Conditions: Plaque Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 855
Healthy volunteers: no

Brief summary:
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a Vehicle Control in the Treatment of Stable Plaque Psoriasis

Detailed description:

Arms:
arm 1: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.) arm 2: TAZORAC® (tazarotene) Cream 0.05% (Allergan, Inc.) arm 3: Placebo (Vehicle of test product) (Fougera Pharmaceuticals Inc.)

Interventions: intervention 1: Tazarotene Cream 0.05% intervention 2: TAZORAC® (tazarotene) Cream 0.05% intervention 3: Placebo
Intervention descriptions: intervention 1: Tazarotene Cream 0.05% to cover only the lesions with a thin film. intervention 2: TAZORAC® (tazarotene) Cream 0.05% to cover only the lesions with a thin film. intervention 3: Placebo (vehicle of the test product) to cover only the lesions with a thin film.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 1 of 67 
1.0 TITLE PAGE 
Protocol Title: 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-
Group Study Comparing Tazarotene Cream 0.05% to TAZORAC® 
(tazarotene) Cream 0.05% and Both Active Treatments to a Vehicle Control 
in the Treatment of Stable Plaque Psoriasis 
Investigational Product: 
Tazarotene Cream 0.05% 
Population: 
Study Design: 
Sponsor: 
Protocol Number: 
 
Protocol Date: 
Protocol History: 
Approximately 855 males and non-pregnant females, 18 years of age and 
older, with clinical diagnosis of stable plaque psoriasis  
A multi-center, double-blind, randomized, vehicle-controlled, parallel-
group bioequivalence study with clinical endpoints comparing Tazarotene 
Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and both active 
treatments to a vehicle control in the treatment of stable plaque psoriasis 
Fougera Pharmaceuticals Inc. 
0453-01-01 / NCT02886702
 
07/26/2016 FINAL 
12/20/2016 Rev. 1 FINAL 
12/22/2016 Rev. 2 FINAL 
7/26/2016 (Original Protocol) 
12/20/2016 (Rev. 1) 
12/22/2016 (Rev. 2) 
This document is a privileged and confidential communication of Fougera Pharmaceuticals Inc. and 
. Receipt of this document constitutes an agreement by the 
recipient that no unpublished information contained herein will be disclosed without 
 and 
Fougera’s written approval. This protocol should be stored in a limited access area. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 2 of 67 
 
 
2.0 KEY STUDY PERSONNEL AND FACILITIES 
Sponsor: 
 
Fougera Pharmaceuticals Inc. 
60 Baylis Road 
Melville, New York, 11747 
 
CRO: 
 
 
 
 
 
Sponsor’s Representative: 
 
 
 
 
Tel: 
 
Fax: 
 
Email: 
 
 
 
 
Tel: 
 
Fax: 
 
Email: 
 
 
CRO Representative: 
 
 
 
 
Tel: 
 
Fax: 
 
Email: 
 
 
Medical Monitor: 
 
 
 
Tel: 
 
Fax: 
 
Email: 
 
 
Biostatistician: 
 
 
 
Tel: 
 
Fax: 
 
Email: 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 3 of 67 
 
 
3.0 SIGNATURE PAGE 
 
We, the undersigned, have carefully read this protocol and agree that it contains all the necessary 
information required to conduct the study. The study will be performed according to this protocol, 
all applicable Food and Drug Administration (FDA) regulations, International Conference on 
Harmonisation (ICH) guidelines and Good Clinical Practice (GCP) standards. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Date 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
Date 
 
 
 
 
__________________________________________ 
 _________________________ 
 
 
 
 
 
 
 
 
 
 
 
  
Date 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 4 of 67 
 
 
PRINCIPAL INVESTIGATOR’S SIGNATURE 
 
 
I agree to conduct protocol 0453-01-01 Rev. 2 in accordance with FDA regulations, ICH guidelines and 
Good Clinical Practices. I have carefully read and understand the foregoing protocol and agree that it 
contains all the necessary information for conducting this study safely. I will conduct this study in strict 
accordance with this protocol, the Code of Federal Regulations, the Health Insurance Portability and 
Accountability Act (HIPAA), and local regulatory guidelines. I will attempt to complete the study within 
the time designated. I will ensure that the rights, safety and welfare of subjects under my care are protected. 
I will ensure control of the drugs under investigation in this study. I will provide copies of the protocol and 
all other study-related information supplied by the sponsor to all personnel responsible to me who 
participate in the study. I will discuss this information with them to assure that they are adequately informed 
regarding the drug and conduct of the study. I agree to keep records on all subject information (case report 
forms, shipment and drug return forms, and all other information collected during the study) and drug 
disposition in accordance with FDA regulations. I will not enroll any subjects into this protocol until IRB 
approval and sponsor approval are obtained. I understand that no deviations from the protocol may be made. 
 
 
Principal Investigator’s Name 
 
 
Principal Investigator’s Title 
 
 
Principal Investigator’s Email Address 
 
 
Site Address 
 
 
 
Site Telephone Number 
 
 
Site Fax Number 
 
 
 
 
 
___________________________________  
 
____________________________________ 
Principal Investigator’s Signature 
 
 
 
 
Date 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 5 of 67 
 
 
4.0 TABLE OF CONTENTS 
 
1.0 TITLE PAGE .......................................................................................................................................... 1 
2.0 KEY STUDY PERSONNEL AND FACILITIES .................................................................................. 2 
3.0 SIGNATURE PAGE .............................................................................................................................. 3 
4.0 TABLE OF CONTENTS ........................................................................................................................ 5 
5.0 SYNOPSIS .............................................................................................................................................. 9 
6.0 STUDY SCHEMATIC ......................................................................................................................... 18 
7.0 LIST OF ABBREVIATIONS AND TERMS ....................................................................................... 19 
8.0 INTRODUCTION ................................................................................................................................ 20 
8.1 Disease Being Treated ...................................................................................................................... 20 
8.2 Availability and Efficacy of Already Approved Therapies .............................................................. 20 
8.3 Scientific and Statistical Considerations ........................................................................................... 21 
8.4 Justification for use of Placebo ......................................................................................................... 21 
8.5 Risks and Benefits ............................................................................................................................ 21 
9.0 STUDY OBJECTIVES ......................................................................................................................... 22 
10.0 INVESTIGATIONAL PLAN ............................................................................................................. 22 
10.1 Study Design and Plan Description ................................................................................................ 22 
10.2 Selection of Study Design ............................................................................................................... 23 
10.3 Selection of Study Population ......................................................................................................... 24 
10.3.1 Inclusion Criteria...................................................................................................................... 24 
10.3.2 Exclusion Criteria .................................................................................................................... 25 
10.3.3 Restrictions During the Study .................................................................................................. 26 
10.3.4 Withdrawal of Subjects from the Study ................................................................................... 27 
10.3.5 Early Termination .................................................................................................................... 28 
10.4 Treatments ...................................................................................................................................... 29 
10.4.1 Treatments Administration ...................................................................................................... 29 
10.4.2 Identity of IP ............................................................................................................................ 30 
10.4.3 Study Blind .............................................................................................................................. 30 
10.4.4 IP Shipment, Retention and Storage ........................................................................................ 31 
10.4.5 Method of Assigning Subjects to Treatment Groups ............................................................... 32 
10.4.6 Compliance .............................................................................................................................. 33 
10.5 Study Conduct ................................................................................................................................. 34 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 6 of 67 
 
 
10.5.1 Visit 1 (Day -14 to Day 1): Screening and Baseline Evaluation .............................................. 34 
10.5.2 Visit 2 (Day 28 ± 4 days): Interim Visit ................................................................................... 35 
10.5.3 Visit 3: (Day 56 ± 4 days): Interim Visit ................................................................................. 36 
10.5.4 Visit 4: (Day 85 ± 4 days) End of Study Visit or Early Termination....................................... 36 
10.6 Study Procedures ............................................................................................................................ 37 
10.6.1 Informed Consent ..................................................................................................................... 37 
10.6.2 Demographics .......................................................................................................................... 37 
10.6.3 Medical History........................................................................................................................ 37 
10.6.4 Pregnancy Test ......................................................................................................................... 37 
10.6.5 Vital Signs ................................................................................................................................ 37 
10.6.6 Concomitant Medication .......................................................................................................... 38 
10.6.7 Dermatologic Assessment ........................................................................................................ 38 
10.6.8 IGA .......................................................................................................................................... 38 
10.6.9 PASI ......................................................................................................................................... 38 
10.6.10 Application Site Reactions ..................................................................................................... 39 
10.6.11 Inclusion and Exclusion Criteria Review ............................................................................... 39 
10.6.12 Randomization ....................................................................................................................... 39 
10.6.13 Dispensing IP ......................................................................................................................... 39 
10.6.14 Returning IP ........................................................................................................................... 39 
10.6.15 Subject Dosing Instructions and Diary .................................................................................. 40 
10.6.16 Standardized Sunscreen ......................................................................................................... 40 
10.6.17 Health Status/AEs .................................................................................................................. 40 
10.7 AEs/SAEs ....................................................................................................................................... 40 
10.7.1 Definitions ................................................................................................................................ 41 
10.7.2 Severity of AEs ........................................................................................................................ 42 
10.7.3 Relationship to the IP ............................................................................................................... 42 
10.7.4 AE Documentation ................................................................................................................... 42 
10.7.5 SAE Reporting ......................................................................................................................... 43 
10.7.6 Pregnancies .............................................................................................................................. 46 
10.7.7 Quality Complaints .................................................................................................................. 46 
 46 
10.7.9 Reconciliation .......................................................................................................................... 47 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 7 of 67 
 
 
11.0 STATISTICAL METHODS ............................................................................................................... 47 
11.1 Statistical Plan ................................................................................................................................. 47 
11.2 Sample Size Determination ............................................................................................................. 48 
11.3 Study Populations ........................................................................................................................... 48 
11.3.1 PP Population ........................................................................................................................... 48 
11.3.2 Modified Intent-to-Treat (mITT) Population ........................................................................... 49 
11.3.3 Safety Populations.................................................................................................................... 49 
11.4 Baseline Comparability ................................................................................................................... 49 
11.5 Efficacy Endpoints .......................................................................................................................... 50 
11.6 Primary and Secondary Endpoint Analyses .................................................................................... 50 
11.7 Treatment-by-Site Interaction and Pooling of Clinical Sites .......................................................... 51 
11.8 Safety Analysis ............................................................................................................................... 51 
12.0 REGULATORY OBLIGATIONS ...................................................................................................... 51 
12.1 Institutional Review Board ............................................................................................................. 51 
12.2 Subject Confidentiality ................................................................................................................... 52 
12.3 Study Documentation...................................................................................................................... 52 
12.3.1 Protocol .................................................................................................................................... 52 
12.3.2 Informed Consent ..................................................................................................................... 53 
12.3.3 Protocol and Informed Consent Changes ................................................................................. 53 
12.3.4 Source Documents and Case Report Forms ............................................................................. 53 
12.3.5 Drug Accountability ................................................................................................................. 54 
12.3.6 Drug Storage ............................................................................................................................ 54 
12.3.7 Retention of Reserve Samples ................................................................................................. 54 
12.3.8 Return of Clinical Supplies ...................................................................................................... 55 
12.3.9 Pregnancy and Breastfeeding ................................................................................................... 55 
12.3.10 Reporting Safety Information to the IRB ............................................................................... 56 
12.3.11 Record Retention.................................................................................................................... 56 
12.3.12 Study Monitoring and Auditing ............................................................................................. 57 
12.3.13 Confidentiality, Use of Information and Publication ............................................................. 60 
12.3.14 End of the Trial ...................................................................................................................... 60 
12.3.15 Clinical Study Report ............................................................................................................. 61 
12.3.16 Termination of the Study ....................................................................................................... 61 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 8 of 67 
 
 
 62 
14.0 APPENDICES .................................................................................................................................... 63 
14.1 APPENDIX A: Investigator’s Global Assessment of Disease Severity ......................................... 63 
14.2 APPENDIX B: Psoriasis Area Severity Index at the Target Lesion Site ....................................... 64 
14.3 APPENDIX C: Application Site Reactions .................................................................................... 65 
14.4 APPENDIX D: TAZORAC® (tazarotene) Product Insert .............................................................. 66 
14.5 APPENDIX E: Amendments to the Protocol ................................................................................. 67 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 9 of 67 
 
 
5.0 SYNOPSIS 
 
Protocol Number 
0453-01-01 
Title 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-
Group Study Comparing Tazarotene Cream 0.05% to TAZORAC® 
(Tazarotene) Cream 0.05% and Both Active Treatments to a Vehicle 
Control in the Treatment of Stable Plaque Psoriasis 
Objectives 
1. Evaluate the therapeutic equivalence of the Test product, Tazarotene 
Cream 0.05% (Fougera Pharmaceuticals Inc.) to the Reference product, 
TAZORAC® (tazarotene) Cream 0.05% (Allergan, Inc.) in the treatment 
of stable plaque psoriasis. 
2. Demonstrate the superiority of the efficacy of the Test and Reference 
(active) products over that of the Placebo in the treatment of stable 
plaque psoriasis. 
3. Compare the safety of the Test, Reference and Placebo products in the 
treatment of stable plaque psoriasis. 
Sponsor 
Fougera Pharmaceuticals Inc. 
Investigational 
Products 
• 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.) 
• 
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
• 
Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
Dose and Route of 
Administration 
Subjects will be instructed to apply the investigational product (IP) 
topically, once daily, in the evening, for 84 days ± 4 days (12 weeks). 
Enough cream should be applied (2 mg/cm2) to cover only the lesions with 
a thin film. Hands should be washed thoroughly before and after each 
application. It is recommended that if a bath or shower is taken before 
application, the skin should be dry before applying the cream.  
Treatment Period 
84 days (12 weeks) ± 4 days 
Treatment 
Randomization 
1: 1: 1 (Test: Reference: Placebo) 
Subject Populations 
Approximately 855 male and non-pregnant female subjects, at least 18 years 
of age who meet all of the inclusion criteria and none of the exclusion 
criteria, will be enrolled in order to obtain
 subject in the modified Intent-
to-Treat (mITT) population and 
 subjects in the per-protocol (PP) 
population. 
The primary inclusion criteria are: 
• 
Clinical diagnosis of stable (at least 6 months) plaque psoriasis 
involving at least 2% and no more than 20% of Body Surface Area 
(BSA) not including the scalp and intertriginous areas 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 10 of 67 
 
 
• 
An Investigator's Global Assessment (IGA) of disease severity of at 
least moderate severity (Score ≥ 3) as an overall assessment of 
lesions to be treated 
• 
A minimum plaque elevation of at least moderate severity (Score ≥ 
3) at the target lesion (the most severe lesion at Baseline) 
Study Design 
A multi-center, double-blind, randomized, vehicle-controlled, parallel-
group bioequivalence study with clinical endpoints comparing Tazarotene 
Cream 0.05% to TAZORAC® (tazarotene) Cream, 0.05% and both active 
treatments to a vehicle control in the treatment of stable plaque psoriasis. 
Investigative Sites 
Approximately 30 sites in the United States 
Study Conduct 
Eligible subjects will be randomized in a 1:1:1 ratio to one of the three 
treatment groups (Test, Reference or Placebo) at Visit 1. IP will be 
dispensed at Visit 1. Subjects will be instructed to apply enough cream 
(2 mg/cm2) to cover only the psoriatic lesions with a thin film. The first dose 
will be applied on the evening of Day 1. The subject will then continue to 
apply a thin film (2 mg/cm2) of the product once daily, in the evening, to 
cover only psoriatic lesions until the evening before Visit 4 (Day 85 ± 4 
days). Subjects will attend the following scheduled clinic visits: 
• 
Visit 1 - Screening/Baseline: Day -14 to 1 
• 
Visit 2 - Interim Visit: Day 28 ± 4 days 
• 
Visit 3 - Interim Visit: Day 56 ± 4 days 
• 
Visit 4 - End of Study/Early Termination: Day 85 ± 4 days 
Efficacy evaluations will be based on dermatological assessments 
performed in the clinic. The primary endpoint is the proportion of subjects 
with treatment success on the IGA at the Week 12 visit (Day 85 ± 4, End of 
Study). See Appendix A for IGA scale. 
Inclusion Criteria 
1. Male or non-pregnant, non-lactating female, ≥ 18 years of age with a 
clinical diagnosis of stable (at least 6 months) plaque psoriasis. 
2. 
 
 
3. Females of childbearing potential must not be lactating or pregnant at 
Visit 1 (as confirmed by a negative urine pregnancy test with a 
sensitivity of less than 50 mlU/mL or equivalent units of human 
chorionic gonadotropin) and 
 
 
Childbearing Potential 
Defined as: 
Non-Childbearing Potential 
Defined as: 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 11 of 67 
 
 
Evidence of menses in the past 
12 months 
Post-menopausal, defined as 
women who have been 
amenorrheic for at least 12 
consecutive months, without 
other known or suspected 
primary cause. 
Amenorrhea for ≥ 12 months, but 
the amenorrhea is possibly due to 
other causes, including prior 
chemotherapy, anti-estrogens or 
ovarian suppression 
Sterilized surgically or who are 
otherwise proven sterile (i.e., 
total hysterectomy, or bilateral 
oophorectomy) with surgery at 
least 4 weeks before Screening. 
Tubal ligation will not be 
considered a surgically sterile 
method. 
4. 
5. Have clinical diagnosis of stable (at least 6 months) plaque psoriasis 
involving at least 2% and no more than 20% BSA not including the 
scalp and intertriginous areas. 
6. Have an IGA of disease severity grade of at least moderate severity 
(score ≥ 3 per Appendix A). 
7. Have a Psoriasis Area Severity Index (PASI) minimum plaque elevation 
grade of at least moderate severity (score ≥ 3 per Appendix B) at the 
target lesion site. The most severe lesion at Baseline should be identified 
as the target lesion. 
8. 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 12 of 67 
 
 
9. Willing to avoid constant sun exposure and the use of tanning booths or 
other ultraviolet light sources during their participation in the study. 
10. 
 
 
 
Exclusion Criteria 
1. Females who are pregnant, breast feeding, planning a pregnancy or do 
not agree to use an acceptable form of birth control throughout the 
study. 
2. Has a current diagnosis of unstable forms of psoriasis in the treatment 
area including guttate, erythrodermic, exfoliative or pustular psoriasis. 
3. Has clinically infected psoriasis at Baseline. 
4. In the Investigators opinion, subject has other inflammatory skin disease 
in the treatment area that may confound the evaluation of the plaque 
psoriasis (i.e., atopic dermatitis, contact dermatitis, eczema, tinea 
corporis). 
5. Has presence of pigmentation, extensive scaring, pigmented lesions or 
sunburn in the treatment area which could interfere with the rating of 
efficacy parameters. 
6. Has a history of psoriasis unresponsive to topical treatments and/or 
biologic treatments. 
7. Has a history of hypersensitivity or allergy to tazarotene, retinoids, 
and/or any component of the IP (Test, Reference or Placebo). Please 
refer to the Reference Listed Drug Package Insert for the components 
of the IP 
8. Current signs or symptoms of immunosuppression. 
9. 
 
 
 
 
 
 
 
10. Has treated with any marketed or investigational biologics for psoriasis 
(i.e., infliximab, adalimumab, alefacept, etc.) within 6 months before 
Baseline. 
11. Has been treated with chemotherapy or radiation therapy within 3 
months before Baseline. 
12. Has treated with any immunosuppressive drugs (i.e., tacrolimus, 
pimecrolimus) or oral retinoids within 2 months before Baseline. 
13. Has treated with systemic steroids, systemic antibiotics, systemic anti-
psoriatic treatment (i.e., methotrexate, cyclosporine, hydroxyurea), 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 13 of 67 
 
 
PUVA therapy, ultraviolet-B Therapy or systemic anti-inflammatory 
agents within 1 month before Baseline. 
 
