A Phase 1/2a Single Dose and 28-day Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety, Pharmacokinetics and Efficacy of ARQ-151 Cream 0.5% and 0.15% in Adults With Mild to Moderate Chronic Plaque Psoriasis
Phase: PHASE1
Conditions: Psoriasis
Sponsor: Arcutis Biotherapeutics, Inc.

Confidential 
 Page 1 of 51 
Protocol ARQ-151-101 
A Phase 1/2a Single Dose and 28-day Parallel Group, 
Double Blind, Vehicle-Controlled Study of the Safety, 
Pharmacokinetics and Efficacy of ARQ-151 Cream 0.5% 
and 0.15% in Adults with Mild to Moderate Chronic 
Plaque Psoriasis 
GCP Statement 
This study is to be performed in full compliance with the protocol, Good Clinical Practices (GCP), 
and applicable regulatory requirements. All required study documentation will be archived as 
required by regulatory authorities. 
Confidentiality Statement 
This document is confidential. It contains proprietary information of Arcutis, Inc. Any viewing or 
disclosure of such information that is not authorized in writing by Arcutis, Inc. is strictly prohibited. 
Such information may be used solely for the purpose of reviewing or performing this study. 
NCT03392168

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
 
19 March 2018 
Confidential 
 Page 2 of 51 
 
1 
PROTOCOL REVISION HISTORY 
 
Version/Date 
Description 
ARQ-151-101 
17 October 2017 
Original Protocol  
ARQ-151-101 
Amendment 1.0 
06 December 2017 
• Added Protocol Revision History section. 
• Added footnote “k” to the Study Events Flowchart for Cohort 2 under 
Schedule of Visits and Assessments to allow a window for follow-up 
visits. 
• Revised Inclusion Criterion #7 to more completely define Women of 
Non-Child Bearing Potential to include those who are post-menopausal 
and surgically sterile. 
• Revised Exclusion Criterion #12 to clarify the washout period for 
excluded biologic medications and to update the washout period for 
investigational medications. 
• Updated Ethics Review Board information to include information 
relevant to clinical studies performed in the US. 
• Editorial and administrative changes throughout the protocol to clarify 
language and formatting to improve readability. 
ARQ-151-101 
Amendment 1.1 
27 February 2018 
• This amendment applies only to the US site to add optional dermal 
imaging assessment (photography). 
• Revised Study Events Flowchart for Cohort 2 under Schedule of Visits 
and Assessments to show optional photography for Baseline, Visit 3, 
Visit 4, and Visit 6 for US site. 
• Revised footnote “c” of the Study Events Flowchart for Cohort 2 under 
Schedule of Visits and Assessments to show photography assessment 
visits for Canadian (Baseline and Visit 6 only) and US sites (Baseline, 
Visit 3, Visit 4, and Visit 6). 
• Revised section 8.13.2 Dermal Imaging to show photography 
assessment visits for Canadian (Baseline and Visit 6 only) and US sites 
(Baseline, Visit 3, Visit 4, and Visit 6). 
ARQ-151-101 
Amendment 2.0 
19 March 2018 
• This amendment increases the number of optional dermal photography 
assessments from two to four and applies to all sites participating in 
dermal imaging (both Canadian and US). 
• Revised Study Events Flowchart for Cohort 2 under Schedule of Visits 
and Assessments to show optional photography for Baseline, Visit 3, 
Visit 4, and Visit 6 for all sites. 
• Revised section 8.12.1 Screening to indicate four rather than three 
investigational centers participating in dermal imaging. 
• Revised section 8.13.2 Dermal Imaging to show photography 
assessment visits for all photography sites at Baseline, Visit 3, Visit 4, 
and Visit 6. 
 
 

20 Mar 2018
Protocol ARQ-151-1 01 
Amendment 2.0 
2 
PRINCIPAL INVESTIGATOR AND SPONSOR- SIGNATORIES 
Arcutis, Inc. 
A Phase 1/2a Single Dose and 28-day Parallel Group, Double Blind, Vehicle.Controlled Study of 
the Safety, Phannacokinetics and Efficacy of ARQ-151 Cream 0.5% and 0.15% in Adults with 
Mild to Moderate Chronic Plaque Psoriasis 
SPONSOR: 
Arcutis, Inc. 
70 Willow Rd., Suite 200 
Menlo Park, CA 94025 
 
 
Tel.: 
 
SPONSOR'S 
Cell: 
 
REPRESENTATIVE: E-mail:
 
PRINCIPAL INVESTIGATOR 
AND CLINICAL SITE: 
Signature 
19 March 2018 
Confidential 
Date 
Page 3 of 51 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
 
19 March 2018 
Confidential 
 Page 4 of 51 
 
3 
ADDITIONAL KEY CONTACTS FOR THE STUDY 
 
Sponsor Study Director 
, MD 
 
Tel.:  
 
Cell:  
 
E-mail: 
  
 
Sponsor Contact for Serious 
Adverse Event Reporting 
, MD 
 
Tel.:  
 
Cell:  
 
E-mail:
  
 
 
Certified Clinical Laboratory 
Clinical Reference Laboratory 
8433 Quivira Road 
Lenexa, KS 66215 
 
Bioanalytical Laboratory 
Q Squared Solutions BioSciences, LLC 
19 Brown Road 
Ithaca, NY 14850 
 
Pharmacokinetic and Statistical 
Analyses 
 
ADME Solutions, Inc. 
3525 Del Mar Heights Rd. #336 
San Diego, CA 92130 
 
Statistical Analysis 
Premier Research 
One Park Drive, Ste. 150 
Durham, NC 27709 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 5 of 51 
 
4 
TABLE OF CONTENTS 
1 
PROTOCOL REVISION HISTORY ..................................................................................... 2 
2 
PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES...................................... 3 
3 
ADDITIONAL KEY CONTACTS FOR THE STUDY............................................................ 4 
4 
TABLE OF CONTENTS ..................................................................................................... 5 
5 
SYNOPSIS ......................................................................................................................... 8 
6 
SCHEDULE OF VISITS AND ASSESSMENTS .................................................................12 
7 
ABBREVIATIONS .............................................................................................................16 
8 
BACKGROUND AND RATIONALE ..................................................................................18 
8.1 
Introduction ....................................................................................................................18 
8.1.1 
Preclinical Studies ...................................................................................................18 
8.1.2 
Clinical Studies ........................................................................................................22 
8.2 
Rationale ........................................................................................................................22 
8.2.1 
Dose Selection ........................................................................................................23 
8.2.2 
Risks and/or Benefits to Subjects ............................................................................23 
8.3 
Study Objectives ............................................................................................................24 
8.3.1 
Primary Objectives ..................................................................................................24 
8.4 
Efficacy Endpoints ..........................................................................................................24 
8.4.1 
Primary Endpoint .....................................................................................................24 
8.4.2 
Secondary Endpoints ..............................................................................................25 
8.5 
Overall Study Design and Plan .......................................................................................25 
8.6 
Randomization ...............................................................................................................26 
8.7 
Numbering of Subjects ...................................................................................................26 
8.8 
Blinding ..........................................................................................................................26 
8.9 
Selection of Study Population .........................................................................................26 
8.9.1 
Inclusion Criteria ......................................................................................................26 
8.9.2 
Exclusion Criteria ....................................................................................................27 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
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8.9.3 
Removal of Subjects from the Study ........................................................................29 
8.10 
Study Restrictions ..........................................................................................................29 
8.10.1 
Prohibitions and Concomitant Therapy ....................................................................29 
8.11 
Treatments .....................................................................................................................30 
8.11.1 
Drug Administration .................................................................................................30 
8.11.2 
Treatment Stopping Rules .......................................................................................30 
8.11.3 
Treatment Compliance ............................................................................................31 
8.12 
Safety Assessments .......................................................................................................31 
8.12.1 
Screening ................................................................................................................31 
8.12.2 
Physical Examination ..............................................................................................31 
8.12.3 
Vital Signs and Weight ............................................................................................31 
8.12.4 
ECG Monitoring .......................................................................................................32 
8.12.5 
Laboratory Tests .....................................................................................................32 
8.12.6 
Application Site Reaction Assessment (Cohorts 1 and Cohort 2) ............................34 
8.13 
Efficacy Evaluations (Cohort 2 Only) ..............................................................................35 
8.13.1 
Product of the Target Plaque Severity Score (TPSS) and the Target Plaque Area 
(TPA) 
35 
8.13.2 
Dermal Imaging .......................................................................................................36 
8.14 
Depressive Symptomatology Questionnaire (Cohort 2 Only) ..........................................36 
8.15 
Pharmacokinetic Assessment .........................................................................................36 
8.15.1 
Blood and Skin Sampling and Processing ...............................................................36 
8.16 
Adverse Events ..............................................................................................................37 
9 
DATA ANALYSIS ..............................................................................................................39 
9.1 
Statistical Methods .........................................................................................................39 
9.1.1 
Determination of Sample Size .................................................................................40 
9.1.2 
Subjects to Analyze .................................................................................................40 
9.1.3 
Interim Analysis .......................................................................................................40 
9.1.4 
Background and Demographic Characteristics ........................................................40 
9.1.5 
Study Medication Compliance .................................................................................40 
9.2 
Efficacy (Cohort 2) ..........................................................................................................41 
9.2.1 
Primary Efficacy Endpoint .......................................................................................41 
9.2.2 
Secondary Efficacy Endpoints .................................................................................41 
9.3 
Safety Evaluation ...........................................................................................................41 
9.4 
Pharmacokinetic Analysis ...............................................................................................43 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
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9.5 
Ethics .............................................................................................................................43 
9.5.1 
Ethics Review Board ...............................................................................................43 
9.5.2 
Ethical Conduct of the Study ...................................................................................43 
9.5.3 
Subject Information and Consent ............................................................................44 
9.6 
Study Monitoring ............................................................................................................44 
9.7 
Data Quality Assurance ..................................................................................................44 
9.8 
Drug Supplies, Packaging and Labeling .........................................................................45 
9.9 
Data Handling and Record Keeping ...............................................................................45 
9.10 
Report Format ................................................................................................................45 
9.11 
Publication Policy ...........................................................................................................45 
10 
REFERENCES ...............................................................................................................46 
APPENDIX 1: TARGET PLAQUE SEVERITY SCORE (TPSS) ................................................47 
APPENDIX 2 DEPRESSIVE SYMPTOMATOLOGY QUESTIONNAIRE ..................................48 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 8 of 51 
 
