Conditions: Seborrheic Dermatitis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 408
Healthy volunteers: no

Brief summary:
This is an open-label, long-term safety study of roflumilast ARQ-154 foam 0.3% in subjects with seborrheic dermatitis involving up to 20% total Body Surface Area (BSA). Study was applied topically once daily for 52 weeks. Cohort 1 subjects are rollover subjects from study ARQ-154-203 (NCT04091646) and were rolled into treatment in the current study without interruption. Cohort 2 includes participants from ARQ-154-203 who began treatment in the current study after a gap from completing treatment in the prior study.

Detailed description:

Arms:
arm 1: Open-label, Long-term Safety of ARQ-154

Interventions: intervention 1: ARQ-154
Intervention descriptions: intervention 1: ARQ-154 foam 0.3% applied once daily for 52 weeks

Protocol document:
Prot_000.pdf: 








Protocol ARQ-154-214 
Arcutis Biotherapeutics, Inc. 
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TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
1.1. 
Synopsis ......................................................................................................................10 
1.2. 
Study Schema .............................................................................................................15 
1.3. 
Schedule of Visits and Assessments ...........................................................................16 
2. 
ABBREVIATIONS ....................................................................................................19 
3. 
BACKGROUND AND RATIONALE .......................................................................21 
3.1. 
Introduction .................................................................................................................21 
3.2. 
Preclinical Studies ......................................................................................................22 
3.2.1. 
Toxicity Summary ......................................................................................................22 
3.3. 
Clinical Studies ...........................................................................................................23 
3.3.1. 
Topical Roflumilast Cream .........................................................................................23 
3.3.1.1. 
Psoriasis Phase 2a .......................................................................................................23 
3.3.1.2. 
Psoriasis Phase 2b .......................................................................................................24 
3.3.1.3. 
Atopic Dermatitis Phase 1 ..........................................................................................28 
3.3.1.4. 
Atopic Dermatitis Phase 2 ..........................................................................................28 
3.3.2. 
Oral Roflumilast Tablet ..............................................................................................29 
3.4. 
Rationale for Development .........................................................................................29 
3.4.1. 
 
3.4.2. 
 
4. 
STUDY ENDPOINTS AND OBJECTIVES ..............................................................31 
4.1. 
Study Objective ..........................................................................................................31 
4.2. 
Study Endpoints ..........................................................................................................31 
4.2.1. 
Primary Endpoints ......................................................................................................31 
4.2.2. 
Secondary Endpoints ..................................................................................................31 
5. 
INVESTIGATIONAL PLAN .....................................................................................32 
5.1. 
Overall Study Design and Plan ...................................................................................32 
5.2. 
Number of Sites and Subjects .....................................................................................32 
5.3. 
Subject Participation ...................................................................................................33 
5.3.1. 
Numbering of Subjects ...............................................................................................33 
5.4. 
Selection of Study Population ....................................................................................33 
5.4.1. 
Inclusion Criteria ........................................................................................................33 


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5.4.2. 
Exclusion Criteria .......................................................................................................34 
5.4.3. 
Removal of Subjects from Investigational Product ....................................................36 
5.4.4. 
Removal of Subjects from the Study ..........................................................................36 
5.5. 
Study Restrictions .......................................................................................................37 
5.5.1. 
Prohibitions and Concomitant Therapy ......................................................................37 
5.6. 
Treatment ....................................................................................................................38 
5.6.1. 
IP Supplies, Packaging and Labeling .........................................................................38 
5.6.2. 
Blinding ......................................................................................................................38 
5.6.3. 
Treatment Administration ...........................................................................................38 
5.6.4. 
Treatment Compliance ................................................................................................39 
6. 
STUDY PROCEDURES ............................................................................................40 
6.1. 
Safety Assessments .....................................................................................................40 
6.1.1. 
Physical Examination .................................................................................................41 
6.1.2. 
Vital Signs, Height and Weight ..................................................................................41 
6.1.3. 
Laboratory Tests .........................................................................................................41 
6.1.4. 
Patient Health Questionnaire depression scale (PHQ-8) ............................................42 
6.1.5. 
Patient Health Questionnaire depression scale (Modified PHQ-A) ...........................42 
6.1.6. 
Children’s Depression Inventory 2 .............................................................................43 
6.1.7. 
Columbia-Suicide Severity Rating Scale (C-SSRS) ...................................................43 
6.1.8. 
Local Tolerability Assessments ..................................................................................44 
6.1.9. 
Pigmentation Assessment ...........................................................................................45 
6.1.10. 
Adverse Events ...........................................................................................................45 
6.1.11. 
Phone Visits ................................................................................................................45 
6.1.12. 
Pharmacokinetic Assessment ......................................................................................45 
6.1.13. 
Malassezia Testing ......................................................................................................46 
6.2. 
Efficacy Evaluations ...................................................................................................46 
6.2.1. 
Investigator Global Assessment (IGA) .......................................................................46 
6.2.2. 
Overall Assessment of Erythema ................................................................................46 
6.2.3. 
Overall Assessment of Scaling ...................................................................................47 
6.2.4. 
Body Surface Area (BSA) ..........................................................................................47 
6.2.5. 
Worst Itch Numerical Rating Scale (WI-NRS) ..........................................................47 
6.2.6. 
Scalpdex ......................................................................................................................48 


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6.2.7. 
Dermal Imaging ..........................................................................................................48 
6.3. 
Final Study Visit .........................................................................................................48 
6.4. 
Early Termination Visit ..............................................................................................48 
6.5. 
Unscheduled Visit .......................................................................................................48 
6.6. 
Adverse Events ...........................................................................................................49 
6.6.1. 
Adverse Event Definition ...........................................................................................49 
6.6.2. 
Serious Adverse Event ................................................................................................49 
6.6.3. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) .....................................51 
6.6.4. 
Safety Review .............................................................................................................51 
6.6.5. 
Adverse Event Reporting ............................................................................................51 
6.7. 
Reporting Pregnancy ..................................................................................................52 
6.8. 
Treatment Stopping Rules ..........................................................................................52 
7. 
DATA ANALYSIS ....................................................................................................54 
7.1. 
Statistical Methods ......................................................................................................54 
7.1.1. 
Baseline Definition .....................................................................................................54 
7.1.2. 
Determination of Sample Size ....................................................................................54 
7.1.3. 
Subjects to Analyze ....................................................................................................55 
7.1.4. 
Interim Analysis ..........................................................................................................55 
7.1.5. 
Background and Demographic Characteristics ..........................................................55 
7.1.6. 
Study Disposition........................................................................................................55 
7.1.7. 
Protocol Deviations and Eligibility Deviations ..........................................................55 
7.1.8. 
Investigational Product Compliance ...........................................................................55 
7.2. 
Safety Evaluation ........................................................................................................55 
7.2.1. 
Adverse Events ...........................................................................................................55 
7.2.2. 
Local Tolerance Assessments .....................................................................................56 
7.2.3. 
Medical History and Physical Examinations ..............................................................56 
7.2.4. 
PHQ-8 and Modified PHQ-A .....................................................................................56 
7.2.5. 
C-SSRS .......................................................................................................................56 
7.2.6. 
Clinical Laboratory Results and Vital Signs/Weight Measurements .........................56 
7.2.7. 
Prior and Concomitant Medications ...........................................................................57 
7.3. 
Patient Reported Outcomes Analyses .........................................................................57 
7.3.1. 
WI-NRS ......................................................................................................................57 


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7.3.2. 
Scalpdex ......................................................................................................................57 
7.4. 
Efficacy Endpoints ......................................................................................................57 
7.4.1. 
Achievement of IGA ‘Completely Clear’ or ‘Almost Clear’ .....................................57 
7.4.2. 
Achievement of IGA ‘Completely Clear’ or ‘Almost Clear’ plus a 2-grade 
Improvement from Baseline .......................................................................................57 
7.4.3. 
Achievement of a 2-grade improvement in IGA from Baseline .................................57 
7.4.4. 
Duration of IGA Success ............................................................................................57 
7.4.5. 
Treatment-free Interval ...............................................................................................58 
7.4.6. 
Pharmacokinetic Analysis ..........................................................................................58 
8. 
STUDY ADMINISTRATION ...................................................................................58 
8.1. 
Ethics ..........................................................................................................................58 
8.1.1. 
Ethics Review Board ..................................................................................................58 
8.1.2. 
Ethical Conduct of the Study ......................................................................................58 
8.1.3. 
Subject Information and Consent ...............................................................................58 
8.2. 
Study Completion and Termination ............................................................................59 
8.2.1. 
Study Completion .......................................................................................................59 
8.2.2. 
Study Termination ......................................................................................................59 
8.3. 
Study Monitoring ........................................................................................................59 
8.4. 
Data Quality Assurance ..............................................................................................60 
8.5. 
Data Handling and Record Keeping ...........................................................................60 
8.6. 
Protocol Amendments and Deviations .......................................................................60 
8.7. 
Confidentiality and Privacy ........................................................................................61 
8.8. 
Conflict of Interest ......................................................................................................61 
8.9. 
Report Format .............................................................................................................61 
8.10. 
Publication Policy .......................................................................................................62 
9. 
REFERENCES ...........................................................................................................63 
10. 
APPENDICES ............................................................................................................64 
APPENDIX 1. PATIENT HEALTH QUESTIONNAIRE DEPRESSION SCALE 
(PHQ-8) ..............................................................................................................64 
APPENDIX 2. PATIENT HEALTH QUESTIONNAIRE DEPRESSION SCALE 
(MODIFIED PHQ-A) .........................................................................................65 
APPENDIX 3. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) 
BASELINE/SCREENING VERSION ...............................................................66 




Protocol ARQ-154-214 
Arcutis Biotherapeutics, Inc. 
Amendment 2 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: 
A Phase 2, Multicenter, Open-Label Study of the Long-Term Safety 
of ARQ-154 Foam 0.3% in Subjects with Seborrheic Dermatitis 
Investigational Product: 
ARQ-154 investigational product will be supplied as a 0.3% foam 
IND: 
142047 
Clinical Indication: 
Seborrheic dermatitis 
Study Design: 
ARQ-154-214 is an open-label, single-arm, long-term safety study of 
ARQ-154 foam 0.3% in subjects with seborrheic dermatitis involving 
up to 20% total BSA.  
Cohort 1 eligible subjects will enroll into the long-term safety study 
on the same day as the final visit for a previous ARQ-154 study. 
Cohort 1 Group 1 will be subjects who rolled over from the previous 
ARQ-154-203 study. Group 2 will be subjects who rolled over from 
the previous ARQ-154-116 study. Cohort 2 eligible subjects will 
enroll on Day 1 of this study.  Investigational product will be applied 
by the eligible subjects topically QD for up to 52 weeks at home. 
Periodic clinic visits will include assessments for clinical safety, 
application site reactions evaluated in the clinic using the method of 
Berger and Bowman, and disease improvement or progression. 
Final analysis will be performed when subjects in Cohort 1 Group 1 
and Cohort 2 (approximately 400 subjects) finish up to 52 weeks of 
treatment.    
Subjects in Cohort 1 Group 2 (approximately 10 subjects) will only 
be summarized in the listings and will be updated once all Group 2 
subjects finish up to 52 weeks of treatment. A CSR addendum will be 
provided based on the updated Cohort 1 Group 2 listing.   
Study Objectives: 
To assess long-term safety in a multicenter, open-label, single-arm 
52-week study in subjects with seborrheic dermatitis treated with 
ARQ-154 foam 0.3%. 
Study Sites: 
Up to approximately 40 sites in North America 
Study Population: 
Up to approximately 410 subjects total will be enrolled across 
Cohorts 1 and 2. 
For Cohort 1, subjects will be male and female adolescents (9-17 y/o) 
and adults (>18 y/o) who have completed the treatment period in a 
prior ARQ-154 study and immediately enroll in this safety study.  
Cohort 1 Group 1 subjects will be the ones who rolled over from 
ARQ-154-203. Cohort 1 Group 2 subjects will be the ones who 
rolled over from ARQ-154-116. For Cohort 2, subjects will be male 
and female adolescents (12 – 17 y/o) and adults (>18 y/o) subjects 
who may or may not have participated in a prior ARQ-154 study, 
i.e. either de novo subjects who did not participate in ARQ-154-203 


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or subjects who completed a ARQ-154 study prior to initiation of the 
current ARQ-154-214 study.  
Inclusion Criteria: 
All Subjects 
1. Participants legally competent to sign and give informed consent 
or (for adolescents) assent. 
2. Males and females ages 9 years and older (inclusive) at the time 
of consent. 
3. Females of childbearing potential (FOCBP) must have a 
negative urine pregnancy test at all study visits. In addition, 
sexually active FOCBP must agree to use at least one form of an 
acceptable effective contraception throughout the trial.  
Acceptable effective forms of contraception may include: 
oral/implant/injectable/ transdermal contraceptives, intrauterine 
device, or partner’s vasectomy.  If barrier methods are used 
(e.g., condom with spermicide, diaphragm with spermicide), 
then 2 forms of contraception are required. The use of abstinence 
as a contraceptive measure is acceptable as long as this is a 
consistent part of a lifestyle choice and a backup method has 
been identified if the subject becomes sexually active. 
4. Females of non-childbearing potential must be either 
premenarchal or post-menopausal women with spontaneous 
amenorrhea for at least 12 months or have undergone surgical 
sterilization (permanent sterilization methods include 
hysterectomy, bilateral oophorectomy, hysteroscopic 
sterilization, bilateral tubal ligation or bilateral salpingectomy).  
Inclusion Criteria: 
Cohort 1 Only 
5. Subjects with seborrheic dermatitis who met eligibility criteria 
for a prior ARQ-154 study, successfully completed a prior 
ARQ-154 study through the final visit and are able to 
immediately enroll into this long-term safety study on the final 
visit of a previous ARQ-154 study. 
Inclusion Criteria: 
Cohort 2 Only 
For subjects that have not participated in a prior ARQ-154 study: 
6. Clinical diagnosis of seborrheic dermatitis of at least 3 months 
duration as determined by the Investigator.  Stable disease for 
the past 4 weeks.   
7. Seborrheic dermatitis of the scalp and/or face and/or trunk 
and/or intertriginous areas up to ≤20% BSA involvement. 
8. An Investigator Global Assessment (IGA) of disease severity of 
at least Moderate (‘3’) at Day 1. 
9. Overall Assessment of Erythema and Overall Assessment of 
Scaling scores of Moderate (‘2’) at Day 1. 
 
For subjects that have completed a prior ARQ-154 study prior to 
initiation of the current ARQ-154-214 study: 
10. Clinical diagnosis of seborrheic dermatitis of at least 3 months 
duration as determined by the Investigator.   
11. Seborrheic dermatitis of the scalp and/or face and/or trunk 
and/or intertriginous areas up to ≤20% BSA involvement. 