 
 
 
 
 
 
 
 
14. Has treated with topical anti-psoriatic drugs (i.e., salicylic acid, 
anthralin, coal tar, calcipotriene, tazarotene), topical corticosteroids or 
topical retinoids within 2 weeks before Baseline. 
15. Inability to understand the protocol requirements, instructions and 
study-related restrictions, the nature, scope and possible consequences 
of the clinical study. 
16. Receipt of any drug and/or IP as part of a research study within the 30 
days before Baseline. 
17. Subjects who consume excessive amounts of alcohol, abuse drugs, or 
have any social condition that would, in the Investigator’s opinion, 
compromise compliance with this protocol. 
18. Previous participation in this study. 
19. Employees of the Investigator or research center or their immediate 
family members. 
Efficacy Endpoints 
 
Primary Efficacy Endpoint 
Proportion of subjects with treatment success (defined as none, minimal or 
mild disease, a score of 0, 1 or 2 within the treatment area) on the IGA at 
the Week 12 visit (Day 85 ± 4, End of Study). 
Secondary Efficacy Endpoints 
1. Proportion of subjects with disease severity at the Week 12 visit (Day 
85 ± 4, End of Study) consistent with none or minimal, a score of 0 or 
1, within the treatment area on the IGA, and 
2. Proportion of subjects with target site plaque elevation, scaling and 
erythema scores of less than or equal to 1on the PASI at the Week 12 
visit (Day 85 ± 4, End of Study). 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 14 of 67 
 
 
Measures 
The following scales will be used for evaluation of Baseline disease 
severity and treatment effect. 
IGA of Disease Severity 
Score Grade 
Definition 
0 
None 
No plaque elevation above normal skin level; may 
have residual non-erythematous discoloration; 
no psoriatic scale; no erythema
1 
Minimal 
Essentially flat with possible trace elevation; faint 
erythema; no psoriatic scale 
2 
Mild 
Slight but definite elevation of plaque above normal 
skin level; may have up to moderate erythema (red 
coloration); fine scales with some lesions partially 
covered 
3 
Moderate Moderate elevation with rounded or sloped edges to 
plaque; moderate erythema (red coloration); 
somewhat coarse scales with most lesions partially 
covered 
4 
Severe 
Marked elevation with hard, sharp edges to plaque; 
severe erythema (very red coloration); coarse, thick 
scales with virtually all lesions covered and a rough 
surface 
5 
Very 
Severe 
Very marked elevation with very hard, sharp edges to 
plaque; very severe erythema 
(extreme red coloration); very coarse, thick scales 
with all lesions covered and a very rough surface
Subjects with IGA grade of ≥ 3 will be enrolled in the study 
PASI at the Target Lesion Site 
Score Grade 
Erythema 
Scaling 
Plaque 
Elevation 
0 
Clear 
No evidence 
of erythema 
No evidence of 
scaling 
No evidence of 
plaques above 
normal skin 
level 
1 
Almost 
Clear 
Pink 
discoloration, 
minimal 
erythema 
Occasional fine 
scales hardly 
noticeable 
Slight, just 
discernible 
elevation 
above normal 
skin level 
2 
Mild 
Light red 
coloration 
Slight but 
definite 
roughness, fine 
Discernible 
elevation 
above normal 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 15 of 67 
 
 
scale present, no 
cracking 
skin level upon 
examination, 
but not 
pronounced 
3 
Moderate Moderate 
redness, but 
not dark 
Moderate 
roughness, 
somewhat 
coarse scaling 
Definite 
plaque 
formation with 
rounded/sloped 
edges to 
plaque 
4 
Severe 
Dark red 
coloration 
Marked 
roughness, 
coarse/thick 
scaling, cracking 
may be evident 
Marked 
elevation with 
hard, distinct 
edges to 
plaque 
5 
Very 
Severe 
Very dark 
red 
coloration 
with 
induration 
present 
Very thick 
scales covering 
extensive area 
severe 
cracking/fissures 
may be evident 
Very marked 
elevation, very 
hard and sharp 
edges to 
plaque 
Evaluation of 
Therapeutic 
Equivalence and 
Superiority 
The primary analyses for evaluating the therapeutic equivalence of the Test 
and Reference treatments, and the superiority of each active treatment over 
the Placebo, will be based on the proportion of subjects with treatment 
success (defined as "none, minimal or mild disease, a score of 0, 1 or 2, 
within the treatment area") on the IGA at Week 12 visit (Day 85 ± 4, End 
of Study). 
The statistical analyses for equivalence for binary outcomes for the primary 
and two secondary endpoints will be based on a Yates’ continuity-corrected 
confidence interval on the Test minus Reference difference (T-R) in 
proportions. Superiority will be tested at the 5% significance level using a 
Cochran-Mantel-Haenszel exact test stratified by clinical site for Test versus 
Placebo and Reference versus Placebo for the three endpoints. 
Therapeutic Equivalence Analysis 
Therapeutic equivalence will be evaluated for both primary and secondary 
endpoints using the PP population, with results in the mITT population 
being supportive. For the dichotomized primary endpoint (proportion of 
treatment success), if the 90% confidence interval (with Yates’ Correction 
Factor) of the difference between the proportion of subjects considered a 
“treatment success” in the Test and the Reference treatment groups at Week 
12, compared to Baseline, is contained within the pre-defined equivalence 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 16 of 67 
 
 
limits [-20%, +20%], then therapeutic equivalence will be considered to 
have been supported for the endpoint. The same statistical approach will be 
conducted for analysis of the two dichotomized secondary endpoints in the 
PP and mITT populations. 
To declare therapeutic equivalence of the Test product to the Reference 
product, therapeutic equivalence must be demonstrated for only the primary 
endpoint in the PP population. 
Superiority to Placebo Analysis 
The primary measure of superiority will be evaluated using the mITT 
population and last observation carried forward (LOCF) for missing 
efficacy values. The results in the PP population will be considered 
supportive. The superiority of the Test and Reference products over Placebo 
will be concluded for the primary endpoint if the proportion of treatment 
success at Week 12 is statistically superior to Placebo (p < 0.05, two-sided) 
using the mITT population and LOCF. The same statistical approach will 
be conducted for analysis of the two dichotomized secondary endpoints in 
the mITT and PP populations. 
To declare superiority of the Test and Reference products over Placebo, 
their superiority must be demonstrated for only the primary endpoint in the 
mITT population. 
Safety Analysis 
Adverse events (AEs) will be classified using standard MedDRA 
terminology Version 18.1 or higher and summarized by treatment group. 
Summary tables comparing the type, date of onset, date of resolution, 
incidence, severity, relationship to the IP, outcome and action taken will be 
prepared by treatment group. Should sufficient data exist, AE frequencies 
will be compared among treatments using Fisher’s exact test or a similar 
test. Application site reactions (erythema, dryness, burning/stinging, 
erosion, edema, pain, itching) recorded at each visit will be compared 
among treatment groups. A descriptive analysis comparing the application 
site reactions for each treatment group will be created. 
Concomitant medication use during the treatment period will be tabulated 
by subject. 
Signs and symptoms of psoriasis will not be considered AEs, unless in the 
Investigator’s opinion, they have increased in frequency and/or severity to 
such an extent that the Investigator/subject considers that it is in the 
subject’s best interest to be dropped from continued participation in the 
study and given alternative therapy for their condition. 
All randomized subjects who received IP will be included in the 
comparative safety analysis.  
Sample Size 
Determination 
Sample size calculations were performed using 
 
For the primary endpoint analysis, the rate of treatment success for the 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 17 of 67 
 
 
Reference treatment after 12 weeks of treatment is expected to be 
approximately 
 in the PP population. Assuming that the rates of 
treatment success for Test and Reference treatments are the same, a sample 
size of 
 subjects in each active group in the PP population will provide 
approximately 
 power to demonstrate therapeutic equivalence (i.e., the 
90% confidence interval (Yates’ continuity-corrected) of the absolute 
difference between the Test and Reference rates of treatment success is 
within a defined equivalence range [-20% to + 20%]). 
The rates of treatment success for the Placebo and active treatment groups 
after 12 weeks of treatment are assumed to be approximately 
 and at 
least 
 respectively, in the mITT population. Using a 1:1 (active: 
placebo) randomization scheme, and assuming the conversion rate from 
mITT to PP population will be about 
 
 subjects in each treatment 
group (Test, Reference and Placebo) of the mITT population will provide at 
least 
 power to demonstrate superiority of active over Placebo at the 
 
significance level (p < 0.05, two-sided continuity-corrected Z-Tests and a 
pooled response rate for the standard error of the difference in proportions). 
Under the above assumptions, the overall study power to demonstrate 
therapeutic equivalence and superiority is estimated to be at least 
. To 
allow for approximately 
 of subjects who may drop out from the study 
or are otherwise non-evaluable, up to 855 subjects may be randomized to 
obtain 
 subjects in the mITT population (i.e., 
 per treatment arm). 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 18 of 67 
 
 
6.0 STUDY SCHEMATIC 
 
PROCEDURE 
VISIT 1 
(Day -14 to 
1) 
Screening/ 
Baseline  
VISIT 2 
(Day 28 
± 4 Days) 
Interim Visit 
 
VISIT 3 
(Day 56 
± 4 Days) 
Interim Visit 
 
VISIT 4 
(Day 85 
± 4 Days)* 
End of Study/ 
Early 
Termination 
Informed Consent 
X‡ 
 
 
 
Medical History/ 
Demographics 
X‡ 
 
 
 
Pregnancy Test†  
X‡ 
X 
X 
X 
Vital Signs 
X
‡ 
 
 
X 
Dermatologic Assessment 
X
‡ 
 
 
 
IGA 
X
‡ 
X 
X 
X 
PASI Assessment 
X
‡ 
X 
X 
X 
Application Site Reactions 
X 
X 
X 
X 
Inclusion/Exclusion Criteria 
Review  
X
‡ 
 
 
 
Concomitant Medication 
X
‡ 
X 
X 
X 
Randomization 
X 
 
 
 
Dispense IP 
X 
X** 
X** 
 
Return of IP  
 
X** 
X** 
X 
Dispense Subject 
Diary/Supplies 
X 
X 
X 
 
Collect/Review Subject Diary  
 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
Discharge from Study 
 
 
 
X 
* Dosing regimen is once daily in the evening for 84 days (Day 1 to Day 84) through the evening before 
Visit 4 (Day 85 ± 4) 
** If applicable, based on use of previously dispensed product. 
† For females of childbearing potential 
‡ Procedures performed as part of the screening assessment, before randomization 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 19 of 67 
 
 
7.0 LIST OF ABBREVIATIONS AND TERMS 
AE 
Adverse Event 
ADR 
Adverse Drug Reaction 
ADaM 
Analysis Dataset Model 
ANOVA 
Analysis of Variance 
BSA 
Body Surface Area 
C 
Celsius 
CDER 
Center for Drug Evaluation and Research 
CDISC 
Clinical Data Interchange Consortium 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
cm 
Centimeter 
CRO  
Clinical Research Organization 
eCRF 
electronic Case Report Form 
eCTD 
electronic Common Technical Document 
F 
Fahrenheit 
FDA 
g  
Food and Drug Administration 
Gram 
GCP 
Good Clinical Practices 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF  
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA 
Investigator’s Global Assessment 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
Intrauterine Device 
LOCF 
LPPV 
Last Observation Carried Forward 
Local Person for Pharmacovigilence 
MedDRA 
mg 
Medical Dictionary for Regulatory Activities 
Milligram 
mITT 
modified Intent-to-Treat 
ml 
milliliter 
NDA  
New Drug Application 
OGD 
Office of Generic Drugs 
OHRP 
Office of Human Rights Protection 
OTC 
Over-The-Counter 
PASI 
Psoriasis Area Severity Index 
PD 
Protocol Deviation 
PP 
Per-Protocol 
RLD 
Reference Listed Drug 
SADR 
Serious Adverse Drug Reaction 
SAE  
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SDTM 
Study Data Tabulation Model 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 20 of 67 
 
 
8.0 INTRODUCTION 
8.1 Disease Being Treated 
Psoriasis is an immune (T-cell)-mediated inflammatory skin disease that affects approximately 2% of 
the western population.1 The most common type of psoriasis is plaque psoriasis, which is characterized 
by the presence of raised, thickened red lesions that are covered by silvery white scales, most commonly 
seen on the knees and/or elbows. Although there are reports implicating a genetic association with the 
disease, there are also studies that have established a set of psoriasis triggers including stress, 
medications (such as lithium, antimalarials, indomethacin, quinidine and beta blockers), injury or 
infection. The condition is considered chronic although the frequency and severity of outbreak in an 
individual can fluctuate without apparent cause.1-3 
Treatment of plaque psoriasis depends on the severity of the condition, previous treatment regimens 
and personal preference of the subject. For mild to moderate plaque psoriasis, topical treatments and 
phototherapy are the preferred treatment modalities. For more severe cases, oral or injectable systemic 
therapy may be warranted; however, the side effect profiles of these products limit their use. 
Psoriasis is typically described as mild, moderate or severe and by assessing the percentage of body 
surface area (BSA) affected and covered by psoriasis lesions. Several scale systems have been 
developed and many are in use in the clinical setting; however, a severity scale, despite being a 
convenient scoring system, does not capture the true burden of psoriasis for many patients. Psoriasis is 
associated with a broad range of medical and psychosocial comorbidities that erode quality of life of 
the patients. Subjects selected for this study suffer from plaque psoriasis of at least moderate severity 
and an IGA of 3 or more. 
8.2 Availability and Efficacy of Already Approved Therapies 
Treatment of plaque psoriasis depends on the severity of the condition, previous treatment regimens 
and personal preference of the subject. Psoriasis treatments historically include topical creams, sprays, 
lotions and foams. Examples of marketed products include corticosteroids (Topicort®, Clobex™), 
Vitamin A & D derivatives (Tazorac®, Dovonex®), NSAIDs (salicylic acid), etc. For more severe cases, 
systemic therapy (methotrexate, oral retinoids, UV light, biologics, etc.) may be warranted; however, 
the side effect profiles of these products limit their use.1,2,4-6 
Tazarotene is one of a class of drugs known as the acetylenic retinoids. Psoriasis is a chronic immune-
mediated disease that is characterized by the hyperproliferation and abnormal differentiation of 
keratinocytes and by inflammation. The epidermal changes associated with psoriasis may be due to the 
infiltration of inflammatory T lymphocytes and the release of cytokines in response to antigenic 
stimulation. Tazarotene is a retinoic acid receptor-specific retinoid with demonstrated efficacy in the 
topical treatment of psoriasis. Tazarotene down-regulates markers of keratinocyte differentiation, 
keratinocyte proliferation and inflammation. The drug also up-regulates three novel genes TIG-1 
(tazarotene-induced gene-1), TIG-2 and TIG-3, which may mediate an antiproliferative effect. The 
effect of tazarotene on these markers is probably a direct effect on gene expression rather than an 
indirect effect associated with disease improvement. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 21 of 67 
 
 
8.3 Scientific and Statistical Considerations 
Tazarotene has low systemic absorption and rapid elimination from semi-solid topical formulations 
of TAZORAC®. In a multiple-dose study with a once daily dose of tazarotene cream, 0.1% 
administered for 14 consecutive days to nine psoriatic subjects, mean peak plasma concentrations 
of 2.31 ng/mL occurring 8 hours after the final dose were observed for the active metabolite of 
tazarotene (tazarotenic acid).7 The 21 Code of Federal Regulations Sections 320.24 (Revised 
April 1, 2014) requires that in-vivo pharmacokinetic testing in humans is the preferred method in 
evaluating therapeutic equivalence. However, circumstances for which measurement of the active 
moieties in biological fluids is not possible or provides low concentrations, a pharmacodynamic 
response study indicative of clinical safety and efficacy can be considered.8-10 Based on the low 
systemic bioavailability of tazarotene from the topical cream product, a comparative clinical 
efficacy study is considered the most appropriate method to evaluate the therapeutic equivalence 
of two tazarotene topical cream, 0.05% formulations. 
 
 
 
 
 
 
 
8.4 Justification for use of Placebo 
A Placebo group is included to confirm the sensitivity of the study and minimize the possibility of 
a false positive result of therapeutic equivalence. Therefore, in addition to demonstrating 
therapeutic equivalence between Test and Reference products, both active products must show 
statistical superiority to the Placebo.11,12 
Eligible subjects will have a 33.33% chance of being randomized to Placebo (1:1:1 randomization 
scheme of Test: Reference: Placebo). 
 
 
 
 
 
 
 
 
8.5 Risks and Benefits 
The risks and benefits to subjects enrolled in clinical research studies that include a Placebo 
treatment group must be carefully considered based on three main criteria, namely: the disease 
being treated, the availability, efficacy and safety of approved therapies, and the scientific and 
statistical requirements of the desired outcome of the research study. The Office of Human Rights 
Protection (OHRP), a Division of the United States Federal Government’s Department of Health 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 22 of 67 
 
 
and Human Services, has issued a detailed guidebook to IRBs that includes discussion on the use 
of placebos in clinical studies.13 
Randomized subjects will be enrolled in the study for 85 ± 4 days. Although the potential for any 
drug-related side effects of significance occurring during the study is low, the risk is higher in the 
two active treatment groups than in the Placebo group. Topical application of Tazarotene can lead 
to drug-related effects, mainly affecting the application sites: skin itching, irritation, dryness and 
burning or pain sensation represent the most common side effects. 
All subjects enrolled in this study will receive Investigator evaluation of their condition over 85 
days. In addition, the subject will be paid for their participation, and any payments will be reviewed 
by the IRB and disclosed to the subject, via the informed consent form (ICF). 
9.0 STUDY OBJECTIVES 
The objectives of this study are to: 
1. Evaluate the therapeutic equivalence of the Test product, Tazarotene Cream 0.05% (Fougera 
Pharmaceuticals Inc.) to the Reference product, TAZORAC® (tazarotene) Cream, 0.05% 
(Allergan) in the treatment of stable plaque psoriasis. 
2. Demonstrate the superiority of the efficacy of the Test and Reference (active) products over that of 
Placebo in the treatment of stable plaque psoriasis. 
3. Compare the safety of the Test, Reference and Placebo products in the treatment of stable plaque 
psoriasis. 
10.0 INVESTIGATIONAL PLAN 
10.1 Study Design and Plan Description 
This multi-center, double-blind, randomized, vehicle-controlled, parallel-group, bioequivalence 
clinical study has been designed to evaluate the efficacy and safety of a generic tazarotene cream 0.05% 
(Fougera Pharmaceuticals Inc.) compared to the FDA Reference Listed Drug (RLD) TAZORAC® 
(tazarotene) Cream 0.05% (Allergan) in subjects with a clinical diagnosis of stable plaque psoriasis of 
at least moderate severity. Additionally, both the Test product and Reference (i.e., the RLD) products 
will be tested for superiority to a Placebo. Subjects with confirmed stable plaque psoriasis will apply 
the investigational product (IP) once daily, in the evening, to psoriatic lesions for 84 ± 4 days (12 
weeks). 
Before any study-specific procedures are performed, all subjects will read and sign the IRB-approved 
ICF. 
Each site will develop an individualized recruitment plan to collectively enroll approximately 855 
eligible subjects, 18 years of age and older, with a clinical diagnosis of stable plaque psoriasis and 
meeting the inclusion/exclusion criteria. Subjects will be randomized to one of the three IPs as follows: 
• 
Test: Tazarotene Cream, 0.05% (Fougera Pharmaceuticals Inc.) 
• 
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
• 
Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 23 of 67 
 
 
Subjects will attend the following scheduled clinic visits: 
• 
Visit 1 - Screening/Baseline: Day -14 to Day 1 
• 
Visit 2 - Interim Visit: Day 28 ± 4 days 
• 
Visit 3 - Interim Visit: Day 56 ± 4 days 
• 
Visit 4 - End of Study/Early Termination: Day 85 ± 4 days 
At Visit 1, eligible subjects will be randomized to the Test, Reference or Placebo product in a 1:1:1 
ratio using the 
 system, which is an interactive response technology (IRT) system provided 
by the IRT provider. Study subjects will be provided with 
 of IP. 
 may be 
dispensed to the subject at the discretion of the Investigator if the subject has a high BSA affected with 
plaque psoriasis at the time of dispensation that would warrant additional product. At Visit 2 and Visit 
3, subjects who continue to be eligible for continuation in the study can be dispensed 
 
, as needed based on the subject's current BSA affected and the amount of IP 
remaining from the tube(s) previously dispensed. Further, any empty tubes will be collected at these 
visits. At Visit 4, all tubes will be collected (used and unused). A subject may return for an Unscheduled 
Visit at any time, should they require a resupply of IP (i.e., tube lost; all IP used between visits). It is 
estimated that approximately  tubes, but up to  tubes may be needed to dose a subject with high BSA 
involvement (~20% BSA) for the treatment period (depending upon their treatment response over the 
12 weeks). Subjects with less BSA involvement will need significantly less IP (approximately  to  
tubes). 
The day that the subject administers their first dose of IP will be considered Day 1. 
 
 
 
 
For all other subjects, the first dose (Day 1) of IP 
will be applied on the evening of Visit 1. 
The subject will be instructed to apply enough cream (2 mg/cm2) to cover only the psoriatic lesions 
with a thin film (2 mg/cm2) once daily, in the evening, until the evening before Visit 4 (Day 85 ± 4 
days).There will be no application of the product on the day of the End of Study visit. 
Efficacy evaluations will be based on dermatological assessments in the clinic. The primary statistical 
analysis of interest is the (1) proportion of subjects with treatment success (defined as none, minimal 
or mild disease, a score of 0, 1 or 2, within the treatment area) on the Investigator’s Global Assessment 
(IGA) at the Week 12 visit. The secondary analyses are (1) proportion of subjects with disease severity 
at the Week 12 visit consistent with none or minimal, a score of 0 or 1, within the treatment area on the 
IGA, and (2) proportion of subjects with target site plaque elevation, scaling, and erythema scores of 
less than or equal to one on the PASI at the Week 12 visit. 
10.2 Selection of Study Design 
This protocol is designed based on studies conducted as a part of the NDA (21-184) for TAZORAC® 
Cream, 0.05% and the FDA draft guidance for tazarotene cream 0.05%, released in April, 2011.14 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 24 of 67 
 
 
Statistical analyses of the clinical data will be based on recommendations in the FDA guidance or 
communications with the Office of Generic Drugs (OGD)/FDA.9,15 
10.3 Selection of Study Population 
10.3.1 Inclusion Criteria 
1. Male or non-pregnant, non-lactating female, ≥ 18 years of age with a clinical diagnosis of stable 
(at least 6 months) plaque psoriasis. 
2. 
 
3. Females of childbearing potential must not be lactating or pregnant at Visit 1 (as confirmed by 
a negative urine pregnancy test with a sensitivity of less than 50 mlU/mL or equivalent units 
of human chorionic gonadotropin) and 
 
Childbearing Potential 
Defined as: 
Non-Childbearing Potential 
Defined as: 
Evidence of menses in the past 12 months 
Post-menopausal, defined as women who 
have been amenorrheic for at least 12 
consecutive months, without other known or 
suspected primary cause. 
Amenorrhea for ≥ 12 months, but the 
amenorrhea is possibly due to other causes, 
including prior chemotherapy, anti-
estrogens or ovarian suppression 
Sterilized surgically or who are otherwise 
proven sterile (i.e., total hysterectomy, or 
bilateral oophorectomy) with surgery at least 
4 weeks before Screening. Tubal ligation 
will not be considered a surgically sterile 
method. 
4. 
5. Have clinical diagnosis of stable (at least 6 months) plaque psoriasis involving at least 2% and 
no more than 20% BSA not including the scalp and intertriginous areas. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 25 of 67 
 
 
6. Have an IGA of disease severity grade of at least moderate severity (score ≥ 3 per Appendix 
A). 
7. Have a Psoriasis Area Severity Index (PASI) minimum plaque elevation grade of at least 
moderate severity (score ≥ 3 per Appendix B) at the target lesion site. The most severe lesion 
at Baseline should be identified as the target lesion. 
8. 
 
 
 
 
9. Willing to avoid constant sun exposure and the use of tanning booths or other ultraviolet light 
sources during their participation in the study. 
10. 
 
