visits out of window, missed assessments, etc.) will be 
differentiated from other protocol deviations.  
Subjects who were affected by COVID-19 disruptions by either missing their Week 8 visit or 
being discontinued before having a Week 8 visit due to COVID-19 related disruptions will be 
excluded from the mITT population, as described in Section 5. 
7. 
STUDY PATIENTS/SUBJECTS AND DEMOGRAPHICS 
7.1. 
Disposition of Patients/Subjects and Withdrawals 
Disposition will include tabulations of the number of the screened subjects, the number of the 
subjects who failed screen, the number of subjects randomized into each treatment group, the 
number of subjects who received treatment, subjects completing the study, the reasons for 
discontinuation from the study overall and due to COVID-19 disruption, and the number of 
subjects in each analysis population. Disposition will be summarized for all subjects who were 
entered into database by treatment group and overall. 
A listing of subject’s disposition will be provided. The reasons for screen failures will be listed. 
7.2. 
Protocol Deviations 
Important deviations will be identified based on a blinded review at the end of the study 
performed by the study team. The number of subjects with important protocol deviations will be 
summarized in categories by treatment group and overall, for subjects in the ITT population.   
A listing of all protocol deviations will also be provided.  
In addition, all the protocol deviations associated with COVID-19 will be summarized by deviation 
category and listed as described above. 


 
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7.3. 
Demographics and Baseline Characteristics 
Summary statistics for age, age groups (9-17 years,  18-64 years and ≥ 65 years old), gender 
(including child-bearing potential), race, ethnicity, height, weight, BMI, baseline disease 
characteristics (IGA, Overall Assessment of Erythema, Overall Assessment of Scaling, Scalpdex, 
average weekly WI-NRS, daily WI-NRS, DLQI, CDLQI), Fitzpatrick skin type, percent BSA 
affected by disease, and body parts involved will be presented by treatment group and overall.    
A summary of seborrheic treatment history, including history of response, intolerance, or 
contraindication to topical corticosteroids and/or topical antifungals, and off-label use of topical 
calcineurin inhibitors will be provided. 
For the continuous variables, the number of non-missing values and the mean, standard 
deviation, median, Q1, Q3, minimum, and maximum will be tabulated.  
For the categorical variables, the counts and proportions of each value will be tabulated.    
For ordinal variables such as the IGA, Overall Assessment of Erythema, Overall Assessment of 
Scaling, and daily WI-NRS, summary statistics including the mean, median, Q1, Q3, and range 
of the ordinal variable will be presented.  Frequency counts of each level of the categorized 
variables will also be presented.   
These analyses will be conducted for the ITT and Safety populations separately (if these two 
populations include different sets of subjects).  
A listing of all demographics, analysis population flag, reasons not included in the efficacy 
analysis will be provided. 
7.4. 
Exposure and Compliance 
The number of expected IP applications will be summarized by treatment group.  
The number of IP applications by each subject based on diary data will be summarized by 
treatment group using descriptive statistics appropriate for continuous variables.  
The amount of IP used by each subject based on can weight will be summarized descriptively by 
treatment group using continuous methods.    
The number of days on IP will be summarized descriptively by treatment group.  
A subject will be considered compliant with the dosing regimen if the subject applies at least 
80% of the expected applications during the IP application period and does not miss more than 
3 consecutive doses. 
Investigational product application compliance will be calculated based on number of 
applications divided by the expected number of IP applications. Compliance will be summarized 
descriptively by treatment group using the following categories: 


 
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• 100% 
• ≥ 80% - ≤100% 
• < 80% 
A listing of drug exposure will also be provided. 
8. 
EFFICACY ANALYSIS 
Efficacy analysis will be based on ITT population unless specified otherwise. The randomized 
treatment arm and strata will be used in the efficacy analysis.  
The efficacy analyses that include the stratification factors (pooled sites, IGA strata (“3” 
(moderate) and “4” (severe)) will use the data as collected in the interactive web response system 
(IWRS).  A table of randomized strata vs. actual strata will be provided if there is any mis-
randomization.  
8.1. 
Primary Efficacy Analysis 
The order of testing for the primary and secondary endpoints is discussed in Section 6.1.3. Other 
secondary endpoints are not included in the testing strategy. 
In general, for efficacy analysis, the CMH test is performed on both imputed and observed data. 
Numerical summaries, categorical frequencies of each severity group are summarized using 
observed data only. Analysis of imputation results are summarized for ITT population only 
unless specified otherwise. In rare cases, the odds ratio is not estimable due to zero event in one 
of the categories, the odds ratio and associated p-value will not be reported. If a non-estimable 
odds ratio and associated p-value occur as part of the multiple testing strategy, the p-value to be 
used in the testing strategy will be based on a test of a difference in proportions. 
8.1.1. IGA Success 
The IGA is an ordinal scale with five severity grades which is reported only in integers.  Table 3 
illustrates the description of each severity grade.  
Table 4: 
IGA 
Score Description 
0 
Clear: No erythema, no scaling (hypo-hyperpigmentation can be present) 
1 
Almost Clear: Slight erythema and/or trace (barely perceptible) amounts of 
scaling 
2 
Mild: Pink to red color and/or slight scaling 
3 
Moderate: Distinct erythema (redness) and/or clearly visible scaling 


 
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4 
Severe: Severe erythema (intense, fiery red) and/or severe scaling (coarse, 
thick scales with flaking onto clothes or skin) 
The primary efficacy endpoint is success in IGA of disease severity, defined as IGA score of 
“Clear” or “Almost Clear” plus at least 2-point improvement from baseline at Week 8. The 
definition is the same as IGA score of “Clear” or “Almost Clear” given all subjects are enrolled 
in this study with moderate or severe IGA.   
The primary statistical comparison will be as follows: 
• Roflumilast foam 0.3% versus Vehicle foam 
The primary estimand is based on feedback from FDA received after database lock and unblinding 
and is described by the following attributes: 
Population: Seborrheic Dermatitis  
Intercurrent events: In the course of the 8-week randomized treatment period, subjects may be 
exposed to possible known or unknown intercurrent events that could possibly impact the 
estimates of the estimand, such as treatment discontinuation due to a specific adverse effect or 
perhaps a lack of effect. A composite strategy will be implemented that handles subjects who 
discontinue due to lack of efficacy or adverse event as missing not at random, differently than all 
other subjects.  The “Treatment Policy Strategy” has been adopted for handling all other known 
or unknown intercurrent events in this study other than discontinuation due to lack of efficacy or 
adverse event.  Subjects who discontinue due to lack of efficacy or adverse event will be treated 
as non-responders at all analysis visits that occurred or would have occurred on or after the date 
of last dose of treatment application.  
The original primary estimand has been left unchanged, but re-labeled as a supplemental 
estimand and will handle all intercurrent events using a “Treatment Policy Strategy”, including 
discontinuation due to lack of efficacy or adverse event.  Multiple imputation procedures are 
described in Section 6.1.4.1.2. 
Population-level summary: ratio of the odds of achieving IGA success after 8 weeks of using 
ARQ-151 (roflumilast foam 0.3%), relative to the odds of success after 8 weeks using a 
matching vehicle foam.  
The supportive population-level summary: the proportion difference between ARQ-151 foam 
0.3% and vehicle groups will be provided for the patients who achieve IGA success at week 8. 
Rationale for the estimands: Odds ratio of achieving IGA success for ARQ-151 (roflumilast 
foam 0.3%) relative to vehicle after 8 weeks and the proportion difference of achieving IGA 
success will be evaluated regardless of the occurrence of any such intercurrent event. The odds 
ratio will be obtained from CMH test stratified by the randomization factors (by baseline IGA 