5 
SYNOPSIS 
Compound: 
ARQ-151 cream 0.15 % and ARQ-151 cream 0.5%  
Clinical Indication: 
Chronic Plaque Psoriasis 
Study Phase and 
Type: 
A Phase 1/2a Single Dose and 28-day Parallel Group, Double Blind, 
Vehicle-Controlled Study of the Safety, Pharmacokinetics and Efficacy 
of ARQ-151 cream 0.5% and 0.15% in Adults with Mild to Moderate 
Chronic Plaque Psoriasis 
Study Objectives: 
1. To assess the safety and PK of a single dose application of 
ARQ-151 cream 0.5% to 25 cm2 of psoriatic plaque(s) (Cohort 1) 
2. To assess the safety, pharmacokinetics and efficacy of ARQ-151 
cream 0.5% vs. vehicle and ARQ-151 cream 0.15% vs vehicle 
applied QD x 28 days to individuals with 0.5% to 5.0% BSA of 
chronic plaque psoriasis (Cohort 2) 
Summary of Study 
Design: 
There are 2 cohorts of subjects. 
Cohort 1 is a single dose study to 25 cm2 of psoriatic plaque(s) in 
8 psoriasis subjects.  Cohort 1 subjects will then be enrolled, if they 
meet entry criteria, into Cohort 2 of the study. 
Cohort 2 is a parallel group, double blind, vehicle controlled study in 
which ARQ-151 cream 0.5%, ARQ-151 cream 0.15% or vehicle cream 
is applied QD x 28 days to subjects with at least 0.5% BSA of chronic 
plaque psoriasis; area for application will not exceed 5.0% BSA. 
Blinding: 
The single dose assessment (Cohort 1) to 25 cm2 of psoriatic 
plaque(s) is open label. 
The parallel group study (Cohort 2) is double blind and vehicle 
controlled. 
Countries:  
Canada (Cohorts 1 and 2) and United States (Cohort 2 only) 
Number of sites: 
7 sites in Canada; 1 site in the United States. 
Study Population: 
Subjects will be adults, male and female (>18 y/o). Cohort 1 subjects 
will have at least 25 cm2 of chronic plaque psoriasis; Cohort 2 subjects 
will have 0.5 – 5.0% total BSA of chronic plaque psoriasis and at least 
one target plaque of psoriasis at least 9 cm2 in size and with a 
TPSS ≥ 4.  
Number of 
Subjects: 
1. Cohort 1 = Up to 8 subjects 
2. Cohort 2 (can include Cohort 1 subjects) = 84 subjects; 
randomized 1:1:1 to ARQ-151 cream 0.5%: ARQ-151 cream 
0.15%: vehicle/placebo. Total subjects in both cohorts = 84-92. 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 9 of 51 
 
Duration of 
Participation for 
Subjects: 
1. Cohort 1: 22 days (Screening, Day 1, Day 2 and Day 8).  If 
subjects roll into Cohort 2, then total study duration prior to start of 
Cohort 2 is approximately 22 days.  Screening is up to 2 weeks.   
2. Cohort 2 (not in Cohort 1):  Screening (up to 6 weeks) + Treatment 
phase and follow-up (5 weeks), 77 days. 
Study Products: 
ARQ-151 cream drug product will be supplied as a 0.15% and 0.5% 
cream. 
Matching vehicle cream will contain only excipients of ARQ-151 cream. 
Planned Dose 
Level: 
Cohort 1 subjects will receive ARQ-151 cream 0.5% applied to 25 cm2 
of psoriatic plaque(s). 
Cohort 2 subjects will receive ARQ-151 cream 0.15% or 0.5% or 
matching vehicle cream applied to all psoriatic lesions up to an area of 
5.0% BSA (if subject rolled over from Cohort 1, lesions treated in 
Cohort 1 can also be treated in Cohort 2). 
Safety 
Assessments: 
Safety will be monitored through application site assessments, safety 
labs and AEs. 
Safety Analysis: 
The following analyses will be performed; however, no formal 
inferential statistics will be done on safety assessments. 
Descriptive statistics will be calculated for quantitative safety data and 
frequency counts will be compiled for classification of qualitative safety 
data.  
Adverse Events: 
A subject-by-subject treatment-emergent AE (TEAE) data listing, 
including verbatim term, preferred term, treatment, severity, and 
relationship to study drug, will be provided. 
The number of subjects experiencing AEs and number of AEs will be 
summarized by treatment using frequency counts. 
Medical History and Physical Examinations: 
Medical history will be listed by subject.  Physical examinations will be 
performed at screening, baseline and end-of-study. 
Clinical Laboratory Results: 
Routine blood chemistries and 12-lead ECGs will be obtained 
throughout the study. 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 10 of 51 
 
Efficacy Analysis 
The single dose Cohort 1 will have analyses only for safety and 
pharmacokinetics. 
The parallel group assessment (Cohort 2) will have analyses for 
safety, pharmacokinetics, and efficacy. 
In the parallel group assessment (Cohort 2), the Primary Efficacy 
Endpoint will be:  
• 
Difference in mean percent change from baseline at week 4 in 
the product of: [Target Plaque Severity Score (TPSS) x Target 
Plaque Area (TPA)] (TPSS x TPA) between each dose 
concentration level of ARQ-151 cream and vehicle control.  
This will be assessed as a sum of up to 3 target plaques per 
subject. 
The secondary efficacy endpoints will include: 
1. Difference in mean percent change from baseline at weeks 1, 2 
and 3 in TPSS x TPA between each dose concentration level of 
ARQ-151 cream and vehicle control.  This will be assessed as a 
sum of up to 3 target plaques per subject. 
2. Difference in mean percent change from baseline at weeks 1, 2, 3 
and 4 in TPSS between each dose concentration level of ARQ-151 
cream and vehicle control.  This will be assessed as a sum of up to 
3 target plaques per subject. 
3. Difference in mean percent change from baseline at weeks 1, 2, 3, 
and 4 in TPA between each dose concentration level of ARQ-151 
cream and vehicle control.  This will be assessed as a sum of up to 
3 target plaques per subject. 
Pharmacokinetic 
Sample Collection:  
(Cohort 1 n = up to 
8; Cohort 2 n = 45) 
1. Cohort 1: PK draws will be done at 1, 2, 4, 6 and 24 hours after 
ARQ-151 cream 0.5% application to 25 cm2 of psoriatic plaques 
2. Cohort 2: PK draws will be done on day 1: 1, 2, 4 and 6 hours; day 
14: pre-dose (trough) and 1-hour post-dose; and day 28: pre-dose 
(trough), 1, 2, 4, 6 and 24 hours post-dose 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 11 of 51 
 
Statistical Analysis: 
Four analysis populations will be defined: 
• 
Safety population will include all subjects who are enrolled and 
received at least one confirmed dose of study medication; this 
population will be defined separately for each cohort. 
• 
Modified Intent-to-Treatment (mITT) population will include all 
subjects who are in the safety population for Cohort 2 with at 
least one post-baseline efficacy evaluation. 
• 
Per-Protocol (PP) Population will include all subjects who are 
in the safety population for Cohort 2, were at least 80% 
compliant with study medication, and showed no other serious 
deviations from the study protocol. 
• 
PK population will include all subjects receiving the active drug 
with sufficient plasma concentrations of ARQ-151 cream to 
define a profile, as determined by the pharmacokineticist; this 
population will be defined separately for each cohort. 
The primary endpoint of mean percent change from baseline at Week 
4 in TPSS x TPA will be analyzed using a mixed model for repeated 
measures (MMRM). The difference between treatment groups in 
TPSS x TPA at Weeks 1, 2, and 3 will also be analyzed using the 
MMRM. Descriptive statistics will be provided for observed and 
percent change from baseline in TPSS x TPA at Weeks 1, 2, 3, and 4.  
A comparison of changes in TPSS and TPA between treatment groups 
will be analyzed similarly to TPSS x TPA. 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 12 of 51 
 
