Conditions: Psoriasis
Keywords: Psoriasis Plaque Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 91
Healthy volunteers: no

Brief summary:
This study assessed the safety and pharmacokinetics (PK) of a single dose application of ARQ-151 cream 0.5% to 25 cm\^2 of psoriatic plaque(s) (Cohort 1). The study also assessed the safety, PK and efficacy of ARQ-151 cream 0.5% vs vehicle and ARQ-151 cream 0.15% vs vehicle applied once a day for 28 days to individuals with 0.5% to 5.0% body surface area (BSA) of chronic plaque psoriasis (Cohort 2).

Detailed description:
There were 2 cohorts of participants. Cohort 1 was a single dose study of ARQ-151 0.5% cream applied to 25 cm\^2 of psoriatic plaque(s) in 8 psoriasis participants. Cohort 2 was a parallel group, double blind, vehicle controlled study in which ARQ-151 cream 0.5%, ARQ-151 cream 0.15% or vehicle cream was applied once a day for 28 days to participants with between 0.5% to 5.0% BSA of chronic plaque psoriasis. Participants were adult (≥18 years old) males or females with chronic plaque psoriasis.

Arms:
arm 1: Single-dose application of ARQ-151 cream 0.5% to 25 cm\^2 of psoriatic plaque(s) arm 2: ARQ-151 cream 0.5% applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA arm 3: ARQ-151 cream 0.15% applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA arm 4: Vehicle cream applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA

Interventions: intervention 1: ARQ-151 cream 0.5% intervention 2: ARQ-151 cream 0.15% intervention 3: ARQ-151 vehicle cream
Intervention descriptions: intervention 1: 0.5% active concentration intervention 2: 0.15% active concentration intervention 3: Vehicle cream

Protocol document:
Prot_000.pdf: 
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 
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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 
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 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 


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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 
 
 
 


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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 
Berger, RS, Bowman JP. A reappraisal of the 21-day Cumulative Irritation Test in man.  J. Toxicol 
Ot & Ocular Toxicol 1982:1(2);109-115. 
Bethke, TD, Lahu, G.  High absolute bioavailability of the new oral phosphodiesterase-4 inhibitor 
roflumilast.  Int. J Clin Pharmacol Ther.  2011; 49:51-57. 
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, 
DE USA; 2017. 
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. 
 


Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 47 of 51 
 
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 
 
 
19 March 2018 
Confidential 
 Page 49 of 51 
 
 


Protocol ARQ-151-101 
Arcutis, Inc. 
Amendment 2.0 
 
 
19 March 2018 
Confidential 
 Page 50 of 51 
 


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

SAP_001.pdf: 
Arcutis, Inc. 
Clinical Study Report ARQ-151-101 
AD-MW-36.02 25-Aug-2017 
CONFIDENTIAL 
16.1.9 
Documentation of Statistical Methods 
Final Statistical Analysis Plan, Version 1.0, dated 06-May-2018 
Page 1
16.1 Study Information
NCT03392168


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
PCN Number ARCU7063
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 1 of 107 
Sponsor 
Arcutis, Inc. 
Protocol Title: 
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 
Protocol Number: 
ARQ-151-101 
Premier Research PCN: 
ARCU7063 
Document Version: 
Final Version 1.0 
Document Date: 
06-May-2018
Approvals 
Role 
Signatures 
Date (dd-Mmm-yyyy) 
Lead 
Biostatistician 
Print Name:
 
Sign Name:
Arcutis, Inc. 
Representative 
Print Name: 
 
Sign Name:
	
	
		
Page 2
SIGN


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 2 of 107 
Document History 
Not applicable. 
Page 3


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
PCN Number ARCU7063
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 3 of 107 
Table of Contents 
Approvals ........................................................................................................................................ 1 
Document History ........................................................................................................................... 2 
Table of Contents ............................................................................................................................ 3 
List of Tables .................................................................................................................................. 5 
List of Figures ................................................................................................................................. 5 
1.
Overview ............................................................................................................................. 6 
2.
Study Objectives and Endpoints ......................................................................................... 6 
2.1.
Study Objectives ........................................................................................................... 6 
2.1.1. Primary Objectives........................................................................................................ 6 
2.2.
Study Endpoints ............................................................................................................ 7 
2.2.1. Safety Endpoints ........................................................................................................... 7 
2.2.2. Efficacy Endpoints ........................................................................................................ 7 
2.2.3. Pharmacokinetic Variable(s) ......................................................................................... 7 
2.2.4. Other Endpoints ............................................................................................................ 8 
3.
Overall Study Design and Plan ........................................................................................... 8 
3.1.
Overall Design .............................................................................................................. 8 
3.2.
Sample Size and Power ................................................................................................. 8 
3.3.
Study Population ........................................................................................................... 9 
3.4.
Treatments Administered .............................................................................................. 9 
3.5.
Method of Assigning Subjects to Treatment Groups .................................................... 9 
3.6.
Blinding and Unblinding............................................................................................... 9 
3.7.
Schedule of Events ........................................................................................................ 9 
4.
Statistical Analysis and Reporting .................................................................................... 14 
4.1.
Introduction ................................................................................................................. 14 
4.2.
Interim Analysis and Data Monitoring ....................................................................... 14 
5.
Analysis Populations ......................................................................................................... 14 
6.
General Issues for Statistical Analysis .............................................................................. 15 
6.1.
Statistical Definitions and Algorithms ........................................................................ 15 
6.1.1. Baseline ....................................................................................................................... 15 
6.1.2. Adjustments for Covariates......................................................................................... 15 
6.1.3. Multiple Comparisons ................................................................................................. 15 
6.1.4. Handling of Dropouts or Missing Data ....................................................................... 16 
6.1.5. Analysis Visit Windows ............................................................................................. 16
Page 4


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 4 of 107 
6.1.6. Pooling of Sites ........................................................................................................... 17 
6.1.7. Derived Variables ....................................................................................................... 17 
6.1.8. Data Adjustments/Handling/Conventions .................................................................. 18 
7.
Study Subjects and Demographics.................................................................................... 20 
7.1.
Disposition of Subjects and Withdrawals ................................................................... 20 
7.2.
Protocol Violations and Deviations ............................................................................ 20 
7.3.
Demographics and Other Baseline Characteristics ..................................................... 20 
7.4.
Exposure and Compliance .......................................................................................... 20 
8.
Efficacy Analysis .............................................................................................................. 21 
8.1.
Primary Efficacy Analysis .......................................................................................... 21 
8.2.
Secondary Efficacy Analysis ...................................................................................... 21 
9.
Safety and Tolerability Analysis ....................................................................................... 22 
9.1.
Adverse Events ........................................................................................................... 22 
9.1.1. Adverse Events Leading to Discontinuation............................................................... 23 
9.1.2. Deaths and Serious Adverse Events ........................................................................... 23 
9.1.3. Other Significant Adverse Events ............................................................................... 23 
9.2.
Application Site Reaction Assessments ...................................................................... 24 
9.3.
Clinical Laboratory Evaluations ................................................................................. 24 
9.4.
Vital Signs ................................................................................................................... 24 
9.5.
12-Lead Electrocardiogram ........................................................................................ 25 
9.6.
Further Safety Evaluations .......................................................................................... 25 
9.7.
Prior and Concomitant Medications ........................................................................... 25 
10.
Changes from Planned Analysis ....................................................................................... 26 
11.
Other Planned Analysis..................................................................................................... 26 
11.1.
Blood Pharmacokinetic Analysis ................................................................................ 26 
11.2.
Tissue Pharmacokinetic Analysis ............................................................................... 26 
12.
References ......................................................................................................................... 27 
13.
Tables, Listings, and Figures ............................................................................................ 27 
13.1.
Planned Table and Figure Descriptions ...................................................................... 27 
13.1.1. Demographic Data ...................................................................................................... 27 
13.1.2. Efficacy Data .............................................................................................................. 29 
13.1.3. Safety Data .................................................................................................................. 30 
13.2.
Planned Listing Descriptions ...................................................................................... 32 
14.
Tables, Listings, and Listing Shells .................................................................................. 35 
Page 5