 
10.3.2 Exclusion Criteria 
1. Females who are pregnant, breast feeding, planning a pregnancy or do not agree to use an 
acceptable form of birth control throughout the study. 
2. Has a current diagnosis of unstable forms of psoriasis in the treatment area including guttate, 
erythrodermic, exfoliative or pustular psoriasis. 
3. Has clinically infected psoriasis at Baseline. 
4. In the Investigators opinion, subject has other inflammatory skin disease in the treatment area 
that may confound the evaluation of the plaque psoriasis (i.e., atopic dermatitis, contact 
dermatitis, eczema, tinea corporis). 
5. Has presence of pigmentation, extensive scaring, pigmented lesions or sunburn in the treatment 
area which could interfere with the rating of efficacy parameters. 
6. Has a history of psoriasis unresponsive to topical treatments and/or biologic treatments. 
7. Has a history of hypersensitivity or allergy to tazarotene, retinoids, and/or any component of 
the IP (Test, Reference or Placebo). Please refer to the RLD Package Insert for the components 
of the IP. 
8. Current signs or symptoms of immunosupression. 
9. 
 
 
 
 
 
10. Has treated with any marketed or investigational biologics for psoriasis (i.e., infliximab, 
adalimumab, alefacept, etc.) within 6 months before Baseline. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 26 of 67 
 
 
11. Has been treated with chemotherapy or radiation therapy within 3 months before Baseline. 
12. Has treated with any immunosuppressive drugs (i.e., tacrolimus, pimecrolimus) or oral 
retinoids within 2 months before Baseline. 
13. Has treated with systemic steroids, systemic antibiotics, systemic anti-psoriatic treatment (i.e., 
methotrexate, cyclosporine, hydroxyurea), PUVA therapy, ultraviolet-B Therapy or systemic 
anti-inflammatory agents within 1 month before Baseline. 
 
 
 
 
 
 
 
14. Has treated with topical anti-psoriatic drugs (i.e., salicylic acid, anthralin, coal tar, 
calcipotriene, tazarotene), topical corticosteroids or topical retinoids within 2 weeks before 
Baseline. 
15. Inability to understand the protocol requirements, instructions and study-related restrictions, 
the nature, scope and possible consequences of the clinical study. 
16. Receipt of any drug and/or IP as part of a research study within the 30 days before Baseline. 
17. Subjects who consume excessive amounts of alcohol, abuse drugs, or have any social condition 
that would compromise compliance, in the Investigator’s opinion, with this protocol. 
18. Previous participation in this study. 
19. Employees of the Investigator or research center or their immediate family members. 
10.3.3 Restrictions During the Study 
The following concomitant medications, products or procedures will not be allowed while enrolled 
in the study. 
• 
Use of the following topical products on or near the treatment area: 
o Moisturizers 
o New brands of Make-up 
o Creams, ointments, lotions, powders 
o Topical Corticosteroids 
• 
Topical or systemic anti-psoriatic treatments (e.g., anthralin, coal tar, tazarotene, retinoids, 
tacalcitol, inflixamab, adalumumab, alefacept, PUVA therapy, UVB therapy, salicylic acid, 
calcipotriene) 
• 
Systemic corticosteroids or systemic steroids, systemic anti-inflammatory agents or 
immunosuppressive drugs. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 27 of 67 
 
 
 
 
 
 
 
• 
Photosensitizers 
(e.g., 
thiazides, 
tetracyclines, 
fluoroquinolones, 
phenothiazines, 
sulfonamides) 
• 
More than 10,000 IU/day of Vitamin A supplements 
• 
Initiation or changes to non-antipsoriatic concomitant medication that could affect psoriasis 
(e.g., beta blockers, lithium) during the study 
• 
The use of tanning booths, sun lamps, non-prescription ultraviolet light sources or excessive 
sun exposure 
• 
Phototherapy 
• 
Application of IP to unaffected skin 
The treated areas should not be bandaged, covered or wrapped as to be occlusive. The use of 
hormonal contraceptives should not be initiated, changed or stopped during the study. Subjects 
should be instructed to minimize exposure to natural sunlight and to use study provided sunscreens 
of at least SPF 15 and wear protective clothing during the day. Subjects should not allow the IP to 
come in contact with the eyes, eyelids or mouth, should not use IP on skin that has eczema, and to 
always wash hands thoroughly after application of IP. 
Subjects will be questioned about all prescription and over-the-counter (OTC) concomitant 
medication use (including vitamins or nutritional supplements) at each study visit. All concomitant 
medications will be recorded in the subject’s source documents. Any subject who has violated any 
of the listed restrictions may be discontinued from the study. If discontinued, all End of Study/Early 
Termination procedures (Visit 4 procedures) should be performed. 
10.3.4 Withdrawal of Subjects from the Study 
Subjects will be advised that they are free to withdraw from the study at any time. Additionally, 
the sponsor may cease the study at any time. If necessary, the Investigator may withdraw a subject 
from the study to protect the health of that subject. The clinical study report will include all reasons 
for early withdrawals. 
Reasons for removal may include the following: 
• 
Subject withdraws consent for any reason 
• 
Subject’s condition has worsened to the degree that the Investigator feels it is unsafe for 
the subject to continue in the study 
• 
Lack of treatment effect 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 28 of 67 
 
 
• 
Significant adverse event (AE) that could affect the safety of the subject or the validity of 
evaluation of the subject’s clinical state to an extent considered significant by the 
Investigator 
• 
Subject’s IP becomes unblinded 
• 
There is a protocol deviation that, in the Investigator’s, Medical Monitor’s or Sponsor’s 
opinion, would compromise the safety of the subject or integrity of the data 
• 
The subject is lost to follow-up. The Investigator will document efforts to attempt to reach 
the subject at least twice by telephone and by a certified follow-up letter before considering 
that the subject as lost to follow-up 
• 
Pregnancy 
• 
Administrative reasons 
• 
Other (If the reason for withdrawal is not listed, ‘Other’ will be specified and the reason 
noted) 
Subjects who withdraw or are removed from the study will not be replaced. The Investigator may 
refer the subject for appropriate care if the subject withdraws due to safety concerns, as applicable. 
All subjects who are randomized will be included in the safety monitoring tabulating all AEs 
experienced after dosing until withdrawal from the study. 
10.3.5 Early Termination 
If a subject terminates from the study early, all efforts will be made to complete Visit 4 study 
procedures, obtain any outstanding data and collect all IP. For early termination, the Investigator 
shall fully document the reason for early termination and the date of removal. 
In the event that a subject discontinues from the study at any time due to an AE, the reason for 
discontinuation, the nature of the event and its clinical course must be fully documented. For such 
a subject, the Investigator should follow the subject until the AE has resolved, has become clinically 
insignificant, is stabilized, is confirmed to be ongoing at the end of the study, or the subject is lost 
to follow-up. Should a serious adverse event (SAE) be noted, procedures stated in section 10.7.4 
must be followed. Should pregnancy be noted, procedures stated in section 10.7.6 must be followed. 
Subjects who discontinue early because of lack of treatment effect after completing four weeks of 
treatment will be included in the per-protocol (PP) population as treatment failures provided they 
had no significant protocol deviations (PDs). Any PD that would compromise the integrity of the 
data will be considered significant. 
Subjects who discontinue early due to worsening condition and require alternate or supplemental 
therapy for the treatment of their plaque psoriasis during the study should be discontinued, included 
in the PP population analysis as treatment failures (provided they had no significant PDs during 
their time of study participation), and referred for effective treatment outside of the study. 
Subjects who discontinue early for reasons besides lack of treatment effect or worsening of 
condition should be excluded from the PP population, but included in the modified Intent-to-Treat 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 29 of 67 
 
 
(mITT) population using the last observation carried forward (LOCF), provided they administered 
at least one dose of randomized IP and completed at least one post-dose evaluation. 
10.4 Treatments 
10.4.1 Treatments Administration 
At Visit 1, eligible subjects will receive 
 of randomized IP (Test, Reference or 
Placebo). 
 may be dispensed to the subject at the discretion of the Investigator if the 
subject has a high BSA affected with plaque psoriasis at the time of dispensation that would warrant 
. Enough IP should be dispensed to allow the subject to dose daily until the next 
scheduled visit. 
At Visit 2 and Visit 3, subjects who continue to be eligible for continuation in the study can be 
dispensed 
, as needed based on the subject's current BSA and 
the amount of IP remaining from the tube(s) previously dispensed. Further, any empty tubes will 
be collected at these visits. At Visit 4, all tubes will be collected (used and unused). A subject may 
return for an Unscheduled Visit at any time, should they require a resupply of IP (i.e., tube lost; all 
IP used between visits; tube significantly damaged [became punctured]). 
The subject will be instructed on when to apply their first dose of IP, which will be considered Day 
1. Females of childbearing potential must administer their first dose (Day 1)
 
 
 
 For all other subjects, the first dose (Day 1) of IP will be applied 
on the evening of Visit 1. 
Subjects will be instructed to apply enough cream (2 mg/cm2) to cover only the lesions with a thin 
film. If a bath or shower is taken before application, the skin should be dry before applying the 
cream. Subjects will be instructed to apply the medication once daily, in the evening and to wash 
hands thoroughly before and after each application. The first dose will be applied on the evening 
of Day 1. The subject will then continue to apply a thin film (2 mg/cm2) of the product once daily, 
in the evening, to cover only psoriatic lesions until the evening before Visit 4 (Day 85 ± 4 days). 
The amount of IP required for each subject will vary greatly based on the subject's BSA affected 
with psoriasis at Baseline, as well as their rate of improvement or disease worsening over the course 
of the study. For subjects with BSA involvement close to 20% at Baseline, it is estimated that up 
to approximately 
 may be required for each subject to dose for the full 
duration of the study (84 days) depending upon their treatment response. Significantly less IP would 
be required for subjects with BSA involvement close to 2% (approximately
). Therefore, 
the amount of IP dispensed to each subject will be dependent upon their BSA involvement at 
Baseline and as the study progresses, at the discretion of the Investigator. Subject kits will each 
contain 
 of IP and will be randomized using the 
 system. After initial 
assignment of the first kit, additional kits of IP may be assigned to the subject as needed for dosing 
and/or to replace a missing tube and/or significantly damaged tube (i.e., punctured), also using the 
 system. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 30 of 67 
 
 
 
 
At each visit, the subject will be provided with a dosing diary in which they will be required to 
record the date of Day 1, all dosing dates and times and any missed doses. Each diary should be 
returned at the following visit so that the study staff may check compliance and file in the subject’s 
source documentation. 
10.4.2 Identity of IP 
The following products will be used in the study: 
• Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.) 
• Reference: TAZORAC® (tazarotene) Cream 0.05% (Allergan, Inc.) 
• Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
10.4.3 Study Blind 
The sponsor, clinical research organization (CRO), Investigator, staff at the study site, study 
monitors, and data analysis/management personnel will be blinded to the subject’s treatment 
assignment. The subject will be requested not to discuss the appearance of the IP tube with the 
Investigator or study staff outside of the 
. The tubes of Test, Reference and 
Placebo products will be blinded with identical outer cartons and labels. This will allow the study 
to be conducted under double-blind conditions (i.e., such that neither the subject nor the 
Investigator or study staff members will know the identity of the subject’s treatment). 
Each study site will have an 
 is blinded to the 
treatment arm that each subject has been randomized to. 
 
 
 
 
 
 
 
To ensure that information that could potentially bias handling of data is not disclosed, access to 
the master randomization code will be extremely limited. A sponsor representative who is not 
involved in clinical development or the study conduct will provide initial approval of the final code 
to 
 upon code generation. A member of the sponsor Pharmacovigilence department will have 
access to the code in case of a safety emergency and in order to expedite FDA reporting, if 
applicable. Otherwise, the packaging company 
 will hold the master 
randomization code until after database lock. No parties (CRO, clinical sites or sponsor) involved 
in the conduct of the study will have access to the master randomization code until after database 
lock. 
Breaking the blind must be considered only when knowledge of the treatment assignment is deemed 
essential by the Investigator for the subject's care. Whenever possible, if the Investigator feels that 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 31 of 67 
 
 
the subject should be unblinded, the Investigator should contact the 
 Medical Monitor to 
discuss the circumstances and come to an agreement before breaking the blind. If the 
 
Medical Monitor cannot be reached, then the 
 or 
designee should be contacted before unblinding. 
 staff will notify the sponsor if they have 
received any requests to break the blind. This process will be documented, shared with the sponsor 
and filed. 
CRO Contacts 
 
Cell Phone: 
 
Phone: 
 
Fax: 
 
Email: 
 
Or: 
 
 
Phone: 
 
Fax: 
 
Email: 
 
 
If a decision is made to unblind the subject, the Investigator will contact the 
 
 telephone number for the subject's treatment assignment information and document the 
process in the subject's source documentation. The 
 unblinding telephone number is available 
24 hours a day. 
 
 
In the event the blind is broken for any reason, the Investigator will notify 
 as soon as 
possible, preferably within 24 hours, in writing with the details of the occurrence. 
 staff will 
notify the sponsor. 
At the conclusion of the study, after the database has been locked, each site will be sent a sealed 
envelope containing the full study randomization scheme that should be retained with the study 
documents in the event of an FDA Inspection. 
10.4.4 IP Shipment, Retention and Storage 
The IP will be shipped to each Investigator’s site from 
, a centralized 
distribution center. Upon receipt of the IP, the Principal Investigator (or designee), must 
immediately inventory the material and confirm receipt with the sponsor, per the instructions 
included in the shipment.
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 32 of 67 
 
 
The Principal Investigator at each site will then ensure that all IP is stored in a locked, secure 
location, with access limited to the Investigator and his/her designee(s). 
 
 All IP will be stored at 20°C to 25°C 
(68°F to 77ºF), with excursions permitted from -5°C to 30°C (23ºF to 86ºF). The temperature of 
the storage location must be monitored on a daily basis and any excursion beyond the required 
temperature storage range should be reported to the sponsor. An accurate inventory of the IP over 
the course of the study (i.e., dispensed and returned) will be maintained in accordance with federal 
regulations. 
Initial supply quantities will be based on each site’s projected enrollment quantities. Resupply will 
be conducted as needed based on remaining in-house supply and continued enrollment projections. 
Multiple full blocks of IP will be included in every shipment to the Investigator. 
 
 
 
 
 
 
 
 
 
 
Once 
 has notified the site that they may return the IP, all unused tubes/kits and empty or 
partially used tubes/kits, other than those randomly selected for retention samples, will be returned 
to the sponsor (or designee). It is important that retention samples not be returned to 
 the 
sponsor or the packaging company during or at the end of the study. Sufficient IP must be retained 
among the sites participating in the study to meet the sample retention requirements as outlined by 
the FDA.16 
10.4.5 Method of Assigning Subjects to Treatment Groups 
The IP will be randomized, packaged and blinded by an 
 
. The randomization code will be generated using a validated computer program. 
 
 Each site will receive 
multiple, full blocks of IP in each delivery. The quantity received may vary. 
The IP will be
 
 
 
 
Over the course of the study, additional kits may be 
assigned to the subject using 
, as needed as determined at the discretion of the 
Investigator, based on the amount of BSA that remains to be treated. For subjects with BSA 
involvement close to 20% at Baseline, it is estimated that approximately  tubes, but up to  tubes, 
may be required for each subject to dose for the full duration of the study (84 ± 4 days) depending 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 33 of 67 
 
 
upon their treatment response. Significantly less IP would be required for subjects with BSA 
involvement closer to 2% (approximately 
). Therefore, the amount of IP dispensed to 
each subject will be dependent upon their BSA involvement at Baseline and as the study progresses, 
at the discretion of the Investigator. Each subject will maintain the same treatment assignment 
throughout the study. 
Randomization will be pre-planned according to a computer-generated randomization scheme. The 
randomization code will be retained within 
 which is maintained by 
 
. 
 will also retain the kit boxes numbers supplied to each site and the kit boxes 
numbers that have been selected for retention and are therefore unavailable for dispensing to 
subjects. 
Each kit and tube will be labeled and contain a unique identifying numbers. 
 
 
 
 
 
 
 
Upon confirmation of subject eligibility, the subject’s information (i.e., subject’s initials, date of 
birth, etc.) will be entered into 
, and the system will assign a 
 
number to the subject based upon a 
. 
 will then assign the 
subject a 
 in a blinded fashion at Visit 1. This kit box number will 
correspond to a specific treatment group within 
; however, the treatment group will be 
unknown to the Investigator, the CRO, the sponsor and the subject. The site will record the 
randomization number and kit box number in the subject’s source documentation and drug 
dispensing log. The 
 will then dispense 
 
 
 
 At Visit 2 and/or Visit 3 
and/or an Unscheduled Visit, additional IP may be dispensed to the subject, as needed. The 
 
dispense it to the subject and record the tube number. If an additional kit is required at 
either of these visits, the subject’s information will again be entered into 
; however, 
 will now assign an additional kit containing tubes from the same treatment arm. The 
same process will be followed for the dispensing and recording of additional kit boxes and tubes. 
Each subject will maintain the same treatment assignment throughout the study. 
10.4.6 Compliance 
Subjects will be provided with a diary to record the date of Day 1, the time and date of dosing, any 
missed doses, other concomitant medications and any AEs. Subjects taking fewer than 
 or more 
than 
 of the required doses over the 84 days ± 4 days, or who missed scheduled applications 
for 
 consecutive days will be considered non-compliant with dosing, and excluded from the PP 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 34 of 67 
 
 
population. Compliance with dosing will be verified by the use of the subject diaries and discussion 
with the subject. Compliance criteria are as outlined in the table below: 
Study Design 
Compliance Criteria 
 
 
Treatment 
Duration 
Scheduled 
Doses 
 
 
 
 
 
84 Days 
84 
 
 
For subjects who are terminated from the study early, compliance will be determined from their 
duration in the study, up to the time they are considered early terminated. Subjects taking fewer 
than 
 of the required doses will be considered non-compliant with dosing. 
For example, if a subject is dropped from the study after 
 days of enrollment and doses 
 times, 
then percent compliance is 
. 
10.5 Study Conduct 
10.5.1 Visit 1 (Day -14 to Day 1): Screening and Baseline Evaluation 
1. Informed Consent: Subjects who are willing to comply with study procedures will read, 
understand and sign the IRB-approved ICF. 
2. Medical History, Baseline Demographics and Concomitant Medications: Review the 
subject’s demographics and medical history including concomitant medication use within the 
last 6 months. 
3. Pregnancy Test: A urine pregnancy test will be required of all female subjects of childbearing 
potential before randomization. 
4. Vital Signs: Blood pressure, pulse, temperature and respiration rate will be recorded for each 
subject. In addition, height and weight will be measured to calculate total BSA. 
5. Application Site Reactions: A Medical Investigator (MD, DO, CRNP or PA) will grade the 
individual signs and symptoms. This will serve as a baseline for subsequent assessments of 
application site reactions. See Appendix C. 
6. Dermatologic Assessment: A Medical Investigator (MD, DO, CRNP or PA) will identify and 
measure the target lesion (the most severe lesion at the Baseline visit) and the location of the 
treatment area. The treatment area will be measured by assessing % BSA affected. 
7. Investigator’s Global Assessment: A Medical Investigator (MD, DO, CRNP or PA) will 
confirm the diagnosis of stable plaque psoriasis and perform a severity rating according to the 
IGA to determine the severity of the plaque psoriasis in the treatment area. See Appendix A. 
8. PASI Assessment: A Medical Investigator (MD, DO, CRNP or PA) will perform the PASI 
Assessment on the target lesion site. See Appendix B. 
9. Inclusion/Exclusion Criteria Review: Confirm the subject meets all inclusion criteria and 
none of the exclusion criteria. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 35 of 67 
 
 
10. Randomization: Eligible subjects selected for enrollment will be assigned a randomization 
number using 
. 
11. Dispense IP, Supplies, Subject Instructions and Diary: Randomized subjects will be 
allocated a specific kit of IP via 
. The site will pull this specific kit for the subject 
and dispense 
 tubes, as needed. The site will also dispense study supplies (i.e., 
sunscreen) and a diary. The site will instruct the subject on the use of the IP, the completion of 
the diary and review the medications and/or treatments that are prohibited during the study. 
12. First Dose with IP: The site will instruct the subject on when the first dose of IP will be 
applied, which will be considered Day 1. The subject will record the date of Day 1 in their 
diary. 
 
 
 
 
For all other subjects, the first dose (Day 1) of IP will be applied on the evening of Visit 1. 
10.5.2 Visit 2 (Day 28 ± 4 days): Interim Visit 
1. Assess Health Status: Review the subject’s use of any new or ongoing concomitant medications 
and report any AEs. 
2. Pregnancy Test: A urine pregnancy test will be required of all female subjects of childbearing 
potential. 
3. IGA: A Medical Investigator will perform a severity rating according to the IGA to determine 
the severity of the plaque psoriasis in the treatment area. See Appendix A. 
4. PASI Assessment: A Medical Investigator will perform the PASI Assessment on the target 
lesion site. See Appendix B. 
5. Application Site Reactions: A Medical Investigator will evaluate any application site reactions 
since the last visit. See Appendix C. 
6. Collect and Review Subject's Diary: Collect the diary from the subject and review for 
compliance with the protocol requirements. If the diary is not returned, the staff will collect 
available information based on discussion with the subject. 
7. IP Collection, Assessment and Dispensing (as needed): Review the previously dispensed IP 
for usage. If a tube is empty, collect it from the subject. If a tube still contains significant product, 
redispense the tube to the subject. The subject should be dispensed enough IP to complete all 
required doses until Visit 3. 
 