6 
SCHEDULE OF VISITS AND ASSESSMENTS 
STUDY EVENTS FLOW CHART: COHORT 1; SINGLE DOSE APPLICATION TO 25 cm2 
Study Procedure 
 
Days  
 
Screening 
 
Day 1 
 
Day 2 
 
Day 8 
 
Weeks 
2 weeks 
 
 
 
Informed consent 
X 
 
 
 
Medical history 
X 
 
 
 
Physical examinationa 
X 
X 
 
 
Hematology, Serum Chemistries, and 
Urine Analysis  
X 
 
X 
 
Urine Drug Screen 
X 
 
 
 
I/E criteria 
X 
X 
 
 
Vital signs, height, weight 
X 
X 
 
 
Urine pregnancy testb 
X 
X 
 
 
Resting 12-lead ECG 
X 
 
 
 
ARQ-151 cream applicationc 
 
X 
 
 
PK samplingd 
 
X 
X 
 
Application Site Reaction Assessment 
 
X 
X 
 
Adverse events assessments 
 
X 
X 
 
Concomitant medications 
X 
X 
X 
 
Telephone Follow-upe 
 
 
 
X 
a Limited physical examination: skin, lungs, and heart only 
b A urine pregnancy test will be administered to all females of child-bearing potential. A negative result is required for 
continued participation in the study, and results must be available prior to dispensing of study drug. 
c ARQ-151 cream application to 25 cm2 of target plaque(s) 
d PK sampling: 1, 2, 4, 6 (±10 minutes for 1, 2, 4 and 6 hour collections) and 24 hours (± 1 hour) after ARQ-151 cream 
application to 25 cm2 of psoriatic plaque(s) 
e Telephone call to the subjects for follow up on any continuing adverse events related to study drug.  Telephone call 
will also assess any emergent adverse event post Day 1 ARQ-151 cream application. Any emergent AEs will be 
followed in the clinic at the investigator’s discretion for up to one month until resolved or otherwise judged as clinically 
stable. 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 13 of 51 
 
STUDY EVENTS FLOW CHART: COHORT 2;  28 DAY APPLICATION TO 0.5 – 5% BSA; 
DOUBLE BLIND, PLACEBO CONTROLLED  
Study 
Procedure 
Screen 
 
 
Visit 1 
Baseline 
 
Day 1 
Visit 2 
Week 1 
 
Day 7k 
Visit 3 
Week 2 
 
Day 14k 
Visit 4 
Week 3 
 
Day 21k 
Visit 5 
Week 4 
 
Day 28k 
Visit 6 
Week 4 
 
Day 29k 
Visit 7 
Week 5 
 
Day 35k 
 
Weeks 
-6 
0 
1 
2 
3 
4 
 
 
Informed 
consent 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Physical 
examinationa 
X 
X 
 
 
 
X 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
 
Hematology, 
Serum 
Chemistries, and 
Urine Analysis  
X 
X 
 
X 
 
X 
 
 
Urine Drug 
Screen 
X 
 
 
 
 
 
 
 
Vital signs, 
weight, height 
X 
X 
X 
X 
X 
X 
 
 
TPSS x TPA 
measurementsb 
X 
X 
X 
X 
X 
X 
 
 
Application Site 
Reaction 
Assessment 
 
X 
X 
X 
X 
X 
 
 
Depressive 
Symptomatology 
Questionnaire 
X 
 
 
X 
 
X 
 
 
Optional 
Photographyc 
 
Xc 
Xc 
Xc 
 
Xc 
 
 
Urine pregnancy 
testd 
X 
X 
X 
X 
X 
X 
 
 
Resting 12-lead 
ECG 
X 
X 
 
 
 
X 
 
 
PK samplinge 
 
X 
 
X 
 
X 
X 
 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 14 of 51 
 
STUDY EVENTS FLOW CHART: COHORT 2; 28 DAY APPLICATION TO 0.5 – 5% BSA; 
DOUBLE BLIND, PLACEBO CONTROLLED (Continued) 
Study Procedure 
Screen 
 
 
Visit 1 
Baseline 
 
Day 1 
Visit 2 
Week 1 
 
Day 7 k 
Visit 3 
Week 2 
 
Day 14 k 
Visit 4 
Week 3 
 
Day 21 k 
Visit 5 
Week 4 
 
Day 28 k 
Visit 6 
Week 4 
 
Day 29 k 
Visit 7 
Week 5 
 
Day 35 k 
 
Weeks 
-6 
0 
1 
2 
3 
4 
 
 
Vehicle 
Application in 
Clinic (subject 
training)f 
 
 
Xf 
 
Xf 
 
 
 
Drug/Vehicle 
Application in 
Clinicg 
 
Xg 
 
Xg 
 
Xg 
 
 
ARQ-151 
cream/Vehicle 
application at 
home 
 
X 
X 
Xh 
X 
Xh 
 
 
Dispense study 
medication 
 
X 
X 
X 
X 
 
 
 
Weigh study 
medication 
 
X 
X 
X 
X 
X 
 
 
Dispense/Review 
Diary 
 
X 
X 
X 
X 
X 
Xl 
 
Adverse events 
assessments 
 
X 
X 
X 
X 
X 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
 
 
Optional Skin 
biopsyi 
 
 
 
 
 
X 
 
 
Telephone follow 
up j 
 
 
 
 
 
 
 
X 
a Limited physical examination: skin, lungs, and heart only 
b Target Plaque Severity Score: Sum of erythema, induration, and scaling each scored 0-4 (maximum score = 12).  
Target plaque area = Longest diameter (cm) x Widest perpendicular diameter (cm).  Up to three target plaques will 
be chosen, each at least 9 cm2.  The target plaques must each have a TPSS ≥4.  Subjects much have at least one 
target plaque. 
c Photography will be at selected investigational sites.  Photography will be optional and confined to the target lesions.  
All efforts will be made to de-identify the subjects. 
d A urine pregnancy test will be administered to all females of child-bearing potential. A negative result is required for 
continued participation in the study, and results must be available prior to dispensing of study drug at each visit. 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 15 of 51 
 
STUDY EVENTS FLOW CHART: COHORT 2;  28 DAY APPLICATION TO 0.5 – 5% BSA; 
DOUBLE BLIND, PLACEBO CONTROLLED (Continued) 
e PK draws on day 1: 1, 2, 4 and 6 hours (± 10 minutes for 1, 2, 4 and 6 hour collections); day 14: pre-dose (trough) 
and 1-hour (± 10 minutes) post-dose; and day 28: pre-dose (trough), 1, 2, 4, 6 (± 10 minutes for 1, 2, 4 and 6 hour 
collections); and 24 hours (± 1 hour) post-dose for analysis. PKs will be collected from at least 45 volunteer subjects; 
PK collections will continue until PKs have been collected from 15 subjects in each treatment group. 
f Vehicle application training post baseline will be conducted as needed on Visits 3 (week 1) and 5 (week 3). 
g Drug or vehicle will be applied in clinic. 
h Visits 4 (week 2) and 6 (week 4) only: ARQ-151 cream or vehicle application will be done at home in the morning 
of Days 13 and 27 and in the morning at the clinic on PK collection Days 1, 14 and 28.  ARQ-151 cream or vehicle 
will not be applied in the evening of Days 13 and 27. 
I 4 mm skin punch biopsy for analysis of Roflumilast and metabolites (n = 15 for analysis).  Tissue will be collected 
from at least 15 volunteer subjects; tissue collection will continue until samples have been collected from 5 subjects 
in each treatment group. 
j Telephone call to the subjects for follow up on any continuing adverse events related to study drug.  Telephone call 
will also assess any emergent adverse event post Visit 6. 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 Follow-up visits should occur within +/- 1 day of the targeted date. 
l For those subjects participating in the PK assessment, diary is completed by subject and reviewed by study staff 
during visit (Possible Side Reactions / Comments Section of the diary). 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 16 of 51 
 
7 
 
ABBREVIATIONS 
AE 
Adverse Event 
AMP 
Adenosine Monophosphate 
AUC 
Area Under the Curve 
BSA 
Body Surface Area 
Cmax 
Maximum Concentration 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DNA 
Deoxyribonucleic Acid 
ECG 
Electrocardiography 
ERB 
Ethics Review Board 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practices 
HC 
Health Canada 
HCA 
Alpha-Hydroxycinnamaldehyde 
HPRT 
Hypoxanthine-guanine Phosphoribosyl Transferase 
IB 
Investigational Brochure 
IC50 
Half Maximal Inhibitory Concentration 
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation 
IGA 
Investigator Global Assessment 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IVRT 
In Vitro Release Testing 
mcg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
MMRM 
Mixed Model for Repeated Measures 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NOAEL 
No Observed Adverse Effect Level 
NDA 
New Drug Application 
ng 
Nanogram 
PDE-4 
Phosphodiesterase 4 
PK 
Pharmacokinetics 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 17 of 51 
 