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 5 of 107 
14.1.
Standard Layout for all Tables, Listings, and Figures ................................................ 35 
14.2.
Planned Table and Figure Shells................................................................................. 37 
14.3.
Planned Listing Shells................................................................................................. 72 
Appendix 1: Premier Research Library of Abbreviations ............................................................ 99 
List of Tables 
Table 1: Schedule of Events (Cohort 1) ........................................................................................ 10 
Table 2: Schedule of Events (Cohort 2) ........................................................................................ 11 
Table 3: Visit Windows (Cohort 1) .............................................................................................. 16 
Table 4: Visit Windows (Cohort 2) .............................................................................................. 16 
Table 5: Demographic Data Summary Tables .............................................................................. 27 
Table 6: Efficacy Data Summary Tables ...................................................................................... 29 
Table 7: Safety Data Summary Tables ......................................................................................... 30 
Table 8: Planned Listings.............................................................................................................. 33 
List of Figures 
Figure 1: Standardized Layout ...................................................................................................... 36 
Page 6


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 6 of 107 
1.
Overview 
This statistical analysis plan (SAP) describes the planned analysis and reporting for Arcutis, Inc. 
protocol number 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), dated 19-
Mar-2018, Amendment 2.0. Reference materials for this statistical plan include the protocol and 
the accompanying sample data collection documents. Operational aspects related to collection 
and timing of planned clinical assessments are not repeated in this SAP unless relevant to the 
planned analysis. 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials1. All work planned and reported for this SAP will follow internationally accepted 
guidelines, published by the American Statistical Association2 and the Royal Statistical Society3, 
for statistical practice. 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc 
or unplanned, exploratory analysis performed will be clearly identified as such in the final CSR. 
The statistical plan described hereafter is an a priori plan. It will be submitted to file prior to any 
unblinded inferential or descriptive analysis of data pertaining to Arcutis, Inc.’s study 
ARQ-151-101. 
2. 
Study Objectives and Endpoints 
2.1. 
Study Objectives 
2.1.1. Primary Objectives 
The primary objectives are: 
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 (PK), and efficacy of ARQ-151 cream 0.5% and 
ARQ-151 cream 0.15% vs. vehicle applied once daily (QD) x 28 days to individuals in 
the range of 0.5% to 5.0% body surface area (BSA) of chronic plaque psoriasis (Cohort 
2). 
Page 7


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 7 of 107 
2.2.
Study Endpoints 
2.2.1. Safety Endpoints 
The safety endpoints of this study include the following: 
• Treatment emergent adverse events (TEAEs) 
• Application site assessments 
• Medical history and physical examinations 
• Changes in clinical laboratory results 
• Changes in 12-lead electrocardiograms (ECGs) 
• Changes in vital signs 
2.2.2. Efficacy Endpoints 
2.2.2.1. 
Primary Efficacy Endpoint 
In the parallel group assessment (Cohort 2), the primary efficacy endpoint is:  
• 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. 
2.2.2.2.
Secondary Efficacy Endpoint(s) 
The secondary efficacy endpoints in the parallel group (Cohort 2) assessment 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. 
2.2.3. Pharmacokinetic Variable(s) 
The PK endpoints of the study include plasma concentrations (both cohorts) and tissue 
concentrations (Cohort 2 substudy) of roflumilast and any metabolites, as follows:  
• Mean plasma concentrations and parameters (parameters may include AUC0-t, AUC0-inf, 
Cmax, tmax, and others as data permit); and 
Page 8


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 8 of 107 
•
Mean tissue concentrations. 
2.2.4. Other Endpoints 
The other endpoint includes changes in depressive symptomatology (Cohort 2). 
3.
Overall Study Design and Plan 
3.1. 
Overall Design 
There are 2 cohorts of subjects: 
Cohort 1 
Cohort 1 is an open label, single dose study to 25 cm2 of psoriatic plaque(s) in up to up to 8 
subjects with psoriasis. 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; however, a 
minimum of 14 days of wash-out is required between Cohort 1 drug application and the baseline 
visit of Cohort 2. This cohort involves a minimum of 3 clinic visits including Screening, 
Baseline, 1 follow-up visit (24 hours after the baseline visit) and 1 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 
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 0.5% to 
5.0% BSA of chronic plaque psoriasis, inclusive. This cohort involves a minimum of seven 
clinic visits including Screening, Baseline and 4 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 AEs. 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. 
Including both Cohorts, a total of about 92 subjects will be enrolled at 7 study sites in Canada 
and 1 site in the U.S. Subjects will be adult (≥18 years old) 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. 
3.2.
Sample Size and Power 
A sample size of 24 per arm (72 total) will provide 80% power to detect a difference of 23% in 
Page 9


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 9 of 107 
the mean percent change from baseline in TPSS x TPA (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 
1-way analysis of variance (ANOVA) at the α = 0.025 significance level. With a 16% dropout 
rate, the sample size for the study has been increased to 84 subjects. 
3.3. 
Study Population 
Subjects in this study are male or female adults (≥18 years old) with chronic plaque psoriasis (at 
least 25 cm2 for Cohort 1; covering 0.5% to 5.0% of total BSA excluding the face, scalp, 
intertriginous areas, palms, and soles for Cohort 2). 
3.4. 
Treatments Administered 
All subjects in Cohort 1 will receive ARQ-151 cream 0.5%. 
Subjects in Cohort 2 will be randomized to receive ARQ-151 cream 0.5%, ARQ-151 cream 
0.15%, or matching vehicle (ie, placebo). 
If a subject is terminated from the study due to non-resolution or reoccurrence of a skin reaction 
after having undergone up to a 1-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. 
3.5. 
Method of Assigning Subjects to Treatment Groups 
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 the Baseline Visit after the subject has been 
found to be fully eligible for participation. A kit containing 10 tubes of study medication will be 
assigned to each subject. Each kit has a unique kit number (randomization number). 
3.6. 
Blinding and Unblinding 
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. 
3.7.
Schedule of Events 
A detailed schedule of events for the study is provided in Table 1 and Table 2, for Cohorts 1 
and 2, respectively. 
 