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Exclusion Criteria: 
Cohort 2 Only 
17. Previous participation in this ARQ-154-214 study. 
15. Subjects who cannot discontinue treatment with therapies for the 
treatment of seborrheic dermatitis prior to the Day 1 visit and 
during the study according to Excluded medications and 
Treatment (Table 1). 
16. Subjects with PHQ-8 >10 or modified PHQ-A >10 at Screening 
or Day 1. 
For subjects that have completed a prior ARQ-154 study prior to 
initiation of the current ARQ-154-214 study: 
18. Subjects who experienced an ARQ-154 treatment-related AE or 
a serious AE (SAE) that precluded further treatment with 
ARQ-154 foam. 
Duration of Participation 
for Subjects: 
Up to approximately 52 weeks 
Key Assessments: 
Safety will be monitored through application site assessments, safety 
labs, vital signs, physical examinations, clinical laboratory testing, 
and Adverse Events (AEs). Safety will also be monitored by C-SSRS 
(for adolescents and adults 12 years old and older), Children’s 
Depression Inventory 2 (CDI-2, parent report for children 9-11 years 
old, inclusive), PHQ-8 (in adults) and modified PHQ-A 
(in adolescents 12-17 years old, inclusive) assessments.  
Efficacy assessments will include IGA, Overall Assessment of 
Erythema, Overall Assessment of Scaling, WI-NRS, Scalpdex, and 
BSA.  
Study Endpoints: 
Primary Endpoints 
• 
Occurrence of treatment emergent AEs (TEAEs) 
• 
Occurrence of Serious Adverse Events (SAEs)  
Secondary Endpoints 
• 
Achievement of an Investigator Global Assessment (IGA) of 
‘completely clear’ or ‘almost clear’, as observed over time  
• 
A 2-grade improvement in IGA from Baseline  
(see Section 7.1.1) as observed over time 
• 
‘IGA Success’, defined as achievement of an IGA of 
‘completely clear’ or ‘almost clear’ plus a 2-grade 
improvement in IGA from Baseline (see Section 7.1.1) as 
observed over time 
• 
Duration of IGA Success, defined as the time from the first 
observation of IGA Success to the last time a subject’s 
disease response meets the criteria for IGA success.  The 
duration of IGA Success for subjects who end treatment in 
IGA Success will be censored at the last disease assessment 
date 


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• 
Treatment-free interval, defined among subjects who achieve 
a 'completely clear' IGA and stop treatment to all lesions as 
the time from attainment of a score of ‘completely clear’ to 
re-starting IP.  
Statistical Considerations: 
Up to approximately 410 subjects total across Cohorts are planned 
for this study.   
The sample size will be sufficient to evaluate the long-term safety of 
ARQ-154 foam 0.3% up to 52 weeks of treatment. 
Descriptive statistics will be presented for the endpoint 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, Q1, Q3, minimum, and maximum for continuous 
data.   
Adverse Events 
For the primary endpoints, the occurrence of treatment-emergent AEs 
(TEAEs) and the occurrence of Serious Adverse Events (SAEs) will 
be tabulated by preferred term and system organ class.   
In addition, summary tables of TEAEs by severity, by relationship to 
investigational product, and those leading to withdrawal from 
investigational product will be created. 
Vital Signs 
Descriptive statistics will be calculated for vital signs and change 
from baseline and percent change from baseline in vital signs over 
time. 
Clinical Laboratory Results 
Descriptive statistics of the laboratory parameters will be calculated 
at each scheduled time point.  Change from Baseline and percent 
change from Baseline will be summarized at each scheduled time 
point. Shifts from Baseline will be tabulated. 
Patient Health Questionnaires 
PHQ-8/PHQ-A/CDI-2 and C-SSRS questionnaires will be completed 
by the subjects at all study visits. Descriptive statistics will be 
calculated for the PHQ-8/PHQ-A/CDI-2. The C-SSRS will be 
analyzed per the Scoring and Data Analysis Guide from the 
Columbia Lighthouse Project. 
Descriptive statistics will be presented for the efficacy data collected 
in the clinical trial for the subjects who enroll in this study and 
receive at least one day of IP. For the binary endpoints related to 
IGA, the proportions of subjects achieving each endpoint will be 
tabulated at each scheduled visit. For subjects who withdraw from 
study due to lack of efficacy. 
The duration of response and treatment-free interval will be analyzed 
using the Kaplan-Meier method. 
 


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1.2. 
Study Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 1 Day 1 
Final visit of prior 
ARQ-154 study 
 
 
Day 1  
First Day of Treatment 
  
Up to 52-Week Treatment Period (Visits 1, 2, 3, 4 & 5) 
Phone Visit at Weeks 18, 30 & 44 
A Phase 2, Multicenter, Open-Label Study of the Long-Term Safety of 
ARQ-154 Foam 0.3% in Subjects with Seborrheic Dermatitis 
 
Up to Approximately 410 subjects total across two cohorts with seborrheic 
dermatitis will be receive ARQ-154 foam 0.3%. Cohort 1 will consist of 
roll over subjects from a prior ARQ-154 study on the final visit and 
Cohort 2 will consist of subjects that may or may not have participated on 
in a prior ARQ-154 study. 
 
Cohort 2 Screening 
  


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1.3. 
Schedule of Visits and Assessments 
Study Procedure 
Washout 
Cohort 2 
Day 1 
(Cohort 2) 
Wk 4 
D 29 
Wk 12 
D 85 
Wk 18 
D 127 
Wk 24 
D 169 
Wk 30 
D 211 
Wk 36 
D 253 
Wk 44 
D 309 
Wk 52/ 
ET 
D 365 
Visit 
Screening 
Final Visit 
of prior 
ARQ-154 
Study l 
(Cohort 1) 
1 
2 
Phone 
Visit 
3 
Phone 
Visit 
4 
Phone 
Visit 
5 
Visit Window 
-35 days 
+/- 3 
days 
+/- 5 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
Informed 
consent/assent 
Xk 
Xk 
 
 
 
 
 
 
 
 
Physical 
examinationa 
X 
Xl 
 
 
 
X 
 
 
 
X 
Medical history 
X 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
 
 
 
Hematology, Serum 
Chemistries, and 
Urine Analysis  
X 
Xl 
X 
X 
 
X 
 
X 
 
X 
Vital signs, height, 
weightb 
X 
Xl 
X 
X 
 
X 
 
X 
 
X 
IGAc, Overall 
Assessment of 
Erythemac, Overall 
Assessment of 
Scalingc , WI-NRS, 
Scalpdex 
X 
Xl 
X 
X 
 
X 
 
X 
 
X 
BSA 
X 
Xl 
 
 
 
X 
 
X 
 
X 
C-SSRS, PHQ‑8/ 
PHQ-A/CDI-2d  
X 
Xl 
X 
X 
 
X 
 
X 
 
X 
Pregnancy teste 
X 
Xl 
X 
X 
 
X 
 
X 
 
X 
Local Tolerability 
Assessmentf 
 
Xl 
X 
X 
 
X 
 
X 
 
X 
Pigmentation 
Assessmentg 
X 
Xl 
X 
X 
 
X 
 
X 
 
X 
Medical 
Photographyh 
 
X 
X 
X 
 
X 
 
X 
 
X 
Dispense study 
medication kiti 
 
X 
X 
X 
 
X 
 
X 
 
 
IP application at the 
study site 
 
X 
 
 
 
 
 
 
 
 
Dispense/review 
diary 
 
X 
X 
X 
 
X 
 
X 
 
X 


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Study Procedure 
Washout 
Cohort 2 
Day 1 
(Cohort 2) 
Wk 4 
D 29 
Wk 12 
D 85 
Wk 18 
D 127 
Wk 24 
D 169 
Wk 30 
D 211 
Wk 36 
D 253 
Wk 44 
D 309 
Wk 52/ 
ET 
D 365 
Visit 
Screening 
Final Visit 
of prior 
ARQ-154 
Study l 
(Cohort 1) 
1 
2 
Phone 
Visit 
3 
Phone 
Visit 
4 
Phone 
Visit 
5 
Visit Window 
-35 days 
+/- 3 
days 
+/- 5 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
Weigh study 
medication 
 
X 
X 
X 
 
X 
 
X 
 
X 
Adverse event 
assessmentj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK Samplingm 
 
 
X 
 
 
 
 
 
 
 
Malassezia testn 
 
 
X 
X 
 
X 
 
X 
 
X 
a  
Limited physical examination: skin, lungs, and heart only. 
b  
Height will be collected at Day 1, Week 24 and Week 52/ET only. Weight will be collected at all study visits. 
Subject to void prior to weight being taken. Remove any jackets, outerwear and shoes. Remove any objects of 
significant weight (i.e. cell phones, wallet, key chains). A 5% unintentional weight loss from Baseline should be 
reported to the medical monitor. 
c  
IGA will be a 5-point scale ranging from completely clear (0) to severe (4). IGA should be completed prior to 
other physician assessments. Overall assessment of erythema (0-3 scale) and overall assessment of scaling 
(0-3 scale) will be completed.  Total BSA affected by seborrheic dermatitis will be determined at each visit. A 
body diagram should be used to record areas of seborrheic dermatitis involvement. 
d  
Adolescents and adults will complete the C-SSRS (12 years of age and older). Adults will complete the PHQ-8. 
Adolescents (ages 12 -17, inclusive) will complete the modified PHQ-A. Parents/caregivers will complete CDI-
2 (parent report) for children 9-11 years of age, inclusive. 
e  
A pregnancy test will be administered to all females of child-bearing potential. A serum pregnancy test will be 
performed at the Screening visit only for Cohort 2. A urine pregnancy test will be performed at Day 1, Weeks 4, 
12, 24, 36 and 52. A negative result is required for continued participation in the study, and results must be 
available prior to dispensing of IP at each visit. 
f  
Local tolerability will be assessed prior to IP application in the clinic for the Investigator assessment of skin 
(Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s ‘0-3’ 
burning/stinging assessment at Baseline.  Note for Investigator tolerability assessments: 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.  At Weeks 4, 12, 24, 36, and 52 will be a 
recall assessment of burning/stinging experienced post drug application on the previous day of the clinic visit.  
g  
An assessment for hypopigmentation and hyperpigmentation will be performed by the investigator at all clinic 
visits. 
h  
At selected sites, medical photography will be obtained for target lesions. 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. 
i  
Kits will be dispensed based on %BSA affected. See IP Handling Manual for details.   
j  
Any emergent AEs will be followed in the clinic for up to one month at the Investigator’s discretion until 
resolved or otherwise judged as clinically stable. 
k  
For Cohort 1, the consent will be signed after completion of the final visit in prior ARQ-154 study. Cohort 2 
will sign consent prior to any study-related procedures at the Screening Visit.  
 
 


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l  
For Cohort 1, this data will be obtained from the final visit of the prior ARQ-154 Study and used as the Day 1 
data for this long-term safety study (ARQ-154-214). If after the prior ARQ-154 study completion, subjects 
should complete the screening visit procedures. The Baseline values for Safety tabulations will be taken from 
the day that the subject received their first active IP (across prior ARQ-154 studies and ARQ-154-214). 
Baseline values for efficacy will be those recorded on Day 1 of the prior ARQ-154 Study. For Cohort 2, 
Baseline evaluations will be obtained for all procedures and the Baseline/Screening version of the C-SSRS will 
be utilized at Screening.  For Cohort 2, Screening labs that are collected within 14 days of Day 1 do not need to 
be repeated.  
m  
For Cohort 2 adolescent subjects PK samples will be collected on Week 4 for adolescent subjects between 
12 – 16 years old. Collect PK sample with the safety lab collection. Ensure PK will not be drawn on the area 
where investigational product is applied. 
n  
At select sites, the Investigator will collect samples for Malassezia testing on Cohort 1 Group 2 subjects at 
Weeks 4, 12, 24, 36, and 52. Samples will be collected from treated and untreated areas by swabbing the skin 
surface. Samples should be collected from the same areas as samples collected during the ARQ-154-116 
Baseline visit. 
 
 
 
 


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2. 
ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse Event 
AMP 
Adenosine Monophosphate 
AUC 
Area Under the Curve 
BSA 
Body Surface Area 
Cmax 
Maximum Concentration 
CDI 
Children’s Depression Inventory 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
FDA 
U.S. Food and Drug Administration 
FOCBP 
Female of Child Bearing Potential 
GCP 
Good Clinical Practices 
IB 
Investigational Brochure 
IC50 
Half Maximal Inhibitory Concentration 
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation 
IGA 
Investigator Global Assessment 
I-IGA 
Intertriginous IGA  
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System  
LED 
Light Emitting Device 
µg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NOAEL 
No Observed Adverse Effect Level 
Ng 
Nanogram 


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Abbreviation 
Definition 
NRS 
Numerical Rating Score  
PASI 
Psoriasis Area and Severity Index 
PDE-4 
Phosphodiesterase 4 
PHQ-A 
Modified PHQ-9 for Adolescents 
PHQ-8 
Patient Health Questionnaire depression scale 
PI 
Principal Investigator  
PK 
Pharmacokinetics 
QD 
Once Daily ("quaque die") 
SAE 
Serious Adverse Event 
TEAE 
Treatment Emergent Adverse Event 
Tmax 
Time to reach maximum concentration 
WI-NRS 
Worst Itch – Numeric Rating Scale 
 
 
 


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3. 
BACKGROUND AND RATIONALE 
3.1. 
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. 
The Sponsor is developing topical roflumilast in several formulations (ARQ-151 cream and 
ARQ-154 foam) and indications.  To date, ARQ-151 cream has been evaluated in studies in 
psoriasis and atopic dermatitis.  Additionally, two PDE-4 inhibitors have been marketed for 
dermatologic indications in the US and elsewhere, including OTEZLA® as an oral therapy for 
moderate to severe plaque psoriasis in adults and EUCRISA® as a topical therapy for mild to 
moderate atopic dermatitis in individuals 2 years of age and older.   
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.  It may be associated with certain medications and conditions 
such as Parkinson’s disease and other neurologic conditions, Down syndrome, and HIV 
infection.  Seborrheic dermatitis is generally a clinical diagnosis.  The exact cause of seborrheic 
dermatitis remains unknown.  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 
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. 






















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5. 
INVESTIGATIONAL PLAN 
5.1. 
Overall Study Design and Plan 
This is an open-label, single-arm, long-term safety study of ARQ-154 foam 0.3% in subjects 
with seborrheic dermatitis involving up to 20% total BSA. Cohort 1 eligible subjects will enroll 
into the long-term safety study on the same day as the final visit for a previous ARQ-154 study. 
For Cohort 1, subjects will be male and female adolescents (9-17 y/o) and adults (>18 y/o) with 
seborrheic dermatitis. Cohort 1 Group 1 will be subjects who rolled over from the prior 
ARQ-154-203 study and Cohort 1 Group 2 will be subjects who rolled over from the prior 
ARQ-154-116 study.  
Cohort 2 eligible subjects will enroll on Day 1 of this study.  For Cohort 2, subjects will be male 
and female adolescents (12 – 17 y/o) and adults (>18 y/o) subjects who may or may not have 
participated in a prior ARQ-154 study, i.e., either de novo subjects who did not participate in 
ARQ-154-203 or subjects who completed ARQ-154-203 prior to initiation of the current study, 
ARQ-154-214. 
For each Cohort, investigational product will be applied by the qualifying subjects topically QD 
for up to 52 weeks. Periodic clinic visits will include assessments for clinical safety, application 
site reactions evaluated in the clinic using the method of Berger and Bowman, and disease 
improvement or progression. 
Final analysis will be performed when subjects in Cohort 1 Group 1 and Cohort 2 
(approximately 400 subjects) finish up to 52 weeks.    
Subjects in Cohort 1 Group 2 (approximately 10 subjects) will only be summarized in the listings 
and will be updated once all Group 2 subjects finish up to 52 weeks of treatment. A CSR 
addendum will be provided based on the updated Cohort 1 Group 2 listing.    
5.2. 
Number of Sites and Subjects 
A total of up to approximately 410 subjects total across both Cohorts will be enrolled at 
approximately 40 study sites in North America.  Additional countries or study sites may be 
added as necessary. Subjects in Cohort 1 will be male and female adolescents (9-17 y/o) and 
adults (>18 y/o) with seborrheic dermatitis. Subjects in Cohort 2 will be adolescent and adult 
males or females with seborrheic dermatitis that may or may not have participated in a prior 
ARQ-154 study.  Subjects in Cohort 2 that have not participated in a prior ARQ-154 study 
(i.e., de novo subjects) must have an IGA of disease severity of at least Moderate (‘3’) at 
Baseline.  Subjects that completed a prior ARQ-154 study prior to initiation of the current 
ARQ-154-214 study may be eligible to enroll in Cohort 2 of the present study, and these subjects 
may have any IGA at Day 1 of the present study.  All subjects in each Cohort must have no more 
than 20% Body Surface Area (BSA) of seborrheic dermatitis.  All lesions on a subject will be 
treated including the scalp, face, trunk, and intertriginous areas.     