 
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score and by pooled study site). The strata-adjusted proportion difference will be obtained from 
CMH method based on stratification factors of baseline IGA and study sites. 
Statistical significance will be concluded as described in section 6.1.3. 99% CIs for the odds 
ratios and for the stratified proportion difference between treatment arm will be provided. 
Additionally, the 99% CI for proportion of subjects who achieved IGA successes in each 
treatment group will be presented. 95% CIs for the odds ratios and the stratified proportion 
difference in each treatment arm are provided as well. Both 99% CI & 95% CI will be presented 
for all the efficacy endpoints. For the primary analysis, missing IGA scores will be imputed 
using multiple imputation as described in Section 6.1.4. These imputations will result in a total of 
150 complete analysis datasets. 
The CMH analyses will be performed separately for each of the complete analysis data sets, and 
the results will be combined into one multiple imputation inference (stratified proportion 
differences and associated CI, odds ratio and associated CI and p-value). The proportion of 
subjects who achieved IGA success and associated CI, using an extension of Wilson’s method 
proposed by Lott and Reiter, will be reported using multiple imputation as well.  
IGA numeric data and change from baseline will be summarized using descriptive summaries 
(mean, median, inter quartile range) by treatment group and study visit using observed data.  
8.1.2. Hypothesis Testing 
Primary hypothesis testing on the odds ratio: The null hypothesis is that the IGA Success does not 
differ between roflumilast foam 0.3% and matching vehicle foam. The alternative hypothesis is 
that the IGA Success does differ between roflumilast foam 0.3% and matching vehicle foam. 
 
Null Hypothesis (H0): PR QV / PV QR = 1.0,  
Alternative Hypothesis (HA): PR QV / PV QR  ≠ 1.0, where 
 
PR = the proportion of IGA Success in roflumilast foam 0.3% 
PV = the proportion of IGA Success in matching vehicle foam  
QR = 1 - PR 
QV = 1 – PV. 
8.1.3. Sensitivity and Supplemental Analyses of the Primary Efficacy Endpoint  
The following sensitivity and supplemental analyses will be performed for primary efficacy 
endpoint, based on the CMH test as described in Section 8.1.1: 
• The primary efficacy endpoint analysis repeated on subjects in the PP population using 
observed data. 
• The primary efficacy endpoint analysis repeated on subjects in the mITT population on 


 
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MI imputed data.  
• The primary efficacy endpoint analysis repeated on subjects in the ITT population using 
observed data.  
• The primary efficacy endpoint analysis repeated on subjects in the ITT population using 
non-responder imputation in which the post baseline missing will be considered as non-
responder (no IGA success).  
• The primary efficacy endpoint analysis repeated on subjects in the ITT population on MI 
imputed data using CMH model without site stratification.  
• A tipping point analysis will be performed as described in Section 6.1.4.2 
8.1.4. Impact of Site on the Primary Efficacy Endpoint  
The following supportive analysis will be performed to investigate the impact of site on the 
primary endpoints.  
• To assess the impact of site on the primary analysis endpoint, the proportion of subjects 
achieving IGA success and 99% CI within each site will be plotted by treatment groups.  
No p-values will be provided. 
• An additional analysis to examine the impact of study site will examine the changes in p-
values that occur after removal of subjects from a site.  First, remove subjects from one site 
from the MI datasets, recalculate the combined CMH p-value as described for the primary 
analysis, and repeat removing a different site for each iteration. The p-values from the 
iterations will be plotted by the site removed.   
8.2. 
Secondary Efficacy Analysis 
All secondary efficacy analyses will be performed using the ITT unless specified otherwise. The 
sensitivity analysis will be performed in a similar fashion as those in the primary efficacy 
endpoint as described in Section 8.1.3.  See the list of sensitivity analysis for secondary 
endpoints in table 6).    
The statistical comparison will be as follows: 
• Roflumilast foam 0.3% versus Vehicle foam 
8.2.1. Investigator Global Assessment (IGA)  
Secondary efficacy endpoints in the multiple testing scheme related to the IGA include the 
following: 
• IGA Success at Week 4 
• IGA Success at Week 2 


 
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• Achievement of an IGA score of ‘clear’ at Week 8. 
The above analysis will be performed on subjects in the ITT, for imputed and observed data, unless 
otherwise specified using the similar CMH test and the stratified proportion difference as described 
in Sections 8.1.1. and 8.1.3. The sensitivity analysis for IGA endpoints (IGA success at Week 2, 
Week 4 and IGA score of 0 at Week 8) will be provided in a similar fashion as those in the primary 
endpoint as summarized in Table 6. 
8.2.2. Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score 
Secondary efficacy endpoints related to WI-NRS pruritus score, which are all based on average 
weekly WI-NRS unless specified otherwise, include the following: 
• In subjects with baseline WI-NRS pruritus score of ≥ 4, achievement of at least 4-point 
improvement from baseline in WI-NRS pruritus score at Week 8 (“WI-NRS Success at 
Week 8”). 
• WI-NRS Success at Week 4. 
• WI-NRS Success at Week 2. 
The following analyses are performed for WI-NRS: 
• In subjects with a baseline WI-NRS score ≥ 4, WI-NRS success endpoint (at Week 2, at 
Week 4 and at Week 8) will be analyzed in a similar fashion as those for the primary 
endpoint.  
• The primary efficacy endpoint analysis repeated on subjects in the PRU4-ITT population 
using non-responder imputation in which the post baseline missing will be considered as 
non-responder (no WI-NRS success).  
8.2.3. Other Efficacy Endpoints 
Other efficacy endpoints related to average weekly WI-NRS pruritus score: 
• Change and percent change from baseline in average weekly WI-NRS pruritus score at 
Weeks 2, 4, and 8 will be performed using descriptive summaries (mean, median, inter 
quartile range) by treatment group and study visit using observed values.  
• Change and percent change from baseline in average weekly WI-NRS at Weeks 2, 4, and 
8 will be analyzed using an analysis of covariance (ANCOVA) model with terms for 
treatment, pooled study site, and baseline IGA  as covariate. The observed value will be 
used. Statistical comparisons between the treatment groups will be obtained using 
contrasts. The LS Means, standard errors, 95% and 99% confidence intervals, and p-
values will be presented at each visit. These analyses will be performed on the ITT 
populations. The p-values are nominal and there is no formal inferential testing on other 
efficacy endpoints. 