Page 10


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 10 of 107 
Table 1: Schedule of Events (Cohort 1) 
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. 
Page 11


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 11 of 107 
Table 2: Schedule of Events (Cohort 2) 
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 
Vehicle 
Application in 
Clinic (subject 
training)f 
 
 
Xf 
Xf
Drug/Vehicle 
Application in 
Clinicg 
 
Xg 
 
Xg 
 
Xg 
 
 
Page 12


Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
 Page 12 of 107 
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 
 
 
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-upj 
 
 
 
 
 
 
 
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. 
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 
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
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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).
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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4.
Statistical Analysis and Reporting 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations, except for PK parameter estimation, will be performed primarily using 
SAS (release 9.4 or higher). All PK parameter estimations will be performed using WinNonlin® 
version 6.4 or later. If the use of other software is warranted, the final statistical methodology 
report will detail what software was used for what purposes. 
For purposes of this SAP, “treatment within cohort” is defined as enrolled subjects (“Overall”) 
for Cohort 1 and treatment group (“ARQ-151 0.5%,” “ARQ-151 0.15%,” and “Vehicle”) for 
Cohort 2. For background and efficacy summaries for Cohort 2, this will be the randomized 
(ie, planned) treatment group; for safety summaries, this will be the actual (ie, received) 
treatment group. 
Where possible, data for both cohorts will be summarized in the same output. 
Continuous (quantitative) variable summaries will include the number of subjects (n) with 
non-missing values, mean, standard deviation (SD), median, minimum, and maximum.  
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular category or each possible value. In general, the denominator 
for the percentage calculation will be based upon the total number of subjects in the study 
population for the treatment groups within cohort, unless otherwise specified.  
The minimum and maximum will be reported with the same degree of precision (ie, the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
reported to 1 degree of precision more than the observed data and measures of spread (SD) will 
be reported to 2 degrees of precision more than the observed data. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
Unless otherwise indicated, all statistical tests will be conducted at the 0.05 significance level 
using 2-tailed tests, and p values will be reported. Corresponding 95% confidence intervals (CIs) 
will be presented for statistical tests. 
4.2. 
Interim Analysis and Data Monitoring 
No interim analyses are planned. 
5. 
Analysis Populations 
The following analysis populations are planned for this study:  
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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• Safety Population: The Safety Population includes all subjects who are enrolled and 
received at least 1 confirmed dose of study medication in each cohort. This population 
will be defined separately for each cohort. Analyses using the Safety Population for either 
cohort will be based on treatment received. 
• Modified Intent-To-Treat (mITT) Population: The mITT Population includes all 
subjects who are in the Safety Population for Cohort 2 with at least 1 post-baseline 
efficacy evaluation. Analyses using the mITT Population will be based on randomized 
treatment. 
• PK Population: The PK Population includes all subjects, who consented to PK draws, 
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. Analyses using the PK Population will be presented in a 
separate PK report, provided by the pharmacokineticist. 
• Per Protocol (PP) Population: The PP Population includes all subjects who are in the 
Safety Population for Cohort 2, were at least on average 80% compliant with study 
medication, and showed no other serious deviations from the study protocol. Analyses 
using the PP Population will be based on randomized treatment. 
6. 
General Issues for Statistical Analysis 
6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
The last observation recorded before the first dose of study drug in each cohort will be used as 
the baseline observation for all calculations of change from baseline.  
6.1.2. Adjustments for Covariates 
Where statistical modelling is performed, the baseline value of that assessment will be used as a 
covariate. 
6.1.3. Multiple Comparisons 
The type I error rate of α = 0.05 will be maintained for the entirety of the primary endpoint by 
using the Bonferroni method to control for multiplicity, where the significance level for each of 
the 2 comparisons of active versus placebo is α = 0.025.  
No adjustments will be made for multiple comparisons for other endpoints; all analyses will be 
conducted at the α = 0.05 level. 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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6.1.4. Handling of Dropouts or Missing Data 
Any subject who withdraws from the study may be replaced at the discretion of the Sponsor. For 
AEs, if severity or relationship to study drug is missing, then it will be treated as missing. In 
general, missing data will not be imputed, except as described in Section 6.1.8. 
6.1.5. Analysis Visit Windows 
For all analyses, unscheduled and/or repeated measurements will only be included if a scheduled 
measurement is not available and the unscheduled/repeated measurement falls within the 
analysis visit windows as described below (Table 3 and Table 4). Otherwise, visits will be 
analyzed as scheduled. 
Table 3: Visit Windows (Cohort 1) 
Visit 
Target Start Day 
Lower Limit 
Upper Limit 
Screening 
-14 
-14 
-1 
Day 1 
1 
1 
1 
Day 2 
2 
2 
2 
Day 8 
8 
3 
9 
Table 4: Visit Windows (Cohort 2) 
Visit 
Target Start Day 
Lower Limit 
Upper Limit 
1 
-6 
-6 
-1 
2 
1 
1 
1 
3 
7 
2 
8 
4 
14 
9 
15 
5 
21 
16 
22 
6 
28 
23 
28 
7 
29 
29 
30 
-- 
35 
31 
36 
Visits should occur ±1 day of the targeted date. The lower limit for each visit after 
Visit 2 (Day 1) starts 1 day after the upper limit for the previous visit (+1 of the 
targeted date). 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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6.1.6. Pooling of Sites 
All sites will be pooled together for analysis. 
6.1.7. Derived Variables 
• TPSS = sum of erythema (graded 0-4), thickness (graded 0-4), and scaling (graded 0-4) 
for each target plaque. The sum of TPSS scores of up to 3 target plaques within a visit 
will be used for analysis. 
• TPA (cm2) = the longest diameter (cm) of the target plaque multiplied by the widest 
perpendicular diameter (cm) (ie, perpendicular to the longest diameter of the target 
plaque). The sum of TPA (cm2) of up to 3 target plaques within a visit will be used for 
analysis. 
• TPSS x TPA = sum of TPSS x TPA of up to 3 target plaques within a visit. Note that 
TPSS x TPA is calculated for each target plaque before summing up the results for all 
plaques. If a plaque is resolved after baseline with a score of 0 for all descriptors for 
TPSS (ie, erythema, thickness, and scaling), TPSS x TPA will be recorded as 0. 
• Cream used (g) in a tube = dispensed tube weight (g) – returned tube weight (g). 
• Overall cream used (g) = sum of cream used in a tube over all tubes 
• Number of doses of study drug = number of expected doses (number of days on study 
[including BID dosing on Days 1, 14, and 28], where number of days on study is derived 
as last treatment – first treatment + 1) minus total number of missed doses, as collected in 
the CRF. Add a 1 for each of the Day 1, 14, and 28 visits that are completed (meaning, 
study drug discontinuation did not occur until at least the next day; so if a subject finished 
the study, 3 doses would be added to the final amount). 
• Percent compliance (for purposes of determining the PP Population as described in 
Section 5) = average of compliance as recorded in the eCRF, calculated as sum of [100% 
if “Was the subject compliant?” marked Yes in the eCRF or percent compliance as 
recorded in the eCRF comments when “Was the subject compliant?” is marked as No] / 
number of non-missing compliance records from the eCRF. 
• Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) total score = 
(highest score on questions 1-4) + item 5 + (highest score on questions 6-9) + item 10 + 
item 11 + item 12 + item 13 + item 14 + (highest score on questions 15-16). The range 
for the QIDS-SR total score is 0 to 27. 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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• QIDS-SR severity level4: 
• 
No depression: total score ≤ 5 
• 
Mild depression: total score = 6 to 10 
• 
Moderate depression: total score = 11 to 15 
• 
Severe depression: total score = 16 to 20 
• 
Very severe depression: total score ≥ 21 
• Change from baseline = value at current time point – value at baseline.  
• Percent change from baseline = (change from baseline / baseline) * 100. 
• TEAE = any AE with an onset date/time after first dose of study drug in each cohort. 
6.1.8. Data Adjustments/Handling/Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings. 
All p-values will be displayed in 4 decimals and rounded using standard scientific notation 
(eg, 0.XXXX). If a p-value less than 0.0001 occurs, it will be shown in tables as <0.0001. 
All AEs and medical histories will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) version 20.1 thesaurus. Prior and concomitant medications will be coded 
using the World Health Organization-Drug Dictionary Enhanced (WHO-DDE) version 
September 2017. 
A treatment related AE is any AE with a relationship to the study drug of possibly, probably, or 
likely related. 
If partial dates occur, the convention for replacing missing dates for the purpose of statistical 
analysis is as follows:  
For partial AE and medication start dates: 
• if just day is missing then the day assigned is the first day of the month or the date of first 
dose (if in the same month), whichever is later;  
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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• if just month is missing then the month assigned is the month of the first dose, unless that 
results in a date prior to the first dose in which case the month after the first dose is used; 
and  
• if both month and day are missing then the month assigned is the month of the first dose 
and the day assigned is the first dose day. 
For partial AE and medication end dates: 
• if just day is missing then the day assigned is the day of the last date on study (ie, date of 
last contact if subject lost to follow-up or date of completion / early termination) if month 
and year do match the month and year of the last date of the study, or the last day of the 
month otherwise;  
• if just month is missing then the month assigned is the month of the last date on study, 