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5.3. 
Subject Participation 
Subject participation involves a minimum of 5 clinic visits at Week 4, Week 12, Week 24, 
Week 36 and Week 52 and phone visits at Week 18, Week 30 and Week 44. The Day 1 visit of 
this study will be the final visit of a preceding ARQ-154 study for Cohort 1 and Day 1 of this 
study for Cohort 2. The anticipated duration of subject participation up to approximately 
52 weeks.  
5.3.1. 
Numbering of Subjects 
Cohort 1 subjects enrolled may retain their unique five-digit subject ID number previously 
assigned during the prior ARQ-154 study or may be assigned a unique ID. Cohort 2 subjects will 
be numbered with the 2-digit site number and a three-digit subject number starting with 500. 
The clinical site is responsible for maintaining a current log of subject ID number assignments 
and the investigational product kit numbers assigned to that subject and entering into the IRT 
system.  The subject ID number 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.).  
5.4. 
Selection of Study Population 
5.4.1. 
Inclusion Criteria 
All Subjects 
Subjects must fulfill all of the following inclusion criteria to be eligible for participation in the 
study: 
1. Participants legally competent to sign and give informed consent or (for adolescents) 
assent. 
2. Males and females ages 9 years and older (inclusive) at the time of consent. 
3. Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at 
all study visits. In addition, sexually active FOCBP must agree to use at least one form of 
an acceptable effective contraception throughout the trial.  Acceptable effective forms of 
contraception may include: oral/implant/injectable/transdermal contraceptives, 
intrauterine device, or partner’s vasectomy.  If barrier methods are used (e.g., condom 
with spermicide, diaphragm with spermicide), then 2 forms of contraception are required. 
The use of abstinence as a contraceptive measure is acceptable as long as this is a 
consistent part of a lifestyle choice and a backup method has been identified if the subject 
becomes sexually active. 
4. Female of non-childbearing potential must be either pre-menarchal or post-menopausal 
women with spontaneous amenorrhea for at least 12 months or have undergone surgical 
sterilization (permanent sterilization methods include hysterectomy, bilateral 
oophorectomy, hysteroscopic sterilization, bilateral tubal ligation or bilateral 
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6. Known or suspected:  
 severe renal insufficiency, or moderate to severe hepatic disorders (Child-Pugh B or 
C) 
 history of severe depression, suicidal ideation or C-SSRS (for adolescents and adults 
12 years old and older) indicative of suicidal ideation, whether lifetime or 
recent/current 
7. Females who are pregnant, wishing to become pregnant during the study, or are 
breast-feeding. 
8. Subjects with any serious medical condition or laboratory abnormality that would prevent 
study participation or place the subject at significant risk, as determined by the 
Investigator. 
9. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of 
investigational product. 
10. Current or a history of cancer within 5 years with the exception of fully treated skin basal 
cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. 
11. Subjects who are unable to communicate, read or understand the local language, or who 
display another condition, which in the Investigator’s opinion, makes them unsuitable for 
clinical study participation. 
12. Subjects who are family members of the clinical study site, clinical study staff, or 
Sponsor. 
Cohort 1 Only 
13. Subjects who experienced an ARQ-154 treatment-related AE or a serious AE (SAE) that 
precluded further treatment with ARQ-154 foam in a prior ARQ-154 study. 
14. Subjects that use any Excluded Medications and Treatments (Table 1). 
17. Previous participation in this ARQ-154-214 study. 
Cohort 2 Only 
15. Subjects who cannot discontinue treatment with therapies for the treatment of seborrheic 
dermatitis prior to the Day 1 visit and during the study according to Excluded 
medications and Treatment (Table 1). 
16. Subjects with PHQ-8 >10 or modified PHQ-A >10 at Screening or Day 1. 
For subjects that have completed a prior ARQ-154 study prior to initiation of the current 
ARQ-154-214 study: 
18. Subjects who experienced an ARQ-154 treatment-related AE or a serious AE (SAE) that 
precluded further treatment with ARQ-154 foam. 


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5.4.3. 
Removal of Subjects from Investigational Product 
A subject may discontinue from receiving the investigational product 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 investigational product administration as per the 
protocol. 
• Occurrence of a treatment-emergent adverse event (TEAE) or considerable worsening 
of an AE 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. 
• Pregnancy. 
• Subject's decision to withdraw from administration of the investigational product. 
• Weight loss of >5% from Baseline if not dieting or intentionally trying to lose weight 
and after consultation with the Sponsor, at the Investigator’s discretion. 
• C-SSRS indicative of suicidal ideation. 
• PHQ-8 or modified 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 (see Table 1) after 
consultation with the Sponsor and Medical Monitor. 
• Subject’s repeated failure to comply with protocol requirements or study related 
procedures. 
5.4.4. 
Removal of Subjects from the Study 
A subject may be removed from study participation for any of the following reasons: 
• Subject death 
• Subject’s decision to withdraw from the study. 
• 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. 


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5.5. 
Study Restrictions 
5.5.1. 
Prohibitions and Concomitant Therapy 
Prohibited medications and products are detailed in Table 1.   
Table 1: 
Excluded Medications and Treatments 
Excluded Medications and Treatments 
Wash Out Period Prior to Day 1 
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 
4 weeks 
Strong systemic P-450 cytochrome inhibitors  
(e.g. indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, 
ketoconazole, nefazodone, saquinavir, suboxone and telithromycin) 
2 weeks 
Phototherapy, tanning beds, other light emitting devices  
4 weeks  
Investigational drugs (other than ARQ-154) 
12 weeks (biologics) or 5 half-lives, 
whichever is longer; 
5 half-lives (orals);  
2 weeks (topical) 
Note:  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. 
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. 
Generally, the addition of new medications, including nonprescription medications, during the 
course of 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 ‘Exclusions’ (Table 1).  


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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.   
5.6. 
Treatment 
5.6.1. 
IP Supplies, Packaging and Labeling 
ARQ-154 foam 0.3% will be provided in a dispense Can containing approximately 60 grams of 
foam.  The Cans will be packaged in Kits. The number of Kits dispensed to a subject will be 
based on the BSA involvement. The Kit(s) and Cans will be labeled including a location to 
record the subject ID on the label.  
The Sponsor will supply sufficient quantities of the investigational product (ARQ-154 foam 
0.3%) 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 foam. 
5.6.2. 
Blinding 
This is an open-label study and no blinding is planned. 
5.6.3. 
Treatment Administration 
Seborrheic dermatitis lesions that have completely resolved, in the opinion of the Investigator, do 
not require continued treatment. At every clinic visit the Investigator will determine if the IGA 
are considered ‘clear’ and the subject will stop applying the investigational product. The subject 
will contact the clinical study site and document in diary when seborrheic dermatitis returns prior 
to restarting investigational product. Subjects that clear between scheduled visits should return 
for an unscheduled visit for the Investigator to confirm IGA score are considered ‘clear’.  
Unless otherwise instructed by the Investigator, subjects will apply investigational product once 
daily.  At the Day 1 visit, the study staff will demonstrate to the subject how to apply ARQ-154 
foam using the first Can from the Kit that is provided to the subject at Day 1.  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 layer and rubbed in thoroughly but gently, until the foam 
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. Cohort 1 Group 2 subjects will apply the last dose of IP for ARQ-154-116 Week 2 
(Day 15) study visit; subjects will enroll in ARQ-154-214 on the same day but will start applying 
IP the following day (Day 2). The study staff will review with the subject the appropriate IP 


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dispensing and application technique for the ARQ-154-214 study during the Baseline visit 
(Day 1).   
IP will be applied in the evening to areas of lesions of seborrheic dermatitis.  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 actually 
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.   
Re-training will be conducted at subsequent visits as needed (i.e., if the returned Can(s) weighs 
substantially different than the expected weight). 
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 investigational product to all active seborrheic dermatitis 
lesions including any new lesions that develop during the study unless otherwise instructed by 
the Investigator. Application will be to all areas affected including the face, scalp 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. 
Each IP Can will be weighed prior to dispensing at the Day 1 visit or subsequent visits. IP Cans 
must be returned by subjects at each study visit, both empty and full, and will be weighed 
individually. If the subject’s actual use is substantially different than the expected use for the 
subject’s BSA (see IP Handling Manual), the subject will be retrained on the IP application 
technique. 
5.6.4. 
Treatment Compliance 
Weight of the IP applied will be measured for reporting purposes. Each IP Can will be weighed 
individually at each follow-up clinic visit and recorded in the source notes and in the eCRF. 
Subjects will complete a daily diary recording the date and time of each dose applied, any missed 
doses, and a comment section should the subjects have a comment, e.g., record potential Adverse 
Events (AEs). Site personnel will review the diaries at each clinic visit and use the information to 
question the subject regarding compliance and AEs and then record appropriate information in 
source documents and complete Case Report Forms (CRFs).  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 IP application period and does not miss more than 
3 consecutive doses.  


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Compliance will be assessed by review of the dosing diary. If the diary shows less than 80% of 
expected use, the subject is using too little IP and retraining must be conducted and documented.  
Compliance will be documented in source and in eCRF. 
6. 
STUDY PROCEDURES 
6.1. 
Safety Assessments 
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. 
This study assesses the safety and efficacy of ARQ-154 foam. Safety will be determined by 
evaluating physical examinations, local tolerability assessments, vital signs/weight, 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. 
Screening Visit (Cohort 2) 
Within 35 days prior to the first dosing (Day 1), subjects will be provided details of study 
requirements and sign an informed consent.  Medical history and demographic data including 
sex, age, race, ethnicity, body weight (kg), and height (cm) will be recorded.  Each subject will 
undergo seborrheic dermatitis assessments, a physical examination, vital sign measurements 
(blood pressure, heart rate, and temperature), PHQ-8/PHQ-A, C-SSRS, and laboratory tests: 
hematology, chemistry, urinalysis and serum pregnancy tests for female subjects of childbearing 
potential. 
All screened subjects will receive a screening number according to Section 5.3.1 and be entered 
into the IRT system and eCRF. Subjects that fail to meet the eligibility criteria will be designated 
as a screen failure and entered into the IWRS and eCRF as such. 
Subjects may be re-screened one time, the original assigned Subject ID screening number will be 
used for re-screening. 
Day 1 Visit 
For Cohort 1, at Day 1 (Final visit of the prior ARQ-154 study) subjects will be provided details 
of study requirements and sign an informed consent.  Each subject will undergo seborrheic 
dermatitis assessments, a physical examination, vital sign measurements (blood pressure, heart 
rate, and temperature), PHQ-8/PHQ-A/CDI-2, C-SSRS, and laboratory tests: hematology, 
chemistry, urinalysis and urine pregnancy tests for female subjects of child bearing potential will 
be obtained at the final visit of the prior ARQ-154 study and will serve as Day 1 for Cohort 1 
subjects. Cohort 2 Day 1 assessments for this long-term safety study (ARQ-154-214) will be 
completed within 35 days of Screening. 


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For Cohort 2, if the Day 1 visit occurs within 14 days of Screening, the Screening lab results may 
be utilized. Cohort 2 subjects must meet the required wash out period for any excluded 
medications and treatment according to Table 1.  
IP will be dispensed at the Day 1 visit (via IWRS) after the Investigator confirms the subject to 
be fully eligible for participation based on the study criteria listed in Section 5.4.1 and 
Section 5.4.2. A subject is considered enrolled into the study upon the first IP application.  
6.1.1. 
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, lungs and heart only. 
6.1.2. 
Vital Signs, Height and Weight 
Vital signs will be collected according to the Schedule of Visits and Assessments (Section 1.3): 
Blood pressure, heart rate, and temperature will be measured. Blood pressure will be collected 
while the subject is sitting/resting for at least 5 minutes. 
Height will be collected at Day 1, Week 24 and end of study Week 52/Early Termination.  
Subject to void prior to weight being taken and remove any jackets, outerwear and shoes. 
Remove any objects of significant weight (i.e. cell phones, wallet, key chains). A 5% 
unintentional weight loss from Baseline should be reported to the medical monitor.  
6.1.3. 
Laboratory Tests 
All tests listed in Table 2 below will be performed according to the Schedule of Visits and 
Assessments (Section 1.3), unless otherwise noted. No food restrictions are required for the 
collection of specimens. In addition, laboratory safety tests may be performed at various 
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, ship, 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  


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Table 2: 
Laboratory Tests (Continued) 
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)** 
• 
Pharmacokinetic (PK) assessments 
• 
Malassezia Test*** 
* 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 only 
*** Samples collected for Cohort 1 Group 2 subjects only and may be used for Malassezia testing. 
6.1.4. 
Patient Health Questionnaire depression scale (PHQ-8) 
The 8 item PHQ-8 Assessment (see Appendix 1) will be completed by adult subjects according 
to the Schedule of Visits and Assessments (Section 1.3).  
A subject with a PHQ-8 score of ‘15’ or above should be referred promptly to a mental health 
care professional and, if currently applying investigational product, consideration should be 
given to discontinuation from investigational product.   
Subjects with PHQ-8 >10 at Screening (Cohort 2 only) or Day 1 will be excluded from the study. 
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) 
6.1.5. 
Patient Health Questionnaire depression scale (Modified PHQ-A) 
The 8 item Modified PHQ-A Assessment (see Appendix 2 will be completed by adolescent 
subjects (12-17 years old, inclusive) according to the Schedule of Visits and Assessments 
(Section 1.3).  