 
 
8. Dispense Supplies, Subject Instructions and Diary: Dispense the study supplies (i.e., 
sunscreen), as needed and a new diary with Subject Instruction sheet. Re-review proper use of 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 36 of 67 
 
 
the IP, the completion of the diary and the medications and/or treatments that are prohibited 
during the study. 
10.5.3 Visit 3: (Day 56 ± 4 days): Interim Visit 
1. Assess Health Status: Review the subject’s use of any new or ongoing concomitant medications 
and report any AEs. 
2. Pregnancy Test: A urine pregnancy test will be required of all female subjects of childbearing 
potential. 
3. IGA: A Medical Investigator will perform a severity rating according to the IGA to determine 
the severity of the plaque psoriasis in the treatment area. See Appendix A. 
4. PASI Assessment: A Medical Investigator will perform the PASI Assessment of the Target 
Lesion Site. See Appendix B. 
5. Application Site Reactions: A Medical Investigator will evaluate any application site reactions 
since the last visit. See Appendix C. 
6. Collect and Review Subject's Diary: Collect the diary from the subject and review for 
compliance with the protocol requirements. If the diary is not returned, the staff will collect 
available information based on discussion with the subject. 
7. IP Collection, Assessment and Dispensing (as needed): Review the previously dispensed IP 
for usage. If a tube is empty, collect it from the subject. If a tube still contains significant product, 
redispense the tube to the subject. The subject should be dispensed enough IP to complete all 
required doses until Visit 4. 
 
 
 
8. Dispense Supplies, Subject Instructions and Diary: Dispense the study supplies (i.e., 
sunscreen), as needed, and a new diary with Subject Instruction sheet. Re-review proper use of 
the IP, the completion of the diary and the medications and/or treatments that are prohibited 
during the study. 
10.5.4 Visit 4: (Day 85 ± 4 days) End of Study Visit or Early Termination 
1. Assess Health Status: Review the subject’s use of any new or ongoing concomitant medications 
and report any AEs. 
2. Pregnancy Test: A urine pregnancy test will be required of all female subjects of childbearing 
potential. 
3. Vital Signs: Blood pressure, pulse, temperature and respiration rate will be recorded for each 
subject. 
4. IGA: A Medical Investigator will perform a severity rating according to the IGA to determine 
the severity of the plaque psoriasis in the treatment area. See Appendix A. 
5. PASI Assessment: A Medical Investigator will perform the PASI Assessment of the target 
lesion site. See Appendix B. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 37 of 67 
 
 
6. Application Site Reactions: A Medical Investigator will evaluate any application site reactions 
(see Appendix C) since the last visit. 
7. Collect and Review Subject's Diary: Collect the diary from the subject and review for 
compliance with the protocol requirements. 
8. IP Collection: Collect all used and unused tubes and return them to their corresponding kit 
box(s) for storage. Record any lost or significantly damaged (i.e., punctured) IP. 
9. Discharge from Study: Discharge the subject from the study. 
10.6 Study Procedures 
10.6.1 Informed Consent 
At Visit 1, before performing any study-related procedures the study subject must sign the IRB-
approved ICF. The ICF will be reviewed and approved by an IRB before study commencement. 
No subject will be entered into the study without reading, understanding and signing an ICF. If the 
ICF is required in any other language besides English, translation will be performed by a certified 
translator and then approved by the IRB. 
10.6.2 Demographics 
At Visit 1, each subject shall be required to provide basic demographic information: date of birth, 
gender, ethnicity and race. 
10.6.3 Medical History 
At Visit 1 subjects will be questioned about their personal medical history, including psoriasis 
history. The medical history will include a complete review of all current diseases and their 
respective durations and treatments. 
10.6.4 Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed at each visit. The 
test must be negative at Visit 1 for the subject to be eligible for inclusion in the study. If a subject 
has to wait for her menstrual period to start before applying the first dose of IP, the first dose of IP 
must be applied within 14 days of the negative Visit 1 pregnancy test. If the subject is female and 
not considered of childbearing potential, then the reason must be documented in the subject’s 
source document. 
Any subject who becomes pregnant during the study should be discontinued and Early Termination 
procedures (Visit 4 procedures) completed. Pregnancy reporting procedures should be followed, as 
outlined in section 10.7.6. The outcome of the pregnancy should be followed by the Investigator to 
the conclusion of the pregnancy (i.e., birth, termination or miscarriage). The pregnancy will be 
reported as an AE from the time of first IP dose. 
10.6.5 Vital Signs 
The subject’s vital signs will be recorded (blood pressure, pulse, temperature, and respiration rate) 
at Visits 1 and 4. At Visit 1, height and weight will also be measured to calculate BSA. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 38 of 67 
 
 
10.6.6 Concomitant Medication 
At Visit 1, subjects will be questioned about current and prior concomitant medication use over the 
6 months before the Baseline visit. Subjects will also be questioned about ongoing or new 
concomitant medication use during the treatment period at Visits 2, 3 and 4. The medications to be 
recorded will include prescription and OTC medications and dietary supplements. 
At Visits 2 and 3, any subject who has used medications restricted by the protocol may be 
discontinued from the study. If discontinued, all Early Termination procedures (Visit 4 procedures) 
should be performed. 
10.6.7 Dermatologic Assessment 
At Visit 1, the Medical Investigator (MD, DO, CRNP or PA) will assess the subject’s plaque 
psoriasis and calculate the % BSA involvement using the subject’s hand (palm plus extended 
fingers) as an estimate of 1% BSA. For inclusion in the study, % BSA affected must be at least 2% 
but no more than 20%. The Investigator will then identify and measure the size of the treatment 
area and identify the most severe psoriasis lesion within the treatment area. This lesion will be 
designated as the target lesion. 
10.6.8 IGA 
At Visit 1, a Medical Investigator (MD, DO, CRNP or PA) should document a confirmed diagnosis 
of stable plaque psoriasis. 
At each visit, a Medical Investigator will perform a psoriasis severity rating according to the IGA 
(see Appendix A). At Visit 1, the IGA must be a score of 3, 4 or 5 for the subject to be eligible for 
inclusion. At Visit 4 (or Early Termination), the IGA score will be used to determine Treatment 
Success or Treatment Failure for the primary endpoint, with treatment success defined as none, 
minimal or mild disease, a score of 0, 1 or 2 within the treatment area. Further, at Visit 4 (or Early 
Termination), the IGA score will be used to evaluate the secondary endpoint, which is the 
proportion of subjects with disease severity consistent with none or minimal, a score of 0 or 1, 
within the treatment area. 
 
The IGA is a static scale and no reference to previous scores for the subject should be made during 
this assessment. 
10.6.9 PASI 
At Visit 1, a Medical Investigator (MD, DO, CRNP or PA) will identify the most severe lesion, and 
this will be designated the target lesion. 
At each visit, a Medical Investigator will perform the PASI at the target lesion site according to the 
PASI scale (see Appendix B). At Visit 1, the PASI score for plaque elevation at the target lesion 
must be a 3, 4 or 5 for the subject to be eligible for inclusion. At Visit 4 (or Early Termination), the 
PASI score will be used to evaluate the secondary endpoint, which is the proportion of subjects 
with target site plaque elevation, scaling and erythema scores of less than or equal to 1. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 39 of 67 
 
 
10.6.10 Application Site Reactions 
At Visit 1, the Investigator will grade the individual signs and symptoms per Appendix C. This will 
serve as a baseline for subsequent assessments of application site reactions. At Visits 2, 3 and 4, 
the Investigator will evaluate the subject for local application site reactions (erythema, dryness, 
burning/stinging, erosion, edema, pain, and itching) based on the scale provided in Appendix C. 
Reactions will be documented in source documents for each subject. 
10.6.11 Inclusion and Exclusion Criteria Review 
At Visit 1, the site will confirm that the subject meets all inclusion criteria and none of the 
exclusion criteria. If the subject does, they are eligible for enrollment in the study and will be 
randomized to a treatment group. If the subject does not, their participation will be complete and 
they will be discontinued as a screen failure. 
10.6.12 Randomization 
At Visit 1, eligible subjects selected for enrollment will be assigned a randomization number 
using 
. The system will allocate a kit box of IP to the subject in a double-blind fashion. 
The kit box will contain 
 of product for a single treatment arm (Test, Reference or 
Placebo). 
10.6.13 Dispensing IP 
An 
 will dispense an initial supply of IP at Visit 1, and will resupply the 
subject at Visit 2 and/or 3 or an Unscheduled Visit, as needed. The amount of IP dispensed is at the 
discretion of the Investigator based on the amount of BSA affected with psoriasis. After the initial 
 of IP have been dispensed and fully used and/or the tube has become lost or significantly 
damaged (i.e., became punctured), an additional kit box(s) of the same treatment group may be 
allocated to the subject using 
. 
 
 
 
 
 
will ensure that all Drug Dispensing Logs are completed correctly. Any 
dispensing task conducted by the 
, will be verified by a second person using 
the 
. 
10.6.14 Returning IP 
At Visit 2 and/or 3, an 
 will review the previously dispensed IP. If a tube is 
empty, it will be collected from the subject. If a tube still contains significant product, the tube will 
be re-dispensed to the subject. At Visit 4, all used and unused tubes will be collected. The 
 will ensure that all Drug Dispensing Logs are completed correctly. Any 
collection task conducted by the 
, will be verified by a second person using 
the 
 
Any lost IP will be recorded in the drug dispensing log and the Comments section of the source 
document. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 40 of 67 
 
 
Any observed tube unblinding will be recorded in the Comments section of the source document 
and reported to the CRO and sponsor immediately. 
10.6.15 Subject Dosing Instructions and Diary 
Subjects will be instructed to use the IP as described in section 10.4.1. 
The site will instruct the subject on when the first dose of IP will be applied, which will be 
considered Day 1. The subject will record the date of Day 1 in their diary. 
 
 
 
 
For all other subjects, the first dose (Day 1) of IP will be applied on the evening of Visit 1. 
Subjects will be provided with a diary at Visits 1, 2 and 3. Subjects will be asked to record the date 
of Day 1, the time and date of each dose, any missed doses, any AEs that have occurred and any 
concomitant medications utilized throughout the study. The site will review the diary and evaluate 
the subject’s compliance with the protocol at Visits 2, 3 and 4, based on any new additions to their 
medical history, new or changed concomitant medications, AEs and dosing compliance. If the diary 
is not returned, the staff will collect available information based on discussion with the subject. 
The subject will also be reminded of the medications and/or treatments that are prohibited during 
the study. 
If the subject is no longer eligible for participation at Visit 2 and/or 3, the site will conduct Early 
Termination (Visit 4) procedures. 
10.6.16 Standardized Sunscreen 
Along with the IP at Visit 1, the subject will be provided with standardized sunscreen (Neutrogena 
Ultra Sheer or similar) for use when needed. The use of the sunscreen should be documented on 
the concomitant medication page on the source documents and eCRFs. If additional sunscreen is 
needed during the study, additional sunscreen can be dispensed at Visit 2 and/or Visit 3 or an 
Unscheduled Visit. 
10.6.17 Health Status/AEs 
At Visits 2, 3 and 4 subjects will be questioned regarding any changes in their medical status since 
their previous visit. Any significant health changes observed after signing of the ICF into the study 
will be reported as AEs, as deemed appropriate by the Investigator. 
10.7 AEs/SAEs 
The subjects will be monitored throughout the study for any AEs. AEs will be collected through both 
solicited and unsolicited means and subsequently coded in tabular form using the MedDRA® (Version 
18.1 or higher) Adverse Event Dictionary. The subjects will be requested to report signs, symptoms 
and any changes in health to the clinic staff. Observed changes during the dermatology exam and/or 
clinical assessment at each visit (i.e., changes in the application site reaction) should be assessed by the 
Investigator to determine (in their opinion) if the change should be reported as an AE or not. Severity 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 41 of 67 
 
 
of each AE will be determined by the staff based on observation and questioning of the subjects. The 
Investigator will judge the relationship of the event to the study treatments. 
10.7.1 Definitions 
An Adverse Event / Experience is any untoward medical occurrence in a subject administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. 
An SAE is any untoward medical occurrence that at any dose: 
• 
results in death 
• 
is life-threatening 
• 
requires inpatient hospitalization or prolongation of existing inpatient hospitalization 
• 
results in persistent or significant disability / incapacity 
• 
is a congenital anomaly / birth defect 
• 
is medically significant: Medical and scientific judgment should be exercised in deciding 
whether expedited reporting is appropriate in other situations, such as important medical 
events that may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed above. These should also usually be considered serious. 
These characteristics/consequences have to be considered at the time of the event. For example, 
regarding a life- threatening event, this refers to an event in which the subject was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might have caused death 
if it were more severe. 
An Adverse Drug Reaction (ADR) is any AE for which the Investigator or sponsor assess a 
reasonable possibility for a causal relationship to a medicinal product, see 10.7.3 below. 
An Unexpected Adverse Reactions is defined as an ADR, the nature or severity of which is not 
consistent with the Reference Safety Information (Appendix D). The term ‘severity’ is used here 
to describe the intensity of a specific event. This has to be distinguished from the term ‘serious’. 
Reports which add significant information on the specificity, increase of occurrence or severity of 
a known, already documented serious adverse reaction constitute unexpected events. 
Information about common side effects already known about the IP can be found in the Reference 
Safety Information (Appendix D) or will be communicated in the form of Investigator 
Notifications. These common side effects are also listed in the informed consent. The common side 
effects will be discussed with the subject prior to their signing of the informed consent. 
For further details, please refer to the “Quick Reference Guide for Completing the SAE Form” for 
completing the “Serious Adverse Event Report Form” (Novartis form). 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 42 of 67 
 
 
10.7.2 Severity of AEs 
The term ‘severity’ is used here to describe the intensity of a specific event. This has to be 
distinguished from the term ‘serious’. In the course of the study, the Investigator will determine 
whether any AE’s have occurred and will grade their severity as follows: 
Mild: 
Transient or mild discomfort (< 48 hours); no medical intervention/therapy 
required 
Moderate: 
Mild to moderate limitation in activity - some assistance may be needed; no 
or minimal medical intervention/therapy required 
Severe: 
Marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalization possible 
10.7.3 Relationship to the IP 
The Investigator should evaluate all AEs considering all accessible data, at any time new 
information becomes available. The definition of IP includes the Test product under evaluation and 
the Reference product or Placebo that is given during any phase of the study. 
The Investigator should assess whether or not, in his/her expert opinion, the AE is suspected to the 
drug according to the following considerations: 
Suspected: 
The temporal relationship of the clinical event to study treatment 
administration makes a causal relationship possible, and other 
drugs, therapeutic interventions or underlying conditions do not 
provide a sufficient explanation for the observed event. 
Not suspected: 
The temporal relationship of the clinical event to study treatment 
administration makes a causal relationship unlikely, or other drugs, 
therapeutic interventions or underlying conditions provide a sufficient 
explanation for the observed event. 
Causality assessments are critical and must be provided for each unique AE in relation to each IP. 
Missing causality assessments will be handled as suspected to IP by the sponsor. 
10.7.4 AE Documentation 
Any AE (non-serious and serious) occurring after the subject has provided study-specific informed 
consent, and until the last study visit of the subject, has to be recorded on the AE pages of the eCRF. 
The occurrence of AEs should be sought by non-directive questioning of the subject at each visit 
during the study. AEs also may be identified when they are volunteered by the subject during or 
between visits or during physical examination, laboratory test or other assessments. All AEs should 
be given appropriate medical care. Treatment may include one or more of the following: no action 
taken (i.e., further observation only); IP dosage adjusted/temporarily interrupted; IP permanently 
discontinued due to this AE; concomitant medication given; non-drug therapy given, subject 
hospitalized / subject’s hospitalization prolonged. The treatment of the AE should be documented 
in the eCRF. In addition, the action taken with the IP should be documented, and should be assigned 
to one of the following categories: not changed, withdrawn, reduced, increased, interrupted, 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 43 of 67 
 
 
unknown and not applicable. Concomitant medication, other treatments or changes in the 
administration of the IP should be specified and documented. 
Medical conditions/diseases present before starting IP are only considered AEs if they worsen after 
enrollment. Abnormal laboratory values or test results constitute AEs only if they induce clinical 
signs or symptoms, are considered clinically significant or require therapy. 
Once an AE is identified, the Investigator should follow-up as specified below. Each time, the 
outcome should be documented and assigned to one of the following categories: not 
recovered/unchanged, 
condition 
deteriorating, 
recovered/resolved, 
improving/recovering, 
recovered/resolved with sequelae, fatal or unknown. The assessment of an AE should be made at 
each planned visit (or more frequently, if necessary). The Investigator should document in the 
eCRF any changes in seriousness, severity, the suspected relationship with the IP, the interventions 
required to treat it, and the outcome. 
AEs occurring between informed consent and first dosing 
Any AE occurring between study-specific informed consent and first dosing will be documented 
as “screening event”, with a IP causality assessment “IP not yet administered”. 
AEs occurring after first dosing 
The Investigator should follow all AEs which occurred from first dosing and during the course of 
the study to the last visit of the subject until the AE has resolved or stabilized or the subject has 
been lost to follow-up. 
Ongoing SAEs at the time of last visit 
For any SAEs still ongoing at the time of last visit, the Investigator should continue to follow-up 
until the SAE has resolved or has stabilized / is judged permanent, for SAEs considered to be related 
to IP (serious adverse drug reaction [SADR]), and for up to 30 days after the last visit of subject 
for non-related SAEs. The Investigator should send SAE follow-up reports to recipients as per the 
‘SAE Reporting’ section 10.7.5 below. 
SAEs occurring after the last visit 
At the last visit, the Investigator should instruct each subject to report any new SAE (beyond the 
protocol observation period) that the subject, believes might reasonably be related to study 
treatment. The Investigator must report the SADR to recipients as per the ‘SAE Reporting’ section 
10.7.5 below. 
10.7.5 SAE Reporting 
It is vitally important that the Investigator reports immediately, (i.e., no later than 24 hours 
after awareness), any SAEs or updates to previously reported SAEs, even if the Investigator does 
not consider the AE to be drug-related. 
The Investigator should send SAE reports on the “Serious Adverse Event Report Form” (Novartis 
form), as initial or follow-up reports, via fax or email to the Local Person for Pharmacovigilence 
(LPPV) (listed below), and in copy to the responsible Medical Monitor/CRO Contact and the 
sponsor (listed below), to the email addresses provided in the table below. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 44 of 67 
 
 
The Investigator should also send all updates / new information on a new SAE Report Form as a 
follow-up to the previously reported SAE. The follow-up information should describe whether the 
event has resolved or continues, if a diagnosis is available, if and how it was treated, and whether 
the subject continued or withdrew from study participation. 
Recurrent episodes, complications or progression of the initial SAE must be reported as follow-up 
to the original episode, regardless of when the event occurs. 
Any new SAE (that is considered completely independent of a previously reported SAE) should be 
reported as a new and separate initial SAE report. 
Any queries from the LPPV, CRO or sponsor regarding SAE reports should be answered by the 
Investigator within 24 hours. 
For more detailed information refer to the “Quick Reference Guide for Completing the SAE Form”. 
The Investigator should retain a delivery notification for all recipients in the Investigator study file. 
 
 
 
 
 
 
 
 
Addresses for SAE and other Safety Reporting 
LPPV, Sandoz (United States) 
Name: 
 
 
Email: 
 
Fax: 
 
CRO Contacts 
 
Cell Phone: 
 
Phone: 
 
Fax: 
 
Email: 
 
 
 
Phone: 
 
Fax: 
 
Email: 
 
Sponsor Contacts 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 45 of 67 
 
 
 
 
Phone: 
 
Fax: 
 
Email: 
 
 
 
 
Phone: 
 
Fax: 
 
Email: 
 
 
The responsible contact persons for questions are: 
 
 
Phone: 
 
Fax: 
 
email: 
 
 
 
Phone: 
 
eFax: 
 
email: 
 
 
Investigator Notification 
If an ADR is not listed in the Reference Safety Information (e.g., Package Insert), the sponsor may 
urgently require further information from the Investigator for Health Authority reporting. 
The sponsor may, if applicable, issue Investigator Notifications of unlisted SADRs (Suspected 
Unexpected Serious Adverse Reactions [SUSARs]) to all Investigators concerned with any study 
with the same IP. 
The submission of these Investigator Notifications, if applicable, to IRBs is the responsibility of 
the Investigator or the CRO as stipulated in the study contract. 
Health Authority Reporting 
The sponsor will submit all reportable cases within the requested timelines to all concerned 
authorities. 
Under 21 CFR 320.31(d)(3), the sponsor or CRO must inform other Investigators involved in the 
study plus the FDA within 15 days of becoming aware of the occurrence of the SAEs. When a 
serious AE is death, sponsor or CRO must inform other Investigators involved in the study plus the 
FDA within 7 days of becoming aware of the event. SAEs that occur with the Test, Reference or 
Placebo product must be reported. 
IRB Reporting 
AEs that are evaluated by the Investigator as "Serious" should be reported by the Investigator to 
the sponsor and CRO within 24 hours, and the IRB as soon as is practically possible, preferably 
within 24 hours, whether or not they are considered expected or drug-related. 
Investigator Safety Reporting Training 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 46 of 67 
 
 
The Principal Investigator will be trained on the sponsor SAE/AE and pregnancy reporting 
obligations as defined in the study protocol. Training will be documented. 
10.7.6 Pregnancies 
Tazarotene may cause fetal harm when administered to a pregnant woman by potentially inducing 
teratogenic and developmental effect associated with retinoids. Compliance with adequate birth 
control measures described in this protocol, including a negative pregnancy test before dosing and 
its commencement during a normal menstrual period, is of paramount importance. The Investigator 
must report any cases of pregnancy of subjects in the course of a study immediately (within 24 
hours) of awareness to the LPPV and with copy to the responsible Medical Monitor/CRO Contact 
and the sponsor, to the email addresses provided in the table above, as described in section 10.7.5. 
 
 
The Investigator should immediately withdraw the subject from the study, and should follow-up 
each case of pregnancy through the expected delivery date, and report the outcome, including 
spontaneous or voluntary termination, details of the birth and any birth defects, congenital 
abnormalities, or maternal and/or newborn complications. 
 