unless that results in a date after the last date on study, in which case the month before 
the last date on study is used; and  
• if both month and day are missing then the month assigned is the month of the last date 
on study and the day assigned is the day of last date on study, unless that results in a date 
after the last date on study, in which case the first day of the month is assigned. 
If partial times occur, the convention is as follows:  
• if the missing time occurs on the day of the first dose and both the hour and minute are 
missing then the time assigned is the time of the first dose, otherwise if both the hour and 
minute are missing and the date is not the date of first dose the time assigned is 12:00;  
• if the date is the same as the date of the first dose and  
o only hour is missing the hour assigned is 12 or the hour of first dose, whichever is 
later; 
o only the minute is missing the minute assigned is 30 or the minute of first dose, 
whichever is later;  
• Otherwise if the date is not the same as the date of first dose, the hour assigned is 12 if 
the hour is missing and the minute assigned is 30 if the minute is missing. 
The time imputation only applies to Cohort 1. If a Cohort 2 time is missing, set to 12:00; if time 
is incomplete, set to 12 (hour) or 00 (minute). 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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7.
Study Subjects and Demographics 
Individual subject listings will be prepared for all study subjects and demographics data. 
7.1.
Disposition of Subjects and Withdrawals 
Disposition will include tabulations of the number of subjects enrolled (Cohort 1) and/or 
randomized (Cohort 2), the number of subjects rolled over from Cohort1 to Cohort 2, the number 
of subjects who received treatment, tabulated reasons for discontinuation from the study, and 
number of subjects in each analysis population by treatment within cohort. 
Percentages will be based on the number of subjects in the Safety Population for each cohort. 
7.2.
Protocol Violations and Deviations 
All protocol deviations recorded by the site (classified as major or minor) will be listed. 
7.3.
Demographics and Other Baseline Characteristics 
Summary statistics for age, gender, race, ethnicity, height, weight, and BSA will be presented by 
treatment within cohort.  
For the continuous variables, the number of non-missing values and the mean, standard 
deviation, minimum, median, and maximum will be tabulated.  
For the categorical variables, the counts and proportions of each value will be tabulated.    
These analyses will be conducted for the Safety Population for each cohort. 
The number and percent of subjects reporting various medical histories, grouped by MedDRA 
system organ class and preferred term, will be tabulated by treatment within cohort. This analysis 
will be conducted for the Safety Population for each cohort.  
Subjects rolling over from Cohort 1 into Cohort 2 will have demographics and baseline 
characteristics tabulated for both cohorts. 
7.4. 
Exposure and Compliance 
The number of doses received by each subject based on diary data will be summarized by 
treatment for Cohort 2 subjects only, in both a continuous manner (using summary statistics) and 
a categorical manner (using number and percentages), presenting the following categories: 1 to 8 
doses (up to 1 week of treatment); 9 to 15 doses (1-2 weeks of treatment); 16-23 doses 
(2-3 weeks of treatment); and 24 to 31 doses (3-4 weeks of treatment). 
Similarly, the amount of study medication applied by each subject based on tube weight will be 
summarized by treatment for Cohort 2 subjects only, using summary statistics.  
These analyses will be conducted for the Safety Population for each cohort.  
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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Drug application for each cohort, vehicle training application for Cohort 2, study medication 
dispensation and return weight, and missed doses will be presented in the listings. 
8.
Efficacy Analysis 
Efficacy will be assessed for Cohort 2 only. Individual subject listings will be prepared for all 
efficacy data. 
8.1.
Primary Efficacy Analysis 
The primary efficacy endpoint is difference in mean percent change from baseline at Week 4 in 
the product of 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 within country, treatment, study visit, and treatment-by-study visit interaction as 
fixed effects and baseline TPSS x TPA score as a covariate. In comparing the visit value to 
baseline within each treatment group, least squares (LS) mean percent change from baseline will 
be presented along with associated 95% confidence interval (CI). In comparing treatments 
(ARQ-151 minus Vehicle), LS mean differences in percent change from baseline will be 
presented along with associated 95% CI and pairwise treatment P value. An unstructured 
covariance structure will be used, unless the model does not converge; in that case, the 
appropriate covariance structure will be investigated. Possible covariance structures include 
autoregressive (AR [1]), compound symmetry (CS), and variance components (VC) with each 
model fit to find the covariance structure with the best fit. The fit statistics will be compared for 
all covariance structures; the structure with the smallest Akaike information criterion will be 
retained as the preferred model.  
The Bonferroni method will be used to control for multiplicity, where the significance level for 
each of the 2 comparisons of active versus placebo is α = 0.025. 
Descriptive statistics for absolute and percent change from baseline at Week 4 will be presented 
by treatment group. 
The primary efficacy analysis will be based on the mITT Population. This analysis will be 
repeated for the PP Population.  
As a sensitivity analysis, the primary endpoint will be analyzed using an analysis of covariance 
(ANCOVA) with factors for center within country and treatment as fixed effects and baseline 
TPSS x TPA score as a covariate.  
8.2.
Secondary Efficacy Analysis 
The secondary efficacy endpoints for Cohort 2 include the following: 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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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.  
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. 
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.  
Each of the secondary efficacy endpoints will be analyzed using MMRM methods similar to the 
primary endpoint; however, no adjustments for multiplicity will occur, and all analyses will be 
conducted at the α = 0.05 level. 
Additionally, descriptive statistics for absolute and percent change from baseline to each week 
(ie, Weeks 1, 2, 3, and 4) will be presented by treatment group. 
9.
Safety and Tolerability Analysis 
Safety will be evaluated from reported AEs, application site reaction assessments, physical 
examinations, and changes in clinical laboratory values, vital signs, and 12-lead ECGs. 
Descriptive statistics will be calculated for quantitative safety data and frequency counts will be 
compiled for classification of qualitative safety data. No formal inferential statistics will be 
performed on safety assessments. Individual subject listings will be prepared for all safety data. 
All safety analyses will be performed on the Safety Population for each cohort. All safety data 
will be presented in the listings. 
9.1. 
Adverse Events 
An event that is temporally associated with administration of study product is defined as a 
treatment emergent adverse event (TEAE). Events meeting this definition will be those with a 
start date during or after administration of the first dose of study drug through the telephone 
follow-up in each cohort. For AEs occurring on the date of the first dose of study drug, if the 
time of onset is missing, the AE will be assumed to be treatment emergent. 
The causal relationship of the AE to the study drug is determined by the investigator as 
Unrelated, Unlikely Related, Possibly Related, Probably Related, and Likely Related. These can 
be mapped to Unrelated (Unrelated and Unlikely Related) and Related (Possibly Related, 
Probably Related, and Likely Related).  
Adverse event severity grades are reported on a 5-point scale of Grade 1 (Mild), Grade 2 
(Moderate), Grade 3 (Severe), Grade 4 (Life-threatening consequences), or Grade 5 (Death 
related to AE).  
An AE summary table will be presented for the following: 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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• All TEAEs 
• TEAEs by maximum severity 
• Treatment-related TEAE 
• TEAEs leading to discontinuation of study drug 
• Serious AEs (SAEs)  
• Deaths 
Summaries of incidence rates (frequencies and percentages) of individual TEAEs by MedDRA 
(v20.1) system organ class (SOC) and preferred term (PT). Such summaries will be displayed for 
all TEAEs, TEAEs by maximum severity, and treatment-related. Analysis of TEAEs will be 
performed by treatment within cohort. 
Each subject will be counted only once within each summation level (SOC and preferred term). 
If a subject experiences more than 1 TEAE within each summation level only, the TEAE with 
the strongest relationship or the maximum severity, as appropriate, will be included in the 
summaries of relationship and severity. 
Incidences will be presented by descending frequency of SOC and PT within SOC, and then 
alphabetically within PT where the incidence is the same; this is based on overall subjects. 
Missing and partially missing AE start and/or stop dates will be imputed, for the purpose of 
statistical analysis, according to the specifications described in Section 6.1.8. 
In the AE data listings, all AEs will be displayed. AEs that are treatment emergent will be 
flagged. 
9.1.1. Adverse Events Leading to Discontinuation 
A summary of incidence rates (frequencies and percentages) of TEAEs leading to 
discontinuation of study drug, by treatment within cohort, SOC, and PT will be prepared for 
subjects in the Safety Population for each cohort. No inferential statistical tests will be 
performed. 
A data listing of AEs leading to discontinuation of study drug will also be provided, displaying 
details of the event(s) captured on the CRF. 
9.1.2. Deaths and Serious Adverse Events 
Serious AEs will be listed and also tabulated by SOC and PT and presented by treatment within 
cohort. 
Any deaths that occur during the study will be listed. 
9.1.3. Other Significant Adverse Events 
Not applicable. 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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9.2.
Application Site Reaction Assessments 
Application site reaction assessments will be performed on Days 1 and 2 for Cohort 1 and 
Baseline (Visit 2), Visit 3, Visit 4, Visit 5, and Visit 6 for Cohort 2.  
Dermal response reactions are graded using a scale of 0 (no evidence of irritation) to 7 (strong 
reaction spreading beyond application site). Additionally, other effects on an A (slight glazed 
appearance) to F scale (small petechial erosions and/or scabs) will be noted (where G = no 
other effects may be recorded). 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. 