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A subject with a PHQ-A score of 15 or above should be referred promptly to a mental health care 
professional and, if currently applying IP, consideration be given to discontinuation from 
investigational product.   
Subjects with PHQ-A >10 at Screening (Cohort 2 adolescents only) or Day 1 will be excluded 
from the study. 
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) 
6.1.6. 
Children’s Depression Inventory 2 
The CDI-2 Assessment will be performed according to the Schedule of Visits and Assessments 
(Section 1.3) for subjects 9 to 11 years old, inclusive. 
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 Report Form is 
presented in Appendix 6.  
A subject with a CDI-2 raw score of > 21 for females and > 22 for males should be referred to a 
mental health professional. 
A subject with a CDI-2 raw score of > 32 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. 
6.1.7. 
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. 
On all visits, the Since Last Visit version (Appendix 4) will be used for Cohort 1. Cohort 2 will 
use the Baseline-Screening version (Appendix 3) for Screening and Since Last Visit version 
(Appendix 4) for Day 1 and all remaining visits.   
If a subject has a score greater than 0 in suicidal ideation at Screening (Cohort 2 only) or Day 1, 
this is important and may indicate the need for mental health intervention. The investigator 
should not enroll the subject in the study. 


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Any score greater than 0 in the suicidal ideation score is important and may indicate the need for 
mental health intervention and consideration be given to discontinuation from IP. This should 
result in prompt referral to a mental health professional and/or possibly the emergency room. 
The Medical Monitor should be contacted.  
The trained administrator will conduct the C-SSRS.  The C-SSRS administrator will be trained 
via the C-SSRS training video. A training certificate for the administer(s) will be on file in the 
trial master file at the site. 
An 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. 
6.1.8. 
Local Tolerability Assessments 
The Investigator Local Tolerability Assessment will be an overall assessment of local 
tolerability. 
Application site reactions will be graded at the timepoints outlined in the Schedule of Visits and 
Assessments (Section 1.3).  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.   
The Investigator assessments will be conducted by the Investigator prior to any investigational 
product application in the study site.  
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 edema 
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 an overall assessment of local tolerability and 
performed at the timepoints outlined in the Schedule of Visits and Assessments (Section 1.3). 


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This assessment will be administered on Day 1 at the site 10 to 15 minutes after IP application at 
the study site. Assessments at the study site during Weeks 4, 12, 24, 36 and 52 will be a recall 
assessment of the subject’s experience 10-15 minutes after IP application since the last study 
visit.  
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  
6.1.9. 
Pigmentation Assessment 
The Investigator will assess for pigmentation in areas affected previously and/or currently by 
seborrheic dermatitis at the timepoints outlined in 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. 
6.1.10. 
Adverse Events 
Adverse events (AEs) will be collected beginning at informed consent and assessed at the 
following visits and throughout the study according to the Schedule of Visits and Assessments 
(Section 1.3). 
AE collection will end upon completion of study participation for subjects who complete or early 
terminate from the study without any new or ongoing AEs. Subjects with new or ongoing related 
AEs upon study completion or early termination will be followed for up to one month after the 
end of treatment until the symptoms or clinically significant abnormal laboratory test value(s) 
return to normal or acceptable levels, as judged by the Investigator. 
Treatment emergent AEs will be followed in the clinic for up to one month at the Investigator’s 
discretion until resolved or otherwise judged as clinically stable. 
Refer to Section 6.6 for further details on Adverse Events. 
6.1.11. 
Phone Visits 
Phone visits at Weeks 18, 30 and 44 will be conducted for all subjects to review any adverse 
event or concomitant medication changes. 
6.1.12. 
Pharmacokinetic Assessment 
An optional pharmacokinetic sample will be collected during the Week 4 visit for Cohort 2 
subjects between 12 – 16 years of age. Adolescent subjects must give assent and the parent/legal 
guardian give consent for the PK collection. Collect the PK sample while the subject is having 
safety laboratory samples drawn. Ensure the PK sample is not drawn on the area where IP is 
applied.   




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Overall Assessment of Erythema 
Symptom 
Score 
Description 
Erythema 
0 
None:
 
1 
Mild:
 
2 
Moderate:
 
3 
Severe: 
 
6.2.3. 
Overall Assessment of Scaling 
Overall Assessment of Scaling will be performed at the timepoints outlined in 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. 
Overall Assessment of Scaling 
Symptom 
Score 
Description 
Scaling 
0 
None:
 
1 
Mild:
 
2 
Moderate: 
  
3 
Severe: 
 
6.2.4. 
Body Surface Area (BSA) 
BSA Assessments will be performed at the timepoints outlined in 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 (BSA).   
6.2.5. 
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 Assessments will be performed at the timepoints outlined in the Schedule of Visits and 
Assessments (Section 1.3). 


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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”). Subjects will 
complete the WI-NRS pruritus assessment. 
 
6.2.6. 
Scalpdex 
The Scalpdex will be completed at the timepoints outlined in the Schedule of Visits and 
Assessments (Section 1.3). 
Subjects will complete the Scalpdex. See Appendix 5 for the Scalpdex. 
6.2.7. 
Dermal Imaging 
Medical photography will be performed at selected sites at Day 1, Weeks 4, 12, 24, 36 and 52 
using Canfield photography equipment. Photography should be focused on single lesions or 
specific body sections (e.g. forehead). Body or half body photos should only be taken if 
necessary. 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. 
6.3. 
Final Study Visit 
The approximate final study visit will occur at the end of Week 52 of overall involvement in the 
study. The procedures performed during this visit is described in the Schedule of Visits and 
Assessments (Section 1.3). A 7-day scheduling window is allowed for this visit. Adverse events 
will be recorded as reported by the subject or followed to resolution as outlined in Section 6.6.5. 
6.4. 
Early Termination Visit 
If a subject is withdrawn from the study, a termination visit will be scheduled. This visit should 
include the procedures and assessments that would be performed at the Week 52 visit. It will be 
noted in the database which subjects have completed the study and which were early 
terminations. 
6.5. 
Unscheduled Visit 
Subjects that clear between scheduled visits should return for an unscheduled visit for the 
Investigator to confirm IGA score are considered ‘clear’ and subject will stop application of 
investigational product after Investigator confirmation. Subjects will call the site when 
seborrheic dermatitis returns prior to restarting application of investigational product. 
Unscheduled visits may also be necessary to repeat testing following abnormal laboratory 


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results, for follow-up of AEs, or for any other reason, as warranted in the judgment of the 
Investigator.  
The following information will be collected for all subjects: 
• AEs 
• Concomitant medications/procedures 
The following information will be collected for those subjects that had stopped study medication 
but are experiencing a reoccurrence of seborrheic dermatitis. These subjects may have an 
unscheduled visit (although an unscheduled visit is not required as subjects only need to call the 
site) when seborrheic dermatitis returns prior to restarting application of investigational product: 
• IGA 
An updated Body Diagram of seborrheic dermatitis involvement should be provided to the 
subject. 
6.6. 
Adverse Events 
6.6.1. 
Adverse Event Definition 
An AE means 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 a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.  
AEs will be collected following informed consent of the subject through subject study 
completion.  
A treatment emergent adverse event (TEAE) is defined as an AE that started post application of 
IP at the Day 1 visit through study completion.  
Application site reactions will be considered adverse events if they require intervention, 
suspension or discontinuation of IP.  
6.6.2. 
Serious Adverse Event 
The definitions and reporting requirements of Health Canada/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. If any AEs are serious, as defined by 
ICH Guidelines for Clinical Safety, required procedures will be followed.  
All SAEs will be reported to the Sponsor via fax or e-mail within 24 hours of becoming aware of 
the event, whether or not the SAEs are deemed drug-related. refer to the Safety Reporting 
Instructions for details on how to submit the SAE Report. 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 IRB will be notified of 
the Alert Reports as per FDA, ICH and the IRB’s policies and procedures. 


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An SAE is any AE that in the view of either the PI or Sponsor, results in any of the following 
outcomes:  Death, a life-threatening AE, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect.  Important medical events 
that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes listed in the above 
definition. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.  
Life-threatening is defined as an AE that in the view of the PI or Sponsor, places the subject at 
immediate risk of death. It does not include an AE that, had it occurred in a more severe form, 
might have caused death. 
Hospitalization does not include the following: 
• Rehabilitation facilities, hospice facilities or respite care (e.g. caregiver relief) 
• Nursing homes or skilled nursing facilities 
• Emergency room 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 Day 1 
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 elsewhere in the current IND/CTA. 
If a SAE occurs to a subject on this study, contact the Medical Monitor within one business day 
of knowledge of event.  


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6.6.3. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
This 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.  
6.6.4. 
Safety Review 
At each follow-up 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.   
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s) 
will be evaluated by the Investigator and treated and/or followed up for up to one month after 
end of treatment until the symptoms or value(s) return to normal, 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). Outcome may be classified. 
6.6.5. 
Adverse Event Reporting 
The Investigator will review each event and assess its relationship to drug treatment (unrelated, 
unlikely, possibly, probably, likely). Each sign or symptom reported will be graded on the most 
current version of 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 IP will be assessed using the following definitions: 
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. 


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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 
(e.g., 21.0 or higher). 
6.7. 
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 the conclusion of the pregnancy.   
The Investigator is responsible for reporting all available pregnancy information on the 
pregnancy report and submitting to the Medical Monitor 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. Any infant death that occurs after the 30-day reporting period that the 
Investigator suspects is related to the Investigational Product must also be reported as a SAE.    
Partner pregnancies of a male subject do not need to be reported. 
6.8. 
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 IP, 
the Investigator should immediately contact the Medical Monitor to discuss if the subject should 
be discontinued from the investigational product.   


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Treatment for any individual subject will be discontinued if the subject:  
• Experiences a serious adverse event (SAE) or a clinically significant non-serious AE 
which in the opinion of the Principal Investigator or Medical Monitor warrants 
discontinuation from the IP for that subject’s well-being. 
• A severe (Grade 3) laboratory abnormality (confirmed by repeat sample and 
considered related to IP).  
Dosing of IP for an individual subject may be suspended for safety concerns other than those 
described above, at the discretion of the Investigator if he/she feels the subject’s safety may be 
threatened. 
A subject with a PHQ-8 or modified PHQ-A score of 15 or above should be referred promptly to 
a mental health care professional and consideration be given to discontinuation from IP.   
A subject with a CDI-2 raw total score of 32 or above should be referred to a mental health 
professional, and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the IP.  
• Subjects with a CDI-2 raw score of 21 or above in females and 22 or above in males 
should be referred to a mental health professional for evaluation 
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, study treatment must be discontinued immediately in the event of a female 
subject’s pregnancy.   
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.   
Treatment should be discontinued: 
• If the reaction reoccurs, treatment should be discontinued permanently, and the 
subject followed until the reaction resolves.  Given the excellent local toleration in the 
Phase 1/2a study, such reactions are possible, but unlikely. 


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7. 
DATA ANALYSIS 
Data will be handled and processed according to the Contract Research Organization’s Standard 
Operating Procedures, which are written based on the principles of GCP. 
7.1. 
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 safety and efficacy 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, Q1, Q3, minimum, and maximum. 
No missing efficacy or safety data will be imputed unless specified otherwise. The observed 
values will be used in the analysis.  
The final analysis will be conducted after all treated subjects in Cohort 1 Group 1 and Cohort 2 
have had the opportunity to be followed to the Week 52 assessment. Once all treated subjects in 
Cohort 1 Group 2 have had the opportunity to be followed to the Week 52 assessment, listings 
for these subjects will be provided for the CSR addendum.  
7.1.1. 
Baseline Definition 
For subjects in Cohort 1, the baseline value for safety and efficacy parameters will be defined as 
the last observation prior to the first dose of ARQ-154 foam 0.3% in either the prior ARQ-154 
study or this study (See Section 7.2.1 for the definition of a treatment emergent event).  
Additional analyses will be performed where in the baseline value for subjects in Cohort 1 is 
defined as the last observation prior to the first dose of ARQ-154 foam 0.3% in this study.  For 
the purpose of these latter analyses, study procedures will not be repeated; the information from 
the prior ARQ-154 study final visit will be carried over to the Day 1 visit for this study.   
For subjects in Cohort 2, baseline values for efficacy and safety will be defined as the last 
observation prior to the first dose of ARQ-154 foam 0.3% in this study. 
7.1.2. 
Determination of Sample Size 
A sample size of up to approximately 410 subjects is planned for the study. This sample size will 
provide a sufficient population size to evaluate the long-term safety of ARQ-154 foam 0.3% over 
52 weeks of treatment, and in the combination with other studies provide the development 
program with sufficient numbers of subjects to meet ICH exposure goals. 


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7.1.3. 
Subjects to Analyze 
All analyses will be performed using the Safety Population which includes all subjects who are 
enrolled and received at least one confirmed dose of ARQ-154 foam 0.3% in this safety study. 
The number of subjects included in the Safety Population will be summarized. 
Subjects in Cohort 1 Group 2 will be summarized in listings only.  
7.1.4. 
Interim Analysis 
No interim analysis will be performed. 
7.1.5. 
Background and Demographic Characteristics 
Baseline disease characteristics and vital sign information will be summarized descriptively for 
all enrolled subjects.  
7.1.6. 
Study Disposition 
Number of subjects enrolled, receiving investigational product, completing study, and 
withdrawing prematurely (with reason for withdrawal) will be summarized. 
7.1.7. 
Protocol Deviations and Eligibility Deviations 
The number of subjects with important protocol deviations and/or eligibility deviations will be 
summarized.   
7.1.8. 
Investigational Product Compliance 
The number of investigational product applications by each subject will be summarized using 
descriptive statistics.  
The amount of investigational product used by each subject based on Can weight will be 
summarized using descriptive statistics.   
Investigational product compliance will be calculated based on number of applications and 
amount of IP used divided by the expected number (amount) of study medication for each 
subject.  Compliance will be summarized descriptively. 
7.2. 
Safety Evaluation 
Descriptive statistics will be calculated for safety data and presented by scheduled study visit for 
quantitative safety data and frequency counts will be compiled for classification of qualitative 
safety data. Summaries of local tolerability will be presented by scheduled study visit. 
7.2.1. 
Adverse Events 
All treatment-emergent AEs occurring during the study will be recorded and classified on the 
basis of MedDRA terminology for the safety population. Treatment-emergent AEs are those AEs 
with an onset on or after the first date of study treatment in this study. All treatment-emergent 
AEs will be summarized by treatment group, the number of subjects reporting treatment-
emergent AEs, system organ class, preferred term, severity, relationship, and seriousness. 


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Serious adverse events (SAEs) will be listed by subject. SAEs will be summarized by treatment 
group, severity, and relationship to study treatment.  
For AEs, each subject will be counted only once within a system organ class or a preferred term 
using the event with the greatest relationship and greatest severity. 
All information pertaining to AEs noted during the study will be listed by subject, detailing the 
verbatim description given by the Investigator, preferred term, system organ class, start date, 
stop date, severity, action taken regarding IP, corrective treatment, outcome, and drug 
relatedness. The event onset will also be shown relative (in number of days) to date of first 
application. In addition, a listing of subjects who prematurely discontinue from the IP due to 
adverse events will also be provided. 
7.2.2. 
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.   
7.2.3. 
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. 
7.2.4. 
PHQ-8 and Modified PHQ-A 
Data for PHQ-8 and Modified PHQ-A will be analyzed by a shift in state of severity using the 
following scoring system: 
• 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) 
7.2.5. 
C-SSRS 
The C-SSRS will be analyzed per the Columbia–Suicide Severity Rating Scale Scoring and Data 
Analysis Guide. 
7.2.6. 
Clinical Laboratory Results and Vital Signs/Weight Measurements 
All clinical laboratory results and vital signs measurements and their change from baseline and 
percent change from Baseline, will be summarized by treatment group along with time point of 
collection. 
A shift table summarizing out-of-normal range shifts from baseline by treatment group will be 
provided for clinical laboratory results.  