 
Statistical Analysis Plan,  
 
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Other efficacy endpoints related to daily WI-NRS pruritus score: 
• Change and percent change from baseline in daily WI-NRS score will be provided by 
treatment groups along with plots of daily WI-NRS (mean and SD of observed value and 
percent change from baseline). 
• Similar ANCOVA model will be performed for change and percent change from baseline 
daily WI-NRS every day in the first week, at Weeks 2, 4 and 8 using observed data. 
8.2.4. Overall Assessment of Erythema 
The assessment is performed at Screening, Baseline, and Weeks 2, 4, and 8. The score is 
reported in ordinal scale with severity grades ranging from 0-3. Table 4 illustrates description of 
erythema grades.  
Table 3: 
Erythema Grades 
Score 
Description 
0 
None: No evidence of erythema 
1 
Mild: Barely perceptible erythema which is faint or patchy 
2 
Moderate: Distinct erythema, 
3 
Severe: Intense (fiery red) erythema 
Secondary endpoint that is included in the multiple testing scheme is  
• Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at Week 8 
The analysis of Erythema of 0 is performed similar to the primary endpoint including the 
sensitivity analysis on both imputed and observed data.  
Analysis of efficacy endpoints related to erythema score will be performed using ITT population 
using observed value: 
• The number and percentage of subjects in each category will be summarized by treatment 
and study visit descriptively 
• An ANCOVA model similar to what is defined in Section 8.2.3 will be used for analysis 
of the change and percent change from Erythema baseline. 
8.2.5. Overall Assessment of Scaling 
This assessment is performed at Screening, Baseline, and Weeks 2, 4, and 8. The score is 


 
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reported in ordinal scale with severity grades ranging from 0-3. 
Table 5 illustrates description of scaling grades.  
Table 4: 
Scaling Grades 
Score 
Description 
0 
None: No scaling evident on lesions 
1 
Mild: Barely detectable, scattered, small flaking scales 
2 
Moderate: Scales clearly visible and prominent 
3 
Severe: Coarse, thick scales, with flaking into clothes or skin 
The analysis of Scaling will be performed similar to those of erythema score as indicated in 
Section 8.2.3. 
Separate listings of IGA, average weekly WI-NRS, daily WI-NRS score, Overall assessment of 
Erythema, and overall assessment of scale score will be provided along with IGA success, and 
WI-NRS success flag.  
Table 6: Summary of Primary and Secondary Efficacy Analyses 
Efficacy Endpoint 
Primary Analysis 
Sensitivity or Supplemental Analysis 
Primary 
IGA Success  
(IGA score of ‘0’ or ‘1’ 
plus at least 2-point 
improvement from 
baseline) at week 8 
ITT, multiple 
imputation (CMH) 
#1 PP, observed data (CMH) 
#2 mITT, multiple imputation (CMH) 
#3 ITT, observed data (CMH) 
#4 ITT, non-responder imputation (CMH) 
#5 ITT, Tipping point 
#6 ITT based on different site pooling 
strategy 
#7 ITT without site stratification 
Secondary 


 
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Family 1 (α=0.0033): 
Average weekly WI-
NRS Success 
(achievement of at least a 
4-point improvement) at 
Weeks 2, 4, 8 
PRU4-ITT 
population, multiple 
imputation (CMH) 
#1 PRU4-ITT, observed data (CMH) 
#2 PRU4-ITT, non-responder imputation 
(CMH) 
 
Family 2 (α=0.0067): 
IGA Success at weeks 4 
ITT, multiple 
imputation (CMH, 
odds ratio) 
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 2 (α=0.0067): 
Scaling score of ‘0’ at 
weeks 8 
 
ITT, multiple 
imputation (CMH, 
odds ratio) 
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 2 (α=0.0067): 
Erythema Score of ‘0’ at 
Week 8 
 
ITT, multiple 
imputation (CMH, 
odds ratio) 
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 2 (α=0.0067): 
IGA score of ‘0’ at Week 
8 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 2 (α=0.0067): 
IGA Success at Week 2 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
 
8.3. 
Other Efficacy Analysis 
Other secondary efficacy analysis will be performed for subjects belonging to ITT population on 
the observed data. 
The other secondary efficacy endpoints include: 
• Change and percent change in Scalpdex total score from baseline at Weeks 2, 4, and 8. 
• Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at 
Weeks 2, and 4. 
• Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 at Weeks 
2, and 4. 


 
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• Change and percent change from baseline in DLQI/CDLQI at Weeks 2, 4, and 8. 
• Change and percent change from baseline in BSA affected at Weeks 2, 4, and 8. 
• Change and percent change from baseline in Overall Assessment of Erythema at 
Weeks 2, 4, and 8. 
• Change and percent change from baseline in Overall Assessment of Scaling at Weeks 2, 
4, and 8. 
• Achievement of an IGA score of ‘clear’ at Week 4. 
• Achievement of an IGA score of ‘clear’ at Week 2. 
• Achievement of daily WI-NRS score of 0 or 1 at Weeks 2, 4, 8. 
• Change and percent change in WI-NRS from average weekly baseline score. 
All the categorical analyses involving achievement of Erythema, Scaling, IGA, WI-NRS are 
summarized using CMH and proportion difference stratified by pooled site and baseline IGA and 
presented by study visit. 
Continuous endpoints including change and percent change from baseline in average weekly WI-
NRS, % BSA, Scalpdex, DLQI/CDLQI, Erythema, Scaling at Week 2, Week 4 and Week 8 will 
be analyzed using an analysis of covariance (ANCOVA) with the factors of treatment, pooled 
study site, baseline IGA score, and baseline of the variable under analysis. Similar analysis will be 
performed for daily WI-NRS every day in the first week and at Week 2, Week 4 and Week 8. 
Statistical comparisons between the treatment groups will be obtained using contrasts. The LS 
Means, standard errors, 95% and 99% confidence intervals, and p-values will be presented at each 
visit. These analyses will be performed on the ITT populations.  
Scalpdex questionnaire consists of 23 questions which are categorized into emotions, symptoms 
and functioning scales. The scale scores and total score are calculated as described in the  
Section 6.1.7. Analyses of Scalpdex will be limited to subjects in the ITT population who have 
Seborrheic Dermatitis involvement on the scalp.  Change and percent change from baseline for 
Scalpdex scale scores along with total score are summarized descriptively. In addition, number 
and percentages for each Scalpdex question is summarized by study visit and treatment group. 
An ANCOVA model similar to what is defined in Section 8.2.2 will be used for analysis of the 
change and percent change from Scalpdex (total score, emotions, symptoms and functioning 
scales) baseline. 
Change and percent change from baseline for Overall Assessment of Erythema, Scaling, DLQI, 
CDLQI, and BSA will be summarized descriptively.  