The numeric application site reaction scores will be summarized individually by using number 
and percentage of subjects by visit and treatment within cohort. 
The numeric application site reaction scores will be summarized by visit and treatment within 
cohort, in both a continuous manner (using summary statistics) and a categorical manner (using 
number and percentages). The character other effects scores will be summarized by visit and 
treatment within cohort using number of percentages. 
9.3. 
Clinical Laboratory Evaluations 
All summaries of laboratory values will be presented using SI units. All hematology, chemistry, 
urinalysis, and other results will be listed by subject and timing of collection. Abnormal results 
will be flagged in the listings. 
Observed values and change from baseline at each time point for continuous hematology, 
chemistry, and urinalysis results will be summarized using descriptive statistics by visit and 
treatment within cohort. Categorical urinalysis results will be summarized using frequencies by 
visit and treatment within cohort. Shifts from baseline for clinical laboratory values below, 
within, or above the normal range will be provided for hematology, chemistry, and urinalysis 
results. 
Pregnancy test results and hormonal laboratory results will be listed. 
9.4. 
Vital Signs 
Descriptive summaries of observed values and change from baseline will be calculated for 
systolic blood pressure, diastolic blood pressure, heart rate, and body temperature by visit and 
treatment within cohort. Shift from baseline categories for weight (change <-5%, change 
between -5% and 5%, and change >5%) will be provided by visit and treatment for Cohort 2 
only, as no post-baseline weight was recorded for Cohort 1.  
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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9.5.
12-Lead Electrocardiogram 
Frequencies and percentages of investigator interpretation of ECG results (normal, abnormal 
clinically significant, and abnormal not clinically significant) will be presented by visit and 
treatment within cohort. 
9.6. 
Further Safety Evaluations 
The total score of the QIDS-SR (ie, the sum of the 16 individual item scores as described in 
Section 6.1.7) will be summarized by visit and treatment within cohort. Additionally, the number 
and percentage of subjects meeting the criteria for each severity level based on total score (ie, no 
depression, mild, moderate, severe, and very severe) will be presented by visit and treatment 
within cohort. A shift from baseline in QIDS-SR categories will be presented by visit and 
treatment within cohort. 
Physical examination findings, dermal imaging data, diary dispensation and review, and 
telephone follow-up data for all subjects will be presented in by-subject listings. 
9.7. 
Prior and Concomitant Medications 
Prior and concomitant medications, coded using WHO-DDE (September 2017), will be 
summarized descriptively by Anatomical Therapeutic Chemical (ATC) classification Level 4 and 
preferred term (ie, ATC classification Level 5), if applicable, and by cohort and overall subjects 
(prior) or treatment within cohort (concomitant) using counts and percentages. 
Prior medications will be presented separately from concomitant medications. The assignment of 
medications as prior and/or concomitant will be done as follows: 
• Subjects in either Cohort 1 or Cohort 2, but not both: 
o Prior medications: Medications that started before first dose of study drug in 
either cohort will be considered prior medications whether or not they were 
stopped before first dose of study drug.  
o Concomitant medications: Any medications continuing or starting after first 
dose of study drug through the follow-up visit in each cohort will be considered to 
be concomitant to that cohort.  
• Subjects in both Cohort 1 and Cohort 2: 
o Prior medications: Medications that started before first dose of study drug in 
Cohort 1 will be considered prior medications to Cohort 1; medications that 
started between the Cohort 1 Day 8 follow-up call and first dose of study drug in 
Cohort 2 will be considered prior medications to Cohort 2. This will be the case 
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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whether or not the medications were stopped before first dose of study drug in the 
respective cohort.  
o Concomitant medications: Any medications continuing or starting after first 
dose of study drug through the follow-up visit in each cohort will be considered to 
be concomitant to that cohort. A medication could be considered concomitant to 
both cohorts, depending on start and stop dates. 
10.
Changes from Planned Analysis 
Amount of study medication received by each subject based on tube weight was specified in the 
protocol to be summarized using both continuous and categorical measures; however, this 
compliance measure will only be presented using summary statistics since weight is inherently a 
continuous measure. 
Severity categories for QIDS-SR were listed in the protocol as normal, mild, moderate, moderate 
to severe, and severe; however, literature suggests that no depression, mild, moderate, severe, 
and very severe are more appropriate categories4. 
11.
Other Planned Analysis 
11.1.
Blood Pharmacokinetic Analysis 
Blood samples for PK 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, for subjects consenting to PK draws, 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. 
All PK collection information from the eCRF will be presented in a listing. 
All PK analysis, including calculations of PK parameters and TLF production, will be performed 
by a PK vendor; those results will be presented in a separate PK report.  
11.2.
Tissue Pharmacokinetic Analysis 
An optional 4 mm diameter punch biopsy will be collected from subjects that consented to a 
punch biopsy of a target plaque at the Day 28 Visit. The punch biopsy will include the epidermis, 
dermis, and sub-cutaneous skin layers. As with plasma PK analysis, tissue PK analysis will be 
performed by a PK vendor and the results will be included in a separate PK report. However, 
collection information will be presented in a listing. 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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12.
References 
1. ASA. (1999) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, August 7, 1999. http://www.amstat.org/about/ethicalguidelines.cfm 
2. RSS. (1993) The Royal Statistical Society: Code of Conduct, April 1993. 
http://www.rss.org.uk/main.asp?page=1875. 
3. US Federal Register. (1998) International Conference on Harmonization; Guidance on 
Statistical Principles for Clinical Trials. Department of Health and Human Services: Food 
and Drug Administration [Docket No. 97D-0174]. Federal Register Volume 63, Number 179, 
pages 49583-49598. September 16, 1998. 
4. Brown ES, Murray M, Carmody TJ, et al. The Quick Inventory of Depressive 
Symptomatology–Self-report: a psychometric evaluation in patients with asthma and major 
depressive disorder. Annals of allergy, asthma & immunology : official publication of the 
American College of Allergy, Asthma, & Immunology. 2008;100(5):433-438. 
doi:10.1016/S1081-1206(10)60467-X. 
13. 
Tables, Listings, and Figures 
All listings, tables, and figures will have a header showing the sponsor company name and 
protocol and a footer showing the version of SAS, the file name and path, and the source of the 
data (CRF page or listing number). 
13.1. Planned Table and Figure Descriptions 
The following are planned summary tables and figures for protocol number ARQ-151-101. The 
table numbers and page numbers are place holders only and will be determined when the tables 
and figures are produced. 
13.1.1. Demographic Data  
Table 5: Demographic Data Summary Tables 
Number 
Population 
Title 
Table 14.1.1 
All Subjects 
Summary of Subject Disposition by Treatment and Cohort 
Table 14.1.2 
Safety 
Summary of Demographics and Baseline Characteristics by Treatment 
and Cohort 
Table 14.1.3 
Safety 
Incidence of Medical Histories by SOC, PT, Treatment, and Cohort 
Table 14.1.4 
Safety 
Summary of Prior Medications by ATC Class Level 4, PT, Treatment, 
and Cohort 
Table 14.1.5.1 
Safety 
Summary of Study Drug Compliance using Doses Received by 
Treatment 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Table 14.1.5.2 
Safety 
Summary of Study Drug Compliance using Tube Weight (g) by 
Treatment 
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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13.1.2. Efficacy Data  
Table 6: Efficacy Data Summary Tables 
Number 
Population 
Title 
Table 14.2.1.1.1 
mITT 
Summary of Target Plaque Severity Score (TPSS) x Target Plaque Area 
(TPA) (cm2) by Study Visit and Treatment  
Table 14.2.1.1.2 
mITT 
Percent Change from Baseline in Target Plaque Severity Score (TPSS) x 
Target Plaque Area (TPA) (cm2) by Study Visit and Treatment, 
Tabulation of Fitted Summary Statistics from MMRM 
Table 14.2.1.2.1 
PP 
Summary of Target Plaque Severity Score (TPSS) x Target Plaque Area 
(TPA) (cm2) by Study Visit and Treatment  
Table 14.2.1.2.2 
PP 
Percent Change from Baseline in Target Plaque Severity Score (TPSS) x 
Target Plaque Area (TPA) (cm2) by Study Visit and Treatment, 
Tabulation of Fitted Summary Statistics from MMRM 
Table 14.2.1.3 
mITT 
Percent Change from Baseline in Target Plaque Severity Score (TPSS) x 
Target Plaque Area (TPA) (cm2) by Study Visit and Treatment, 
Tabulation of Fitted Summary Statistics from ANCOVA 
Table 14.2.2.1 
mITT 
Summary of Target Plaque Severity Score (TPSS) by Study Visit and 
Treatment  
Table 14.2.2.2 
mITT 
Percent Change from Baseline in Target Plaque Severity Score (TPSS) 
by Study Visit and Treatment, Tabulation of Fitted Summary Statistics 
from MMRM 
Table 14.2.3.1 
mITT 
Summary of Target Plaque Area (TPA) (cm2) by Study Visit and 
Treatment  
Table 14.2.3.2 
mITT 
Percent Change from Baseline in Target Plaque Area (TPA) (cm2) by 
Study Visit and Treatment, Tabulation of Fitted Summary Statistics 
from MMRM 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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13.1.3. Safety Data 
Table 7: Safety Data Summary Tables 
Number 
Population 
Title 
14.3.1 Displays of Adverse Events 
Table 14.3.1.1 
Safety 
Summary of Treatment Emergent Adverse Events by Treatment and 
Cohort 
Table 14.3.1.2
Safety
Incidence of Treatment Emergent Adverse Events by SOC, PT, 
Treatment, and Cohort 
Table 14.3.1.3 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, Treatment, and Cohort 
Table 14.3.1.4 
Safety
Incidence of Treatment Related Treatment Emergent Adverse Events by 
SOC, PT, Treatment, and Cohort 
Table 14.3.1.5 
Safety 
Incidence of Treatment Emergent Adverse Events Leading to Study 
Drug Discontinuation by SOC, PT, Treatment, and Cohort 
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events 
Table 14.3.2 
Safety
Incidence of Serious Adverse Events by SOC, PT, Treatment, and 
Cohort 
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events
Table 14.3.3.1 
Safety 
Listing of Adverse Events Leading to Study Drug Discontinuation 
Table 14.3.3.2 
Safety 
Listing of Serious Adverse Events 
Table 14.3.3.3 
Safety 
Listing of Deaths 
14.3.4 Abnormal Laboratory Value 
NA 
 