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Shift tables (from baseline) by treatment group will summarize the number of subjects who gain 
or lose >5% body weight over the course of the study, as well as subjects who gain or lose >10% 
body weight over the course of the study. 
7.2.7. 
Prior and Concomitant Medications 
Prior and concomitant medication information for all randomized subjects will be presented in a 
by-subject listing.  Summary tables by treatment group will be presented by World Health 
Organization-Anatomical Therapeutic Chemical Classification System (WHO-ATC) therapeutic 
category and product. 
7.3. 
Patient Reported Outcomes Analyses 
7.3.1. 
WI-NRS 
Change from baseline and percent change from baseline in itch severity will be analyzed by 
treatment group and over time using the WI-NRS scale.  For subjects with WI-NRS pruritus 
score ≥ 4 at baseline, the proportion of subjects with a 4-point reduction in WI-NRS pruritus 
score at Weeks 4, 12, and 24 as compared to baseline will be calculated by treatment group and 
analyzed using a Cochran-Mantel-Haenszel test stratified by study site and baseline disease 
severity (see Section 4.2.2, Secondary Endpoints). 
7.3.2. 
Scalpdex 
The Scalpdex will be analyzed as change from Day 1 in total score as assessed at Weeks 4, 12, 
and 24 using an analysis of covariance with treatment, baseline score, and the stratification 
factors as independent variables.  
7.4. 
Efficacy Endpoints 
7.4.1. 
Achievement of IGA ‘Completely Clear’ or ‘Almost Clear’ 
The subject incidence of an IGA Assessment will be tabulated for each assessment.   
7.4.2. 
Achievement of IGA ‘Completely Clear’ or ‘Almost Clear’ plus a 2-grade 
Improvement from Baseline  
The subject incidence of IGA of ‘Completely Clear’ or ‘Almost Clear’ plus a 2-grade 
improvement from Baseline will be tabulated for each assessment 
7.4.3. 
Achievement of a 2-grade improvement in IGA from Baseline  
The subject incidence of a 2-grade improvement in IGA from Baseline will be tabulated for each 
assessment. 
7.4.4. 
Duration of IGA Success 
Duration of IGA Success will be analyzed with the Kaplan-Meier method.    The rate of subjects 
remaining in IGA Success over time will be summarized descriptively. 


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7.4.5. 
Treatment-free Interval 
The time to re-starting IP will be analyzed with the Kaplan-Meier method.  The rate of subjects 
remaining off treatment over time will be summarized descriptively. 
7.4.6. 
Pharmacokinetic Analysis 
For Cohort 2 adolescent subjects, blood samples for the determination of roflumilast and its 
N-oxide metabolite will be collected as delineated in the Schedule of Visits and Assessments 
(Section 1.3). Plasma drug concentrations at Week 4 will be summarized using descriptive 
statistics. 
8. 
STUDY ADMINISTRATION 
8.1. 
Ethics 
8.1.1. 
Ethics Review Board 
Before enrollment 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 or 
IEC, as required by FDA (21 CFR § 56), Health Canada, and ICH GCP regulations.  A letter 
documenting the IRB or IEC 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 or IEC. However, the frequency of these reports will depend on IRB or IEC requirements. 
As soon as possible after completion or termination of the study, the Investigator will submit a 
final report to the IRB or IEC per the IRB or IEC requirements, and in compliance with FDA and 
Health Canada regulations and ICH GCP guidelines. 
The Investigator, the Sponsor, or designee shall promptly notify the IRB or IEC of any SAEs, 
SUSARs, or any other information that may affect the safe use of the IP during the study, per the 
IRB or IEC local requirements, and in compliance with FDA and Health Canada regulations and 
ICH GCP guidelines. 
8.1.2. 
Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, the principles of the 
Tri-Council Policy Statement (TCPS), the ethical principles set forth in the Declaration of 
Helsinki, and the ICH harmonized tripartite guideline regarding E6 (R2), December 2016. 
8.1.3. 
Subject Information and Consent 
The Investigator is responsible for obtaining written informed consent from each individual 
participating in this study and/or parent(s)/legal guardians, after adequate explanation 
(in non-technical terms) of the purpose of the study, the procedures to be carried out and the 
potential hazards before undertaking any study-related procedures. Subject and/or parent(s)/legal 
guardian(s) must provide their written informed consent prior to enrollment in a clinical trial and 


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before any protocol-specific procedures are performed. The Investigator must use the most 
current approved consent form for documenting written informed consent. Subjects and/or 
parent(s)/legal guardian(s) will be assured that they may withdraw from the study at any time 
without jeopardizing their medical care. Each informed consent will be read, appropriately 
signed and dated by the subject and/or parent(s)/legal guardian(s), the Investigator conducting 
the consent discussion, and by an impartial witness if required by local requirements.   
Adolescents will provide written assent and their parent(s) or legal guardian(s) will provide 
consent, as required by local laws. 
Subjects and/or parent(s)/legal guardian(s) will be given a signed copy of their Consent/Assent. 
8.2. 
Study Completion and Termination 
8.2.1. 
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. 
8.2.2. 
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 IP development 
8.3. 
Study Monitoring 
Prior to the initiation of the clinical investigation, Sponsor representatives or designees will 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 CRFs.  The Study Director or designees shall 
be available for consultation with the Investigator and serve as liaisons between the clinical site 
and the Sponsor. 


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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. 
8.4. 
Data Quality Assurance 
In order to ensure the collection of accurate, 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.   
The Clinical Study Report will be audited by the Premier Research’s Quality Assurance (QA) 
department and the QA audit certificate will be included in the study report. 
All clinical data will undergo a 100% quality control check prior to clinical database lock. Edit 
checks are then 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. 
8.5. 
Data Handling and Record Keeping 
During the clinical study, the Investigator will maintain adequate records, including medical 
records, records detailing the progress of the study for each subject, laboratory reports, signed 
informed consent forms, investigational product disposition records, correspondence with the 
IRB 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.   
8.6. 
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) will be 
promptly notified. 


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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, 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), 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 
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. 
8.7. 
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 Inc., including but not limited 
to the IB, this protocol, CRF/eCRF, the IP, and any other study information, remain the sole and 
exclusive property of Arcutis 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 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. 
8.8. 
Conflict of Interest 
All study investigators will provide documentation of their financial interest or arrangements 
with Arcutis Biotherapeutics Inc., or proprietary interests in the IP under study. This 
documentation must be provided prior to the Investigator’s participation in the study. 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. 
8.9. 
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).  


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8.10. 
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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9. 
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. 
Bethke TD, Lahu G. High absolute bioavailability of the new oral phosphodiesterase-4 inhibitor 
roflumilast.  Int. J Clin Pharmacol Ther. 2011;49:51-57. 
Borda LJ, Wikramanayake TC. Seborrheic Dermatitis and Dandruff: A Comprehensive Review. 
J Clin Investigat Dermatol. 2015;3(2):10. 
Cohen SR, Gordon SC, Lam AH, et al. Recalcitrant Seborrheic Dermatitis Successfully Treated 
with Apremilast. Journal of Cutaneous Medicine and Surgery. 2020;24(1):90-91.  
DALIRESP (roflumilast) tablets [package insert]. AstraZeneca Pharmaceuticals LP, Wilmington, 
DE USA, 2017. 
DAXAS (roflumilast) film-coated tablets [product monograph]. AstraZeneca Canada, Inc., 
Mississauga, Ontario Canada; 2017. 
Dessiniot C, Katsambas A. Seborrheic dermatitis: Etiology, risk factors, and treatments: 
Facts and controversies. Clinics in Dermatology. 2013;31:343-351.  
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 al. 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. 
Liu D, Chow P, Strawn S, et al. Chronic Nasolabial Fold Seborrheic Dermatitis Successfully 
Controlled with Crisaborole. Journal of Drugs in Dermatology. 2018;17(5):577-578. 
Michalski JM, Golden G, Ikari J, et al. PDE4: A Novel Target in the Treatment of Chronic 
Obstructive Pulmonary Disease. Clinical Pharmacology & Therapeutics. 2012;91:134-142. 
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. 
Wedzicha JA, Calverley PMA, Klaus FR.  Roflumilast: a review of its use in the treatment of 
COPD.  International Journal of Chronic Obstructive Pulmonary Disease. 2016;11:81-90. 
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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10. 
APPENDICES 
APPENDIX 1. PATIENT HEALTH QUESTIONNAIRE DEPRESSION 
SCALE (PHQ-8) 
 
 
 


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


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APPENDIX 3. COLUMBIA-SUICIDE SEVERITY RATING SCALE 
(C-SSRS) BASELINE/SCREENING VERSION 
 


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APPENDIX 4. COLUMBIA-SUICIDE SEVERITY RATING SCALE 
(C-SSRS) SINCE LAST VISIT VERSION 
 


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APPENDIX 5. SCALPDEX 
 
 
 


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APPENDIX 6. CHILDREN’S DEPRESSION INVENTORY 2 
(PARENT REPORT) 
 
 
 
 
 

SAP_001.pdf: 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |    Date 17-Feb-2022      |    AD-PR-109.02  Effective date: 17-Aug-2020 
 Page 1 of 38 
   Statistical Analysis Plan 
Sponsor 
Arcutis Biotherapeutics, Inc. 
Protocol Title: 
A Phase 2, Multicenter, Open-Label Study of the Long-Term 
Safety of ARQ-154 Foam 0.3% in Subjects with Seborrheic 
Dermatitis 
Protocol Number: 
ARQ-154-214 
Premier Research PCN: 
ARCU211880 
Document Version: 
Version 1.0 
Document Date: 
18-Feb-2022
Approvals 
Role 
Signatures 
Biostatistician 
Print Name:  
Sign Name: 
Peer Reviewer 
Print Name:  
Sign Name: 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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Role 
Signatures 
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-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 3 of 38 
Document History 
Not applicable. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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Table of Contents 
Contents 
Approvals ........................................................................................................................................ 1 
Document History ........................................................................................................................... 3 
Table of Contents ............................................................................................................................ 4 
List of Abbreviations ...................................................................................................................... 5 
1.
Overview ........................................................................................................................... 10 
2.
Study Objectives and Endpoints ....................................................................................... 10 
2.1. 
Study Objectives ......................................................................................................... 10 
2.1.1. Primary Objective ....................................................................................................... 10 
2.2. 
Study Endpoints .......................................................................................................... 11 
2.2.1. Efficacy Endpoints ...................................................................................................... 11 
2.2.2. Safety Endpoints ......................................................................................................... 12 
3.
Overall Study Design and Plan ......................................................................................... 12 
3.1. 
Overall Design ............................................................................................................ 12 
3.2. 
Sample Size and Power ............................................................................................... 13 
3.3. 
Study Population ......................................................................................................... 13 
3.4. 
Method of Assigning Treatment ................................................................................. 13 
3.5. 
Treatment Administeration ......................................................................................... 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 ......................................................................................................... 17 
6.
General Issues for Statistical Analysis .............................................................................. 17 
6.1. 
Statistical Definitions and Algorithms ........................................................................ 18 
6.1.1. Baseline ....................................................................................................................... 18 
6.1.2. Multiple Comparisons ................................................................................................. 19 
6.1.3. Handling of Dropouts or Missing Data ....................................................................... 19 
6.1.4. Analysis Visit Windows ............................................................................................. 19 
6.1.5. Pooling of Sites ........................................................................................................... 20 
6.1.6. Subgroup ..................................................................................................................... 21 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
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6.1.7. Derived Variables ....................................................................................................... 21 
6.1.8. Data Adjustments/Handling/Conventions .................................................................. 24 
6.2. 
Special Handling for COVID-19 Disruptions ............................................................. 26 
7.
Study Subjects and Demographics.................................................................................... 26 
7.1. 
Subject Disposition ..................................................................................................... 26 
7.2. 
Demographics and Baseline Characteristics ............................................................... 27 
7.3. 
Prior and Concomitant Medications ........................................................................... 27 
7.4. 
Surgical and Medical History ..................................................................................... 28 
7.5. 
Protocol Deviations ..................................................................................................... 28 
7.6. 
Exposure and Compliance .......................................................................................... 28 
8.
Efficacy Analysis .............................................................................................................. 29 
8.1. 
Primary Efficacy Analysis .......................................................................................... 30 
8.2. 
Secondary Efficacy Analysis ...................................................................................... 30 
8.2.1. Investigator Global Assessment (IGA) ....................................................................... 30 
8.3. 
Other Secondary Efficacy Analysis ............................................................................ 32 
9.
Safety and Tolerability Analysis ....................................................................................... 33 
9.1. 
Adverse Events ........................................................................................................... 33 
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 34 
9.1.2. Deaths and Serious Adverse Events ........................................................................... 34 
9.2. 
Local Tolerability Assessments .................................................................................. 34 
9.3. 
Clinical Laboratory Evaluations ................................................................................. 35 
9.4. 
Vital Signs ................................................................................................................... 35 
9.5. 
PHQ-8 ......................................................................................................................... 36 
9.6. 
CDI-2 .......................................................................................................................... 36
9.7. 
C-SSRS ....................................................................................................................... 36
9.8. 
Physical Examination.................................................................................................. 37 
9.9. 
Pigmentation Assessment ........................................................................................... 37 
10.
Changes from Planned Analysis ....................................................................................... 37 
11.
Other Planned Analysis..................................................................................................... 37 
11.1. Pharmacokinetic Analysis ........................................................................................... 37 
12.
References ......................................................................................................................... 37 
List of Abbreviations 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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Abbreviation 
Definition 
aCRF 
annotated case report form 
ADR 
adverse drug reactions 
AE 
adverse event 
AESI 
adverse events special interest 
ANCOVA 
analysis of covariance 
ASA 
American Statistical Association 
ATC 
anatomical therapeutic chemical 
BLQ 
below limit of quantification 
BMI 
body mass index 
BSA 
Body Surface Area 
CDI-2
Children’s Depression Inventory 2 
CI 
confidence interval 
CMH 
Cochran Mantel Haenszel 
COVID-19 
novel coronavirus disease 
CRF 
case report form 
CS 
clinically significant 
CSR 
clinical study report 
C-SSRS
Columbia Suicide Severity Rating Scale 
DBL 
database lock 
DBP 
diastolic blood pressure 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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Abbreviation 
Definition 
DLT 
dose limiting toxicity 
DMC 
data monitoring committee 
DOB 
date of birth 
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 
ICH 
International Conference on Harmonization 
IGA 
investigator global assessment 
IP 
investigational product 
IRB 
institutional review board 
IRR 
infusion related reactions 
IRT 
interactive response technology 
ITT 
intent-to-treat 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 8 of 38 
Abbreviation 
Definition 
LLOQ 
lower limit of quantification 
MedDRA 
medical dictionary for regulatory activities 
MI 
multiple imputation 
MMRM 
mixed model for repeated measurements 
MTD 
maximum tolerated dose 
NA 
not applicable 
NCS 
non-clinically significant 
OLE 
Open-Label 
PHQ-A 
Modified PHQ-8 for Adolescents 
PHQ-8 
Patient Health Questionnaire depression scale 
PK 
pharmacokinetic 
PKAP 
pharmacokinetic analysis plan 
PP 
per-protocol 
PT 
preferred term 
RR 
respiratory rate or relative rate 
RSS 
Royal Statistical Society 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
Statistical Analysis System 
SBP 
systolic blood pressure 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 9 of 38 
Abbreviation 
Definition 
SD 
standard deviation 
SE 
standard error 
SOC 
system organ class 
SOP 
standard operating procedure 
SUSAR 
suspected, unexpected, serious adverse (drug) reaction 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TLF 
Tables, Listings and Figures 
WHO-DD 
world health organization drug dictionary 
WI-NRS 
worst itch – numeric rating scale 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 10 of 38 
1.
Overview
This statistical analysis plan (SAP) describes the planned analysis and reporting for Arcutis 
Biotherapeutics, Inc. protocol number ARQ-154-214 (A Phase 2, Multicenter, Open-Label Study 
of the Long-Term Safety of ARQ-154 Foam 0.3% in Subjects with Seborrheic Dermatitis), dated 
04-Nov-2021 Amendment 2. 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. 
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 
inferential or descriptive analysis of data pertaining to Arcutis Biotherapeutics, Inc.’s study 
ARQ-154-214. 
ARQ-154 foam 0.3% will be described as “roflumilast foam 0.3%” throughout this document 
and the tables, listings, and figures (TLFs). 
2.
Study Objectives and Endpoints
2.1. 
Study Objectives 
2.1.1. Primary Objective 
The objective of this study is to assess long-term safety in a multicenter, open-label, single-arm 
52-week study in subjects with seborrheic dermatitis treated with roflumilast foam 0.3%.