QD 
Once Daily ("quaque die") 
SAE 
Serious Adverse Event 
Th1 
Type 1 T Helper Cell 
Th17 
Type 17 T Helper Cell 
Tmax 
Time to reach maximum concentration 
TPA 
Target Plaque Area 
TPSS 
Target Plaque Severity Score 
TPSS x TPA 
Target Plaque Severity Score x Target Plaque Area 
V79 
Chinese hamster cell line 
 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
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8 
BACKGROUND AND RATIONALE 
8.1 
Introduction 
Roflumilast is a phosphodiesterase 4 (PDE-4) inhibitor approved globally to reduce the risk of 
chronic obstructive pulmonary disease (COPD) exacerbations 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. 
Psoriasis is a chronic inflammatory skin disease characterized by raised, well-demarcated, 
erythematous oval plaques with adherent silvery scales.  Numerous past reports have suggested 
a deficiency of cyclic AMP-dependent protein kinases in human psoriatic skin (Brion 1986).  More 
recently, various cytokines produced by Th1 and Th17 cells have been shown to play a crucial 
role in the pathogenesis of psoriasis.  It has been postulated that the anti-inflammatory effects of 
PDE-4 inhibitors may provide a beneficial therapeutic intervention in the treatment of chronic 
plaque psoriasis. 
The past 15 years have witnessed a transformation in the systemic treatment of moderate to 
severe psoriasis with the advent of biological therapies.  However, for patients with milder forms 
of disease, best treated with topical options, the therapeutic landscape really has not changed in 
several decades.  Topical steroids come in all shapes and forms, but the lower potency steroids 
are not effective and the higher potency steroids are beset with issues of local skin atrophy and 
the potential for hypothalamic-pituitary axis suppression when applied over larger body surface 
areas and for prolonged periods of time.  Vitamin D has been the other staple of topical treatment 
but it is irritating, not suitable for use on the face, and its efficacy is rather modest.  Hence, there 
is substantial medical need for additional topical approaches in the treatment of psoriasis. 
8.1.1 Preclinical Studies  
Roflumilast was initially developed as a 500 mcg tablet for oral therapy in patients with COPD, 
and as such has been thoroughly evaluated in nonclinical studies.  The safety profile is well-
established and the results of those studies are relevant to the dermal roflumilast (ARQ-151 
cream) development program.  Oral roflumilast (500 mcg tablet) was approved by Health Canada 
as DAXAS® in December 2010 and by the US FDA as DALIRESP® in February 2011 for the 
treatment of COPD.  The study sponsor is conducting nonclinical studies in which roflumilast is 
applied dermally to supplement the information available through the registration and labeling of 
oral roflumilast and specifically to support initial dermal clinical trials.  Summaries of these new 
data from dermal studies and existing data from the prior oral/systemic studies follow.  In addition, 
since roflumilast N-oxide is a major active metabolite, some studies were conducted on the 
metabolite also. 
 
 

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The dermal nonclinical program for ARQ-151 cream followed current International Conference on 
Harmonisation (ICH) guidelines.  A dermal toxicology program was initiated that included a 13-
week dermal toxicity study in minipigs (with a 28-day interim sacrifice to support Phase 1 studies), 
a skin sensitization study in guinea pigs, a phototoxicity study and an eye irritation study.  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 

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8.1.2 Clinical Studies 
This will be the first study of topical ARQ-151 cream in the human population. 
However, oral roflumilast (DALIRESP®, DAXAS®) has been approved globally for the treatment 
of COPD and has been evaluated in nine Phase III/IV randomized double-blind clinical trials 
(Wedzicha 2016).  Overall, the safety of oral roflumilast has been well established in its targeted 
population of mostly middle- and upper-aged individuals who currently smoke cigarettes or have 
smoked them extensively in the past.  Adverse events (AEs) reported with roflumilast tablets have 
been consistent with those expected for oral PDE-4 inhibitors.  In a pooled analysis of safety data 
from 6-month and 1-year clinical trials (N=8630), the most common AEs were diarrhea, weight 
loss and nausea.  Other AEs reported more frequently with roflumilast treatment than with placebo 
were back pain, influenza, insomnia and decreased appetite (Michalski 2012, Wedzicha 2016). 
In addition to the self-reported cases of weight loss in the 6-month and 1-year trials, clinically 
significant weight loss was also reported in two prospective studies that evaluated weight 
(Michalski 2012). 
Psychiatric-related AEs were also greater in patients treated with roflumilast tablets (5.9%) 
compared to those treated with placebo (3.3%).  The most common psychiatric-related AEs were 
insomnia, depression and anxiety.  A small number of cases of completed suicide and suicide 
ideation have been reported in patients taking oral roflumilast in clinicals trials and also during 
post-marketing experience (Michalski 2012).   
The only contraindication to oral roflumilast, other than hypersensitivity to components of the 
product, is in patients with moderate to severe liver impairment (Child-Pugh B or C), where 
systemic levels of roflumilast may become highly elevated. 
8.2 
Rationale 
In 2016, Snape and colleagues performed a phase 1 randomized clinical trial to assess the effect 
on skin inﬁltrate thickness and tolerability of topical phosphodiesterase inhibitors, including 
roflumilast, in the treatment of psoriasis vulgaris using a modiﬁed psoriasis plaque test.  The 
products evaluated were the active comparators calcipotriol 0.005% and betamethasone 
valerate 0.1% (both in their marketed cream formulations), and investigational cream formulations 
of roﬂumilast 0.5%, TAK-084 0.5% and 5%.  A vehicle cream was used as a control (the vehicle 
cream and roflumilast formulations in this study were different from the ARQ-151 cream 
formulation).  Each treatment was applied daily to different test sites located on a single psoriasis 
plaque of an individual for 3 weeks.  Fifteen patients with psoriasis were studied.  The primary 
endpoint of mean change from baseline in skin inﬁltrate thickness after 3 weeks of treatment 

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showed statistically signiﬁcant improvements for all treatments: betamethasone valerate 
(-286.9 μm), the selective PDE-4 inhibitors roﬂumilast 0.5% (-237.1 μm), TAK-084 0.5% 
(-153.6 μm), TAK-084 5% (-216.7 μm) and calcipotriol 0.005% (-187.7 μm) when compared with 
vehicle cream control (all p < 0.001) (Snape 2016).  
The above data indicated to us that topical roflumilast, in an appropriate market image vehicle, 
could provide an important addition to the dermatologist’s armamentarium in treating chronic 
plaque psoriasis.  
8.2.1 Dose Selection 
The ARQ-151 cream 0.5% dose concentration was selected because of the efficacy observed in 
the Snape, et al study described above (Snape 2016).  
 
  
The dose concentration of ARQ-151 cream 0.15% was selected to determine whether lower 
ARQ-151 cream doses are effective and whether systemic exposure is also reduced. 
Cohort 1 will involve application of ARQ-151 cream 0.5% to 25 cm2 of psoriatic plaque(s). It is 
well known that cutaneous disease states can alter drug permeability as compared to normal 
human skin.  Since psoriatic skin is known to have different drug permeability characteristics than 
normal skin (Tang-Liu 1999), we do not believe there is anything to be gained by prior application 
of topical drug to normal human volunteers.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
8.2.2 Risks and/or Benefits to Subjects 
Subjects in Cohort 1 will not be expected to see an improvement in their psoriasis since it is a 
single dose of drug product and the purpose of Cohort 1 is PK analysis to justify the escalation in 
the area treated in Cohort 2. 

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Subjects randomized to active treatment in Cohort 2 may see an improvement in their psoriasis 
with the use of ARQ-151 cream at either or both dose levels.  Subjects randomized to the vehicle 
arm may also see an improvement as the excipients in the vehicle may have a moisturizing effect 
on the subject’s psoriatic plaques.  ARQ-151 cream is an unprecedented treatment for psoriasis 
and if efficacious, would add substantially to the dermatologist’s armamentarium in treating 
patients with this disease.  
The safety monitoring practices employed in this protocol (i.e., physical examinations, application 
site reaction assessments, hematology, serum chemistry, urinalysis, and AE questioning) are 
adequate to protect the subjects’ safety and should detect expected AEs.  
 
 
   
8.3 
Study Objectives 
8.3.1 Primary Objectives 
1. To assess the safety and PK of a single dose application of ARQ-151 cream 0.5% to 25 cm2 
of psoriatic plaque(s) (Cohort 1). 
2. To assess the safety, pharmacokinetics and efficacy of ARQ-151 cream 0.5% and ARQ-151 
cream 0.15% vs. vehicle applied QD x 28 days to individuals treated with up to 5.0% BSA of 
chronic plaque psoriasis (Cohort 2). 
8.4 
Efficacy Endpoints 
8.4.1 Primary Endpoint 
The single dose Cohort 1 will have analyses only for safety and pharmacokinetics. 
The parallel group assessment (Cohort 2) will have analyses for safety, pharmacokinetics, and 
efficacy. 
In the parallel group assessment (Cohort 2), the Primary Efficacy Endpoint will be:  
• 
Difference in mean percent change from baseline at week 4 in the product of: 
[Target Plaque Severity Score (TPSS) x Target Plaque Area (TPA)] (TPSS x TPA) 
between each dose concentration level of ARQ-151 cream and vehicle control.  This will 
be assessed as a sum of up to 3 target plaques per subject. 
 