 
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8.4. 
Subgroup Analyses of Efficacy Variables 
For the primary endpoint of IGA success (IGA of ‘Clear’ or ‘Almost Clear’ plus at least 2-point 
improvement at Week 8) and tested secondary endpoints, subgroup analysis will be performed 
using the primary estimand on the following: 
• Topical Corticosteroids – Inadequate Response, intolerance or contraindication (Y/N) 
• Topical Antifungals – Inadequate Response, intolerance or contraindication (Y/N) 
• By age categories (9-17, 18-64 and ≥ 65 years) 
• By IGA at baseline 
• Gender (male, female) 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
• Race (White, Black, Others) 
• Baseline BSA% (< 5% vs. ≥ 5%) 
• Baseline BSA% based on tertiles 
• Fitzpatrick score of I-III vs IV-VI 
• Subjects with facial involvement only vs. subjects with scalp involvement only vs. 
subjects with facial and scalp involvement 
The above subgroup analyses are generated for imputed data only. If odds ratio is not estimable 
due to zero counts, associated C.I. will not be provided as well. Specifically, if a result is non-
estimable, then the CMH test will not include the strata for study site and will not include the 
strata for baseline disease severity.  A footnote in the summary table will indicate this change.  
For subgroup analysis, no p-value will be provided. Forest plots of subgroup analysis for primary 
efficacy endpoint and secondary endpoints will be provided. 
9. 
SAFETY AND TOLERABILITY ANALYSIS 
All safety analyses will be performed on the Safety population. No inferential statistical tests will 
be performed. 
9.1. 
Adverse Events 
All the AEs will be coded using the MedDRA dictionary version 24.1.  
An overall summary of TEAEs will be provided; this will present number and percent of subjects 
who reported at least 1: TEAE (including all TEAEs, TEAEs by maximum severity, and TEAEs 
by greatest relationship), treatment emergent serious adverse events (TESAEs), TEAE leading to 
discontinuation of the study drug, TEAE leading to study discontinuation, and TEAE resulting in 
death. 


 
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Tables including the number and percentage of subjects will be provided for the following 
categories: 
1. TEAEs by SOC and PT 
2. TEAEs by SOC, PT and Maximum Severity  
3. TEAEs by SOC, PT, and Strongest Relationship to Study Drug (i.e., related vs. unrelated) 
4. TEAEs by PT in descending order 
5. TESAE by SOC and PT 
6. TEAE leading to discontinuation of the study drug by SOC and PT 
7. TEAE leading to study discontinuation by SOC and PT 
In the summaries showing severity and relationship to study medication the event with the 
maximum severity (mild < moderate < severe) or strongest relationship (not related < related) 
will be reported. If a particular event is missing the severity and/or relationship, then the 
strongest possible severity or relationship will be assumed for analysis (severity = severe, 
relationship = likely). 
In the AE data listings, all AEs will be displayed. AEs that are treatment emergent will be 
flagged and AE occurred in the application site will be flagged.  
Most frequent TEAE (≥ 1%) of PT will be plotted by treatment groups along with overall 
incidence of TEAEs and overall incidence of TESAEs.  
9.1.1. Adverse Events Leading to Discontinuation 
A summary of incidence rates (frequencies and percentages) of TEAEs leading to 
discontinuation of the study drug, by treatment group, SOC, and preferred term will be provided 
for the Safety Population. Additionally, this table will be repeated for TEAEs leading to study 
discontinuation.  
9.1.2. Deaths and Serious Adverse Events 
Any deaths that occur during the study will be flagged in the AE listing. 
9.2. 
Local Tolerability Assessments 
The investigator’s assessment of the application site reaction will be summarized by study visit 
using both categorical methods (number and percentage of subject with each score) as well as 
continuous methods (e.g., mean, median, etc.). Categorical summaries will be provided for 
dermal response as well as other effects.  


 
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Investigator tolerability assessment is performed before the subject is dosed on Baseline Day 0. 
Subject tolerability assessment is performed 10-15 minutes after the application of IP. Subjects 
not meeting this condition are excluded from table summaries for tolerability assessments. 
The subject’s assessment of the application site reaction will be summarized similarly. 
9.3. 
Clinical Laboratory Evaluations 
Laboratory test results will be summarized descriptively by treatment and study visit as both 
observed values and change and percent change from baseline values for continuous hematology, 
chemistry, and urinalysis results. Categorical urinalysis results will be summarized using 
frequencies by study visit and treatment. 
The number of subjects with clinical laboratory values below, within, or above the normal range 
by study visit and in relation to baseline will be tabulated for each clinical laboratory analyte by 
treatment group (shift table). 
Abnormal laboratory values will be listed.  
9.4. 
Vital Signs 
Descriptive summaries of observed values and changes from baseline will be calculated for 
systolic blood pressure, diastolic blood pressure, heart rate, height, weight, body mass index and 
oral body temperature by treatment group and visit.   
Changes in weight by treatment group will summarize the number of subjects who gain or lose ≥ 
5% of their baseline body weight during the course of the study, as well as subjects who gain or 
lose ≥ 10% of their baseline body weight over the course of the study by treatment group and 
visit. 
BMI is derived as specified in Section 6.1.7. Shift tables (overall, subjects who indicated weight 
loss was intentional and subjects weight loss was not intentional at each visit) by treatment group 
for subjects who shift from their baseline BMI category (underweight, normal, overweight, 
obese) to a different BMI category throughout the course of the study will be provided by 
treatment group and visit.  
9.5. 
PHQ-8 and Modified PHQ-A 
PHQ-8 will be completed by adult subjects and modified PHQ-8 is filled by adolescent subjects 
of age 12-17 years inclusive. Data for PHQ-8 and Modified PHQ-A will be classified using each 
subject’s total score at a time point into a category based on the following scoring system:  


 
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• None – Minimal depression (0 to 4) 
• Mild depression (5 to 9) 
• Moderate depression (10 to 14) 
• Moderately severe depression (15 to 19) 
• Severe depression (20 to 24) 
Shift tables showing the category of severity at each time point by treatment group will be 
presented. 
9.6. 
CDI-2 
Parents/caregivers will complete the CDI-2 for subjects belonging to 9-11 years of age inclusive. 
For Children’s Depression Inventory 2(CDI-2), descriptive summaries of observed values and 
changes from baseline will be calculated for the total score and the 2 scales emotional problems 
and functional problems by treatment group and visit.   
9.7. 
C-SSRS 
The C-SSRS is a questionnaire that prospectively assesses Suicidal Ideation and Suicidal 
Behavior. At the Screening study visit, “Baseline/Screening” version of the C-SSRS will be 
used. This version assesses Suicidal Ideation and Suicidal Behavior during the subject’s lifetime 
and during the past 6 months. For the Screening visit, “lifetime” experience of the subject with 
Suicidal Ideation and Suicidal Behavior will be summarized. From Baseline visit, the 
“Since Last Visit” version will be used. 
Tables will include results from the Suicidal Ideation and Suicidal Behavior sections of the C-
SSRS. Frequencies and percentages of subjects with a response of “Yes” at any point on the 
Suicidal Ideation and Suicidal Behavior items will be summarized by study visit and treatment 
group. 
9.8. 
Physical Examination 
The number and percentage of subjects with normal and abnormal findings in the physical 
examination will be displayed at each study visit and treatment group. 