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 11 of 38 
2.2. 
Study Endpoints 
2.2.1. Efficacy Endpoints 
2.2.1.1. 
Primary Efficacy Endpoint 
Not applicable. 
2.2.1.2. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints of this study include the following: 
•
Achievement of an Investigator Global Assessment (IGA) of “completely clear” or
“almost clear”, as observed over time.
•
“IGA success”, defined as achievement of an IGA of “completely clear” or “almost
clear” plus a 2-grade improvement in IGA from Baseline as observed over time.
•
Duration of IGA success, defined as the time from the first observation of IGA success to
the first subsequent time a subject’s disease response does not meet the criteria for IGA
success. The duration of IGA success for subjects who end treatment in IGA success will
be censored at the last disease assessment date.
•
Treatment-free interval, defined as time from when subject achieves disease clearance
(IGA of 0, referred to as “completely clear”) and stop treatment of all lesions to the time
when treatment restarts due to IGA of 2 or above.
2.2.1.3. 
Other Secondary Efficacy Endpoints 
Other secondary efficacy endpoints of this study include the following: 
•
Change and percent change in Scalpdex total score as observed over time.
•
Change and percent change from baseline in Overall Assessment of Erythema score
•
Change and percent change from baseline in Overall Assessment of Scaling score
•
Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 or 1 plus a 2-
grade improvement from Baseline as observed over time.
•
Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 or 1 plus a 2-
grade improvement from Baseline as observed over time.
•
Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 as observed
over time.
•
Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 as observed over
time.


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 12 of 38 
•
Change and percent change from baseline in % body surface area (BSA) affected by
disease as observed over time.
•
Change and percent change in Worst Itch – Numeric Rating Score (WI-NRS) as observed
over time.
•
In subjects with a Baseline WI-NRS pruritus score of ≥4, achievement of a ≥4-point
improvement from Baseline in WI-NRS pruritus score as observed over time.
•
Achievement of Itch-free state which is defined as post-baseline WI-NRS of 0 or 1
2.2.2. Safety Endpoints 
The safety endpoints will be analysis of safety monitored through application site assessments in 
the clinic using the method of Berger and Bowman, clinical laboratory testing, Patient Health 
Questionnaire depression Scale (PHQ-8), Modified PHQ-Adolescents (PHQ-A), Children’s 
Depression Inventory 2 (CDI-2), Columbia-Suicide Severity Rating Scale (C-SSRS), and 
adverse events (AEs). Two primary safety endpoint analyses are planned: 
•
Occurrence of treatment emergent AEs (TEAEs).
•
Occurrence of serious AEs (SAEs).
3.
Overall Study Design and Plan
3.1. 
Overall Design 
This is an open-label, single-arm, long-term 52-week safety  study of subjects with 
seborrheic dermatitis. This study will include both male and female subjects 9 years and 
older. Subjects rolling over from ARQ-154-116 (Cohort 1 Group 2) will not be summarized 
in the tables and would be listed only. 
Cohort 1: This includes subjects of age 9 years or older from ARQ-154-203 and ARQ-154-
116 studies and rolled into this extension study on the final visit from previous study. 
Subjects rolling over from ARQ-154-203 and ARQ-154-116 are separated into groups as 
indicated below. 
Group 1: Subjects rolled over from ARQ-154-203 without gap 
Group 2: Subjects rolled over from ARQ-154-116 (listings only and will not appear 
in summary tables) 
Cohort 2: This includes subjects of age 12 years or older who may or may not have 
participated in a prior ARQ-154 study. The subjects could be either de novo subjects 
(requiring an IGA of disease severity of at least Moderate [“3”] at Baseline) or subjects who 
completed an ARQ-154 study before the initiation of this study (any IGA at Day 1 of this 


 
Statistical Analysis Plan,  
 
Sponsor Arcutis Biotherapeutics, Inc.  
 
Protocol Number ARQ-154-214  
 
PCN Number ARCU211880 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 13 of 38 
 
 
study is allowed). Subjects in Cohort 2 are separated into groups as indicated below: 
Group 3: Subjects rolled over from ARQ-154-203 with gap 
Group 4: De novo subjects 
Subjects will apply study drug once a day for up to 52 weeks. Subjects in both Cohorts 
cannot have more than 20% BSA affected by disease. All lesions on a subject will be treated 
including the scalp, face, trunk, and intertriginous areas. 
3.2. 
Sample Size and Power 
A sample size of approximately 410 subjects is planned for the study. This sample size is not 
based on any calculations of power or precision. This sample size will provide a sufficient 
population size to evaluate the long-term safety of roflumilast foam 0.3% over up to 52 weeks of 
treatment, and in the combination with other studies provide the development program with 
sufficient number of subjects to meet ICH exposure goals. 
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.  
3.4. 
Method of Assigning Treatment  
Not applicable. 
3.5. 
Treatment Administeration 
All subjects will be treated with roflumilast foam 0.3% daily (QD). 
3.6. 
Blinding and Unblinding 
This is an open-label study and no blinding is planned. 
3.7. 
Schedule of Events 
A detailed schedule of events for the study is provided in Table 1. 
Table 1: 
Schedule of Events 
 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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Study Procedure 
Washout 
Cohort 2 
Day 1 
(Cohort 2) 
Wk 4 
D 29 
Wk 12 
D 85 
Wk 18 
D 127 
Wk 24 
D 169 
Wk 30 
D 211 
Wk 36 
D 253 
Wk 44 
D 309 
Wk 52/ 
ET 
D 365 
Visit 
Screening 
Final Visit 
of prior 
ARQ-154 
Study l 
(Cohort 1) 
1 
2 
Phone 
Visit 
3 
Phone 
Visit 
4 
Phone 
Visit 
5 
Visit Window 
-35 days
+/- 3 
days 
+/- 5 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
Days 
+/- 7 
days 
+/- 7 
days 
Informed 
consent/assent 
Xk
Xk
Physical 
examinationa 
X 
Xl 
X 
X 
Medical history 
X 
I/E criteria 
X 
X 
Hematology, Serum 
Chemistries, and 
Urine Analysis 
X 
Xl 
X 
X 
X 
X 
X 
Vital signs, height, 
weightb 
X 
Xl 
X 
X 
X 
X 
X 
IGAc, Overall 
Assessment of 
Erythemac, Overall 
Assessment of 
Scalingc , WI-NRS, 
Scalpdex 
X 
Xl 
X 
X 
X 
X 
X 
BSA 
X 
Xl 
X 
X 
X 
C-SSRS, PHQ‑8/
PHQ-A/CDI-2d
X 
Xl 
X 
X 
X 
X 
X 
Pregnancy teste 
X 
Xl 
X 
X 
X 
X 
X 
Local Tolerability 
Assessmentf 
Xl 
X 
X 
X 
X 
X 
Pigmentation 
Assessmentg 
X 
Xl 
X 
X 
X 
X 
X 
Medical 
Photographyh 
X 
X 
X 
X 
X 
X 
Dispense study 
medication kiti 
X 
X 
X 
X 
X 
IP application at the 
study site 
X 
Dispense/review 
diary 
X 
X 
X 
X 
X 
X 
Weigh study 
medication 
X 
X 
X 
X 
X 
X 
Adverse event 
assessmentj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


 
Statistical Analysis Plan,  
 
Sponsor Arcutis Biotherapeutics, Inc.  
 
Protocol Number ARQ-154-214  
 
PCN Number ARCU211880 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 15 of 38 
 
 
Study Procedure 
Washout 
Cohort 2 
Day 1 
(Cohort 2) 
Wk 4 
D 29 
Wk 12 
D 85 
Wk 18 
D 127 
Wk 24 
D 169 
Wk 30 
D 211 
Wk 36 
D 253 
Wk 44 
D 309 
Wk 52/ 
ET 
D 365 
Visit 
Screening 
Final Visit 
of prior 
ARQ-154 
Study l 
(Cohort 1) 
1 
2 
Phone 
Visit 
3 
Phone 
Visit 
4 
Phone 
Visit 
5 
Visit Window 
-35 days 
+/- 3 
days 
+/- 5 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
days 
+/- 7 
Days 
+/- 7 
days 
+/- 7 
days 
PK Samplingm 
X 
Malassezia testn 
X 
X 
 