 

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8.4.2 Secondary Endpoints 
The secondary efficacy endpoints in the parallel group (Cohort 2) assessment will include: 
1. Difference in mean percent change from baseline at weeks 1, 2, and 3 in TPSS x TPA between 
each dose concentration level of ARQ-151 cream and vehicle control.  This will be assessed 
as a sum of up to 3 target plaques per subject. 
2. Difference in mean percent change from baseline at weeks 1, 2, 3, and 4 in TPSS between 
each dose concentration level of ARQ-151 cream and vehicle control.  This will be assessed 
as a sum of up to 3 target plaques per subject. 
3. Difference in mean percent change from baseline at weeks 1, 2, 3, and 4 in TPA between 
each dose concentration level of ARQ-151 cream and vehicle control.  This will be assessed 
as a sum of up to 3 target plaques per subject. 
8.5 
Overall Study Design and Plan 
There are 2 cohorts of subjects:  
Cohort 1 is a single dose study to 25 cm2 of psoriatic plaque(s) in up to up to 8 psoriasis subjects.  
Cohort 1 subjects may then be enrolled into Cohort 2 of the study if all admission criteria are met 
at the Baseline Visit (Day 1, Visit 2, per Cohort 2).  In this case, the same plaque(s) treated in the 
Cohort 1 study may also be treated in Cohort 2.  
Cohort 2 is a parallel group, double blind, vehicle controlled study in which ARQ-151 cream 0.5%, 
ARQ-151 cream 0.15% or vehicle cream is applied QD x 28 days to subjects with between 0.5% 
to 5.0% BSA of chronic plaque psoriasis. 
Including both Cohorts, a total of up to 92 subjects will be enrolled at 7 study sites in Canada and 
1 site in the U.S.  Subjects will be adult (≥18 y/o) males or females with chronic plaque psoriasis. 
For inclusion into Cohort 2, subjects must have at least 1 target plaque of at least 9 cm2 in size 
with TPSS ≥4.  While 1 target plaque is minimally acceptable, it is strongly recommended that 2 
or 3 target plaques be identified, if present, meeting these criteria.  Target plaques may be on the 
knees and/or elbows, but priority should be given to identifying target lesions in other areas.  All 
psoriasis lesions on a subject will be treated in this Cohort except for those on the face, scalp, 
intertriginous areas, palms and soles. 
Subject Participation 
Cohort 1:  This cohort involves a minimum of three clinic visits including Screening, Baseline, one 
follow-up visit (24 hours after the baseline visit) and one follow up telephone call 7 days after the 
follow up visit.  Subjects may be asked to return for additional visits(s) if an adverse reaction 
occurs.  The interval between the Screening and Baseline visits could be up to 14 days, therefore 
the anticipated maximum duration of subject participation in Cohort 1 is 22 days.  
Cohort 2:  This cohort involves a minimum of seven clinic visits including Screening, Baseline and 
four visits at Week 1, Week 2, Week 3 and Week 4 of treatment and a day 29 visit for a final PK 
collection.  A follow-up telephone call with subjects will occur at week 5 to assess any reactions 
to discontinuing drug product and will decide upon disposition of any ongoing adverse events.  

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The interval between the Screening and Baseline visits could be up to 6 weeks, therefore the 
anticipated maximum duration of subject participation in Cohort 2 is 77 days. 
8.6 
Randomization 
Cohort 1:  Cohort 1 is an open label single dose application of ARQ-151 cream 0.5% to 25 cm2 
of psoriatic plaque(s) in up to eight (8) subjects.  Cohort 1 subjects may enroll in Cohort 2 if the 
eligibility criteria for Cohort 2 are met.  
Cohort 2:  Subjects will apply ARQ-151 cream 0.5% or ARQ-151 cream 0.15% or vehicle to 
psoriatic plaques that will not exceed an application area of 5% BSA.  Assignment of drug or 
vehicle will be made at a 1:1:1 ratio according to a computer generated randomization list.  
Randomization will take place at Baseline after the patient has been found to be fully eligible for 
participation. A kit containing ten (10) tubes of study medication will be assigned to each subject.  
Each kit has a unique kit number (randomization number). 
8.7 
Numbering of Subjects 
All treated subjects will be identified by a unique four-digit subject ID number.  The first two digits 
correspond to the site number (assigned by the Sponsor), the next three digits correspond to the 
sequential order in which the subject was enrolled into the study. Screen failures will not be 
assigned a number. 
The clinical site is responsible for maintaining a current log of subject ID number assignments 
and the kit number assigned to that subject.  The subject’s initials (first/middle/last) and ID number 
are 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.).  
8.8 
Blinding 
Cohort 1: This is an open label Cohort, therefore both the subjects and the clinical personnel will 
be aware that ARQ-151 cream 0.5% will be applied to 25 cm2 of psoriatic plaque(s). 
Cohort 2: This is a double-blind Cohort, therefore neither the subjects nor the clinical personnel 
will be aware of which treatment an individual has received. 
8.9 
Selection of Study Population 
8.9.1 Inclusion Criteria 
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 
2. Cohort 1:  Adult male and female subjects aged ≥18 years with at least 25 cm2 of chronic 
plaque psoriasis (diagnosed by a dermatologist). 
3. Cohort 2: Adult male and female subjects aged ≥18 years with chronic plaque psoriasis 
(diagnosed by a dermatologist) covering 0.5% to 5.0% of total BSA excluding the face, scalp, 
intertriginous areas, palms and soles.   

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4. Subjects must have at least one target plaque, of at least 9 cm2 in size with a TPSS ≥4.  Target 
plaques may be on the knees and/or elbows, but priority should be given to identifying target 
lesions in other areas.  All psoriasis lesions on a subject will be treated in this study except 
for those on the face, scalp, intertriginous areas, palms and soles. 
5. Psoriasis disease duration of ≥6 months at the baseline visit. 
6. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test at 
Screening (Visit 1). In addition, sexually active WOCBP must agree to use at least one form 
of highly effective contraception throughout the trial.  Highly effective forms of contraception 
include: oral/implant/injectable/transdermal contraceptives, intrauterine device, and partner’s 
vasectomy.  If barrier methods are used (e.g., condom with spermicide, diaphragm with 
spermicide), then 2 forms of conception are required. 
7. Women of non-childbearing potential (WONCBP) must either be post-menopausal with 
spontaneous amenorrhea for at least 12 months with a serum follicle stimulating hormone 
(FSH) level of ≥ 30 mIU/mL or have undergone surgical sterilization (permanent sterilization 
methods include hysterectomy, bilateral oophorectomy, hysteroscopic sterilization, bilateral 
tubal ligation or bilateral salpingectomy).  
8. In good health as judged by the Investigator, based on medical history, physical examination, 
12-lead electrocardiogram (ECG), serum chemistry labs, hematology values, and urinalysis. 
9. Subjects agree not to have prolonged sun exposure during the course of the study.  Tanning 
bed use is not allowed. 
10. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule, 
according to the judgment of the Investigator. 
8.9.2 Exclusion Criteria 
1. Subjects with non-plaque forms of psoriasis (erythrodermic, guttate, pustular or palmo-plantar 
psoriasis) 
2. Subjects with drug-induced psoriasis 
3. Evidence of skin conditions at the time of Screening Visit other than psoriasis that would 
interfere with evaluations of the effect of the study medication on psoriasis, as determined by 
the Investigator 
4. Subjects with any serious medical condition or laboratory abnormality, that would prevent 
study participation or place the subject at significant risk, as judged by the investigator 
5. Subjects with any psychiatric illness that would prevent study participation or place the subject 
at significant risk, as judged by the investigator 
6. Pregnant or lactating women or women planning to become pregnant during the study and / 
or within 28 days following the last dose of study medication 
7. Known allergies to excipients in ARQ-151 cream (petrolatum, isopropyl palmitate, 
methylparaben, propylparaben, Diethylene Glycol Monoethyl Ether, hexylene glycol, 
cetylstearyl alcohol, dicetyl phosphase and ceteth-10 phosphate)  

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8. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers 
e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, 
and rifampin for two weeks prior to the baseline visit and during the study period. 
9. Subjects who cannot discontinue the use of strong P-450 cytochrome inhibitors e.g., indinavir, 
nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, 
suboxone and telithromycin for two weeks prior to the baseline visit and during the study 
period. 
10. Subjects who are unwilling to refrain from using a tanning bed for 2 weeks prior to baseline 
and during the study 
11. Subjects who have received oral roflumilast (Daxas®, Daliresp®) within the past 4 weeks  
12. Subjects who cannot discontinue systemic therapies and/or topical therapies for the treatment 
of psoriasis prior to the baseline visits and during the study period according to the table 
below: 
Excluded Medications and treatments 
Wash out period prior to Day 1 
Topical psoriasis medications (corticosteroids, 
calcipotriene, topical vitamin D derivatives, 
retinoids, anthralin, coal tar) 
Cohort 1: 48 hours 
Cohort 2: 14 days 
Systemic non-biologic treatments for psoriasis 
(apremilast, methotrexate, cyclosporine, 
azathioprine, corticosteroids) 
Cohort 1: 48 hours 
Cohort 2:  28 days 
UVB or PUVA phototherapy 
Cohort 1: 48 hours 
Cohort 2: 28 days 
Systemic retinoids 
Cohort 1: 48 hours  
Cohort 2: 12 weeks 
All biologics 
Cohort 1: 48 hours  
Cohort 2: 12 weeks 
Investigational drugs 
Cohort 1: 48 hours 
Cohort 2: 12 weeks (biologics); 
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 as normally used by the 
subjects. 
 