 
14.3.5 Laboratory Data Summary Tables 
Table 14.3.5.1.1 
Safety 
Summary of Serum Chemistry Laboratory Results by Study Visit, 
Treatment, and Cohort 
Table 14.3.5.1.2 
Safety 
Shift from Baseline in Serum Chemistry Laboratory Results by Study 
Visit, Treatment, and Cohort 
Table 14.3.5.2.1 
Safety 
Summary of Hematology Laboratory Results by Study Visit, Treatment, 
and Cohort 
Table 14.3.5.2.2 
Safety 
Shift from Baseline in Hematology Laboratory Results by Study Visit, 
Treatment, and Cohort 
Table 14.3.5.3.1 
Safety 
Shift from Baseline in Quantitative Urinalysis Laboratory Results by 
Study Visit, Treatment, and Cohort 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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Number 
Population 
Title 
Table 14.3.5.3.2 
Safety 
Shift from Baseline in Quantitative Urinalysis Laboratory Results by 
Study Visit, Treatment, and Cohort 
Table 14.3.5.3.3 
Safety 
Summary of Qualitative Urinalysis Laboratory Results by Study Visit, 
Treatment, and Cohort 
14.3.6 Other Safety Data Summary Tables 
Table 14.3.6.1.1 
Safety 
Summary of Quantitative Dermal Response Reaction by Study Visit, 
Treatment, and Cohort 
Table 14.3.6.1.2 
Safety 
Summary of Qualitative Dermal Response Reaction by Study Visit, 
Treatment, and Cohort 
Table 14.3.6.1.3 
Safety 
Summary of Application Site Reaction Other Effects by Study Visit, 
Treatment, and Cohort 
Table 14.3.6.2.1 
Safety 
Summary of Vital Signs by Study Visit, Treatment, and Cohort 
Table 14.3.6.2.2 
Safety 
Shift from Baseline in Weight by Study Visit, Treatment, and Cohort 
Table 14.3.6.3 
Safety 
Summary of 12-Lead Electrocardiogram Interpretation by Study Visit, 
Treatment, and Cohort 
Table 14.3.6.4.1 
Safety 
Summary of Quick Inventory of Depressive Symptomatology-Self-
Report (QIDS-SR) Total Score by Study Visit, Treatment, and Cohort 
Table 14.3.6.4.2 
Safety 
Summary of Quick Inventory of Depressive Symptomatology-Self-
Report (QIDS-SR) Total Score Severity Levels by Study Visit, 
Treatment, and Cohort 
Table 14.3.6.4.3 
Safety 
Shift from Baseline in Quick Inventory of Depressive Symptomatology-
Self-Report (QIDS-SR) Total Score Severity Levels by Study Visit, 
Treatment, and Cohort 
Table 14.3.6.5 
Safety 
Summary of Concomitant Medications by ATC Class Level 4, PT, 
Treatment, and Cohort 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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13.2.
Planned Listing Descriptions  
The following are planned data and patient/subject data listings for protocol number 
ARQ-151-101.  
In general, 1 listing will be produced per CRF domain. 
All listings will be sorted by cohort, treatment, and subject number. 
All calculated variables will be included in the listings. 
In all listings a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (eg, repetition of subject number), then only the first occurrence will be 
displayed. 
In data listings, the information for 1 subject will be kept on 1 page if at all possible, rather than 
splitting a subject’s information across pages. 
 