X 
 
X 
 
X 
Footnotes from table above: 
a Limited physical examination: skin, lungs, and heart only 
b Height will be collected at Day 1, Week 24 and Week 52/ET only. Weight will be collected at all study visits. 
Subject to void prior to weight being taken. Remove any jackets, outerwear and shoes. Remove any objects of 
significant weight (i.e. cell phones, wallet, key chains). A 5% unintentional weight loss from Baseline should be 
reported to the medical monitor. 
c IGA will be a 5-point scale ranging from completely clear (0) to severe (4). IGA should be completed prior to 
other physician assessments. Overall assessment of erythema (0-3 scale) and overall assessment of scaling (0-3 
scale) will be completed. Total BSA affected by seborrheic dermatitis will be determined at each visit. A body 
diagram should be used to record areas of seborrheic dermatitis involvement. 
d Adolescents and adults will complete the C-SSRS (12 years of age and older). Adults will complete the PHQ-8. 
Adolescents (ages 12 -17, inclusive) will complete the modified PHQ-A. Parents/caregivers will complete CDI-
2 (parent report) for children 9-11 years of age, inclusive. 
e A pregnancy test will be administered to all females of child-bearing potential. A serum pregnancy test will be 
performed at the Screening visit only for Cohort 2. A urine pregnancy test will be performed at Day 1, Weeks 4, 
12, 24, 36 and 52. A negative result is required for continued participation in the study, and results must be 
available prior to dispensing of IP at each visit. 
f Local tolerability will be assessed prior to IP application in the clinic for the Investigator assessment of skin 
(Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s “0-3” 
burning/stinging assessment at Baseline. Note for Investigator tolerability assessments: 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. At Weeks 4, 12, 24, 36, and 52 will be a 
recall assessment of burning/stinging experienced post drug application on the previous day of the clinic visit. 
g An assessment for hypopigmentation and hyperpigmentation will be performed by the investigator at all clinic 
visits. 
h At selected sites, medical photography will be obtained for target lesions. 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. 
i Kits will be dispensed based on %BSA affected. See IP Handling Manual for details. 
j Any emergent AEs will be followed in the clinic for up to one month at the Investigator’s discretion until 
resolved or otherwise judged as clinically stable. 
k For Cohort 1, the consent will be signed after completion of the final visit in prior ARQ-154 study. Cohort 2 
will sign consent prior to any study-related procedures at the Screening Visit. 
l For Cohort 1, this data will be obtained from the final visit of the prior ARQ-154 Study and used as the Day 1 
data for this long-term safety study (ARQ-154-214). If after the prior ARQ-154 study completion, subjects 
should complete the screening visit procedures. The Baseline values for Safety tabulations will be taken from 
the day that the subject received their first active IP (across prior ARQ-154 studies and ARQ-154-214). 
Baseline values for efficacy will be those recorded on Day 1 of the prior ARQ-154 Study. For Cohort 2, 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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Baseline evaluations will be obtained for all procedures and the Baseline/Screening version of the C-SSRS will 
be utilized at Screening. 
 For Cohort 2, Screening labs that are collected within 14 days of Day 1 do not need to be repeated. 
mFor Cohort 2 adolescent subjects PK samples will be collected on Week 4 for adolescent subjects between 12 – 
16 years old. Collect PK sample with the safety lab collection. Ensure PK will not be drawn on the area where 
investigational product is applied. 
n At select sites, the Investigator will collect samples for Malassezia testing on Cohort 1 Group 2 subjects at 
Weeks 4, 12, 24, 36, and 52. Samples will be collected from treated and untreated areas by swabbing the skin 
surface. Samples should be collected from the same areas as samples collected during the ARQ-154-116 
Baseline visit. 
4.
Statistical Analysis and Reporting
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will 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 the treatment group unless otherwise specified. The denominator for by-visit 
displays will be the number of subjects in the relevant study population with non-missing data at 
each visit. 
The minimum and maximum will be reported with the same degree of precision (i.e., the same 
number of decimal places) as the observed data. Measures of location (mean, median, Q1, and 
Q3) 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, unless otherwise 
specified or modified upon request of the sponsor. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
4.2. 
Interim Analysis and Data Monitoring 
No interim analyses are planned. Once about 400 subjects finish the treatment period in this 
study, the final analysis will be performed for the full analysis CSR. When all subjects rolled 
over from study ARQ-154-116 (Cohort 1 Group 2), who enrolled into this ARQ-154-214 study 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 17 of 38 
later than the initial about 400 subjects, finish the treatment in this (ARQ-154-116) study, only 
listings will be generated for these subjects and these listings will be added as a CSR addendum. 
No further tables or figures will be generated for these subjects.  
5.
Analysis Populations
The following analysis populations are planned for this study: 
•
All Enrolled (ENRL): All enrolled population includes subjects who are enrolled into
the study (i.e, signed informed consent) and not screen failures.
•
Safety Population (SAF): The Safety population includes all subjects who are enrolled
and received at least 1 confirmed dose of roflumilast foam 0.3% in this extension study.
•
Pruritus Population Primary (PRU4-P): The PRU4-P population is a subset of the
Safety population and includes subjects with WI-NRS pruritus score ≥ 4 at Primary
Baseline. This population will be used for the analysis of achievement of a 4-point
reduction in WI-NRS pruritus score as compared to Primary Baseline.
•
Pruritus Population Open Label Extension (PRU4-OLE): The PRU4-OLE population
is a subset of the Safety population and includes subjects with WI-NRS pruritus score ≥ 4
at OLE Baseline. This population will be used for the analysis of achievement of a 4-
point reduction in WI-NRS pruritus score as compared to OLE Baseline.
•
Pharmacokinetic Population (PK): The PK population will include all subjects 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.
General Issues for Statistical Analysis
For analysis purposes, the tables and figures will be summarized by groups as indicated 
below. 
Cohort 1 Group 1: Subjects rolled over from ARQ-154-203 without gap (Roflumilast 
Foam 0.3%, Vehicle, Total) 
Cohort 2 Group 3: Subjects rolled over from ARQ-154-203 with gap (Roflumilast 
Foam 0.3%, Vehicle, Total) 
Cohort 2 Group 4: De novo subjects 
Cohort 2 Total 
Overall (includes all Cohorts and groups) 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
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6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
There are three baseline definitions for the analyses: 
•
Primary baseline is defined as the last observation before the first dose of roflumilast
foam 0.3% in either ARQ-154 parent study or this study for subjects administered vehicle
previously.
•
Open-label baseline (OLE baseline) is defined the last observation before the first dose of
roflumilast foam 0.3% in this study. For subjects in Cohort 1 who choose to enroll in this
study, study procedures will not be repeated; study sites will carry over the information
from the prior ARQ-154 study to the Day 1 visit for this study. For subjects in Cohort 2
Group 4, the definition for Primary and OLE baseline is the same.
•
Safety baseline is defined as primary baseline for Cohort 1 Group 1, and OLE baseline
for Cohort 2 Group 3 and Group 4.
The following table described the baseline used in the analysis: 
Cohort 
Groups 
Prior 
therapy, 
medical 
history 
Demog and 
Efficacy 
Analysis 
Safety Analysis 
for AE, PHQ8, 
PHQ-A, Prior 
and 
Concomitant 
medications 
Safety Analysis for 
lab, vital signs and 
tolerability 
assessments 
Cohort 1 
Group 1 
OLE baseline 
Primary 
baseline and 
OLE baseline 
OLE baseline 
Primary baseline 
Cohort 2 
Group 3 
OLE baseline 
Primary 
baseline and 
OLE baseline 
OLE baseline 
OLE baseline 
Cohort 2 
Group 4 
OLE baseline 
Primary 
baseline and 
OLE baseline 
OLE baseline 
OLE baseline 
Cohort 2 
Total 
OLE baseline 
Primary 
baseline and 
OLE baseline 
OLE baseline 
OLE baseline 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 19 of 38 
Overall 
OLE baseline 
Primary 
baseline and 
OLE baseline 
OLE basseline 
Safety baseline of 
roflumilast foam 0.3% 
in this study for 
subjects in the safety 
analysis population. 
For subjects in Cohort 
2 Group 4, the 
definition for Primary 
and OLE Baselines is 
the same 
Baseline values will most commonly be from Day 1.  
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. Multiple Comparisons 
No adjustments for multiple comparisons will be made for this study. No inferential statistical 
analyses are planned for this study. 
6.1.3. Handling of Dropouts or Missing Data 
Other than what is mentioned in 6.1.8, no data will be imputed in the analyses for this study. 
6.1.4. 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 and Table 3. The windows follow the Schedule of Events in Table 1. For 
subjects in Cohort 2 Group 3, the gap between completion of parent study and starting of the 
study ARQ-154-214 should not be counted in the analysis visit window. The windowing will be 
applied using the days on study as shown in the Table 2. Unscheduled/repeated measurements 
will be listed. 
Table 2: Analysis Visit Windows (Primary Baseline for Cohort 1 Group 1 & Cohort 2 
Group 3)  
Primary Baseline 
for Group 1 - Roflumilast 
& Group 3 - Roflumilast 
Scheduled Visit 
Target Days 
on Study 
Window 
(Days) 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 20 of 38 
ARQ-154-203 Week 2 
14 
2 to 22 
ARQ-154-203 Week 4 
28 
23 to 42 
ARQ-154-203 Week 8 
56 
43 to 61 
Week 4 OLE 
85 
71 to 113 
Week 12 OLE 
141 
114 to 183 
Week 24 OLE 
225 
184 to 267 
Week 36 OLE 
309 
268 to 365 
Week 52 OLE 
421 
≥ 366 
Table 3: Analysis Visit Windows 
Primary Baseline  
for Cohort 1 Group 1 - Vehicle  
& Cohort 2 Group 3 - Vehicle  
Cohort 2 Group 4 
+ 
OLE Baseline for Cohort 1 Group 1 - 
Roflumilast  
& Cohort 2 Group 3 – Roflumilast 
Scheduled Visit 
Target 
Study Day 
Window (Days) 
ARQ-154-203 Week 2 
n.a.
n.a.
ARQ-154-203 Week 4 
n.a.
n.a.
ARQ-154-203 Week 8 
n.a.
n.a.
Week 4 OLE 
29 
15 to 57 
Week 12 OLE 
85 
58 to 127 
Week 24 OLE 
169 
128 to 211 
Week 36 OLE 
253 
212 to 309 
Week 52 OLE 
365 
≥ 310 
n.a. = not applicable
6.1.5. Pooling of Sites 
Not applicable. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 21 of 38 
6.1.6. Subgroup 
The subgroup analyses of selected safety and efficacy endpoints will be based on the below 
subgroup variables at both primary baseline and OLE baseline: 
•
Age groups (9-11 years, 12-17 years, 18-64 years, and ≥65 years)
•
Gender (Male vs. Female)
•
Race (White, Black vs. Other)
•
Ethnicity (Hispanic vs. Non-hispanic)
•
Baseline IGA (3 vs. 4 for primary baseline, 0 or 1 vs. 2 vs. 3. vs. 4 for OLE baseline)
•
Baseline BSA% (<5% vs. ≥5%)
•
Baseline BSA% tertiles based on overall group
6.1.7. Derived Variables 
•
IGA success = IGA of “completely clear” or “almost clear” plus a 2-grade improvement
from Baseline. For IGA success analysis, the subjects who achieved IGA of 0 or 1 at
baseline will be excluded from the analysis.
•
Erythema success = Erythema score of 0 or 1 plus a 2-grade improvement from Baseline
as observed over time. For erythema success analysis, the subjects who achieved
erythema score of 0 or 1 at baseline will be excluded from the analysis.
•
Scaling success = Scaling score of 0 or 1 plus a 2-grade improvement from Baseline as
observed over time. For scaling success analysis, the subjects who achieved scaling score
of 0 or 1 at baseline will be excluded from the analysis.
•
Compliance = number of applications divided by the expected number of investigational
product (IP) applications for each subject. Compliance will be calculated using drug
accountability data over the entire treatment period for each subject, up to treatment
completion or discontinuation.
•
Number of expected IP applications = calculated as last treatment date - first treatment
date + 1. Excluding treatment-free interval time (defined in this section).
•
Number of IP applications = number of expected IP applications – missed IP
applications as collected in the CRF. Missed IP applications will not be taken into
consideration in determining number of IP applications if the reason for missing dose is
per investigator confirmation of clear.


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 22 of 38 
•
Days on IP = last date of IP application – first date of IP application +1. Subjects that stop
taking IP per investigator confirmation of clear will be excluded from this calculation.
•
Treatment Gap = This will be calculated for subjects belonging to Cohort 2 Group 3
that rolled into the extension study (ARQ-154-214) with a gap. This is derived start
treatment start date in ARQ-154-214 – last treatment date in ARQ-154-203 + 1.
•
Treatment Duration (weeks) = (last date of IP application – first date of IP application
+1)/7.
•
Duration of IGA success = The date of firstobservation where IGA does not meet
success criteria - the date of first observation of IGA success + 1. The duration of IGA
success for subjects who end treatment in IGA success will be censored at the last disease
assessment date. Only the first duration of IGA success will be analyzed.
•
Duration of IGA of 0 = the date of first observation of IGA > 0 - the date of first
observation of IGA of 0 and stop treatment. The duration of IGA of 0 for subjects who
end treatment in IGA success will be censored at the last disease assessment date. This is
for subjects who achieve IGA of 0 and stop the treatment. Subjects who achieve IGA of 0
but never stop treatment will be excluded from the analysis. For subjects who achieve
IGA of 0 but stop the treatment later, the duration starts from the date of stop treatment.
Only the first IGA of 0 duration will be analyzed.
•
Duration of IGA of 0 or 1= the date of first observation of IGA > 1-the date of first
observation of IGA of 0 or 1 + 1. The duration of IGA of 0 or 1 for subjects who end
treatment in IGA of 0 or 1 will be censored at the last disease assessment date. Only the
first IGA of 0 or 1 duration will be analyzed.
•
Disease recurrence = the date of first observation of IGA of 2 or above after achieving
IGA of 0 and stop treatment - the date of first observation of IGA of 0 + 1. Only the first
disease recurrence will be analyzed.
•
Treatment-free interval = the date of re-starting study drug due to IGA score above 0 -
the date of stop treatment due to attainment of score of IGA of 0 +1, among subjects who
achieve a “completely clear” IGA and stop treatment to all lesions. If subjects never re-
start study drug after stopping treatment, the treatment-free interval is censored at the end
of study date. Only the first treatment-free interval will be analyzed.
•
Weight of IP (g) = dispensed can weight – returned can weight.
•
BMI (kg/m2) = (weight in kg)/[(height in cm/100)2]. Day 1 height will be used for BMI
derivation upto Week 24. For visits including week 24 through week 36, week 24 height


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 23 of 38 
will be used to derive BMI. Week 52 BMI is derived using the height and weight collected 
at the same visit. This derivation is applied since height is not collected at all visits.  
•
BMI Categories:
•
Underweight: 
BMI < 18.5
•
Normal:
18.5 ≤ BMI ≤ 24.9 
•
Overweight: 
25.0 ≤ BMI ≤ 29.9
•
Obese:
BMI ≥ 30.0  
•
WI-NRS 4-point reduction = achievement of a 4-point reduction in WI-NRS pruritus
score post-baseline compared to baseline, calculated only for subjects with a pruritus score
of ≥ 4 at baseline.
•
Itch-free state = achievement of in WI-NRS of 0 or 1.
•
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.
•
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).
•
CDI-2 emotional problem scale is a sum of 9 questions (Q1, Q3-6, Q8, Q10 -12)
•
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.
•
Scalpdex 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.


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 24 of 38 
Q refers to question number. Q19 will be reverse scored i.e., 1=100; 2=75; 3=50; 
4=25; 5=0. 
•
Scalpdex Symptoms Scale = average of (Q1, Q3, Q8) after transforming to 0 to 100 scale
as mentioned above. Q refers to question number.
•
Scalpdex 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.
•
Total % BSA (body surface area) = sum of coverage areas of head, limbs, upper limbs,
and lower limbs.
•
Change from baseline = value at current time point – value at baseline. This is derived
separately for primary baseline and OLE baseline.
•
Percent change from baseline = (value at current time point – value at baseline)/value at
baseline. This is derived separately for primary baseline and OLE baseline.
•
TEAE = any AE that started after application of IP at the Baseline Visit in this extension
study, or in parent study through completion.
•
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).
6.1.8. Data Adjustments/Handling/Conventions 
All collected data will be presented in Clinical Data Interchange Standards Consortium (CDISC) 
datasets. Data not subject to analysis according to this plan will not appear in any tables or graphs 
but will be included only in the CDISC datasets. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 25 of 38 
All P values will be displayed in four decimals and rounded using standard scientific notation (eg, 
0.XXXX). If a P value less than 0.0001 occurs it will be shown in tables as <0.0001; similarly, if
a P value 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 thesaurus. 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 related, probably 
related, likely related, 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.
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.