 
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9.9. 
Concomitant Medication 
Prior and concomitant medications will be summarized descriptively by treatment group, ATC 
level 4, and preferred term using counts and percentages. 
Prior medications will be presented separately from concomitant medications. Medications that 
started before the first application of IP will be considered prior medications whether or not they 
were stopped prior to the first application of study drug. Any medications continuing or starting 
after the first application of study drug will be considered to be concomitant. If a medication 
starts before the first application of study drug and continues after the first application of study 
drug it will be considered both prior and concomitant. 
Medications will be coded using WHODrug Global B3, version September 2021. 
9.10. Pigmentation Assessment 
Hypopigmentation and hyperpigmentation are scored individually on a 0-3 scale where ‘0’ 
indicates none, ‘1’ for mild, ‘2’ for moderate and ‘3’ for severe. A shift table of 
hypopigmentation at baseline and at each study visit will be provided by treatment group as well 
as the shift table of hyperpigmentation. Proportion of subjects who achieves no 
hypopigmentation and hyperpigmentation at each study visit will be summarized for those 
subjects who presents of Hypopigmentation or/and hyperpigmentation at baseline. Categorical 
summary of pigmentation assessment will be provided by study visit and treatment group 
stratified by race groups (white, others, overall). 
10. 
CHANGES FROM PLANNED ANALYSIS 
10.1. Version 2.0 
Version 2.0 of the SAP is based on the final signed version of Amendment 2 for the ARQ-154-
304 protocol. At the time of signing this SAP version 2.0, the protocol is in the process of being 
published and is planned to undergo IRB review and approval after database lock.   
The intent of this SAP is to document, prior to study database lock and unblinding, the changes 
specified in protocol amendment 2 regarding the testing strategy used for the secondary 
endpoints and also other minor updates to analyses not detailed in the protocol.   Any changes to 
the final protocol or additional analyses created after database lock and unblinding will be clearly 
labeled as such in the CSR. 
10.2. Version 3.0 
Section 1 Overview provides a description of the rationale for SAP Version 3.  The purpose of 
the SAP is to document the change to the primary estimand and related multiple imputation 
strategies. The revised estimand will be the focus of the Clinical Study Report and NDA.  Key 
results based on the original estimand defined in SAP versions 1 and 2 will be provided as 
supplemental information for the primary and secondary endpoints covered by the multiple 


 
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testing strategy. 
11. 
OTHER PLANNED ANALYSIS 
11.1. Pharmacokinetic Analysis 
Concentration data will be summarized by timepoint and treatment group using descriptive 
statistics, reporting n, mean, standard deviation, median, Q1, Q3, minimum, and maximum, and 
geometric statistics including geometric mean and coefficient of variation. For computation of 
mean plasma concentrations, data that are below the limit of quantification (BLQ) will be set to 
zero. The PK population will be used for these analyses.  
All PK collection information from the eCRF will be presented in a listing. PK concentration 
results will be listed as well. 
12. 
CHANGES TO ANALYSIS PLANNED IN THE PROTOCOL 
12.1. Definition of PK Population 
In this SAP, PK population is defined as subjects who received at least one confirmed dose of 
investigational product (IP) and provided at least one PK sample. This population will be used 
for summary of PK concentration results. The definition is different from that in protocol where 
PK population is defined as subjects receiving active drug with sufficient plasma concentrations 
of roflumilast to define a profile, as determined by the pharmacokineticist, which will be used for 
analysis of PK parameters.  
13. 
REFERENCES 
Blauvelt A., et al. Efficacy and safety of roflumilast foam 0.3% in patients with seborrheic 
dermatitis in a phase 3 trial. European Academy of Dermatology and Venereology (EADV) 
Congress, Sept 7-11, Milano, Italy. 2022.  Abstract 3531 and presentation. 
ASA. (2018) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2018. http://www.amstat.org/about/ethicalguidelines.cfm 
ICH (1998). ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9; 
1998. https://database.ich.org/sites/default/files/E9_Guideline.pdf 
RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014. 
https://rss.org.uk/about/policy-and-guidelines/code-of-conduct/. 
Ratitch, B., Lipkovich, I., & O’Kelly, M. (2013). Combining Analysis Results from Multiply 
Imputed Categorical Data. PharmaSUG. 
https://www.pharmasug.org/proceedings/2013/SP/PharmaSUG-2013-SP03.pdf 


 
Statistical Analysis Plan,  
 
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Lott, A and Reiter, J.P. (2020), “Wilson Confidence Intervals for Binomial Proportions With 
Multiple Imputation for Missing Data,” The American Statistician, 74:2, 109-115 


 
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14. 
TABLES, LISTINGS AND FIGURES 
 
All listings, tables, and graphs will have a header showing the sponsor company name and 
protocol and a footer showing the version of SAS, the file name and path, and the source of the 
data (listing number).  
 
14.1. Planned Table Descriptions  
The following are planned summary tables for protocol number ARQ-154-304. The table 
numbers are place holders only and may be changed when the tables are produced.  
 