 
 

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13. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of study 
medication.  
14. History of and/or concurrent condition of serious hypersensitivity (anaphylactic shock or 
anaphylactoid reaction) to PDE-4 inhibitors. 
15. Current or a history of cancer within 5 years with the exception of fully excised skin basal cell 
carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. 
16. Subjects with active infection that required oral or intravenous administration of antibiotics, 
antifungal or antiviral agents within 7 days of Baseline/Day 1 
17. 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. 
8.9.3 Removal of Subjects from the Study 
Subject participation in this trial may be discontinued for any of the following reasons: 
1. 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 of the Protocol. 
2. Any SAE, clinically significant AE, severe laboratory abnormality, intercurrent illness, or other 
medical condition that occurs which the Investigator determines continued participation is not 
in the best interest of the subject. 
3. Subject's decision to withdraw. 
4. Requirement for use of prohibited concomitant medication. 
5. Subject’s repeated failure to comply with protocol requirements or study related procedures. 
6. The subject interrupts trial study drug application for more than 50% of scheduled doses. 
7. Termination of the study by the Sponsor, FDA, or other regulatory authorities. 
8.10 Study Restrictions 
8.10.1 Prohibitions and Concomitant Therapy 
Prohibited medications and products are detailed in the exclusion criteria (Section 8.9.2).   
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.  

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8.11 Treatments 
8.11.1 Drug Administration 
Cohort 1: ARQ-151 cream 0.5% will be applied by site personnel to 25 cm2 of psoriatic plaque(s) 
(more than one plaque may be identified for a total area of 25 cm2).  
The study sponsor or its representative will ensure the study staff can demonstrate proper dosing 
for Cohort 1 at the Site Initiation Visit. Study staff will be trained to ensure a unit dose (a pea-sized 
amount of ARQ-151 cream vehicle) is properly squeezed from the vehicle training tube and 
applied as a thin film and rubbed in using the index and middle finger, rubbing in thoroughly but 
gently, until the ‘white’ has disappeared. 
Cohort 2:  At the randomization visit, the study staff will demonstrate to the subject how to apply 
ARQ-151 cream or vehicle using the first tube from the kit that is assigned to the subject at 
randomization.  The study staff will demonstrate application to the subject according to the 
technique described above.  The subject will then practice squeezing a similar amount onto their 
index and middle finger and apply a thin film to areas to be treated.  The study staff will confirm 
that the subject’s application technique is correct.  
Re-training will be conducted at subsequent visits (visits 3 and 5) as needed using a vehicle 
training tube (i.e., if a returned tube weighs substantially more or less than the expected weight). 
Subjects will be instructed to apply study medication each evening at least 15 minutes after 
showering or bathing (if they take an evening shower/bath) and then to not wash areas where 
ARQ-151 cream or vehicle have been applied until the following morning.  Study medication 
should be applied at least 10 minutes before going to bed. 
Each study medication tube will be weighed prior to dispensing at the baseline visit and each 
follow up visit.  Study medication tubes returned by subjects will also be weighed and compliance 
will be assessed. If the subject’s actual use is substantially greater than or less than the expected 
use, the subject will retrained on the study drug application technique.  
8.11.2 Treatment Stopping Rules 
Any topically applied product may irritate the skin.  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 (8.12.6), treatment should be discontinued for up to one week and may then be resumed 
if the reaction has, in the opinion of the Investigator, adequately resolved.  If the reaction reoccurs, 
treatment should be discontinued permanently and the subject followed until the reaction 
resolves.   
8.11.2.1 Unblinding Due to Application Site Reactions 
If a subject is terminated from the study due to non-resolution or reoccurrence of a skin reaction 
after having undergone up to a one-week treatment interruption, the Sponsor’s Chief Medical 
Officer (CMO) may be unblinded as to treatment assignment of that subject.  The determination 
of whether or not to unblind will be made by the CMO taking into account the severity of the 
reactions, the number of subjects involved, and the number of discontinuations.   

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8.11.3 Treatment Compliance  
Study medication tubes will be weighed at each follow-up clinic visit.  Additionally, 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 AEs. Site 
personnel will review the diaries 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 dose, they should be instructed to return to the 
per protocol study medication administration schedule.   
8.12 Safety Assessments 
The Schedule of Visits and Assessments (Section 6) 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 PI and/or the Sponsor for reasons related 
to subject safety. 
This study assesses the safety and efficacy of ARQ-151 cream. Safety will be determined by 
evaluating physical examinations, application site reaction assessments, vital signs, ECGs, 
clinical laboratory parameters, and AEs as outlined in the Schedule of Visits and Assessments 
(Section 6). If deemed necessary, additional safety assessments will be performed at the 
discretion of the PI. 
8.12.1 Screening 
Within 14-42 days (depending on which Cohort the subject is enrolled) prior to the first dosing, 
subjects will be provided details of study requirements and sign an informed consent.  Medical 
history and demographic data, including name, sex, age, race, ethnicity, body weight (kg), and 
height (cm) will be recorded. Each subject will undergo psoriatic plaque assessments, a physical 
examination, vital sign measurements (blood pressure, heart rate, and temperature), 12-lead 
ECG, dermal photography (at four investigational centers), and laboratory tests of hematological, 
hepatic and renal function, urinalysis, urine drug screen and a pregnancy test for female subjects. 
8.12.2 Physical Examination 
Physical examinations will be performed as follows: 
Cohort 1 at Screening and Day 1.   
Cohort 2 at Screening, Baseline, and Week 4.   
For both Cohorts, the physical exam will be limited to skin, lungs and heart only. 
8.12.3 Vital Signs and Weight 
Blood pressure, heart rate, temperature, and weight will be measured at every visit for both 
Cohorts. 

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8.12.4 ECG Monitoring 
Single 12-lead ECGs will be performed at Screening for both Cohorts and at Baseline and Week 
4 for Cohort 2. 
ECGs will be performed on subjects in the supine position. All ECG tracings and readouts will be 
reviewed by the Study Physician or his/her designee. 
8.12.5 Laboratory Tests 
All tests listed below will be performed according to the Study Events Flow Chart unless otherwise 
noted. The collection of specimens will be in a non-fasting state. In addition, laboratory safety 
tests may be performed at various unscheduled time points, if deemed necessary by the 
Investigator.  
All tests listed below will be performed as follows: 
Cohort 1: Screening and Day 2 
Cohort 2 and Cohort 1 subjects who rollover into Cohort 2:  Screening, Baseline, Week 2, and 
Week 4.    
 
 

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The collection of specimens will be in a non-fasting state. In addition, laboratory safety tests may 
be performed at various unscheduled time points, if deemed necessary by the PI.  
Hematology 
 
Serum Chemistry 
• 
Hemoglobin 
• 
Hematocrit  
• 
Total and differential leukocyte 
count 
• 
Red blood cell count with 
indices and morphology 
• 
Platelet count 
 
• 
Blood Urea Nitrogen 
• 
Bilirubin (total and direct) 
• 
Alkaline phosphatase 
• 
Aspartate aminotransferase 
• 
Alanine aminotransferase 
• 
Albumin 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Glucose 
• 
Creatinine  
Urinalysis 
 
Additional Tests 
• 
pH 
• 
Specific gravity 
• 
Protein* 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Blood* 
• 
Nitrite* 
• 
Urobilinogen 
• 
Leukocyte esterase* 
 
• 
Urine drug screen** 
➢ Amphetamines 
➢ Barbiturates 
➢ Benzodiazepine 
➢ Cocaine 
➢ Cannabinoid 
➢ Methadone 
➢ Opiates 
➢ PCP 
➢ Propoxyphene  
• 
Urine pregnancy test***  
(for females only) 
* 
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. 
**  Only at Screening visit 
*** All visits for both Cohorts except Day 2 for Cohort 1 
 
 
 

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8.12.6 Application Site Reaction Assessment (Cohorts 1 and Cohort 2) 
Application Site Reaction Assessments will be performed as follows: 
Cohort 1: Day 1 and Day 2 
Cohort 2: Baseline (Visit 2), Visit 3, Visit 4, Visit 5 and Visit 6 
Application site reactions will be graded at the timepoints outlined in the Schedule of Visits and 
Assessments (Section 6).  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 
psoriasis.  Changes in Dermal Response scores, consistent with disease fluctuation, will only be 
recorded as an AE if the Investigator considers the change to be worse than normal fluctuation. 
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 covering all or part of the patch site 
 