 
 
 
 
10.7.7 Quality Complaints 
In case of quality complaints (technical or transport complaints), the Investigator within 24 hours 
of learning of its occurrence informs the Medical Monitor/CRO Contact and the sponsor via the 
email addresses provided in the table above in section 10.7.5. Reporting should include all details 
relevant to the quality complaint. The monitor/CRO Contact and/or sponsor may reach out to the 
site for further detail. Any queries from the CRO or sponsor regarding quality complaints should 
be answered by the Investigator within 24 hours. The Investigator should document the quality 
complaint in the subject's source document (for subject's specific quality complaints) and/or the 
Investigator's study file (for site specific quality complaints), as applicable. 
Any AE associated with a quality complaint needs to be documented and reported in addition by 
the Investigator as described in section 10.7.4 and 10.7.5. 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 47 of 67 
 
 
10.7.9 Reconciliation 
Reconciliation between the safety database of the sponsor and the clinical database at the CRO will 
be done periodically and at the end of the study by comparing line listings from the safety database 
with the data in the clinical database. 
The eCRFs / the clinical database will be reviewed for potentially unreported cases. For any 
reportable case, the following parameters need to match exactly between the clinical and the safety 
database: trial number, site number, subject identification number, investigational drug, 
seriousness, date of death (if applicable) and Investigator causality. All other parameters only need 
to be plausibly and medically consistent. For any SAE assessed as suspected, a more detailed 
reconciliation should be conducted, including also treatment dates and medical history. 
11.0 STATISTICAL METHODS 
11.1 Statistical Plan 
A Statistical Analysis Plan (SAP), including study data report format, detailing the intended statistical 
analysis of the study data, will be prepared as a separate document and finalized before database lock. 
Any deviation from the original statistical plan will be described and justified in the final report, as 
appropriate. The procedure for accounting for missing, unused and spurious data will be included in 
the SAP. 
If not otherwise specified, statistical significance is defined as p < 0.05, two-sided. Data will be 
summarized with respect to demographic and baseline characteristics, efficacy variables and safety 
variables. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 48 of 67 
 
 
All statistical analysis will be conducted using SAS®, Version 9.4 or higher. Datasets will be prepared 
using headings from Clinical Data Interchange Consortium (CDISC), Study Data Tabulation Model 
(SDTM) implementation for human clinical trials, and Analysis Dataset Model (ADaM). 
11.2 Sample Size Determination 
Sample size calculations were performed using 
 For the primary endpoint 
analysis, the rate of treatment success for the Reference treatment after 12 weeks of treatment is 
expected to be approximately 
 in the PP population. Assuming that the rates of treatment success 
for Test and Reference treatments are the same, a sample size of 
 subjects in each active group in 
the PP population will provide approximately 
 power to demonstrate therapeutic equivalence (i.e., 
the 90% confidence interval (Yates’ continuity-corrected) of the absolute difference between the Test 
and Reference rates of treatment success is within a defined equivalence range [-20% to + 20%]). 
The rates of treatment success for the Placebo and active treatment groups after 12 weeks of treatment 
are assumed to be approximately 
 and at least 
 respectively, in the mITT population. Using a 
1:1 (active: placebo) randomization scheme, and assuming the conversion rate from mITT to PP 
population will be about 
 subjects in each treatment group (Test, Reference and Placebo) of 
the mITT population will provide at least 
 power to demonstrate superiority of active over Placebo 
at the 5% significance level (p < 0.05, two-sided continuity-corrected Z-Tests and a pooled response 
rate for the standard error of the difference in proportions). 
Under the above assumptions, the overall study power to demonstrate therapeutic equivalence and 
superiority is estimated to be at least 
 To allow for approximately 
 of subjects who may drop 
out from the study or are otherwise non-evaluable, up to 855 subjects may be randomized to obtain 
 
subjects in the mITT population (i.e., 
 per treatment arm). 
11.3 Study Populations 
11.3.1 PP Population 
The PP population will include subjects that comply with the protocol as follows: 
• 
All randomized subjects who meet all inclusion and exclusion criteria. 
• 
Make the final study visit (Visit 4) within the protocol window of Day 85 ± 4 days with no 
PDs that would affect the integrity of the data. 
• 
Comply with study restrictions including concomitant medications. 
• 
Apply the IP appropriately and are within 
 compliant with dosing during the 12 
weeks (Day 85 ± 4) of treatment. 
• 
Do not miss the scheduled applications for more than 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 49 of 67 
 
 
 
 
 
11.3.2 Modified Intent-to-Treat (mITT) Population 
The mITT population will include all subjects in the PP population plus all randomized subjects 
who meet all inclusion/exclusion criteria, apply at least one dose of assigned product, and return 
for at least one post-Baseline evaluation. 
 
 
 
 
 
 
 
 
 
11.3.3 Safety Populations 
All subjects who are randomized and received the IP will be included in the analysis of safety. 
11.4 Baseline Comparability 
Baseline characteristics will be evaluated separately for the PP, mITT and Safety populations. 
The following baseline demographics and parameters (determined from their initial study visit) will be 
evaluated: 
o Age at the time of consent/assent (years) 
o Gender (Male/Female) 
o Ethnicity (Hispanic/non-Hispanic), Race (White, Black/African American, Native 
Hawaiian or Other Pacific Islander, Asian, American Indian or Alaska Native, Other) 
o Baseline total BSA affected with Psoriasis 
o Baseline percent BSA affected with Psoriasis 
o Baseline PASI Score and Baseline Scores for Individual Components (Erythema, Scaling 
and Plaque Elevation) 
o Baseline IGA Score 
o Treatment location 
o Treatment area size (area) 
o Target lesion size (area) 
Summary tables by treatment group will be presented. Continuous variables will be summarized using 
descriptive statistics (number of observations, median, minimum, maximum, mean and SD). 
Categorical variables will be summarized using frequencies and percentage. Baseline treatment 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
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comparisons will be presented using Chi-Square or Cochran-Mantel-Haenszel tests for the categorical 
variables, and analysis of variance (ANOVA) for the continuous variables. 
All data will be listed by treatment and subject. 
11.5 Efficacy Endpoints 
Primary Efficacy Endpoint 
Proportion of subjects with treatment success (defined as none, minimal or mild disease, a score of 0, 
1 or 2 within the treatment area) on the IGA at the Week 12 visit (Day 85 ± 4 days, End of Study). 
Secondary Efficacy Endpoints 
1. Proportion of subjects with disease severity at the Week 12 visit (Day 85 ± 4 days, End of 
Study) consistent with none or minimal, a score of 0 or 1, within the treatment area on the IGA, 
AND 
2. Proportion of subjects with target site plaque elevation, scaling and erythema scores of less 
than or equal to 1 on the PASI at the Week 12 visit (Day 85 ± 4, End of Study). 
11.6 Primary and Secondary Endpoint Analyses 
Therapeutic Equivalence Analysis 
Therapeutic equivalence will be evaluated for both primary and secondary endpoints using the PP 
population, with results in the mITT population being supportive. For the dichotomized primary 
endpoint (proportion of treatment success), if the 90% confidence interval (with Yates’ Correction 
Factor) of the difference between the proportion of subjects considered a “treatment success” in the 
Test and the Reference treatment groups at Week 12 is contained within the pre-defined equivalence 
limits [-20%, +20%], then therapeutic equivalence will be considered to have been supported for the 
endpoint. The same statistical approach will be conducted for analysis of the two dichotomized 
secondary endpoints in the PP and mITT populations. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary endpoint in the PP population. 
Superiority to Placebo Analysis 
The primary measure of superiority will be evaluated using the mITT population and LOCF for missing 
efficacy values. The results in the PP population will be considered supportive. The superiority of the 
Test and Reference products over Placebo will be concluded for the primary endpoint if the proportion 
of treatment success at Week 12 is statistically superior to Placebo (p < 0.05, two-sided a Cochran-
Mantel-Haenszel exact test stratified by clinical site) using the mITT population and LOCF. The same 
statistical approach will be conducted for analysis of the two dichotomized secondary endpoints in the 
mITT and PP populations. 
To declare superiority of the Test and Reference products over Placebo, their superiority must be 
demonstrated for only the primary endpoint in the mITT population. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 51 of 67 
 
 
11.7 Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated by the Cochran-
Mantel-Haenszel test (stratified by site) at the 5% significance level (p < 0.05, 2-sided) for the primary 
efficacy endpoint in both the PP population (for equivalence testing) and mITT population (for 
superiority testing). 
 
 
 
 
 
 This will include examination of responder rates at each site where 
sample sizes per treatment may be influential in the assessment of the interaction. 
11.8 Safety Analysis 
AEs will be classified using standard MedDRA terminology Version 18.1 or higher and summarized 
by treatment group. Summary tables comparing the type, date of onset, date of resolution, incidence, 
severity, relationship to the IP, outcome and action taken will be prepared by treatment group. Should 
sufficient data exist, AE frequencies will be compared among treatments using Fisher’s exact test or a 
similar test. 
Application site reactions (erythema, dryness, burning/stinging, erosion, edema, pain, itching) recorded 
at each visit will be compared among treatment groups. A descriptive analysis comparing the 
application site reactions for each treatment group will be created. 
Concomitant medication use during the treatment period will be tabulated by subject. 
Signs and symptoms of psoriasis will not be considered AEs, unless in the Investigator’s opinion, they 
have increased in frequency and/or severity to such an extent that the Investigator/subject considers 
that it is in the subject’s best interest to be dropped from continued participation in the study and given 
alternative therapy for their condition. 
All randomized subjects who received IP will be included in the comparative safety analysis. 
12.0 REGULATORY OBLIGATIONS 
12.1 Institutional Review Board 
The study protocol, ICF, subject handouts, if required, and any specific advertising will be submitted 
to, and approved by, an IRB in writing before the start of the study, as defined by FDA regulations. A 
form must be issued by the IRB noting the approvals. Based on the IRB’s internal policy, the form may 
be signed by the IRB chairman or designee. The Reference product package insert will also be 
submitted for the IRB’s review. The notification of the board's approval along with a description by 
profession and gender of the board's composition will be provided to the sponsor. 
Any changes to the protocol, as well as a change of Investigator, which is approved by the 
sponsor/CRO, must also be approved by the IRB(s) and documentation of this approval provided to the 
sponsor or designee. Records of the IRB review and approval of all documents pertaining to this study 
must be kept on file by the Investigator and are subject to inspection by regulatory authorities during 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 52 of 67 
 
 
or after completion of the study. SAEs must also be reported to the IRB per their policy; however, the 
Investigator/CRO is encouraged to report all SAEs to the IRB as soon as practically possible, preferably 
within 24 hours, even if the IRB’s reporting requirement is longer. 
Periodic status reports must be submitted to the IRB per their policy, but at least annually, as well as 
notification of study completion or termination with a final report within one (1) month after close out. 
A copy of all reports submitted to the IRB must be sent to the sponsor. 
The Investigator will ensure that an IRB that complies with the requirements set forth in Part 56 (Title 
21 Code of Federal Regulations) will be responsible for the initial and continuing review and approval 
of the proposed clinical study. 
12.2 Subject Confidentiality 
All applicable Investigators and study staff must comply with the federal medical Privacy Rule 
authorized by the HIPAA), which requires most health care providers to take new measures to protect 
the privacy of individually identifiable health information. The Privacy Rule’s requirements extend to 
identifiable health information used or disclosed in research. The HIPAA Privacy Rule reinforces 
clinical Investigators’ existing obligations to protect the privacy of identifiable health information under 
state law, codes of medical ethics and the federal regulations governing research. 
Also, in compliance with federal guidelines regarding the monitoring of clinical studies and in 
fulfillment of his/her obligations to the sponsor, it is required that the Investigator permit the study 
monitor, sponsor auditor, and/or FDA representative to review that portion of the subject’s medical 
record that is directly related to the study. This shall include all study relevant documentation including 
subject medical histories to verify eligibility, admission/discharge summaries for hospital stays 
occurring while the subject is enrolled in the study and autopsy reports for deaths occurring during the 
study. 
As part of the required content of informed consent, the subjects must be informed that his/her medical 
chart may be reviewed by the sponsor, the sponsor’s authorized representatives or FDA. Should access 
to the medical record require a separate waiver or authorization, it is the Investigator’s responsibility to 
obtain such permission from the subject in writing before the subject is entered into the study. 
12.3 Study Documentation 
This study will be conducted in compliance with the protocol; Good Clinical Practices (GCP) and all 
applicable regulations, including the Federal Food, Drug and Cosmetics Act, US applicable Code of 
Federal Regulations (title 21), parts 50, 56, 312, 320, and any IRB requirements relative to clinical 
studies; and the Declaration of Helsinki, June 1964, as modified by the 64th World Medical Association 
General Assembly, October 2013.8,17-19 The Investigator will permit trial-related monitoring, audits, 
IRB review and regulatory inspections providing direct access to source data/documents. 
12.3.1 Protocol 
The Investigator indicated on Form FDA 1572 will act as the Principal Investigator at his/her 
respective study site. Protocols will be noted as approved by placement of the signatures of the 
sponsor and 
 Representatives on the signature page. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 53 of 67 
 
 
12.3.2 Informed Consent 
An ICF that includes all of the relevant elements currently required by FDA and local state 
regulations will be provided to each prospective study subject before being screened into the study. 
The type and method of study, tests to be administered, any potential or possible hazards, and the 
subject’s right to withdraw from the study at any time will be explained to the subjects by the 
Investigator or designee. Once the Investigator or designee is assured that an individual candidate 
understands the implications of participating in this study, the subject will be asked to give consent 
by signing and dating in the appropriate areas of the ICF. The Investigator or designee will also 
sign and date the form, along with a staff member who will sign the ICF as a witness to verify that 
the subject has indeed received information. If any other language is required, translation will be 
performed by a certified translator and will be IRB-approved. A copy of the ICF will be provided 
to the subject. A notation will be made in the subject’s medical record indicating the date informed 
consent was obtained. 
12.3.3 Protocol and Informed Consent Changes 
The procedures defined in the protocol will be carefully reviewed to ensure that all parties involved 
with the study fully understand the protocol. Sponsor approved changes to the protocol or the ICF 
will be implemented as revisions to the original documents and will require additional review and 
approval by the IRB. Revisions to the original protocol will be documented in amendments, 
incorporated as a preface to the new version. Any revision that substantially alters the study design 
or increases potential risk to the subject requires the subject’s consent to continue in the study. The 
approvals will be processed in accordance with the established IRB procedures. Copies of all 
protocol and ICF amendments/revisions, along with letters noting IRB approval, will be submitted 
to the sponsor. 
The only circumstance in which a protocol amendment may be initiated without prior IRB approval 
is to eliminate apparent immediate hazards to a subject or subjects. However, the Investigator must 
notify the IRB immediately, no later than within five (5) working days after implementation. 
12.3.4 Source Documents and Case Report Forms 
All subjects will be identified by initials and date of birth. Randomized subjects will also have a 
unique subject randomization number. Source documents will be used to record all study-related 
data. Source document entries will be used to complete eCRFs which will record all critical study 
information. A set of eCRFs will be completed for each subject enrolled in the study. All data from 
eCRFs will be reviewed, evaluated and signed by the Investigator, as required. All eCRFs will be 
cross referenced to source documentation by the study monitor and/or the sponsor to ensure 
accurate transcription of the data. 
The original source documents and a copy of the corresponding eCRFs (electronic or print out) will 
be retained by the Investigator. Subjects who terminate early from the study will have the Visit 4 
(End of Study/Early Termination) Source/eCRF completed. 
Primary Source Documents 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 54 of 67 
 
 
The Investigator must maintain source documents supporting significant data for each screened 
subject’s medical notes. Standardized source document forms will be utilized for this study and 
will include original records. 
During monitoring visits the monitor will validate data in the eCRFs against the sources of data. 
If a subject does not qualify for enrollment, they will be considered a screen failure. The reason for 
their disqualification will be included in their source document and summarized in the CSR. 
Case Report Forms 
Source document entries will be used to complete eCRFs for enrolled subjects. All data and eCRFs 
will be reviewed, evaluated and signed by the Investigator, as required. Further details will be 
provided in the data management plan. 
Supporting Documentation 
The Investigator site file will be maintained by the Investigator and study staff and will be available 
for review during monitoring, auditing and regulatory agency inspections, if applicable. 
Details will be provided in the monitoring plan. 
12.3.5 Drug Accountability 
All IP receipt, inventory, selection of retention, dispensing, dosing and reconciliation records will 
be maintained in compliance with federal regulations. The IP will be dispensed to qualified study 
subjects according to established procedures. Drug accountability will be maintained by the site 
throughout the study, and will be reviewed by the monitor throughout the study. At the end of the 
study (i.e., at the Site’s Close Out visit) all used and unused IP, with the exception of required 
retention samples, will have a documented inventory conducted and will be returned to sponsor or 
designee. 
12.3.6 Drug Storage 
All IP will be stored at 20°C to 25°C (68°F to 77ºF), with excursions permitted from -5°C to 30°C 
(23ºF to 86ºF). IP should be stored in a secure place with limited access by authorized individuals 
only. The Investigator will be responsible for maintaining accurate records of IP receipt, retention, 
dispensing and return. 
12.3.7 Retention of Reserve Samples 
For every IP shipment received at the Investigator site, the Investigator (or designee) will randomly 
select one block of IP for retention. As per the Code of Federal Regulations Part 21, Section 
320.38(e), “Each reserve sample shall be stored under conditions consistent with the product 
labeling and in an area segregated from the area where testing is conducted and with access limited 
to authorized personnel. Each reserve sample shall be retained for a period of at least 5 years 
following the date on which the application or supplemental application is approved, or, if such 
application or supplemental application is not approved, at least 5 years following the date of 
completion of the bioavailability study in which the sample from which the reserve sample was 
obtained was used.” 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 55 of 67 
 
 
Instructions on how to select retention samples will be supplied to the Investigator in writing with 
each shipment, along with a shipment/retention acknowledgment form that must be completed by 
the study staff and signed by the Investigator. The selection process will ensure a sufficient amount 
of retention samples are retained as per sponsor requirement. 
 
The number of each kit 
box in the block selected for retention will be noted on the drug accountability form as a retention 
sample, in addition to the retention sample log and sponsor supplied acknowledgment. These blocks 
will be affixed with a label provided by 
 to be clearly marked as retention samples and are 
not to be used for dispensing to study subjects. Retention samples should not be returned to the 
sponsor at any time. At the completion of the retention period, the Investigator must contact the 
sponsor if they wish to destroy the retention samples. If destruction is authorized, the sponsor must 
supply this directive to the Investigator in writing. 
12.3.8 Return of Clinical Supplies 
Once authorized by the sponsor, with the exception of the retention samples, all used and unused 
kits of IP will be inventoried and returned to 
, who will store the IP until 
sponsor authorized destruction: 
 
 
 
12.3.9 Pregnancy and Breastfeeding 
Tazarotene cream is designated as Pregnancy Category X; therefore there is a potential risk of 
teratogenicity. Therefore, all females of childbearing potential should be maintained on an 
appropriate method of contraception throughout the study to prevent pregnancy. Females that are 
lactating, breastfeeding or trying to become pregnant should not be enrolled in the study. The ICF 
will clearly outline the risk and this requirement. 
All females of childbearing potential will have a pregnancy test performed at each clinic visit. The 
pregnancy test will have a minimum sensitivity of at least 50 mIU/ml for hCG. The results of all 
pregnancy tests (positive or negative) will be documented. A negative urine pregnancy result must 
be obtained at screening (Visit 1) before study participation. Subjects with a positive pregnancy 
result during screening will not be enrolled in the study. Before study enrollment, females of 
childbearing potential must be advised of the importance of avoiding pregnancy during study 
participation. 
 