 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Table 8: Planned Listings  
Number 
Population 
Title / Summary 
16.2.1 Subject Discontinuations/Completions 
Listing 16.2.1 
All Subjects 
Subject Disposition 
16.2.2 Protocol Deviations 
Listing 16.2.2.1 
All Subjects 
Inclusion and Exclusion Criteria Not Met 
Listing 16.2.2.2 
All Subjects 
Protocol Deviations 
16.2.3 Subjects Excluded from the Efficacy Analyses 
Listing 16.2.3 
All Subjects 
Analysis Populations 
16.2.4 Demographic Data and Other Baseline Characteristics 
Listing 16.2.4.1 
All Subjects 
Demographics and Baseline Information 
Listing 16.2.4.2 
All Subjects 
Medical History 
Listing 16.2.4.3
All Subjects
Pharmacokinetic, Skin Biopsy, and Dermal Imaging Consent
16.2.5 Compliance and/or Drug Concentration Data 
Listing 16.2.5.1.1 
Cohort 1 Subjects 
Drug Application 
Listing 16.2.5.1.2 
Cohort 2 Subjects 
Vehicle Application (Subject Training/Retraining) 
Listing 16.2.5.2 
Cohort 2 Subjects 
Study Medication Dispensation and Return Weight 
Listing 16.2.5.3
Cohort 2 Subjects
Missed Doses
Listing 16.2.5.4 
All Consenting 
Subjects with 
Pharmacokinetic 
Data Collected 
Pharmacokinetic Blood Collection  
Listing 16.2.5.5 
Consenting Cohort 
2 Subjects 
Skin Biopsy Collection  
16.2.6 Individual Efficacy Response Data 
Listing 16.2.6 
Cohort 2 Subjects 
Target Plaque Severity Score and Area 
16.2.7 Adverse Event Listings (by Subject)  
Listing 16.2.7.1 
All Subjects 
Adverse Events 
16.2.8 Laboratory Values (by Subject) 
Listing 16.2.8.1 
All Subjects 
Clinical Laboratory Data: Serum Chemistry 
Listing 16.2.8.2 
All Subjects 
Clinical Laboratory Data: Hematology 
Listing 16.2.8.3 
All Subjects 
Clinical Laboratory Data: Urinalysis 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
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Number 
Population 
Title / Summary 
Listing 16.2.8.4 
All Subjects 
Clinical Laboratory Data: Urine Drug Screen and Pregnancy Tests 
16.2.9 Other Clinical Observations and Measurements (by Subject)  
Listing 16.2.9.1 
All Subjects 
Application Site Reaction 
Listing 16.2.9.2 
All Subjects 
Vitals Signs 
Listing 16.2.9.3 
All Subjects 
12-Lead Electrocardiogram (ECG) 
Listing 16.2.9.4 
All Subjects 
Limited Physical Examination 
Listing 16.2.9.5 
Cohort 2 Subjects 
Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) 
Listing 16.2.9.6 
All Subjects 
Prior and Concomitant Medications 
Listing 16.2.9.7 
Cohort 2 Subjects 
Dermal Imaging 
Listing 16.2.9.8 
Cohort 2 Subjects 
Diary Dispensation and Review 
Listing 16.2.9.9 
All Subjects 
Telephone Follow-up 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc. 
 