F = small petechial erosions and/or scabs 
G = no other effects 
 
 

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8.13 Efficacy Evaluations (Cohort 2 Only) 
8.13.1 Product of the Target Plaque Severity Score (TPSS) and the Target Plaque Area 
(TPA) 
Target Plaque Severity Score (TPSS) will be determined for each target plaque on each subject 
as the sum of erythema (graded 0-4), thickness (graded 0-4), and scaling (graded 0-4) using the 
descriptors listed below. 
Erythema  
0 = none (includes hyperpigmentation) 
1 = Mild - faint redness 
2 = Moderate - red 
3 = Severe - Bright red / dark red 
4 = Very Severe - Extremely dark red / purple 
Thickness  
0 = none - no elevation over normal skin 
1 = Mild - slight elevation 
2 = Moderate -  moderate elevation with rough or sloped edges 
3 = Severe -  marked elevation with hard or sharp edges 
4 = Very Severe - very marked elevation with hard and sharp edges 
Scaling  
0 = none  
1 = Mild - fine scale that covers part (≤ 50%) of the lesion 
2 = Moderate - fine to rough scale that covers a large part (>50%) of the lesion 
3 = Severe - rough, thick scale that covers almost all the lesion  
4 = Very Severe - very rough, very thick scale that completely covers the lesion 
Target plaque area (cm2) is determined by multiplying the longest diameter (cm) of the target 
plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the 
target plaque).  The same plaque(s) will be measured at each applicable visit.  If a plaque is 
resolved after baseline with a score of 0 for all descriptors (i.e., Erythema, Thickness and Scaling), 
then the TPSS x TPA should be recorded as 0.  
 
 

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Values for TPSS and measurement of the Target Plaque Area will be calculated at Screening, 
Baseline, Visit 3, Visit 4, Visit 5 and Visit 6. 
Investigators should aim to identify up to 3 target plaques of at least 9 cm2 in size with TPSS ≥4.  
One or two target plaques are acceptable, but only if a subject does not have three plaques 
meeting the criteria of at least 9 cm2 with a TPSS ≥4.  Target plaques may be on the knees and/or 
elbows, but priority should be given to identifying target lesions in other areas. 
Whenever possible, the same individual who performs the target plaque analyses for a 
subject at baseline should continue to perform the analyses for that subject during the 
course of the study. 
Changes in Target Plaque Severity Scores consistent with disease fluctuation, will only be 
recorded as an AE if the Investigator considers the change to be worse than normal fluctuation. 
8.13.2 Dermal Imaging 
Photography will be performed at four centers only during the following visits:  Baseline, Visit 3, 
Visit 4, and Visit 6. 
8.14 Depressive Symptomatology Questionnaire (Cohort 2 Only) 
Depressive Symptomatology Questionnaire will be administered at Screening, Week 2 and Week 
4. 
8.15 Pharmacokinetic Assessment 
Cohort 1:  Plasma PK assessments will be performed on all subjects. 
Cohort 2:  Plasma PK assessments will be performed on 45 subjects.  Tissue metabolite 
assessments will be performed on 15 subjects. 
8.15.1 Blood and Skin Sampling and Processing 
Blood samples for pharmacokinetic evaluation will be performed as follows: 
Cohort 1: PK draws will be done at 1, 2, 4, 6, and 24 hours after ARQ-151 cream 0.5% application 
to 25 cm2 of psoriatic plaque(s). 
Cohort 2: PK draws will be done on day 1: 1, 2, 4 and 6 hours; day 14: pre-dose (trough) and 
1-hour post-dose; and Day 28: pre-dose (trough), 1, 2, 4, 6 and 24 hours. On days 1, 14, and 28, 
study medication will be applied in the clinic and blood draws performed subsequently.  Subjects 
will be contacted on days 12 and 26 and reminded to apply their study medication in the morning 
of days 13 and 27.  Study medication will not be applied in the evening of days 13 and 27. 
An optional 4 mm diameter punch biopsy will be collected from a target plaque at the Day 28 Visit.  
The punch biopsy will include the epidermis, dermis, and sub-cutaneous skin layers.  

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8.16 Adverse Events  
8.16.1.1 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. 
8.16.1.2 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 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 
serious events are deemed drug-related. All serious event reporting will adhere to ICH E6: 
Guideline for Good Clinical Practice and ICH E2A: Clinical Safety Data Management: Definitions 
and Standards for Expedited Reporting.:  The ERB/IRB will be notified of the Alert Reports as per 
HC, FDA, ICH and the ERB’s policies and procedures. 
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. 
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. 
If a SAE occurs to a subject on this study, contact the Sponsor personnel listed in Section 3. 
8.16.1.3 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.   

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AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s) 
will be evaluated by the PI and treated and/or followed up for up to one month after end of 
treatment until the symptoms or value(s) return to normal, or acceptable levels, as judged by the 
PI. 
Treatment of SAEs will be performed by a physician. Where appropriate, medical test(s) and/or 
examination(s) will be performed to document resolution of event(s). Outcome may be classified 
as resolved, improved, unchanged, worse, fatal or unknown (lost to follow-up). 
8.16.1.4 Reporting 
The PI 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 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 (resolved, improved, unchanged, worse, 
fatal, or unknown/lost to follow-up) of each event will be noted. 
The relationship of each AE to the study drug 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 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® available at Premier Research (e.g., 18.1 or 
higher). 
9 
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. 
9.1 
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 for Cohort 2.  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) unless otherwise stated. No 
interim efficacy analyses are planned. 
Descriptive statistics will be used to provide an overview of the efficacy, safety and 
pharmacokinetic results.  For categorical parameters, the number and percentage of subjects in 
each category will be presented. The denominator for percentage will be based on the number of 
subjects appropriate for the purpose of analysis.  For continuous parameters, descriptive statistics 
will include n (number of subjects), mean, standard deviation (SD), median, minimum, and 
maximum. 

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P-values of less than 0.05 will be considered statistically significant based on a two-sided test 
unless otherwise specified. 
9.1.1 Determination of Sample Size 
A sample size of 24 per arm (72 total) will provide 80% power to detect a difference of 23% in the 
mean percent change from baseline in TPSS x target plaque area (cm2) between the ARQ-151 
cream and the matching vehicle arms, with a standard deviation for the change of 25%. This is 
based on a one-way analysis of variance (ANOVA) at the α = 0.025 significance level. With a 16% 
dropout rate, the sample size for the study would be increased to 84 subjects. 
9.1.2 Subjects to Analyze 
Safety population will include all subjects who are enrolled and received at least one confirmed 
dose of study medication. This population will be defined separately for each cohort. 
The Modified Intent-to-Treatment (mITT) population will include all subjects who are in the safety 
population for Cohort 2 with at least one post-baseline efficacy evaluation. 
Per-Protocol (PP) Population will include all subjects who are in the safety population for Cohort 
2, were at least 80% compliant with study medication, and showed no other serious deviations 
from the study protocol. 
The PK population will include all subjects receiving the active drug with sufficient plasma 
concentrations of roflumilast to define a profile, as determined by the pharmacokineticist. This 
population will be defined separately for each cohort. 
9.1.3 Interim Analysis 
No interim efficacy analyses are planned. 
9.1.4 Background and Demographic Characteristics 
Descriptive statistics will be used to summarize demographic characteristics (age, sex, and race) 
and background characteristics for the enrolled subjects in Cohort 1 and the randomized subjects 
in Cohort 2.  Past/coexistent medical history information and physical examination observations 
and vital signs information for all randomized subjects will be presented in a by-subject listing.   
9.1.5 Study Medication Compliance 
The number of doses received by each subject based on diary data will be summarized using 
summary statistics (mean, standard deviation [SD], median, minimum, and maximum), and 
categorically.  
The amount of study medication received by each subject based on tube weight will be 
summarized by treatment using summary statistics (mean, SD, median, minimum, and 
maximum), and categorically.   

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9.2 
Efficacy (Cohort 2) 
Efficacy will be assessed for Cohort 2 only. 
9.2.1 Primary Efficacy Endpoint 
In the parallel group assessment (Cohort 2), the Primary Efficacy Endpoint will be the Difference 
in mean percent change from baseline at week 4 in TPSS x TPA between each dose 
concentration level of ARQ-151 cream and vehicle control.  This will be assessed as a sum of up 
to 3 target plaques per subject. 
The primary endpoint will be analyzed using a mixed model for repeated measures (MMRM), with 
center, treatment, study visit, and study visit-by-treatment interaction as fixed effects and baseline 
TPSS x TPA score as a covariate. An unstructured covariance structure will be used, unless the 
model does not converge; in that case, the appropriate covariance structure will be investigated. 
The Bonferroni method will be used to control for multiplicity, where the significance level for each 
of the two comparisons of active versus placebo is α=0.025. 
Descriptive statistics for absolute and percent change from baseline at Week 4 will be provided. 
9.2.2 Secondary Efficacy Endpoints 
1. Difference in mean percent change from baseline at weeks 1, 2, and 3 in TPSS x TPA between 
each dose concentration level of ARQ-151 cream and vehicle control.  This will be assessed 
as a sum of up to 3 target plaques per subject. 
2. Difference in mean percent change from baseline at weeks 1, 2, 3, and 4 in TPSS between 
each dose concentration level of ARQ-151 cream and vehicle control.  This will be assessed 
as a sum of up to 3 target plaques per subject.  
 