Childbearing Potential Defined as: 
Non-Childbearing Potential Defined as: 
Evidence of menses in the past 12 months 
Post-menopausal, defined as women who 
have been amenorrheic for at least 12 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 56 of 67 
 
 
consecutive months, without other known or 
suspected primary cause. 
Amenorrhea for ≥ 12 months, but the 
amenorrhea is possibly due to other causes, 
including prior chemotherapy, anti-estrogens 
or ovarian suppression 
Sterilized surgically or who are otherwise 
proven sterile (i.e., total hysterectomy, or 
bilateral oophorectomy) with surgery at least 
4 weeks before Screening. Tubal ligation will 
not be considered a surgically sterile method. 
Subjects who report that they have become pregnant during the study or have a positive pregnancy 
test at Visit 2, 3 or 4 will be permanently discontinued from the study utilizing protocol-required 
procedures for study discontinuation (Visit 4 procedures). The Principal Investigator or designee 
must immediately notify the Medical Monitor, sponsor LPPV and sponsor representative within 24 
hours of learning of the event. The pregnancy will be reported as an AE and all pregnancy reporting 
criteria will be followed as outlined in section 10.7.6, including the initial use of the 
 
 (Novartis form) and all required follow-up for the mother and child as outlined 
on the form. For more detailed information refer to the 
 
. All follow-up information regarding the course of the pregnancy, 
including perinatal and neonatal outcome will be communicated to the Medical Monitor, sponsor 
 and sponsor representatives as per the sponsor requirements. 
12.3.10 Reporting Safety Information to the IRB 
The Investigator must promptly report to the Investigator’s IRB all unanticipated problems 
involving risks to subjects. This includes death from any cause and all SAEs occurring during the 
study, regardless of the assessed causality.20 
12.3.11 Record Retention 
The study will be conducted according to GCP as outlined in International Conference on 
Harmonisation (ICH) step 5 guidelines by the FDA. It is the responsibility of the Investigator to 
maintain a comprehensive and centralized filing system of all relevant documentation. 
Investigators will be instructed to retain all study records required by the sponsor, as well as the 
regulations, in a secure and safe facility, off of the ground, with limited access. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 57 of 67 
 
 
All study-related documentation must be retained. This includes, but is not limited to: 
• 
Study Contract 
• 
Study Protocol and all Amendment with Investigator Signature Pages 
• 
Source Data 
• 
eCRFs and Data Queries 
• 
Regulatory Documents 
• 
IRB Documentation (i.e., approvals, correspondence, follow ups, close out) 
• 
IP Receipt and Return Records 
• 
Retention Selection and all IP Accountability Records 
• 
ICFs 
• 
All Logs and Forms 
• 
Monitoring Reports and Letters 
• 
Correspondence 
Regulations require the Investigator must retain all records according to 21 CFR 312.62(c) for a 
period of 2 years following the date the marketing application is approved for the IP for the 
indication for which it is being investigated; or, if no application is to be filed or if the application 
is not approved for such indication, until 2 years after the investigation is discontinued and FDA is 
notified. However, Fougera requires the Investigator retain all records for a period of 
 after 
termination of the study unless CRO or sponsor authorizes, in writing, earlier destruction. No 
documents shall be transferred from the site (i.e., to an off-site storage facility) without first 
notifying the sponsor. No documents shall be destroyed without the sponsor's written approval. If 
the Investigator can no longer support the retention of the records (i.e., due to retirement or death), 
the documents must be transferred to a new responsible party. The sponsor must be notified of this 
transfer in writing. 
12.3.12 Study Monitoring and Auditing 
Monitoring and Auditing by the CRO 
 will be responsible for monitoring the study according to GCP and applicable regulations. 
Monitoring visits are for the purpose of training, confirming adherence to the protocol and to verify 
complete and accurate data collection. A monitoring plan will be agreed upon between the sponsor 
and the CRO. The Investigator will be visited by a monitor before the study, at regular intervals 
during the course of the study and at the completion of the study. Investigator audits will also be 
conducted, the details of which would be described in a separate audit plan. Site Monitoring visits 
and audits (as applicable) will be scheduled with the Investigator in advance of the visit at a 
mutually agreed time. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 58 of 67 
 
 
The study monitor will review the ICFs and verify eCRF entries by comparing them with the source 
documents. The monitor will review the maintenance of regulatory documentation and IP 
accountability. The monitor will review the progress of the study on a regular basis with the 
Investigator and other site personnel. The clinical site will make all records associated with the 
study available to 
 representative during such monitoring visits and audits. It is the 
Investigator’s responsibility to: 
• 
Provide the monitor with sufficient time to review the eCRFs and relevant source 
documents 
• 
Be available to answer questions and/or resolve data clarifications and/or implement 
corrective and preventative actions (as required following a site audit) 
• 
Provide adequate time and space for these visits 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 59 of 67 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 60 of 67 
 
 
 
 
Audit by the Sponsor and/or Regulatory Authorities 
The study may be subject to audit by the sponsor, sponsor representative, the IRB or by regulatory 
authorities. The sponsor will schedule any audits in advance of the visit. Regulatory authority audits 
may take place at any time during or after the study without advance notice. If such an audit occurs, 
the Investigator must agree to allow access to required subject records. By signing this protocol, 
the Investigator grants permission to personnel from the sponsor, its representatives and appropriate 
regulatory authorities for on-site monitoring of all appropriate study documentation, as well as on-
site review of study procedures. 
12.3.13 Confidentiality, Use of Information and Publication 
All information supplied by the sponsor in connection with this study and not previously published, 
is considered confidential information. This information includes, but is not limited to, data, 
materials (i.e., the clinical protocol, eCRFs), equipment, experience (whether of a scientific, 
technical, engineering, operational, or commercial nature), designs, specifications, know-how, 
product uses, processes, formulae, costs, financial data, marketing plans and direct selling systems, 
customer lists and technical and commercial information relating to customers or business 
projections used by the sponsor in its business. Any data, inventions or discoveries collected or 
developed, as a result of this study is considered confidential. This confidential information shall 
remain the sole property of the sponsor, shall not be disclosed to any unauthorized person or use in 
any unauthorized manner without written consent of the sponsor, and shall not be used except in 
the performance of the study. 
The information developed during the course of this clinical study is also considered confidential, 
and will be used by the sponsor in connection with the development of the drug. The information 
may be disclosed as deemed necessary by the sponsor. To allow the use of the information derived 
from this clinical study, the Investigator is obliged to provide the sponsor with complete test results 
and all data developed in the study. The information obtained during this study may be made 
available to other Investigators who are conducting similar studies. 
The Investigator shall not make any publication related to this study without the express written 
permission of the sponsor. Should the Investigator wish to publish or present the results of this 
study, the Investigator agrees to provide the sponsor with an abstract, manuscript, and/or 
presentation for review ninety (90) days before submission for publication/presentation. The 
sponsor retains the right to delete from the manuscript confidential information and to object to 
suggested publication and/or its timing (at the sponsor’s sole discretion.) 
12.3.14 End of the Trial 
Upon a subject's completion in the study, the IP will no longer be available to the subject and all 
used and unused IP must be collected. The Investigator can, at their discretion, discuss alternative 
treatments with the subject. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 61 of 67 
 
 
The end of the trial is defined as the time at which the last subject has completed their last visit in 
the study. All eCRFs will be completed in compliance with the protocol and all relevant data and/or 
records will be forwarded to the CRO, as applicable. The Investigator must submit a final report to 
the IRB. The monitor will conduct a close out visit at the site. 
12.3.15 Clinical Study Report 
At the end of the study a full report per requirements of sponsor and regulatory authorities will be 
prepared which will include a narrative of the clinical conduct and results of the study, a statistical 
report including a description of the analysis performed, and other documentation as may be 
appropriate. The report will be in electronic format according to eCTD and ICH formatting 
standards and guidelines.21 ANDA summary tables will also be generated. Data sets will be 
provided in SAS® transport (.xpt) format with appropriate description (Read Me) files as required 
by FDA. 
12.3.16 Termination of the Study 
The sponsor reserves the right to terminate the study at any time for administrative or safety 
reasons. If the sponsor prematurely terminates or suspends the study, or one or more investigative 
sites participating in the study, the Investigator and/or CRO (as contracted) must promptly inform 
the IRB. As applicable, the Investigator may be required to follow up on the subject and/or refer 
them for appropriate care. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 62 of 67 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 63 of 67 
 
 
14.0 APPENDICES 
14.1 APPENDIX A: Investigator’s Global Assessment of Disease Severity 
 
Score  Grade  
Definition  
0 
None 
No plaque elevation above normal skin level; may have residual non-
erythematous discoloration; no psoriatic scale; no erythema 
1 
Minimal  
Essentially flat with possible trace elevation; faint erythema; no psoriatic scale 
2 
Mild 
Slight but definite elevation of plaque above normal skin level; may have up to 
moderate erythema (red coloration); fine scales with some lesions partially 
covered 
3 
Moderate 
Moderate elevation with rounded or sloped edges to plaque; moderate erythema 
(red coloration); somewhat coarse scales with most lesions partially covered 
4 
Severe 
Marked elevation with hard, sharp edges to plaque; severe erythema (very red 
coloration); coarse, thick scales with virtually all lesions covered and a rough 
surface 
5 
Very 
Severe 
Very marked elevation with very hard, sharp edges to plaque; very severe 
erythema (extreme red coloration); very coarse, thick scales with all lesions 
covered and a very rough surface 
To be eligible for participation in the study a subject must have a Baseline IGA score of 3, 4 or 5. 
A subject shall be considered a “treatment success” if he/she has an IGA score of 0, 1 or 2 within the 
treatment area at the Week 12 visit. 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 64 of 67 
 
 
14.2 APPENDIX B: Psoriasis Area Severity Index at the Target Lesion Site 
 
 
 
Score 
 
 
Grade 
 
 
Erythema 
 
 
Scaling 
 
 
Plaque Elevation 
0 
Clear 
No evidence of 
erythema 
No evidence of scaling 
No evidence of plaques 
above normal skin level 
1 
Almost 
Clear 
Pink discoloration, 
minimal erythema 
Occasional fine scales 
hardly noticeable 
Slight, just discernible 
elevation above normal 
skin level 
2 
Mild 
Light red coloration 
Slight but definite 
roughness, fine scale 
present, no cracking 
Discernible elevation above 
normal skin level upon 
examination, but not 
pronounced 
3 
Moderate 
Moderate redness, but 
not dark 
Moderate roughness, 
somewhat coarse 
scaling 
Definite plaque formation 
with rounded/sloped edges 
to plaque 
4 
Severe 
Dark red coloration 
Marked roughness, 
coarse/thick scaling, 
cracking may be 
evident 
Marked elevation with 
hard, distinct edges to 
plaque 
5 
Very 
Severe 
Very dark red 
coloration with 
induration present 
Very thick scales 
covering extensive 
area, severe 
cracking/fissures may 
be evident 
Very marked elevation, 
very hard and sharp edges 
to plaque 
To be eligible for participation in the study a subject must have a minimum plaque elevation of at least 
moderate severity (score ≥ 3) at the target lesion site. The most severe lesion at Baseline should be 
identified as the target lesion. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 65 of 67 
 
 
14.3 APPENDIX C: Application Site Reactions 
The following application site reactions will be evaluated at each visit based on the scale provided 
below: 
 
Signs and Symptoms: 
Erythema 
Dryness 
Burning/Stinging 
Erosion 
Edema 
Pain 
Itching 
Grading Scale: 
Severity 
Grade 
Absent 
0 
Mild 
1 (slight, barely perceptible) 
Moderate 
2 (distinct presence) 
Severe 
3 (marked, intense) 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 66 of 67 
 
 
14.4 APPENDIX D: TAZORAC® (tazarotene) Product Insert 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both Active Treatments to a 
Vehicle Control in the Treatment of Stable Plaque Psoriasis  
 
Confidential  0453-01-01 Rev. 2   12/22/2016  Fougera Pharmaceuticals Inc.    Page 67 of 67 
 
 
14.5 APPENDIX E: Amendments to the Protocol 
Amendment 
Date 
 
1 
12/20/2016 
 
The following revisions were made to the protocol dated 07/26/2016. 
• 
Updated approximate number of sites to be used. 
• 
Section 10.4.5 Black backing on label removed 
• 
Section 10.7.1 Updated reference in Adverse drug reaction section. 
• 
Section 10.7.6 Pregnancy reporting start date clarified; Removed language regarding males 
impregnating females. 
 
Amendment 
Date 
 
2 
12/22/2016 
 
• 
Section 11.6 Updated Cochran-Mantel-Haenszel exact test in Superiority to Placebo Analysis 
 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN 
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           Page 1 of 62         
STATISTICAL ANALYSIS PLAN 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study 
Comparing Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both 
Active Treatments to a Vehicle Control in the Treatment of Stable Plaque Psoriasis 
Protocol Number:  0453-01-01 / NCT02886702
 
Sponsor: 
Fougera Pharmaceuticals Inc. 
60 Baylis Road 
Melville, New York, 11747 
Contract Research Organization: 
 
 
 
April 26, 2017 
Final Version 2.0 


  
 
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SAP FINAL VERSION APPROVALS 
 
 
 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study 
Comparing Tazarotene Cream 0.05% to TAZORAC® (tazarotene) Cream 0.05% and Both 
Active Treatments to a Vehicle Control in the Treatment of Stable Plaque Psoriasis 
         
 
 
 
 
Written By: 
 
Signature: _____________________________  
 
 
 
 
 
 
Date:_____________________ 
Reviewed By: 
 
Signature: ____________________________ 
 
 
 
 
 
    
 
 
 
 
Date:_____________________ 
Approved By: 
 
Signature: ____________________________  
 
 
 
 
 
 
Date:_____________________ 
 
 
 
 


  
 
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Revision History 
  
 


  
 
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List of Abbreviations and Definition of Terms 
ADaM  
 
Analysis Data Model  
AE 
 
 
Adverse Event 
ANOVA 
 
Analysis of Variance 
BSA  
 
Body Surface Area 
C 
 
 
Celsius 
CDISC 
 
Clinical Data Interchange Standards Consortium 
CI 
 
 
Confidence Interval 
CRF 
 
 
Case Report Form 
CRO  
 
Contract Research Organization 
eCRF  
 
Electronic Case Report Form 
EOS   
 
End of Study 
ET 
 
 
Early Termination 
F 
 
 
Fahrenheit 
FDA  
 
Food and Drug Administration 
Hg 
 
 
Mercury 
ICF 
 
 
Informed Consent Form 
ICH 
 
 
International Conference on Harmonisation 
IGA 
 
 
Investigator Global Assessment 
IP 
 
 
Investigational Product 
LOCF  
 
Last Observation Carried Forward 
MedDRA 
 
Medical Dictionary for Regulatory Activities  
mITT  
 
modified Intent-to-Treat Population 
OGD  
 
Office of Generic Drugs 
PASI 
              Psoriasis Area Severity Index 
PD 
 
 
Protocol Deviation 
PP 
 
 
Per-Protocol 
RLD  
 
Reference Listed Drug 
SAE 
 
 
Serious Adverse Event 
SAP 
 
 
Statistical Analysis Plan 
SAS 
 
 
Statistical Analysis System 
SD 
  
 
Standard Deviation 
SDTM  
 
Study Data Tabulation Model 
 
 
 
 
 


  
 
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TABLE OF CONTENTS 
1. INTRODUCTION ............................................................................................................. 7 
2. OBJECTIVES .................................................................................................................... 7 
3. OVERALL STUDY DESIGN ........................................................................................... 7 
4. RANDOMIZATION AND BLINDING.......................................................................... 11 
5. SAMPLE SIZE ................................................................................................................ 11 
6. ANALYSIS POPULATION ............................................................................................ 12 
7. STUDY EFFICACY VARIABLES ................................................................................ 13 
8. STATISTICAL ANALYSIS METHODS ....................................................................... 13 
      8.1 Baseline Characteristics ........................................................................................... 14 
             8.1.1 Demographics Comparability of Treatment Groups ...................................... 14 
             8.1.2 Medical History .............................................................................................. 15 
             8.1.3 Concomitant Medications ............................................................................... 15 
             8.1.4 Pregnancy Test ................................................................................................ 15 
      8.2 Primary and Secondary Endpoint Analyses ............................................................. 15 
      8.3 Safety Analysis ......................................................................................................... 17 
             8.3.1 Adverse Events ............................................................................................... 17 
             8.3.2 Application Site Reactions .............................................................................. 18 
             8.3.3 Vital Signs ....................................................................................................... 18 
      8.4 Multiple Comparisons .............................................................................................. 18 
      8.5 Methods for Handling Missing Data ........................................................................ 18 
      8.6 Interim Analyses....................................................................................................... 19 
9. TABLE, LISTING AND FIGURE SHELLS .................................................................. 19 
T16.1.9.1 Summary of Discontinued Subjects (Safety Population) .................................... 21 
T16.1.9.2 Summary of Protocol Deviations (Safety Population) ........................................ 22 
T16.1.9.3.1 Summary of Subjects Excluded from Efficacy Analysis ................................. 23 
T16.1.9.3.2 Summary of Subjects Included in Analysis Population by Study Center ........ 24 
T16.1.9.4.1 Summary of Demographic Data  (Safety Population) ...................................... 25 
T16.1.9.4.2 Summary of Baseline Parameters (Safety Population) .................................... 26 
T16.1.9.5.1 Summary of Demographic Data  (modified Intent-to-Treat Population) ......... 29 
T16.1.9.5.2 Summary of Baseline Parameters (modified Intent-to-Treat Population) ........ 29 
T16.1.9.6.1 Summary of Demographic Data  (Per-Protocol Population) ............................ 29 
T16.1.9.6.2 Summary of Baseline Parameters (Per-Protocol Population) .......................... 29 
T16.1.9.7.1 Summary of Analysis Results of Primary Efficacy Endpoint .......................... 30 
T16.1.9.7.2 Summary of Supportive Analysis Results of Primary Efficacy Endpoint ....... 31 
T16.1.9.8.1 Summary of Analysis Results of Secondary Efficacy Endpoint ...................... 32 
T16.1.9.8.2 Summary of Supportive Analysis Results of Secondary Efficacy Endpoint  
Proportion of Subjects with Disease Severity (a score of 0 or 1) on IGA at the Week 12 
Visit ........................................................................................................................ 33 
T16.1.9.9.1 Summary of Analysis Results of Secondary Efficacy Endpoint ...................... 34 


  
 
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T16.1.9.9.2 Summary of Supportive Analysis Results of Secondary Efficacy Endpoint ... 35 
T16.1.9.10 Overall Summary of Adverse Events  (Safety Population) ............................... 36 
T16.1.9.11 Summary of Frequency of All Adverse Events by Body System  (Safety Population)
 ................................................................................................................................ 37 
T16.1.9.12 Summary of Frequency for AEs Occurring in at Least 5% of Subjects by Body 
System (Safety Population) .................................................................................... 37 
T16.1.9.13 Summary of Frequency of All Adverse Events by Severity (Safety Population)38 
T16.1.9.14 Summary of Frequency of All Adverse Events by Relationship  (Safety Population)
 ................................................................................................................................ 39 
T16.1.9.15 Summary of Frequency of Serious Adverse Events  (Safety Population)......... 40 
T16.1.9.16 Summary of Application Site Reaction  (Safety Population) ............................ 41 
T16.1.9.17 Summary of Frequency of Application Site Reaction  (Safety Population) ..... 42 
T16.1.9.18 Summary of Vital Signs  (Safety Population) ................................................... 43 
L16.2.1 Listing of Discontinued Subjects............................................................................ 44 
L16.2.2 Listing of Protocol Deviations................................................................................ 45 
L16.2.3.1 Subjects Excluded from the Per-Protocol Population Data Set........................... 46 
L16.2.3.2 Subjects Excluded from the Modified Intent-to-Treat Data Set .......................... 47 
L16.2.4.1 Listing of Demographic Data .............................................................................. 48 
L16.2.4.2 Listing of Medical History .................................................................................. 49 
L16.2.4.3 Listing of Concomitant Medications ................................................................... 50 
L16.2.5.1 Listing of Visit Date Information ........................................................................ 51 
L16.2.5.2 Listing of Drug Administration ........................................................................... 52 
L16.2.6.1 Listing of Investigator Global Assessment (IGA) ............................................... 53 
L16.2.6.2 Listing of Psoriasis Area Severity Index (PASI) at the Target Lesion Site ........ 54 
L16.2.6.3 Listing of Dermatological Examination .............................................................. 55 
L16.2.7.1 Listing of Adverse Events by Treatment Group.................................................. 56 
L16.2.7.2 Listing of Application Site Reactions.................................................................. 57 
L16.2.8.1 Listing of Pregnancy Test Results ....................................................................... 58 
L16.2.8.2 Listing of Vital Signs........................................................................................... 59 
APPENDIX A: Investigator’s Global Assessment of Disease Severity .............................. 60 
APPENDIX B: Psoriasis Area Severity Index at the Target Lesion Site ............................ 61 
APPENDIX C: Application Site Reactions ......................................................................... 62 


  
 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the final Clinical Study Protocol 0453-01-01 
Rev. 2 dated 12/22/2016. The SAP provides details on the planned statistical methodology for 
the analysis of the study data. The SAP also outlines the statistical programming specifications 
for the tables, listings and figures. 
 
This SAP describes the study endpoints, derived variables, anticipated data transformations and 
manipulations, and other details of the analyses not provided in the study protocol. This SAP 
therefore outlines in detail all other aspects pertaining to the planned analyses and presentations 
for this study. 
 
The following documents were reviewed in preparation of this SAP: 
 
• Final Clinical Study Protocol 0453-01-01 Rev. 2 dated 12/22/2016 
• Final eCRF Version 1.0 for 
 
 
The reader of this SAP is encouraged to also read the clinical protocol for details on the 
conduct of this study, and the operational aspects of clinical assessments and timing for 
completing a subject in this study. 
 
2. OBJECTIVES 
The objectives of this study are to: 
 
1. Evaluate the therapeutic equivalence of the Test product, Tazarotene Cream 0.05% 
(Fougera Pharmaceuticals Inc.) to the Reference product, TAZORAC® (tazarotene) 
Cream 0.05% (Allergan, Inc.) in the treatment of stable plaque psoriasis. 
 
2. Demonstrate the superiority of the efficacy of the Test and Reference (active) products 
over that of the Placebo in the treatment of stable plaque psoriasis. 
 
3. Compare the safety of the Test, Reference and Placebo products in the treatment of stable 
plaque psoriasis. 
 
3. OVERALL STUDY DESIGN 
This 
multi-center, 
double-blind, 
randomized, 
vehicle-controlled, 
parallel-group, 
bioequivalence clinical study has been designed to evaluate the efficacy and safety of a 


  
 
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generic tazarotene cream 0.05% (Fougera Pharmaceuticals Inc.) compared to the FDA 
Reference Listed Drug (RLD) TAZORAC® (tazarotene) Cream 0.05% (Allergan) in subjects 
with a clinical diagnosis of stable plaque psoriasis of at least moderate severity. Additionally, 
both the Test product and Reference (i.e., the RLD) products will be tested for superiority to a 
Placebo. Subjects with confirmed stable plaque psoriasis will apply the investigational 
product (IP) once daily, in the evening, to psoriatic lesions for 84 ± 4 days (12 weeks). 
Before any study-specific procedures are performed, all subjects will read and sign the IRB-
approved ICF. 
Each site will develop an individualized recruitment plan to collectively enroll approximately 
855 eligible subjects, 18 years of age and older, with a clinical diagnosis of stable plaque 
psoriasis and meeting the inclusion/exclusion criteria. Subjects will be randomized to one of 
the three IPs as follows: 
• Test: Tazarotene Cream, 0.05% (Fougera Pharmaceuticals Inc.) 
• Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
• Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
Subjects will attend the following scheduled clinic visits: 
• Visit 1 - Screening/Baseline: Day -14 to Day 1 
• Visit 2 - Interim Visit: Day 28 ± 4 days 
• Visit 3 - Interim Visit: Day 56 ± 4 days 
• Visit 4 - End of Study: Day 85 ± 4 days 
Subjects may attend unscheduled clinic visits: 
• Visit 9999 – Unscheduled visit 
At Visit 1, eligible subjects will be randomized to the Test, Reference or Placebo product in a 
1:1:1 ratio using the 
 system, which is an interactive response technology (IRT) 
system provided by the IRT provider. Study subjects will be provided with 
 of 
IP. 
 may be dispensed to the subject at the discretion of the Investigator if the 
subject has a high BSA affected with plaque psoriasis at the time of dispensation that would 
warrant additional product. At Visit 2 and Visit 3, subjects who continue to be eligible for 
continuation in the study can be dispensed an additional 
 of IP, as needed 
based on the subject's current BSA affected and the amount of IP remaining from the tube(s) 
previously dispensed. Further, any empty tubes will be collected at these visits. At Visit 4, all 
tubes will be collected (used and unused). A subject may return for an Unscheduled Visit at 
any time, should they require a resupply of IP (i.e., tube lost; all IP used between visits). It is 
estimated that approximately 
, but up to 
 may be needed to dose a subject with 


  
 
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high BSA involvement (~20% BSA) for the treatment period (depending upon their treatment 
response over the 12 weeks). Subjects with less BSA involvement will need significantly less 
IP (approximately 2 to 4 tubes). 
The day that the subject administers their first dose of IP will be considered Day 1.
 