Protocol Number ARQ-151-101 
 
PCN Number ARCU7063 
 
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14.
Tables, Listings, and Listing Shells 
Page 36
Note: Shell Tables Removed (pages 36-98) 


Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Appendix 1: Premier Research Library of Abbreviations 
Abbreviation 
Definition 
aCRF  
annotated case report form 
AD 
associated documents 
ADR 
adverse drug reactions 
AE 
adverse event
AESI 
adverse events special interest 
ANCOVA
analysis of covariance 
ATC 
anatomical therapeutic chemical 
BLQ 
beneath limit of quantification 
BMI 
body mass index 
BRD 
business requirements document 
BSL 
biostatistician lead
CCGs 
CRF completion guidelines 
CD
compact disc
CDISC 
clinical data interchange standards consortium 
CEC 
central ethics committee 
CFR 
code of federal regulations 
CI 
confidence intervals 
CIOMS 
council for international organizations of medical sciences 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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Abbreviation 
Definition 
CIP 
clinical investigational plan 
CM 
clinical manager 
CMP 
clinical monitoring plan 
COV 
close out visit 
CRA 
clinical research associate 
CRF 
case report form 
CRO 
contract research organization 
CS 
clinically significant 
CSM 
clinical supply manager 
CSR 
clinical study report 
CTA 
clinical trial administrator 
CTM 
clinical trial manager 
CTMS 
clinical trial management system 
DB 
database 
DBL 
database lock 
DBP 
diastolic blood pressure 
DCRF 
data change request form 
DDE 
drug dispensing error form 
DEA 
drug enforcement administration 
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Abbreviation 
Definition 
DIA
drug information association 
DIS 
data integration specification 
DLT 
dose limiting toxicity 
DM 
data management 
DMB
data monitoring board 
DMC
data monitoring committee 
DML 
data management lead 
DMP 
data management plan 
DNA 
deoxyribonucleic acid 
DOB 
date of birth 
DS
document specialist 
DSG 
drug safety group 
DSM 
drug supply management (drug distributor) 
DSMB  
data safety monitoring board 
DSP 
data safety plan 
DSUR 
development safety update report 
DTS 
data transfer specification 
DVD 
digital video disk 
EC
ethics committee 
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Abbreviation 
Definition 
ECD 
edit check and derivation specifications 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European medicines agency 
eTMF 
electronic trial master file 
EU 
European Union 
FA
full analysis 
FDA 
food and drug administration 
FMP 
file management plan 
FPFV 
first patient first visit 
FPI 
first patient in 
GCP 
good clinical practice 
GMP 
good manufacturing practices 
GPV 
global pharmacovigilance 
HR 
heart rate 
IB 
investigator’s brochure 
IC or ICF 
informed consent or informed consent form 
ICH 
international council for harmonization  
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
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Abbreviation 
Definition 
ID 
identification 
IDM 
independent drug monitoring 
IEC 
independent ethics committee 
IM 
investigator meeting 
IMV 
interim monitoring visit 
IND
investigational new drug 
INDSR 
investigational new drug safety reports 
IP 
investigational product 
IRB 
institutional review board 
IRF 
inventory release file 
IRR 
infusion related reactions 
IRT 
interactive response technology 
ISF 
investigator site file 
ITT 
intent-to-treat 
IVRS
interactive voice response system 
IWRS 
interactive web response system 
IxRS 
interactive voice/web response system 
KPI 
key performance indicator 
LAN 
local area network 
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
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Abbreviation 
Definition 
LDM 
lead data manager 
LMS 
learning management system 
LLOQ 
lower limit of quantification 
LPI 
last patient in 
LPLV 
last patient last visit
LPO 
last patient out 
MAAP 
medical affairs and pharmacovigilance teams 
MAH 
marketing authorization holder 
MedDRA 
medical dictionary for regulatory activities 
MHRA 
medicines and healthcare products regulatory agency 
MM 
medical monitor 
MMP 
medical monitoring plan 
MMRM 
mixed effect model repeat measurement 
MTD 
maximum tolerated dose 
MVR
monitoring visit report 
N 
number 
NA 
not applicable 
NCS 
non-clinically significant 
NF
non-functional 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
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Abbreviation 
Definition 
PD
protocol deviation 
PDGP 
protocol deviation guidance plan 
PE 
physical examination 
PI 
principal investigator 
PIN 
personal identification number 
PK
pharmacokinetic 
PKAP 
pharmacokinetic analysis plan 
PM 
project manager
PMP 
project management plan 
PP 
per-protocol 
PRIMS  
Premier Research information management system 
PS 
project specialist 
PV
pharmacovigilance 
PVG 
pharmacovigilance group 
QA 
quality assurance 
QARC
quality assurance, risk and compliance 
QC 
quality control 
QOL 
quality of life 
ROT 
record of training 
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Statistical Analysis Plan,  
Sponsor Arcutis, Inc.  
Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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Abbreviation 
Definition 
RR 
respiratory rate or relative rate 
RSM 
regional site monitor 
SAE 
serious adverse event 
SAP 
statistical analysis plan
SAS®  
a software system used for data analysis 
SBP
systolic blood pressure 
SC 
study coordinator 
SCR 
software change request  
SD
standard deviation 
SDS 
study design specifications 
SDTM 
study data tabulation model  
SDV 
source data verification 
SECC  
self-evident correction conventions  
SECP  
self-evident correction plan 
SF 
screen failure 
SFT or SFTP 
secure file transfer or secure file transfer plan 
SIV 
site initiation visit
SLA 
service level agreement 
SMP 
safety management plan
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Statistical Analysis Plan,  
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Protocol Number ARQ-151-101  
 
PCN Number ARCU7063 
 
AD-ST-33.04 Effective date: 30-Jun-2017 
Version 1.0    |    Date 06-May-2018      |    AD-PR-109.01  Effective date: 26-Jun-2017  
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Abbreviation 
Definition 
SOC 
system organ class 
SOP 
standard operating procedure 
SOW 
statement of work
SQV 
site qualification visit 
SUA 
start-up associate 
SUSAR 
suspected, unexpected, serious adverse (drug) reaction 
TA 
trial assistant 
TEAE 
treatment-emergent adverse event 
TMF 
trial master file 
TOM 
task ownership matrix 
UAT 
user acceptance testing
USA 
United States of America 
UTC 
universal coordinated time 
WAN 
wide area network 
WAR 
work at risk 
WG 
working guideline 
WHO 
world health organization 
WHO-DD 
world health organization drug dictionary 
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