Table Number  
Population 
Table Title/Summary 
14.1 
Disposition, Baseline Characteristics and Exposure Summary 
14.1.1 
All Subjects 
Subject Disposition 
14.1.2.1 
ITT 
Demographics and Baseline Characteristics  
14.1.2.2 
Safety 
Demographics and Baseline Characteristics  
14.1.3 
Safety 
Previous Treatment History for Seborrheic Dermatitis  
14.1.4 
ITT 
Protocol Deviations  
14.1.5 
Safety 
Prior Medications by Anatomic Therapeutic Chemical 
(ATC) Class Level 4 and Preferred Term 
14.1.6 
Safety  
Exposure to Investigational Product 
14.2 
Efficacy Summary 
14.2.1 
ITT 
Hypothesis Testing for Primary and Secondary Efficacy 
Endpoints – Multiple Imputation 
14.2.1.1 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit – Multiple Imputation (Primary 
Analysis) Categorical Results 
14.2.1.1.s 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit – Multiple Imputation (Primary 
Analysis, Supplemental Estimand) Categorical Results 
14.2.1.2.1 
PP 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit – Observed Data (Supplemental 
Analysis) Categorical Results 
14.2.1.2.2 
mITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit – Multiple Imputation 
(Sensitivity Analysis) Categorical Results 
14.2.1.2.3 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit – Observed Data (Sensitivity 
Analysis) Categorical Results 
14.2.1.2.4 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit – Non-responder Imputation 
(Sensitivity Analysis) Categorical Results 
14.2.1.2.5 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success at Week 8 – Tipping Point Analysis (Sensitivity 
Analysis) 
14.2.1.2.6.1 
ITT 
Investigator Global Assessment (IGA) Success at Week 
8 by Site – Observed data (Supporting Analysis) 


 
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Table Number  
Population 
Table Title/Summary 
14.2.1.2.6.2 
ITT 
Investigator Global Assessment (IGA) Success at Week 
8 – Multiple Imputation, Impact of Site (Supporting 
Analysis) 
14.2.1.2.7 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success at Week 8 – Multiple Imputation, without Site 
Stratification (Sensitivity Analysis) Categorical Results 
14.2.1.3.1 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Response to Topical 
Corticosteroids – Multiple Imputation (Subgroup 
Analysis)  
14.2.1.3.2 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Response to Topical 
Antifungals – Multiple Imputation (Subgroup Analysis)  
14.2.1.3.3 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit by Study Visit and Age Group – 
Multiple Imputation (Subgroup Analysis)  
14.2.1.3.4 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit by Study Visit and Baseline IGA 
Disease Severity – Multiple Imputation (Subgroup 
Analysis)  
14.2.1.3.5 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Gender – Multiple 
Imputation (Subgroup Analysis)  
14.2.1.3.6 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Ethnicity – Multiple 
Imputation (Subgroup Analysis)  
14.2.1.3.7 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Race – Multiple Imputation 
(Subgroup Analysis)  
14.2.1.3.8 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Baseline BSA% – Multiple 
Imputation (Subgroup Analysis) 
14.2.1.3.9 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Baseline BSA% Tertiles – 
Multiple Imputation (Subgroup Analysis)  
14.2.1.3.10 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Fitzpatrick Score – Multiple 
Imputation (Subgroup Analysis)  
14.2.1.3.11 
ITT 
Investigator Global Assessment (IGA) Grades and 
Success by Study Visit and Body Part Involvement – 
Multiple Imputation (Subgroup Analysis)  
14.2.1.4 
ITT 
Summary of Investigator Global Assessment (IGA) by 
Study Visit – Observed Data 
14.2.2.1 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit – Multiple Imputation (Primary Analysis) 
14.2.2.1.s 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit – Multiple Imputation (Primary Analysis, 
Supplemental Estimand) 
14.2.2.2.1 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit – Observed Data (Sensitivity Analysis) 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 49 of 56 
Table Number  
Population 
Table Title/Summary 
14.2.2.2.2 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit - Non-responder Imputation (Sensitivity 
Analysis) 
14.2.2.3.1 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Response to Topical Corticosteroids - 
Multiple Imputation (Subgroup Analysis) 
14.2.2.3.2 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Response to Topical Antifungals - 
Multiple Imputation (Subgroup Analysis) 
14.2.2.3.3 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Age Group - Multiple Imputation 
(Subgroup Analysis) 
14.2.2.3.4 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Baseline IGA Disease Severity - 
Multiple Imputation (Subgroup Analysis) 
14.2.2.3.5 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Gender - Multiple Imputation (Subgroup 
Analysis)  
14.2.2.3.6 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Ethnicity - Multiple Imputation 
(Subgroup Analysis) 
14.2.2.3.7 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) by Study 
Visit and Race - Multiple Imputation (Subgroup 
Analysis) 
14.2.2.3.8 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Baseline BSA% - Multiple Imputation 
(Subgroup Analysis) 
14.2.2.3.9 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Baseline BSA% Tertiles - Multiple 
Imputation (Subgroup Analysis) 
14.2.2.3.10 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Fitzpatrick Score - Multiple Imputation 
(Subgroup Analysis) 
14.2.2.3.11 
PRU4-ITT 
Worst Itch-Numeric Rating Scale (WI-NRS) Success by 
Study Visit and Body Part Involvement - Multiple 
Imputation (Subgroup Analysis) 
14.2.2.4 
ITT 
Achievement of Daily Worst Itch-Numeric Rating Scale 
(WI-NRS) 0 or 1 by Study Visit - Observed Data  
14.2.2.5 
ITT 
Summary of Average Weekly Worst Itch-Numeric 
Rating Scale (WI-NRS) by Study Visit - Observed Data 
14.2.2.6 
ITT 
Change from Baseline in Average Weekly Worst Itch-
Numeric Rating Scale (WI-NRS) by Study Week – 
Observed Data (ANCOVA) 
14.2.2.7 
ITT 
Worst Itch-Numeric Rating Score (WI-NRS) by Study 
Visit Categorical Results 
14.2.2.8 
ITT 
Change from Baseline in Daily Worst Itch-Numeric 
Rating Scale (WI-NRS) by Study Week - Observed Data 
(ANCOVA) 
14.2.3.1 
ITT 
Overall Assessment of Erythema Severity Grades by 
Study Visit - Multiple Imputation (Primary Analysis) 
Categorical Results   