 
 
 
For all other 
subjects, the first dose (Day 1) of IP will be applied on the evening of Visit 1. 
The subject will be instructed to apply enough cream (2 mg/cm2) to cover only the psoriatic 
lesions with a thin film (2 mg/cm2) once daily, in the evening, until the evening before Visit 4 
(Day 85 ± 4 days).There will be no application of the product on the day of the End of Study 
visit. 
Efficacy evaluations will be based on dermatological assessments in the clinic. The primary 
statistical analysis of interest is the (1) proportion of subjects with treatment success (defined 
as none, minimal or mild disease, a score of 0, 1 or 2, within the treatment area) on the 
Investigator’s Global Assessment (IGA) at the Week 12 visit. The secondary analyses are (1) 
proportion of subjects with disease severity at the Week 12 visit consistent with none or 
minimal, a score of 0 or 1, within the treatment area on the IGA, and (2) proportion of 
subjects with target site plaque elevation, scaling, and erythema scores of less than or equal to 
one on the PASI at the Week 12 visit. PASI is the sum of the three individual component 
scores. 
 


  
 
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Study Schematic 
 
 
PROCEDURE 
VISIT 1 
(Day -14 to 
1) 
Screening/ 
Baseline  
VISIT 2 
(Day 28 
± 4 Days) 
Interim Visit 
 
VISIT 3 
(Day 56 
± 4 Days) 
Interim Visit 
 
VISIT 4 
(Day 85 
± 4 Days)* 
End of Study/ 
Early 
Termination 
Informed Consent 
X‡ 
 
 
 
Medical History/ 
Demographics 
X‡ 
 
 
 
Pregnancy Test†  
X‡ 
X 
X 
X 
Vital Signs 
X‡ 
 
 
X 
Dermatologic Assessment 
X‡ 
 
 
 
IGA 
X‡ 
X 
X 
X 
PASI Assessment 
X‡ 
X 
X 
X 
Application Site Reactions 
X 
X 
X 
X 
Inclusion/Exclusion Criteria 
Review  
X‡ 
 
 
 
Concomitant Medication 
X‡ 
X 
X 
X 
Randomization 
X 
 
 
 
Dispense IP 
X 
X** 
X** 
 
Return of IP  
 
X** 
X** 
X 
Dispense Subject 
Diary/Supplies 
X 
X 
X 
 
Collect/Review Subject Diary  
 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
Discharge from Study 
 
 
 
X 
* Dosing regimen is once daily in the evening for 84 days (Day 1 to Day 84) through the evening before   
  Visit 4 (Day 85 ± 4) 
** If applicable, based on use of previously dispensed product. 
† For females of childbearing potential 
‡ Procedures performed as part of the screening assessment, before randomization 
 
 
 
 
 
 
 
 


  
 
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4. RANDOMIZATION AND BLINDING 
The IP will be randomized, packaged and blinded by an 
 
. The randomization code will be generated using a validated computer 
program. 
 
Each 
site will receive multiple, full blocks of IP in each delivery. The quantity received may vary. 
Randomization will be pre-planned according to a computer-generated randomization scheme. 
The randomization code will be retained within 
 which is maintained by 
 
. 
 will also retain the kit boxes numbers supplied to each site and the 
kit boxes numbers that have been selected for retention and are therefore unavailable for 
dispensing to subjects. 
Upon confirmation of subject eligibility, the subject’s information (i.e., subject’s initials, date of 
birth, etc.) will be entered into 
, and the system will assign a 
 randomization 
number to the subject based upon 
. 
 will then assign the 
subject a 
 kit box number in a blinded fashion at Visit 1. This kit box number will 
correspond to a specific treatment group within 
; however the treatment group will be 
unknown to the Investigator, the CRO, the sponsor and the subject. The site will record the 
randomization number and the kit box number in the subject’s source documentation and drug 
dispensing log. The 
 will then dispense 
 from the kit box. The 
 will record the tube number of the 
 dispensed to the subject in the 
subject’s source documentation and drug dispensing log. At Visits 2, 3 and/or Unscheduled Visit, 
additional IP may be dispensed to the subject, as needed. The 
 will select 
an additional unused tube from the subject’s previously assigned kit box, dispense it to the 
subject and record the tube number. 
 
 
 
Each subject will 
maintain the same treatment assignment throughout the study. 
 
5. SAMPLE SIZE 
Sample size calculations were performed using 
. For the primary 
endpoint analysis, the rate of treatment success for the Reference treatment after 12 weeks of 
treatment is expected to be approximately 
 in the PP population. Assuming that the rates of 
treatment success for Test and Reference treatments are the same, a sample size of 
 subjects 
in each active group in the PP population will provide approximately 
 power to demonstrate 
therapeutic equivalence (i.e., the 90% confidence interval (Yates’ continuity-corrected) of the 
absolute difference between the Test and Reference rates of treatment success is within a defined 
equivalence range [-20% to + 20%]). 


  
 
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The rates of treatment success for the Placebo and active treatment groups after 12 weeks of 
treatment are assumed to be approximately 
 and at least 
 respectively, in the mITT 
population. Using a 1:1 (active: placebo) randomization scheme, and assuming the conversion 
rate from mITT to PP population will be about 
 subjects in each treatment group (Test, 
Reference and Placebo) of the mITT population will provide at least 
 power to demonstrate 
superiority of active over Placebo at the 5% significance level (p < 0.05, two-sided continuity-
corrected Z-Tests and a pooled response rate for the standard error of the difference in 
proportions). 
Under the above assumptions, the overall study power to demonstrate therapeutic equivalence 
and superiority is estimated to be at least 
. To allow for approximately 
 of subjects who 
may drop out from the study or are otherwise non-evaluable, up to 855 subjects may be 
randomized to obtain 
 subjects in the mITT population (i.e., 
 per treatment arm). 
 
6. ANALYSIS POPULATION  
Per-Protocol Population 
 
The PP population will include subjects that comply with the protocol as follows: 
• All randomized subjects who meet all inclusion and exclusion criteria. 
• Make the final study visit (Visit 4) within the protocol window of Day 85 ± 4 days with 
no PDs that would affect the integrity of the data. 
• Comply with study restrictions including concomitant medications. 
• Apply the IP appropriately and are within 
 compliant with dosing during the 
12 weeks (Day 85 ± 4) of treatment. 
• Do not miss the scheduled applications for more than 
 
 
 
 
 
 
 
 
 
 
 


  
 
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Modified Intent-to-Treat Population (mITT) Population 
 
The mITT population will include all subjects in the PP population plus all randomized subjects 
who meet all inclusion/exclusion criteria, apply at least one dose of assigned product, and return 
for at least one post-Baseline evaluation. 
 
 
 
 
Safety Population 
 
All subjects who are randomized and received IP will be included in the analysis of safety.  
 
7. STUDY EFFICACY VARIABLES  
Primary Efficacy Endpoints 
Proportion of subjects with treatment success (defined as none, minimal or mild disease, a score 
of 0, 1 or 2 within the treatment area) on the IGA at the Week 12 visit (Day 85 ± 4 days, End of 
Study). 
Secondary Efficacy Endpoints 
1. Proportion of subjects with disease severity at the Week 12 visit (Day 85 ± 4 days, End of 
Study) consistent with none or minimal, a score of 0 or 1, within the treatment area on the 
IGA 
 AND 
2. Proportion of subjects with target site plaque elevation, scaling and erythema scores of 
less than or equal to 1 on the PASI at the Week 12 visit (Day 85 ± 4, End of Study).  
 
8. STATISTICAL ANALYSIS METHODS 
If not otherwise specified, statistical significance is defined as p<0.05 and is two-tailed. Data 
will be summarized with respect to demographic and baseline characteristics, efficacy variables 
and safety variables. 
 
For categorical variables, the number and percent of each category within a parameter will be 


  
 
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calculated for non-missing data.  For continuous variables with non-missing values, statistics will 
include number of observations, mean, standard deviation, median, minimum and maximum values.  
All statistical analyses will be conducted using SAS®, Version 9.4 or higher. Datasets will be prepared 
using headings from Clinical Data Interchange Consortium (CDISC) Study Data Tabulation Model 
(SDTM) implementation for human clinical trials and ADaM (Analysis Dataset Model). 
8.1 Baseline Characteristics 
8.1.1 Demographics Comparability of Treatment Groups 
Baseline characteristics will be evaluated separately for the PP, mITT and Safety populations. 
Demographic information collected at baseline includes the following:   
• Age (years) 
• Sex (Male/Female) 
• Ethnicity (Hispanic/non Hispanic) 
• Race (White, Black/African American, Native Hawaiian or Other Pacific Islander,   
 
Asian, American Indian or Alaska Native, Other) 
• Baseline total BSA affected with Psoriasis 
• Baseline percent BSA affected with Psoriasis 
• Baseline PASI Score (the sum of the three individual component scores) 
• Baseline Scores for Individual Components (Erythema, Scaling and Plaque Elevation) 
• Baseline IGA Score 
• Treatment location 
• Treatment area size (area) 
• Target lesion size (area) 
Summary tables by treatment group will be presented. Continuous variables will be summarized 
using descriptive statistics (number of observations, median, minimum, maximum, mean and  
standard  deviation).  Categorical variables will be summarized using frequencies and 
percentage. Baseline treatment comparisons will be presented using Chi-Square test for the 
categorical variables, and Analysis of Variance (ANOVA) for the continuous variables. 
 
All data will be listed by treatment and subject. 


  
 
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8.1.2 Medical History 
At Visit 1 subjects will be questioned about their personal medical history, including psoriasis 
history. The medical history will include a complete review of all current diseases and their 
respective durations and treatments. 
Medical history data will be listed by treatment and subject. 
8.1.3 Concomitant Medications 
At Visit 1, subjects will be questioned about current and prior concomitant medication use over 
the 6 months. Subjects will also be questioned about ongoing or new concomitant medication use 
during the treatment period at Visits 2, 3 and 4.  
All prior and concomitant medications taken since screening until the end of the study will be 
listed by treatment and subject.  
8.1.4 Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed at each 
Scheduled visit. All females of childbearing potential will have a urine pregnancy test performed 
at Visit 1 (Baseline), Visit 2, Visit 3, and Visit 4 (or early termination). 
 
Pregnancy test results will be listed by treatment and subject. 
8.2 Primary and Secondary Endpoint Analyses 
Therapeutic Bioequivalence Analysis 
Therapeutic equivalence will be evaluated for both primary and secondary endpoints using the 
PP population, with results in the mITT population being supportive.  
Based on the usual method used in OGD for binary outcomes, the 90% confidence interval for 
the difference in success proportions between test and reference treatment should be contained 
within [-0.20, +0.20] in order to establish equivalence.  
 
The compound hypothesis to be tested is:  
 
 H0 :   𝑃𝑃𝑇𝑇− 𝑃𝑃𝑅𝑅< −.20  𝑜𝑜𝑜𝑜  𝑃𝑃𝑇𝑇− 𝑃𝑃𝑅𝑅 > .20     versus   
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.05%                                       Protocol / 
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4/26/2017                         
 Fougera Pharmaceuticals Inc.             
           Page 16 of 62                           
 HA : −.20 ≤𝑃𝑃𝑇𝑇− 𝑃𝑃𝑅𝑅≤.20 
 
where   𝑃𝑃𝑇𝑇  =  success rate of test treatment  
             𝑃𝑃𝑅𝑅  =  success rate of reference treatment.  
Let  
𝑛𝑛𝑇𝑇  =  sample size of test treatment group  
𝑐𝑐𝑛𝑛𝑇𝑇=  number of patients considered as Treatment Success in test treatment group  
𝑛𝑛𝑅𝑅  =  sample size of reference treatment group  
𝑐𝑐𝑛𝑛𝑅𝑅=  number of patients considered as Treatment Success in reference treatment group  
𝑃𝑃෠𝑇𝑇= 𝑐𝑐𝑛𝑛𝑇𝑇/𝑛𝑛𝑇𝑇  
 𝑃𝑃෠𝑅𝑅= 𝑐𝑐𝑛𝑛𝑅𝑅/𝑛𝑛𝑅𝑅 ,       and 
 
            𝑠𝑠𝑠𝑠 =  (𝑃𝑃෡𝑇𝑇 (1 −𝑃𝑃෡𝑇𝑇)/𝑛𝑛𝑇𝑇 + (𝑃𝑃෡𝑅𝑅 (1 −𝑃𝑃෡𝑅𝑅)/𝑛𝑛𝑅𝑅 )
1 2
ൗ 
 
The 90% confidence interval for the difference in proportions between test and reference will be 
calculated as follows, using Yates’ correction: 
           L =  ൫𝑃𝑃෠𝑇𝑇−𝑃𝑃෠𝑅𝑅൯−1.645 𝑠𝑠𝑠𝑠−(1/𝑛𝑛𝑇𝑇 + 1/𝑛𝑛𝑅𝑅 )/2 
           U = ൫𝑃𝑃෠𝑇𝑇−𝑃𝑃෠𝑅𝑅൯+ 1.645 𝑠𝑠𝑠𝑠+ (1/𝑛𝑛𝑇𝑇 + 1/𝑛𝑛𝑅𝑅 )/2 
For the proportion of Treatment Success, if the 90% confidence interval (with Yates’ Correction 
Factor) of the difference between the proportion of subjects considered a “treatment success” in 
the Test and the Reference treatment groups at Week 12 is contained within the pre-defined 
equivalence limits [-20%, +20%], then therapeutic equivalence will be considered to have been 
supported for the endpoint. The same statistical approach will be conducted for analysis of the 
two dichotomized secondary endpoints in the PP and mITT populations. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary endpoint in the PP population. 
Superiority to Placebo Analysis 
The primary measure of superiority will be evaluated using the mITT population and LOCF for 
missing efficacy values. The results in the PP population will be considered supportive.  
The superiority of the Test and Reference products over Placebo will be concluded for the 
primary endpoint if the proportion of treatment success at Week 12 is statistically superior to 
Placebo (p < 0.05, two-sided a Cochran-Mantel-Haenszel exact test stratified by clinical site) 
using the mITT population and LOCF. The same statistical approach will be conducted for 
analysis of the two dichotomized secondary endpoints in the mITT and PP populations. 


  
 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.05%                                       Protocol / 
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4/26/2017                         
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           Page 17 of 62                           
.  
To declare superiority of the Test and Reference products over Placebo, their superiority must be 
demonstrated for only the primary endpoint in the mITT population. 
A summary table with frequency and percentage of the proportion of Treatment Success by 
treatment group will be presented. 
Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated by the 
Cochran-Mantel-Haenszel test (stratified by site) at the 5% significance level (p < 0.05, 2-sided) 
for the primary efficacy endpoint in both the PP population (for equivalence testing) and mITT 
population (for superiority testing)..
 
 
 
If the treatment-by-site interaction is found to be statistically significant (p < 0.05) then the 
interaction will also be assessed for clinical relevance before pooling the data across sites. This 
will include examination of responder rates at each site where sample sizes per treatment may be 
influential in the assessment of the interaction. 
 
8.3 Safety Analysis 
All safety analyses will be based on the Safety Population. 
8.3.1 Adverse Events 
All the adverse events (AEs) reported throughout the study will be coded and classified 
according to the MedDRA (Medical Dictionary for Regulatory Activities) coding dictionary 
(Version 18.1 or higher). Each adverse event is to be evaluated for date of start and end, 
seriousness, severity, relationship to the IP, action taken and outcome.   
In each of the following categories, the total number and percentage of subjects with 1) at least 
one AE, 2) discontinued study drug due to AEs, 3) AE severity and AEs related to the IP, 4) 
serious AEs and death will be summarized separately by treatment groups.  
A summary table of the number and percent of subjects with AEs by system organ class, 
preferred term, and treatment group will be presented.  Each subject will be counted only once 
within each preferred term.   


  
 
STATISTICAL ANALYSIS PLAN 
 
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           Page 18 of 62                           
A frequency summary table of the number of AEs by system organ class, preferred term, 
severity, and treatment group will be presented. Severity will be classified as “Mild”, 
“Moderate”, or “Severe”.  
Similarly, a frequency summary table of the number of AEs by system organ class, preferred 
term, and relationship to the IP, and treatment group will be presented. Relationship to a study 
drug will be classified as “Suspected” or “Not Suspected”. 
Should sufficient data exist, adverse event frequencies will be compared between treatments 
using Fisher’s exact test. 
8.3.2 Application Site Reactions 
At Visits 1, 2, 3 and 4 the Investigator will evaluate the subject for local application site 
reactions. 
Signs and Symptoms recorded at each visit will be compared between treatment groups. 
Descriptive summaries (number of observations, mean, standard deviation, minimum, median 
and maximum) comparing the application site reactions for each treatment group will be 
presented by visit. 
 
A frequency summary table comparing the application site reactions for each treatment group 
will be presented by visit. 
 
8.3.3 Vital Signs 
The subject’s vital signs (pulse, blood pressure, temperature and respiration rate) will be 
recorded  at Visit 1 and Visit 4. 
 
Descriptive summaries (number of observations, mean, standard deviation, minimum, median 
and maximum) will be provided by treatment and visit for non-missing values.  
 
All data will be listed by treatment and subject. 
8.4 Multiple Comparisons 
No multiple comparison adjustment will be made in this study. 
8.5 Methods for Handling Missing Data 
For demographic and baseline characteristics, each variable will be analyzed using all available 


  
 
STATISTICAL ANALYSIS PLAN 
 
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4/26/2017                         
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           Page 19 of 62                           
data. Subjects with missing data will be excluded only from analyses for which data are not 
available, including denominators. 
Subjects who discontinue early for reasons besides lack of treatment effect or worsening of 
condition should be excluded from the PP population, but included in the modified Intent-to-
Treat (mITT) population using the last observation carried forward (LOCF), provided they 
administered at least one dose of randomized IP and completed at least one post-dose 
evaluation. 
8.6 Interim Analyses 
There is no interim analysis planned in this study. 
9. TABLE, LISTING AND FIGURE SHELLS 
The following shells are provided in order to provide a framework for the display of data from 
this study. These shells may not be reflective of every aspect of this study but are intended to 
show the general layout of the Tables, Listings and Figures that will be included in the final 
clinical study report. Tables, Listings and Figures are numbered following the ICH structure. 
Table headers, variables names and footnotes will be modified as needed following data 
analyses. All descriptive and inferential statistical analyses will be performed using SAS® 
statistical software Version 9.4 or higher, unless otherwise noted.   


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 20 of 62                                                
 
 
 
 
 
 
 
 
 
 
 
 
 
TABLE, LISTING AND FIGURE SHELLS 
 
 
  
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 21 of 62                                                
 
T16.1.9.1 Summary of Discontinued Subjects 
(Safety Population) 
 
 
Subjects 
 
Test 
Reference 
Placebo 
Total 
Randomized 
xxx 
xxx 
xxx 
xxx 
Completed Study 
xxx 
xxx 
xxx 
xxx 
Terminated Early 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Early Termination Reason 
 
 
 
 
Administrative reasons 
xxx 
xxx 
xxx 
xxx 
Lack of efficacy 
xxx 
xxx 
xxx 
xxx 
Lost to Follow-Up 
xxx 
xxx 
xxx 
xxx 
etc. 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 22 of 62                                                
 
T16.1.9.2 Summary of Protocol Deviations 
(Safety Population) 
 
 
 
 
Test 
Reference 
Placebo 
 
Total 
Total Subjects with Protocol Deviations 
xxx 
xxx 
xxx 
xxx 
Total Deviations 
xxx 
xxx 
xxx 
xxx 
Lost to follow up 
xxx 
xxx 
xxx 
xxx 
Outside visit window 
xxx 
xxx 
xxx 
xxx 
Missed Visit 
xxx 
xxx 
xxx 
xxx 
Restricted Medication 
xxx 
xxx 
xxx 
xxx 
etc 
xxx 
xxx 
xxx 
xxx 
Other 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                               
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 23 of 62                                                
T16.1.9.3.1 Summary of Subjects Excluded from Efficacy Analysis  
(Population Determination) 
 
 
 
 
 
 
Test 
Reference 
Placebo 
 
Total 
Randomized 
Total 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
Safety Population 
Total 
xxx 
xxx 
xxx 
xxx 
Excluded from Safety  
Did not received study product 
xxx 
xxx 
xxx 
xxx 
 
etc. 
 
 
 
 
 
 
 
 
 
 
mITT Population 
Total 
xxx 
xxx 
xxx 
xxx 
Excluded from mITT  
Did not received study product 
xxx 
xxx 
xxx 
xxx 
 
etc. 
 