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 26 of 38 
6.2. 
Special Handling for COVID-19 Disruptions 
The impact of COVID-19 on this clinical trial and participants will be assessed by including in 
summaries/listings relevant information as captured on the eCRF. Information collected will 
include the following: 
•
Any visit disruption caused by COVID-19
•
Early termination due to COVID-19
•
Weight loss due to complications associated with COVID-19
•
Local tolerability assessment and WI-NRS disruption caused by COVD-19
•
Study drug interruption (missed dose) due to COVID-19
•
Delay in any assessment caused by COVID-19
•
Protocol deviation due to COVID-19
7.
Study Subjects and Demographics
The disposition, demographics and baseline characteristics, medical/surgical history, 
prior/concomitant medication, protocol deviations, and exposure will be summarized as indicated 
below in two separate tables for the associated baseline type defined in section 6.1.1: 
Cohort 1 Group 1 (ARQ-154-203 roflumilast foam 0.3%, ARQ-154-203 vehicle, and total 
for subjects that consented to rollover into this extension study without gap),  
Cohort 2 Group 3 (ARQ-154-203 roflumilast foam 0.3%, ARQ-154-203 vehicle, and total 
for subjects that enrolled into this study with a gap),  
Cohort 2 Group 4 (de novo subjects),  
Cohort 2 Total, and  
Overall (includes all the cohorts and groups listed above). 
Due to few number of subjects rolling over from study ARQ-154-116 (Cohort 1 Group 2), 
information collected from ARQ-154-116 will only be included in the listings.  
7.1. 
Subject Disposition 
Disposition summary will include tabulation of the number of subjects who enrolled into each 
cohort/group, the number of subjects who received treatment, number of subjects who completed 
the study, number of subjects who prematurely discontinued the study, the reasons for 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 27 of 38 
discontinuation from the study overall and due to COVID-19 disruption, and number of subjects 
in each analysis population as identified in Section 5. 
7.2. 
Demographics and Baseline Characteristics 
Summary statistics for age, age groups (9-11 years old, 12-17 years old, 18-64 years old, and ≥65 
years old), gender (including child-bearing potential), ethnicity, race, height, weight, baseline 
disease characteristics (IGA, Overall Assessment of Erythema, Overall Assessment of Scaling, 
Scalpdex total score, WI-NRS, percent BSA [total]), and BMI will be presented. 
A summary of treatment history, including history of response, intolerance, or contraindication 
to topical corticosteroids and/or topical antifungals, and subjects having facial involvement and 
current scalp involvement will be provided. 
For the continuous variables, the number of non-missing values and the mean, SD, minimum, 
Q1, Q3, median, 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 WI-NRS, summary statistics including the mean, median, Q1, Q3, and range of the 
ordinal variable will be presented as well as frequency counts of each level of the ordinal 
variable.  
These analyses will be conducted for the Safety population. Baseline characteristics will be 
presented for both primary and OLE baselines. 
7.3. 
Prior and Concomitant Medications 
Prior and concomitant medications will be summarized descriptively by Anatomical Therapeutic 
Chemical (ATC) level 4, and preferred term using counts and percentages for Safety population. 
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 IP. 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. This will include only medications that started after the 
first dose of IP in this extension study (ARQ-154-214).  
Medications will be coded using WHODrug Global B3, version September 2021. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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7.4. 
Surgical and Medical History 
Surgical and medical history will be coded according to the MedDRA, Version 24.1. 
Surgical and medical history will be summarized by system organ class (SOC) and preferred 
term (PT) using the Safety population. A subject who experienced the same surgical and medical 
history event multiple times will be counted only once for the corresponding PT. Similarly, if a 
subject experienced multiple surgical and medical history events within the same SOC, the 
subject will be counted only once for that SOC. Surgical and medical history events will be 
sorted alphabetically by SOC and within each SOC, the PT will be presented by descending 
order. 
7.5. 
Protocol Deviations 
A data review will be conducted before database lock by the Medical Monitor and the Sponsor to 
identify protocol deviations as important or non-important. 
The number of subjects with important protocol deviations and/or eligibility deviations in this 
study will be summarized, including protocol deviations that are related to COVID-19 
disruptions and COVID-19 infections for the subjects in Safety population by groups and overall. 
All of the protocol deviations (including important or non-important protocol devations) will be 
provided in the data listings. 
7.6. 
Exposure and Compliance 
The number of IP applications by each subject based on diary data will be summarized using 
descriptive statistics appropriate for continuous variables.  
The amount of IP used by each subject based on can weight will be summarized descriptively 
using continuous methods.   
The number of days on IP will be derived as indicated in Section 6.1.7 and summarized 
descriptively.  
The gap between completing study ARQ-151-203 and enrolling into this study will not be 
included in the above definition and will be summarized separately for subjects in Cohort 2 
Group 3.  
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. Doses missed due to IGA clearance were not considered as noncompliance. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 29 of 38 
The number and percent of subjects that missed more than 3 consecutive doses will be tabulated 
except for subjects who withheld IP application due to IGA clear per investigator. 
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 using the following categories: 
> 100%
≥ 80% - ≤100%
< 80%
Drug exposure and compliance will be presented using primary and OLE baselines. The number 
of subjects with treatment duration (≥1 day, ≥8 weeks, ≥12 weeks, ≥24 weeks, ≥32 weeks, ≥54 
weeks, and ≥62 weeks) will also be summarized similarly. Study duration will be summarized 
from primary and OLE baseline. 
Similar exposure and compliance information will be summarized for subjects who completed or 
discontinued study before protocol amendment 1.  
8.
Efficacy Analysis
This study is open label without a comparator group; therefore, there will be no formal 
hypothesis testing performed in the study.  
For the continuous variables, the number of nonmissing values and the mean, SD, minimum, Q1, 
Q3, median, and maximum will be tabulated by study visit; similarly, categorical variables will 
have the counts and proportions of each value will be tabulated by study visit. 
For efficacy summaries 2 baselines will be used (primary and OLE) using Safety population as 
defined in Section 6.1.1. 
All efficacy summaries for primary and OLE baselines will be presented as indicated below: 
Cohort 1 Group 1 (ARQ-154-203 roflumilast foam 0.3%, ARQ-154-203 vehicle, and total 
for subjects that consented to rollover into this extension study without gap),  
Cohort 2 Group 3 (ARQ-154-203 roflumilast foam 0.3%, ARQ-154-203 vehicle, and total 
that enrolled into this study with a gap),  
Cohort 2 Group 4 (de novo subjects), 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 30 of 38 
Cohort 2 Total, and  
Overall (includes all Cohorts and groups). 
For vehicle subjects in Cohort 1 Group 1, Cohort 2 Group 3, de nova subjects in Group 4, 
primary baseline is the same as OLE baseline.  
Due to the few number of subjects rolling over from the study ARQ-154-116, information 
collected from ARQ-154-116 will be included in the listings only.  
Missing data for efficacy variables will not be imputed. 
8.1. 
Primary Efficacy Analysis 
Not applicable. 
8.2. 
Secondary Efficacy Analysis 
8.2.1. Investigator Global Assessment (IGA)  
The IGA is an ordinal scale with five severity grades which is reported only in integers. 
Table 4 illustrates the description of each severity grade.  
Table 4: IGA 
Score Description 
0 
Completely clear: No erythema, no scaling (hypo-hyperpigmentation can be 
present) 
1 
Almost clear: Residual slight erythema and/or trace amounts of scaling 
2 
Mild: Pink to red color and/or slight scaling 
3 
Moderate: Distinct 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) 
IGA grade 
IGA grade and change from baseline will be summarized using descriptive statistics at each visit 
by groups and overall.  
The number and percentage of subjects in each IGA grade category will be summarized by 
cohort, group, and overall. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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The number and percentage of subjects who achieve IGA 0 or 1 will be tabulated at each 
scheduled visit by groups and overall. In addition, the achievement of IGA of 0, the achievement 
of IGA success (i.e., IGA of 0 or 1 plus a 2-grade improvement from Baseline) also will be 
tabulated. Furthermore, 95% CIs for proportion of subjects who meet the criteria will be 
provided along with proportions. IGA success from OLE baseline should exclude subjects who 
already achieved IGA of 0 or 1 at OLE baseline.  
IGA success, IGA of 0 or 1, IGA of 0 at any time post baseline including the assessments at the 
unscheduled visit will be summarized by groups and overall, along with 95% CIs for proportion 
of people who meet the criteria.  
These analyses are repeated for both primary and OLE baselines. The subjects who achieved 
IGA of 0 or 1 at baseline will be excluded from the analysis of IGA success from baseline.  
Subgroup analyses will be performed for both primary and OLE baseline for the subgroups 
mentioned in Section 6.1.6. 
Duration of IGA success, Duration of IGA of 0 or 1, and Duration of IGA of 0  
This analysis will be performed using IGA grade assessed in the open-label study. 
Duration of IGA success, for subjects whose IGA grade is not 0 or 1 at OLE baseline, is defined 
as the time from the first observation of IGA success to first subsequent time a subject’s disease 
response does not meet the criteria for IGA Success. The duration of IGA success for subjects 
who end treatment in IGA success will be censored at the last disease assessment date. Only the 
first IGA success duration will be analyzed.  
If there is no IGA assessment after the first observation of IGA success, the duration will be 
censored at the end of study date. 
The median time (number of days) for IGA success will be analyzed using the Kaplan–Meier 
method. Subjects who discontinue study without relapse will be considered censored in the 
Kaplan–Meier analyses. The Kaplan-Meier estimate will be stratified by the IGA success time 
(IGA success by Week 4, between Week 4 and Week 12, between Week 12 and Week 24, 
between Week 24 and Week 36, and between Week 36 and Week 52).  
Duration of IGA success will be summarized by Cohort, Groups, and overall. 
The analysis of duration of IGA of 0 or 1 will be performed in the similar fashion. 
Duration of IGA of 0 will be performed for subjects who achieve IGA of 0 post OLE baseline 
and stop treatment. Subjects who achieve IGA of 0 but never stop treatment will be excluded 
from analysis. If subject achieved IGA of 0 but stop treatment several days later, the duration 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 32 of 38 
will start at the IP stop date. The analysis of duration of IGA of 0 will be in the similar fashion as 
the analysis for duration of IGA success.  
Similar analysis from primary baseline will be performed.  
Disease recurrence 
This analysis will be performed using IGA assessments during the open-label study. 
Time to disease recurrence is defined as time from first observation of IGA of 0 and stop 
treatment to to first observation of IGA of 2 or higher after stop treatment. Subjects who achieve 
IGA of 0 but never stop treatment will be excluded from analysis. If subject achieve IGA of 0 
but stop treatment several days later, the duration will start at the IP stop date. If there is other 
IGA assessment after achieving IGA of 0, the time to disease recurrence will be censored at the 
last disease assessment date. If there is no IGA assessment after the first observation of IGA 
success, the duration will be censored at the end of study date. The analysis of time to disease 
recurrence will be in the similar fashion as the analysis of durationof IGA success.  
Similar analysis from primary baseline will be performed. 
Treatment Free Interval 
Time to restarting study drug (treatment free interval), defined as time from when subject 
achieves disease clearance (IGA of 0) and stop treatment to all lesions to time when treatment 
restarts due to IGA of 2 or above, will be calculated and summarized in the same manner as 
duration of IGA success. The number (%) of subjects who achieved disease clearance (IGA of 0)  
and stopped treatment will be presented as well. If the subjects never restart the study treatment 
after achieving IGA of 0, the subject will be censored at the end of study date.  
8.3. 
Other Secondary Efficacy Analysis 
The other secondary efficacy endpoints are summarized using OLE baseline, except for WI-NRS 
which will be summarized at both primary and OLE baseline. These are summarized as 
discussed in Section 8 and include the following:  
•
Change and percent change in Scalpdex total score as observed over time.
•
Change and percent change in Overall Assessment of Erythema score
•
Change and percent change in Overall Assessment of Scaling score
•
Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 or 1 plus a 2-
grade improvement from Baseline as observed over time.
•
Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 or 1 plus a 2-
grade improvement from Baseline as observed over time.


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 33 of 38 
•
Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 as observed
over time.
•
Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 as observed over
time.
•
Change and percent change from baseline in % BSA affected by disease as observed over
time.
•
Change and percent change in WI-NRS as observed over time.
•
In subjects with a Baseline WI-NRS pruritus score of ≥4, achievement of a ≥4-point
improvement from Baseline in WI-NRS pruritus score as observed over time.
•
Achievement of itch-free state which is defined as WI-NRS of 0 or 1
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. Observed, change, and percent change from baseline for Scalpdex scale scores 
along with total score are summarized descriptively.  
Observed, change, and percent change from baseline for WI-NRS and % BSA (total) affected by 
disease will be summarized descriptively.  
In subjects with WI-NRS pruritus score ≥ 4 at baseline (primary and OLE), achievement of a 4-
point reduction in WI-NRS pruritus score at each scheduled visit will be summarized. The 
number and percentage of subjects for each scale score will be summarized for OLE baseline. 
The number and percentage of subjects who achieve Overall Assessment of Erythema Success, 
Overall Assessment of Scaling Success, Erythema score of 0, and Scaling score of 0 will be 
tabulated at each scheduled visit. In addition, categorical summaries (number and percentage of 
subjects) in each category will be summarized for Erythema and Scaling. 
9.
Safety and Tolerability Analysis
Safety will be evaluated from reported AEs, local tolerability assessments, changes in clinical 
laboratory values, changes in vital signs/weight, C-SSRS, PHQ-8/modified PHQ-A, and CDI-2 
results.  
9.1. 
Adverse Events 
All AEs will be coded using the MedDRA dictionary version 24.1 or above. 
A TEAE is defined as an AE that started after application of IP at the Baseline Visit in this 
extension study. All TEAEs will be summarized from OLE baseline. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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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 SAE (TESAE), TEAE leading to study drug 
withdrawal, TEAE leading to study withdrawal, or TEAE resulting in death. 
The number and percent of subjects reporting TEAEs, grouped by MedDRA system organ class 
(SOC) and preferred term (PT), will be tabulated by all TEAEs, non-serious TEAEs, maximum 
severity, or greatest relationship to study IP; Cohort and by groups and overall. In the case of 
multiple occurrences of the same TEAE within the same subject, each subject will only be 
counted once for each preferred term. 
The number and percent of subjects reporting TEAEs will be tabulated by PT and presented by 
groups and overall.  
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). 
All the AEs will be listed. The AEs that are treatment emergent will be flagged. Any AEs related 
to the application site will be flagged in the listing. 
9.1.1. Adverse Events Leading to Withdrawal 
A summary of incidence rates (frequencies and percentages) of TEAEs leading to withdrawal of 
study drug and TEAEs leading to withdrawal of study, by SOC and preferred term will be 
prepared for the Safety population.  
9.1.2. Deaths and Serious Adverse Events 
TESAEs will be tabulated by SOC and PT and presented by groups and overall. Fatal AEs will 
be flagged in the AE listings.  
9.2. 
Local Tolerability Assessments 
The investigator’s assessment of the application site reaction will be summarized 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.  


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 35 of 38 
The subject’s assessment of the application site reaction will be summarized similarly. 
Primary baseline will be used for Cohort 1 Group 1 and OLE baseline for Cohort 2. Overall group 
will be summarized using Safety baseline. 
9.3. 
Clinical Laboratory Evaluations 
Laboratory test results will be summarized descriptively by groups and study visit as both 
observed values, changes, and percent changes from baseline values for continuous hematology, 
chemistry, and urinalysis results. Categorical urinalysis results will be summarized using 
frequencies by groups and study visit. 
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 
(shift table). 
Primary baseline will be used for Cohort 1 Group 1 and OLE baseline for Cohort 2. Overall 
group will be summarized using Safety baseline. 
Abnormal laboratory values will be presented in the listings. 
9.4. 
Vital Signs 
Descriptive summaries of observed values, changes, and percent 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 group and study visit.  
Categorical percent changes in weight (i.e., shifts from baseline) by group will be summarized 
by 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 groups and study visit. 
BMI is derived as specified in Section 6.1.7. Shift tables 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 groups and study visit.  
Shift tables for weight and BMI will also by summarized by intentional and unintentional weight 
loss (defined from question on vital sign eCRF). Vital signs summaries will use primary baseline 
for Cohort 1 Group 1 and OLE baseline for Cohort 2. Overall group will be summarized using 
Safety baseline. 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 36 of 38 
9.5. 
PHQ-8 
PHQ-8 will be completed by adult subjects and modified PHQ-A will be completed 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:  
•
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 study visit will be presented by group. As 
PHQ-A is not assessed in ARQ-154-203 study, only OLE baseline will be used for this 
summary. 
9.6. 
CDI-2
Parents/caregivers will complete the CDI-2 for subjects belonging to 9-11 years of age inclusive. 
For CDI-2, descriptive summaries of observed values, changes and percent changes from 
baseline will be calculated for the total score and the 2 scales emotional problems and functional 
problems by groups and study visit.  
As CDI-2 is not assessed in ARQ-154-203 study, only OLE baseline will be used for this 
summary. 
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 
for Cohort 2 only; otherwise, the “Since Last Visit” 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. 
Suicidality data collected on the C-SSRS with positive responses will be listed for all subjects if 
there is any. 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 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 37 of 38 
the Suicidal Ideation and Suicidal Behavior items will be summarized by study visit. OLE 
baseline will be used for this summary. 
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 by group for OLE data only. 
9.9. 
Pigmentation Assessment 
The hypopigmentation and hyperpigmentation are scored on a 0-3 scale where 0 = none, 1 = 
mild, 2 = moderate and 3 = severe. A shift table summarizing each category and study visit will 
be summarized for subjects belonging to Cohort 2 Group 4 for OLE baseline. This summary is 
repeated for race subgroups as well (white, black, vs others). 
10.
Changes from Planned Analysis
Per the sponsor request, the following changes have made to the SAP: 
•
The 2-grade improvement in IGA from Baseline as observed over time endpoint has been
removed.
•
TEAE by PT, TESAE by SOC, PT table summaries have been added.
•
Shift in pigmentation assessment summary for Cohort 2 Group 4 is added.
•
Subgroup analysis tables for TEAE by severity have been added.
•
The Durations of IGA Success, Duration of IGA 0/1 and other similar duration variables
have been updated to be defined from first instance of the event to first subsequent
instance of loss of the event, rather than the time from the first instance of the event to the
last subsequent instance of the event.
11.
Other Planned Analysis
11.1. Pharmacokinetic Analysis 
All PK data will be listed and summarized descriptively. 
12.
References
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 


Statistical Analysis Plan,  
Sponsor Arcutis Biotherapeutics, Inc. 
Protocol Number ARQ-154-214  
PCN Number ARCU211880
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.0    |   18-Feb-2022      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 38 of 38 
RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014. 
https://rss.org.uk/about/policy-and-guidelines/code-of-conduct/.