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 50 of 56 
Table Number  
Population 
Table Title/Summary 
14.2.3.1.s 
ITT 
Overall Assessment of Erythema Severity Grades by 
Study Visit - Multiple Imputation (Primary Analysis, 
Supplemental Estimand) Categorical Results   
14.2.3.2.1 
ITT 
Overall Assessment of Erythema Severity Grades by 
Study Visit – Observed Data (Sensitivity Analysis) 
Categorical Results  
14.2.3.2.2 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 - 
Non-responder Imputation – (Sensitivity Analysis)  
14.2.3.3.1 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Response to Topical Corticosteroids - Multiple 
Imputation (Subgroup Analysis) 
14.2.3.3.2 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Response to Topical Antifungals - Multiple 
Imputation (Subgroup Analysis) 
14.2.3.3.3 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Age Group - Multiple Imputation (Subgroup 
Analysis) 
14.2.3.3.4 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Baseline IGA Severity - Multiple Imputation 
(Subgroup Analysis) 
14.2.3.3.5 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Gender - Multiple Imputation (Subgroup Analysis) 
14.2.3.3.6 
ITT 
Overall Assessment of Erythema Score of 0 at 8 by 
Ethnicity - Multiple Imputation (Subgroup Analysis) 
14.2.3.3.7 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Race - Multiple Imputation (Subgroup Analysis) 
14.2.3.3.8 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Baseline BSA% - Multiple Imputation (Subgroup 
Analysis) 
14.2.3.3.9 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Baseline BSA% Tertiles - Multiple Imputation 
(Subgroup Analysis 
14.2.3.3.10 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Fitzpatrick Score - Multiple Imputation (Subgroup 
Analysis) 
14.2.3.3.11 
ITT 
Overall Assessment of Erythema Score of 0 at Week 8 
by Body Part Involvement - Multiple Imputation 
(Subgroup Analysis) 
14.2.3.4 
ITT 
Summary of Overall Assessment of Erythema by Study 
Visit – Observed Data 
14.2.3.5 
ITT 
Change from Baseline in Overall Assessment of 
Erythema by Study Visit – Observed Data (ANCOVA) 
14.2.4.1 
ITT 
Overall Assessment of Scaling Severity Grades by Study 
Visit - Multiple Imputation (Primary Analysis) 
14.2.4.1.s 
ITT 
Overall Assessment of Scaling Severity Grades by Study 
Visit - Multiple Imputation (Primary Analysis, 
Supplemental Estimand) 
14.2.4.2.1 
ITT 
Overall Assessment of Scaling Severity Grades by Study 
Visit – Observed Data (Sensitivity Analysis) Categorical 
Results  


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 51 of 56 
Table Number  
Population 
Table Title/Summary 
14.2.4.2.2 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 – 
Non-responder Imputation (Sensitivity Analysis) 
Categorical Results  
14.2.4.3.1 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Response to Topical Corticosteroids - Multiple 
Imputation (Subgroup Analysis) 
14.2.4.3.2 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Response to Topical Antifungals - Multiple Imputation 
(Subgroup Analysis) 
14.2.4.3.3 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Age Group - Multiple Imputation (Subgroup Analysis) 
14.2.4.3.4 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Age Group - Multiple Imputation (Subgroup Analysis) 
14.2.4.3.5 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Gender - Multiple Imputation (Subgroup Analysis) 
14.2.4.3.6 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Ethnicity- Multiple Imputation (Subgroup Analysis) 
14.2.4.3.7 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Race- Multiple Imputation (Subgroup Analysis) 
14.2.4.3.8 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Baseline BSA% - Multiple Imputation (Subgroup 
Analysis) 
14.2.4.3.9 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Baseline BSA% Tertiles - Multiple Imputation 
(Subgroup Analysis) 
14.2.4.3.10 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Fitzpatrick Score - Multiple Imputation (Subgroup 
Analysis) 
14.2.4.3.11 
ITT 
Overall Assessment of Scaling Score of 0 at Week 8 by 
Body Part Involvement- Multiple Imputation (Subgroup 
Analysis) 
14.2.4.4 
ITT 
Summary of Overall Assessment of Scaling by Study 
Visit - Observed Data 
14.2.4.5 
ITT 
Change from Baseline in Overall Assessment of Scaling 
by Study Visit – Observed Data (ANCOVA) 
14.2.5.1 
ITT* 
Summary of Scalpdex Total Score by Study Visit - 
Observed Data 
14.2.5.2 
ITT* 
Change from Baseline in Scalpdex Total Score by Study 
Visit - Observed Data (ANCOVA) 
14.2.5.3 
ITT* 
Summary of Scalpdex Score - Emotions Scale by Study 
Visit - Observed Data 
14.2.5.4 
ITT* 
Change from Baseline in Scalpdex Score - Emotions 
Scale by Study Visit - Observed Data (ANCOVA) 
14.2.5.5 
ITT* 
Summary of Scalpdex Score - Symptoms Scale by Study 
Visit - Observed Data 
14.2.5.6 
ITT* 
Change from Baseline in Scalpdex Score - Symptoms 
Scale by Study Visit - Observed Data (ANCOVA) 
14.2.5.7 
ITT* 
Summary of Scalpdex Score - Functioning Scale by 
Study Visit - Observed Data 
14.2.5.8 
ITT* 
Change from Baseline in Scalpdex Score - Functioning 
Scale by Study Visit - Observed Data (ANCOVA) 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 52 of 56 
Table Number  
Population 
Table Title/Summary 
14.2.5.9 
ITT* 
Scalpdex Individual Questionnaire Responses by Study 
Visit (Categorical) 
14.2.5.10 
ITT* 
Scalpdex Individual Questionnaire Responses by Study 
Visit (Continuous) 
14.2.6.1 
ITT 
Summary of Dermatology Life Quality Index (DLQI) by 
Study Visit - Observed Data 
14.2.6.2 
ITT 
Change from Baseline in Dermatology Life Quality 
Index (DLQI) by Study Visit - Observed Data 
(ANCOVA) 
14.2.6.3 
ITT 
Summary of Children’s Dermatology Life Quality Index 
(CDLQI) by Study Visit - Observed Data 
14.2.6.4 
ITT 
Change from Baseline in Children’s Dermatology Life 
Quality Index (CDLQI) by Study Visit - Observed Data 
(ANCOVA) 
14.2.7.1 
ITT 
Summary of Body Surface Area (%) by Study Visit - 
Observed Data 
14.2.7.2 
ITT 
Change from Baseline in Body Surface Area (%) by 
Study Visit - Observed Data (ANCOVA) 
14.3 
Safety Summary 
14.3.1.1 
Safety 
Overall Summary of Treatment Emergent Adverse 
Events 
14.3.1.2 
Safety 
Treatment Emergent Adverse Events by System Organ 
Class and Preferred Term 
14.3.1.3 
Safety 
Treatment Emergent Adverse Events by System Organ 
Class, Preferred Term, and Maximum Severity 
14.3.1.4 
Safety 
Treatment Emergent Adverse Events by System Organ 
Class, Preferred Term, and Strongest Relationship to 
Study Drug 
14.3.1.5 
Safety 
Treatment Emergent Adverse Events of Preferred Term 
in Descending Order 
14.3.1.6 
Safety 
Treatment Emergent Serious Adverse Events by System 
Organ Class and Preferred Term 
14.3.1.7 
Safety 
Treatment Emergent Adverse Events Leading to Study 
Drug Discontinuation by System Organ Class and 
Preferred Term 
14.3.1.8 
Safety 
Treatment Emergent Adverse Events Leading to Study 
Discontinuation by System Organ Class and Preferred 
Term 
14.3.2.1 
Safety 
Quantitative Summary of Investigator Local Tolerability 
Assessment (Dermal Response) by Study Visit  
14.3.2.2 
Safety 
Categorical Summary of Investigator Local Tolerability 
Assessment (Dermal Response) by Study Visit 
Categorical Results 
14.3.2.3 
Safety 
Categorical Summary of Investigator Local Tolerability 
Assessment (Other Effects) by Study Visit Categorical 
Results 
14.3.2.4 
Safety 
Quantitative Summary of Subject Local Tolerability 
Assessment by Study Visit  