3. Difference in mean percent change from baseline at weeks 1, 2, 3, and 4 in TPA between 
each dose concentration level of ARQ-151 cream and vehicle control.  This will be assessed 
as a sum of up to 3 target plaques per subject. 
 
All secondary endpoints will be analyzed similarly to the primary endpoint; however, adjustments 
for multiplicity will not occur and all analyses will be conducted at the α=0.05 level.  
9.3 
Safety Evaluation 
The following analyses will be performed; however, no formal inferential statistics will be 
performed on safety assessments. 
Descriptive statistics will be calculated for quantitative safety data and frequency counts will be 
compiled for classification of qualitative safety data.  

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Adverse Events: 
The assessment of safety will be based mainly on the frequency and percent of subjects who 
reported treatment-emergent AEs.  
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA) Version 18.1 or higher.  Treatment emergent adverse events (i.e. events with onset 
dates on or after the start of study drug or with missing onset dates) will be summarized by 
presenting for each treatment group, the number and percentage of subjects having any AE, 
having an AE in an individual body system, and having an AE in an individual preferred term.  Any 
other information collected (e.g. severity or relatedness to study medication) will be listed as 
appropriate. 
Application Site Reaction 
The numeric application site reaction scores will be summarized individually by using number and 
percentage of subjects by visit.   
Medical History and Physical Examinations: 
Medical history for all subjects will be presented in a by-subject listing.  
Physical examination findings for all subjects will be presented in a by-subject listing.  Changes 
in physical examinations will be described in the text of the final report. 
Clinical Laboratory Results, Electrocardiograms and Vital Signs Measurements:12 
All clinical laboratory results, 12-lead ECGs and vital signs measurements and their change from 
baseline (pre-dose), will be summarized along with time point of collection. 
A shift table describing out-of-normal range shifts will be provided for clinical laboratory results.  
Prior and Concomitant Medications: 
Prior and concomitant medication information for all randomized subjects will be presented in a 
by-subject listing.  Summary tables will be presented by World Health Organization-Anatomical 
Therapeutic Chemical Classification System (WHO-ATC) therapeutic category and product. 
Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR): 
The total score of the QIDS-SR (i.e., the sum of the 16 individual item scores) will be summarized 
by visit. Additionally, the number and percentage of subjects meeting the criteria for each severity 
level based on total score (i.e., normal, mild, moderate, moderate to severe, and severe) will be 
presented by visit. 

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9.4 
Pharmacokinetic Analysis 
Pharmacokinetic parameter estimates for roflumilast will be calculated by a standard 
noncompartmental method of analysis; these may include AUC0-t, AUC0-inf, Cmax, tmax, and others, 
as data permit. Pharmacokinetic parameters will be summarized using appropriate descriptive 
statistics. Time to reach maximum concentration (tmax) will be summarized using n, mean, 
standard deviation, median, minimum, and maximum. All other PK parameters will also be 
summarized using geometric mean and coefficient of variation. 
For all subjects, blood samples for the determination of roflumilast and its metabolites will be 
collected at scheduled time points as delineated in the Schedule of Visits and Assessments 
(Section 6).   
Note: the sample times for PK collection are in relation to the start of drug application. 
A manual for blood sampling, collection, processing, and sample shipment will be provided in a 
separate document.  
STUDY ADMINISTRATION 
9.5 
Ethics 
9.5.1 Ethics Review Board  
Before enrollment of patients into the study, the current protocol and ICF 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 study drug(s) during the 
study, per the IRB or IEC local requirements, and in compliance with FDA and Health Canada 
regulations and ICH GCP guidelines. 
9.5.2 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 GCP (E6 Consolidated Guidance, April 1996). 

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9.5.3 Subject Information and Consent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and date 
an ICF summarizing the discussion prior to screening, and will be assured that they may withdraw 
from the study at any time without jeopardizing their medical care. 
Subjects will be given a signed copy of their ICF. 
9.6 
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 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 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. 
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. 
9.7 
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 using SAS® to check 
for missing data, data inconsistencies, data ranges etc. Corrections are made prior to database 
lock. 
 
 

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9.8 
Drug Supplies, Packaging and Labeling 
The Sponsor will supply sufficient quantities of the study drug (ARQ-151 cream 0.5% and 
ARQ-151 cream 0.15%) and placebo (matching vehicle cream) to each site to allow for completion 
of this study. 
Records will be made of the receipt and dispensing of the study drugs supplied. At the conclusion 
of the study, any unused study drugs will be returned to the Sponsor or designee, or destroyed, 
as per Sponsor instructions. 
9.9 
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 
ERB/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 CRFs using black ballpoint pen.  Any change of data 
will be made by marking out the original value with a single line, recording the revised value, the 
date of the change, and the initials of the party making the change alongside the corrected value.  
Liquid correction (i.e., “white out”) and erasing are not permitted on CRFs. 
9.10 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).  
9.11 Publication Policy 
The Sponsor is supportive of publishing clinical trial findings.  The process of coordinating 
publication efforts is detailed in the Clinical Trial Agreement. 
 

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10 REFERENCES 
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Bethke, TD, Lahu, G.  High absolute bioavailability of the new oral phosphodiesterase-4 inhibitor 
roflumilast.  Int. J Clin Pharmacol Ther.  2011; 49:51-57. 
Brion DE, Raynaud F, Plet A, Laurent P, Leduc B, and Anderson W.  Deficiency of cyclic 
AMP-dependent protein kinases in human psoriasis.  Proc. Natl. Acad. Sci.  1986; 83:5272-5276. 
DALIRESP (roflumilast) tablets [package insert]. AstraZeneca Pharmaceuticals LP, Wilmington, 
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DAXAS (roflumilast) film-coated tablets [product monograph]. AstraZeneca Canada, Inc., 
Mississauga, Ontario Canada; 2017. 
Hatzelmann A, Morcillo EJ, Lungarella G, Adnot S, Sanjar S, Beume R, 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, Version 01, October 2017 
Michalski, J. M., Golden, G., Ikari, J. and Rennard, S. I. (2012), PDE4: A Novel Target in the 
Treatment of Chronic Obstructive Pulmonary Disease. Clinical Pharmacology & Therapeutics, 91: 
134–142 
Snape SD, Wigger-Alberti W, Goehring, UM.  A phase I randomized trial to assess the effect on 
skin inﬁltrate thickness and tolerability of topical phosphodiesterase inhibitors in the treatment of 
psoriasis vulgaris using a modiﬁed psoriasis plaque test.  Br J Dermatol.  2016; 175:479-486. 
Tang-Liu DD, Matsumoto RM, Usansky JI. Clinical pharmacokinetics and drug metabolism of 
tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet. 1999; 
37:273-287. 
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. 
 

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Appendix 1: Target Plaque Severity Score (TPSS) 
Rating 
Erythema 
Thickness (induration) 
Scaling (desquamation) 
0 = None 
none (includes 
hyperpigmentation) 
no elevation over normal 
skin 
none 
1 = Mild 
faint redness 
slight elevation 
fine scale that covers part (≤ 
50%) of the lesion 
2 = Moderate 
red 
moderate elevation with 
rough or sloped edges 
fine to rough scale that covers a 
large part (>50%) of the lesion 
3 = Severe 
Bright red / dark red 
marked elevation with 
hard or sharp edges 
rough, thick scale that covers 
almost all the lesion 
4 = Very severe 
Extremely dark red / 
purple 
very marked elevation 
with hard and sharp 
edges 
very rough, very thick scale that 
completely covers the lesion 
Target Plaque Severity Score 
 
0 = None 
1 = Mild 
2 = Moderate 
3 = Severe 
4 = Very Severe 
 
Target Lesion 
1 
Target Lesion 
2 
Target Lesion 
3 
Locations of target Lesions (i.e. R. forearm) 
 
 
 
Erythema (E) 
 
 
 
Induration (I) 
 
 
 
Scaling (S) 
 
 
 
Total Each Column 
 
 
 
Dimensions and Areas of Target Lesions 
 
Target Lesion 
1 
Target Lesion 
2 
Target Lesion 
3 
Longest Diameter (cm) 
 
 
 
Widest Perpendicular diameter (cm) 
 
 
 
Target Plaque Area, cm2 (Longest diameter x 
widest perpendicular diameter) 
 
 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 48 of 51 
 
Appendix 2 Depressive Symptomatology Questionnaire 
 
 

Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
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Confidential 
 Page 49 of 51 
 
 

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Amendment 2.0 
 
 
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Confidential 
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Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 51 of 51