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 53 of 56 
Table Number  
Population 
Table Title/Summary 
14.3.2.5 
Safety 
Categorical Summary of Subject Local Tolerability 
Assessment by Study Visit Categorical Results 
14.3.3.1 
Safety 
Summary of Clinical Chemistry Laboratory Results 
(Standard Units) by Study Visit 
14.3.3.2 
Safety 
Shift from Baseline in Clinical Chemistry Laboratory 
Results (Standard Units) by Study Visit  
14.3.3.3 
Safety 
Summary of Hematology Laboratory Results (Standard 
Units) by Study Visit  
14.3.3.4 
Safety 
Shift from Baseline in Hematology Laboratory Results 
(Standard Units) by Study Visit  
14.3.3.5 
Safety 
Summary of Quantitative Urinalysis Laboratory Results 
(Standard Units) by Study Visit  
14.3.3.6 
Safety 
Shift from Baseline in Quantitative Urinalysis 
Laboratory Results (Standard Units) by Study Visit  
14.3.3.7 
Safety 
Summary of Qualitative Urinalysis Laboratory Results 
(Standard Units) by Study Visit  
14.3.4.1 
Safety 
Summary of Vital Signs by Study Visit  
14.3.4.2 
Safety 
Change in Weight from Baseline by Study Visit 
14.3.4.3 
Safety 
Shift from Baseline in BMI by Study Visit  
14.3.4.4 
Safety 
Change in Weight from Baseline by Study Visit – by 
Weight Loss Intentional/Non-Intentional 
14.3.4.5 
Safety 
Shift from Baseline in BMI by Study Visit - by Weight 
Loss Intentional/Non-Intentional 
14.3.5 
Safety 
Shift from Baseline in Patient Health Questionnaire 
(PHQ-8)/Modified PHQ-Adolescents by Study Visit 
14.3.6 
Safety 
Summary of CDI-2 by Study Visit 
14.3.7 
Safety 
Summary of Columbia-Suicide Severity Rating Scale 
(C-SSRS) Suicidal Ideation and Suicidal Behavior by 
Study Visit 
14.3.8 
Safety 
Summary of Physical Examination by Study Visit 
14.3.9 
Safety 
Summary of Concomitant Medications by Anatomic 
Therapeutic Chemical (ATC) Class Level 4 and 
Preferred Term 
14.3.10 
Safety 
Summary of Pigmentation Assessment by Race 
14.3.10.1 
Safety  
Shift from Baseline in Hypopigmentation by Study Visit 
14.3.10.2 
Safety 
Shift from Baseline in Hyperpigmentation by Study Visit 
14.4 
Pharmacokinetic Data 
14.4.1 
PK 
Summary of Pharmacokinetic Concentration Results by 
Study Visit 
*Analyses of Scalpdex will be limited to subjects in the ITT population who have Seborrheic Dermatitis involvement on the 
scalp 
14.2. Planned Figure descriptions 
 
The following are planned summary figures for protocol ARQ-154-304. The figure numbers are 
place holders only and may be changed when figures are produced.  
 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 54 of 56 
Figure Number  
Population 
Figure Title/Summary 
14.2.1.4 
ITT 
Forest Plot of IGA Success at Week 8 - Multiple Imputation 
(Subgroup Analysis) 
14.2.1.3.1.1 
ITT 
Plot of Proportion (99% CI) of Investigator Global Assessment 
(IGA) Success at Week 8 by Site - Observed Data (Supporting 
Analysis) 
14.2.1.3.2.1 
ITT 
Plot of Proportion (99% CI) of Investigator Global Assessment 
(IGA) Success at Week 8 - Multiple Imputation, Impact of Site 
(Supporting Analysis)  
14.2.2.9.1 
ITT 
Plot of Mean (+/-SD) Change, and Percent Change from Baseline 
of Daily Worst Itch-Numeric Rating Scale (WI-NRS) by 
Treatment Group over Time 
14.2.2.3 
ITT 
Forest Plot of Worst Itch-Numeric Rating Scale (WI-NRS) 
Success by Study Week - Multiple Imputation (Subgroup 
Analysis) 
14.2.3.3 
ITT 
Forest Plot of Overall Assessment of Erythema Score of 0 at Week 
8 - Observed Data (Subgroup Analysis) 
14.2.4.3 
ITT 
Forest Plot of Overall Assessment of Scaling Score of 0 at Week 8 
- Observed Data (Subgroup Analysis) 
14.3.1.2.1 
Safety 
Plot of Most Frequent Treatment Emergent Adverse Event by 
Preferred Term and Treatment Group 
 
14.3. Planned Listing Descriptions 
 
The following are planned data and patient/subject data listings for protocol number ARQ-154-
304.  
 
In general, all listings will be sorted by site, and subject number. Screen failures will only be 
presented in listing 16.1.1.  
 
In all listings, a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (e.g., repetition of subject number), then only the first occurrence will be 
displayed.  
 
In data listings, the information for one subject will be kept on one page if at all possible, rather 
than splitting a subject’s information across pages.  
 
Listing Number  
Population 
Listing Title/Summary 
16.1.1 
Screened Subjects 
Subject Disposition 
16.1.2 
ITT 
Protocol Deviations 
16.1.3 
ITT and Actual 
Stratification 
Factors 
Randomization 
16.1.4 
ITT 
Subject Demographics and Baseline Characteristics 
16.1.5 
Safety 
Study Drug Application and Can weight at the Study Site 
16.2.1 
ITT 
Efficacy Endpoints 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 55 of 56 
Listing Number  
Population 
Listing Title/Summary 
16.2.2 
ITT 
Daily Worst Itch Numerical Rating Scale (WI-NRS)  
16.3.1 
Safety 
Adverse Events 
16.3.2.1 
Safety 
Abnormal Clinical Laboratory Data: Clinical Chemistry 
16.3.2.2 
Safety 
Abnormal Clinical Laboratory Data: Hematology 
16.3.2.3 
Safety 
Abnormal Clinical Laboratory Data: Urinalysis 
16.3.3 
Safety 
Abnormal Vital Signs 
16.4.1 
PK 
Pharmacokinetic Blood Collection 
 
 
 


 
Statistical Analysis Plan,  
 
Sponsor: Arcutis Biotherapeutics, Inc.  
 
Protocol Number: ARQ-154-304  
 
PCN Number: ARCU214357 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version Final 3.0    |    Date 22-Sep-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 56 of 56 
15. 
TABLES, LISTINGS AND FIGURES SHELLS  
15.1. Standard Layout for all Tables, Listings and Figures 
 
Tables, listings and figures shells are provided in a separate document.  
Note that programming notes may be added after each TLF shell if appropriate.