 
 
 
 
 
 
 
 
 
PP Population 
Total 
xxx 
xxx 
xxx 
xxx 
Excluded from Excluded from PP  
Restricted Medication 
xxx 
xxx 
xxx 
xxx 
 
etc. 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 24 of 62                                                
T16.1.9.3.2 Summary of Subjects Included in Analysis Population by Study Center 
 
PP 
 
mITT 
 
Safety 
Site 
No. 
Name 
Total 
Randomized 
Test 
Ref 
Placebo Total  Test 
Ref 
Placebo Total  Test 
Ref 
Placebo Total 
xx 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx xxx 
xxx 
xxx 
xxx xxx 
xxx 
xxx 
xx 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx xxx 
xxx 
xxx 
xxx xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 25 of 62                                                
T16.1.9.4.1 Summary of Demographic Data  
(Safety Population) 
 
 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
P-value 
Age (years) 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Race 
White 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
     x.xxxx 
 
Black/African American 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Native Hawaiian or other Pacific Islander 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Asian 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
American Indian or Alaska Native 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Other 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Sex 
Female 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Male 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Ethnicity 
Hispanic or Latino 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Not Hispanic or Latino 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
 
 
 
 
 
            N= number of subjects in the treatment group;     n= number of subjects with data available;      % is based on N 
            P-values are from Chi-squre test for categorical variables and ANOVA for the continuous variables. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 26 of 62                                                
T16.1.9.4.2 Summary of Baseline Parameters 
(Safety Population) 
 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
P-value 
Total BSA affected with Psoriasis 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Total percent BSA affected with Psoriasis 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Baseline IGA Score 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Baseline PASI Score 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
           Note:  N= number of subjects in the treatment group;     n= number of subjects with data available;      % is based on N 
           P-values are from Chi-squre test for categorical variables and ANOVA for the continuous variables. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 27 of 62                                                
T16.1.9.4.2 Summary of Baseline Parameters  
(Safety Population) 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
P-value 
Erythema 
Clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Almost clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Mild 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Moderate 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Very severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Scaling 
Clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Almost clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Mild 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Moderate 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Very severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Plaque Elevation 
Clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Almost clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Mild 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Moderate 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Very severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
           Note:  N= number of subjects in the treatment group;     n= number of subjects with data available;      % is based on N 
           P-values are from Chi-squre test for categorical variables and ANOVA for the continuous variables. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 28 of 62                                                
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T16.1.9.4.2 Summary of Baseline Parameters 
(Safety Population) 
 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
P-value 
Treatment area size (area) 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Target lesion size (area) 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Treatment location 
Head front 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Head back 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Torso front 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Torso back 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
etc 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
           Note:  N= number of subjects in the treatment group;     n= number of subjects with data available;      % is based on N 
           P-values are from Chi-squre test for categorical variables and ANOVA for the continuous variables. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 29 of 62                                                
 
Similar tables will be created for T16.1.9.5.1, T16.1.9.5.2, T16.1.9.6.1 and T16.1.9.6.2 
 
 
 
 
T16.1.9.5.1 Summary of Demographic Data  
(modified Intent-to-Treat Population) 
 
T16.1.9.5.2 Summary of Baseline Parameters 
(modified Intent-to-Treat Population) 
 
T16.1.9.6.1 Summary of Demographic Data  
(Per-Protocol Population) 
 
T16.1.9.6.2 Summary of Baseline Parameters 
(Per-Protocol Population) 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 30 of 62                                                
T16.1.9.7.1 Summary of Analysis Results of Primary Efficacy Endpoint  
Proportion of Treatment Successes on the IGA (a score of 0 or 1 or 2) at the Week 12 Visit 
Equivalence: Per-Protocol Population 
Number of 
Subjects (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x% 
 
 
Reference 
xxx 
xxx 
xx.x% 
xx.x% 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Treatment  
Group 
 
Number of 
Subjects (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x% 
 
Test 
xxx 
xxx 
xx.x% 
x.xxxx 
Reference 
xxx 
xxx 
xx.x% 
x.xxxx 
                     The 90% confidence interval for the difference in proportions between test and reference was calculated using Yates’ correction. 
       Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) exact test, stratified by   
       clinical site, at the 5% significance level using last observation carried forward (LOCF). 
 
      Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                     Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 31 of 62                                                
T16.1.9.7.2 Summary of Supportive Analysis Results of Primary Efficacy Endpoint  
Proportion of Treatment Successes on the IGA (a score of 0 or 1 or 2) at the Week 12 Visit 
Equivalence: modified Intent-to-Treat Population  
Number of 
Subjects (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x% 
 
 
Reference 
xxx 
xxx 
xx.x% 
xx.x% 
xx.x – xx.x 
 
Superiority: Per-Protocol Population 
Treatment  
Group 
 
Number of 
Subjects (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x% 
 
Test 
xxx 
xxx 
xx.x% 
x.xxxx 
Reference 
xxx 
xxx 
xx.x% 
x.xxxx 
                     The 90% confidence interval for the difference in proportions between test and reference was calculated using Yates’ correction. 
       Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) exact test, stratified by   
       clinical site, at the 5% significance level using last observation carried forward (LOCF). 
 
      Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
       Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 32 of 62                                                
T16.1.9.8.1 Summary of Analysis Results of Secondary Efficacy Endpoint  
Proportion of Subjects with Disease Severity (a score of 0 or 1) on IGA at the Week 12 Visit 
Equivalence: Per-Protocol Population 
Number of 
Subjects (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x% 
 
 
Reference 
xxx 
xxx 
xx.x% 
xx.x% 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Treatment  
Group 
 
Number of 
Subjects (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x% 
 
Test 
xxx 
xxx 
xx.x% 
x.xxxx 
Reference 
xxx 
xxx 
xx.x% 
x.xxxx 
                     The 90% confidence interval for the difference in proportions between test and reference was calculated using Yates’ correction. 
       Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) exact test, stratified by   
       clinical site, at the 5% significance level using last observation carried forward (LOCF). 
 
      Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                     Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 33 of 62                                                
T16.1.9.8.2 Summary of Supportive Analysis Results of Secondary Efficacy Endpoint  
Proportion of Subjects with Disease Severity (a score of 0 or 1) on IGA at the Week 12 Visit 
 
Equivalence: modified Intent-to-Treat Population  
Number of 
Subjects (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x% 
 
 
Reference 
xxx 
xxx 
xx.x% 
xx.x% 
xx.x – xx.x 
 
Superiority: Per-Protocol Population 
Treatment  
Group 
 
Number of 
Subjects (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x% 
 
Test 
xxx 
xxx 
xx.x% 
x.xxxx 
Reference 
xxx 
xxx 
xx.x% 
x.xxxx 
                     The 90% confidence interval for the difference in proportions between test and reference was calculated using Yates’ correction. 
       Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) exact test, stratified by   
       clinical site, at the 5% significance level using last observation carried forward (LOCF). 
 
      Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
       Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 34 of 62                                                
T16.1.9.9.1 Summary of Analysis Results of Secondary Efficacy Endpoint  
Proportion of Subjects with Target Site Plaque Elevation, Scaling and Erythema Scores of Less Than or Equal to 1 on the 
PASI at the Week 12 Visit 
Equivalence: Per-Protocol Population 
Number of 
Subjects (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x% 
 
 
Reference 
xxx 
xxx 
xx.x% 
xx.x% 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Treatment  
Group 
 
Number of 
Subjects (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x% 
 
Test 
xxx 
xxx 
xx.x% 
x.xxxx 
Reference 
xxx 
xxx 
xx.x% 
x.xxxx 
                     The 90% confidence interval for the difference in proportions between test and reference was calculated using Yates’ correction. 
       Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) exact test, stratified by   
       clinical site, at the 5% significance level using last observation carried forward (LOCF). 
 
      Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
         Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 35 of 62                                                
T16.1.9.9.2 Summary of Supportive Analysis Results of Secondary Efficacy Endpoint  
Proportion of Subjects with Target Site Plaque Elevation, Scaling and Erythema Scores of Less Than or Equal to 1 on the 
PASI at the Week 12 Visit 
Equivalence: modified Intent-to-Treat Population  
Number of 
Subjects (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x% 
 
 
Reference 
xxx 
xxx 
xx.x% 
xx.x% 
xx.x – xx.x 
 
Superiority: Per-Protocol Population 
Treatment  
Group 
 
Number of 
Subjects (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x% 
 
Test 
xxx 
xxx 
xx.x% 
x.xxxx 
Reference 
xxx 
xxx 
xx.x% 
x.xxxx 
                     The 90% confidence interval for the difference in proportions between test and reference was calculated using Yates’ correction. 
       Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) exact test, stratified by   
       clinical site, at the 5% significance level using last observation carried forward (LOCF). 
 
      Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
       Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 36 of 62                                                
T16.1.9.10 Overall Summary of Adverse Events  
(Safety Population) 
 
 
Description 
 
Test 
N (%) 
 
Reference 
N (%) 
 
Placebo 
N (%) 
 
Total 
N (%) 
Subjects Randomized 
xxx 
xxx 
xxx 
xxx 
     Subjects with at least one AE 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
     Discontinued study drug due to above AE 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
AEs reported 
xxx 
xxx 
xxx 
xxx 
      Mild 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Not Suspected 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Suspected 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Death 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Serious AE 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                 Path: L:\Studies_Sas_Codes\Clinical Trial\
SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 37 of 62                                                
T16.1.9.11 Summary of Frequency of All Adverse Events by Body System  
(Safety Population) 
 
Body System 
MedDRA Term  
Test  
(N = xxx) 
 
Reference 
(N = xxx) 
   
Placebo 
(N = xxx) 
 
Fisher’s 
P-value 
Events 
Subjects 
Events 
Subjects 
Events 
Subjects 
Subject with at least 
one AE 
Total 
xx 
xx (xx.x%)  
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
x.xxxx 
Ear and labyrinth 
disorders 
Ear pain 
xx 
xx (xx.x%)  
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
x.xxxx 
 
etc. 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Comparison of treatment groups is with respect to the number of subjects with at least one occurrence of the AE. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
T16.1.9.12 Summary of Frequency for AEs Occurring in at Least 5% of Subjects by Body System 
(Safety Population) 
 
 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 38 of 62                                                
T16.1.9.13 Summary of Frequency of All Adverse Events by Severity 
(Safety Population) 
 
 
 
Test 
# Events 
(N=xx) 
 
Reference 
# Events 
(N=xx) 
  
Placebo 
# Events 
(N=xx) 
 
Body System 
MedDRA Term 
Mild 
Moderate 
Severe 
Mild 
Moderate Severe 
Mild 
Moderate 
Severe 
 
Total AEs  
Total AEs 
 xx(xx.x%) xx(xx.x%) xx (xx.x%)  xx(xx.x%) xx(xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%)  
 
 
 
 
 
 
 
 
 
 
 
 
Ear and labyrinth 
disorders 
Ear pain 
 xx(xx.x%) xx(xx.x%) xx (xx.x%)  xx(xx.x%) xx(xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%)  
 
Hypoacusis 
 xx(xx.x%) xx(xx.x%) xx (xx.x%)  xx(xx.x%) xx(xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
          N = Total number of events in each treatment group;       Percentage is based on total number of events. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
          Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 39 of 62                                                
T16.1.9.14 Summary of Frequency of All Adverse Events by Relationship  
(Safety Population) 
 
 
 
Test 
# Events 
(N=xx) 
 
Reference 
# Events 
(N=xx) 
  
 
Placebo 
# Events 
(N=xx) 
 
Body System 
MedDRA Term 
Suspected 
Not Suspected 
Suspected Not Suspected 
Suspected 
Not Suspected  
Total AEs 
Total AEs 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
Ear and labyrinth 
disorders 
Ear pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Hypoacusis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
            N = Total number of events in each treatment group;       Percentage is based on total number of events. 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
            Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 40 of 62                                                
T16.1.9.15 Summary of Frequency of Serious Adverse Events  
(Safety Population) 
 
Body System 
MedDRA Term 
 
Test 
# Events 
Reference 
# Events 
Placebo 
# Events 
Injury, poisoning and procedural complications 
Alcohol poisoning 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                 Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 41 of 62                                                
 
T16.1.9.16 Summary of Application Site Reaction  
(Safety Population) 
 
Signs and  
Symptoms 
Visit 
 
Statistic 
 
Test 
(N = xxx) 
 
Reference 
(N = xxx) 
 
Placebo 
(N = xxx) 
Erythema 
1 
n 
xxx 
xxx 
xxx 
 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x – xx.x 
xx.x – xx.x 
xx.x – xx.x 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4/ET 
 
 
 
 
Dryness 
 
 
 
 
 
Burning/Stinging 
 
 
 
 
 
Erosion 
 
 
 
 
 
Edema 
 
 
 
 
 
Pain 
 
 
 
 
 
Itching 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
       
                      Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 42 of 62                                                
T16.1.9.17 Summary of Frequency of Application Site Reaction  
(Safety Population) 
 
Signs and  
Symptoms 
Visit 
 
Statistic 
 
Test 
(N = xxx) 
 
Reference 
(N = xxx) 
 
Placebo 
(N = xxx) 
Erythema 
1 
Absent 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Mild 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Moderate 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
Severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4/ET 
 
 
 
 
Dryness 
 
 
 
 
 
Burning/Stinging 
 
 
 
 
 
Erosion 
 
 
 
 
 
Edema 
 
 
 
 
 
Pain 
 
 
 
 
 
Itching 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
   
      Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 43 of 62                                                
T16.1.9.18 Summary of Vital Signs  
(Safety Population) 
 
Vital Signs 
Visit 
 
Statistic 
 
Test 
(N = xxx) 
 
Reference 
(N = xxx) 
 
Placebo 
(N = xxx) 
Systolic Blood Pressure (mmHg) 
1 
n 
xxx 
xxx 
xxx 
 
 
Mean ± SD 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
 
Range 
xx.x – xx.x 
xx.x – xx.x 
xx.x – xx.x 
 
4/ET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diastolic Blood Pressure (mmHg) 
 
 
 
 
 
Pulse Rate (beats/min) 
 
 
 
 
 
Respiration Rate (breaths/min) 
 
 
 
 
 
Temperature (F) 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
     Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 44 of 62                                                
 
L16.2.1 Listing of Discontinued Subjects 
 
 Treatment 
 Group 
Subject 
Number 
Discontinuation 
Reason 
Population 
 Test 
xx - xxxx 
Withdrew Consent 
Safety 
 
xx - xxxx 
Lost to Follow-up 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 Reference 
 
 
 
 Placebo 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
          Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 45 of 62                                                
 
L16.2.2 Listing of Protocol Deviations 
 
Treatment  
Group 
Subject 
Number 
Protocol Deviation Summary 
Population 
Test 
xx - xxxx 
Outside Visit Window 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
Placebo 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                  Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 46 of 62                                                
 
L16.2.3.1 Subjects Excluded from the Per-Protocol Population Data Set 
 
Treatment 
Group 
Subject 
Number 
Exclusion 
Reason 
Test 
xx - xxxx 
Subject did not meet IE criterion. 
 
xx - xxxx 
Subject took prohibited medications 
 
 
 
 
 
 
 
Reference 
 
 
Placebo 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
           Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 47 of 62                                                
 
L16.2.3.2 Subjects Excluded from the Modified Intent-to-Treat Data Set 
 
Treatment 
Group 
Subject 
Number 
Exclusion 
Reason 
Test 
xx - xxxx 
Subject did not have at least one post-randomization evaluation 
 
xx - xxxx 
Subject did not have at least one post-randomization evaluation 
 
 
 
 
 
 
Reference 
 
 
Placebo 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
           Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 48 of 62                                                
 
L16.2.4.1 Listing of Demographic Data  
 
Treatment 
Group 
Subject 
Number 
 
Age 
 
Sex 
 
Ethnicity 
Race 
  Test 
xx - xxxx 
30 
Female 
Not Hispanic or Latino 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
                Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 
 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 49 of 62                                                
 
L16.2.4.2 Listing of Medical History 
 
Treatment 
Group 
Subject 
Number 
Category 
 
Reported Term 
 
Onset Date 
 
End Date 
 
Ongoing 
Test 
xx - xxxx 
Gynecologic 
Menopause 
2003 
2003 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
   
    Path: L:\Studies_Sas_Codes\Clinical Trial\
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 50 of 62                                                
 
L16.2.4.3 Listing of Concomitant Medications 
 
Test: Tazarotene Cream 0.05% 
 
Subject 
Number 
Medication/ 
Therapy Name 
Dosage 
Frequency 
 
Route 
Start/End 
Date 
 
Indication 
xx - xxxx 
LISINOPRIL 
20 MG 
QD 
PO 
yyyy-mm-dd/ 
HYPERTENSION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: table will continue for reference and placebo group 
 
 Path: L:\Studies_Sas_Codes\Clinical Trial\
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 51 of 62                                                
 
L16.2.5.1 Listing of Visit Date Information 
 
Treatment  
Group 
Subject 
Number 
Inform Consent 
Date 
Visit 1 
Visit 2 
Visit 3 
Visit 4 or  
Early Termination 
Test 
xx - xxxx 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
   Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 52 of 62                                                
 
L16.2.5.2 Listing of Drug Administration 
 
Treatment  
Group 
Subject 
Number 
Date of  
First Dose 
Date of 
Last Dose 
Total  Doses 
Applied 
Dosing  
Compliance (%) 
Test 
xx - xxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
    Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 53 of 62                                                
 
L16.2.6.1 Listing of Investigator Global Assessment (IGA) 
 
Treatment  
Group 
Subject 
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 or  
Early Termination 
Treatment  
Success* 
Treatment  
Success** 
Test 
xx - xxxx 
4 
4 
3 
0 
Yes 
Yes 
 
xx - xxxx 
4 
4 
3 
2 
Yes 
No 
 
xx - xxxx 
4 
4 
3 
3 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
*Treatment Success: defined as none, minimal or mild disease, a score of 0, 1 or 2 within the treatment area on the IGA at the Week 12 visit 
 (Day 85 ± 4 days, End of Study). 
**Treatment Success: defined as subjects with disease severity at the Week 12 visit (Day 85 ± 4 days, End of Study) consistent with none or minimal,  
a score of 0 or 1, within the treatment area on the IGA 
 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 54 of 62                                                
L16.2.6.2 Listing of Psoriasis Area Severity Index (PASI) at the Target Lesion Site 
 
Treatment  
Group 
Subject 
Number 
Visit  
Scaling 
Erythema 
Plaque 
Elevation 
PASI 
Score 
Clinical  
Success 
Test 
xx - xxxx 
1 
2 
3 
1 
6 
 
 
 
2 
2 
3 
1 
6 
 
 
 
3 
1 
2 
1 
4 
 
 
 
4/ET 
1 
1 
0 
2 
Yes 
 
xx - xxxx 
1 
2 
3 
1 
6 
 
 
 
2 
2 
3 
1 
6 
 
 
 
3 
1 
2 
1 
4 
 
 
 
4/ET 
1 
2 
0 
3 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
            Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 55 of 62                                                
L16.2.6.3 Listing of Dermatological Examination 
 
 
 
Treatment  
Group 
 
 
Subject 
Number 
Height 
(cm) 
Weight 
(kg) 
BSA 
(m^^2) 
 
Location  
of the 
Target Lesion 
Target Lesion 
Area 
(cm^^2) 
 
% BSA Affected 
V1 
V2 
V3 
V4/ET 
Test 
xx - xxxx 
xxx 
xxx.x 
xxx.x 
Head front 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
            Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 56 of 62                                                
 
L16.2.7.1 Listing of Adverse Events by Treatment Group 
 
Test: Tazarotene Cream 0.05% 
 
 
 
Subject 
Number 
 
Body System/ 
MedDRA Term/ 
AE Term 
 
 
TX 
Area 
Start /End  
Date 
Severity 
 
Relationship  
to Investigational  
Drug 
 
 
 
Outcome 
Action Taken with 
Investigational  
Drug / 
Other Action Taken 
 
 
 
SAE? 
xx - xxxx 
Nervous system disorders/ headache/  
Headache 
No 
yyyy-mm-dd / 
yyyy-mm-dd 
Mild 
Not Suspected 
Recovered 
Drug withdrawn/ None 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: table will continue for reference and placebo group 
 
Path: L:\Studies_Sas_Codes\Clinical Trial\
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 57 of 62                                                
 
L16.2.7.2 Listing of Application Site Reactions 
 
 
Treatment 
Group 
 
Visit 
 
Erythema 
 
Dryness 
Burning 
/Stinging 
 
Erosion 
 
Edema 
 
Pain 
 
Itching 
 
Test 
1 
0 
0 
0 
1 
0 
0 
0 
 
2 
0 
1 
0 
0 
0 
0 
0 
 
3 
0 
0 
0 
1 
0 
0 
0 
 
4/ET 
0 
0 
0 
1 
0 
0 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 58 of 62                                                
 
L16.2.8.1 Listing of Pregnancy Test Results 
 
Treatment  
Group 
Subject   
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 or  
Early Termination 
Test 
xx - xxxx 
Negative 
Negative 
Negative 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
          Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
          Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
                        Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                          Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.05%                                                        
 
Protocol / 
 0453-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 59 of 62                                                
 
L16.2.8.2 Listing of Vital Signs 
 
Treatment 
Group 
Subject   
Number 
Visit 
Systolic BP 
(mmHg) 
Diastolic BP 
(mmHg) 
Pulse Rate 
(beats/min ) 
Respiration Rate 
(breaths/min) 
Temperature 
(F) 
 
Test 
xx - xxxx 
1 
120 
70 
84 
18 
98.6 
 
 
 
4/ET 
140 
80 
74 
18 
97 
 
 
 
 
 
 
 
 
 
 
 
xx - xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     Test: Tazarotene Cream 0.05% (Fougera Pharmaceuticals Inc.)  
     Reference: TAZORAC® (tazarotene) Cream, 0.05% (Allergan, Inc.) 
     Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
Path: L:\Studies_Sas_Codes\Clinical Trial\
\SAS\OUT                    Created on: ddmmmyy hh:mm                       Page 1 of N


 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.05%                                       Protocol / 
 0453-01-01/
 
 
4/26/2017                    Fougera Pharmaceuticals Inc.             
        Page 60 of 62                                               
 
APPENDIX A: Investigator’s Global Assessment of Disease Severity 
  
Score  Grade  
Definition  
0 
None 
No plaque elevation above normal skin level; may have residual non-
erythematous discoloration; no psoriatic scale; no erythema 
1 
Minimal  Essentially flat with possible trace elevation; faint erythema; no psoriatic 
scale 
2 
Mild 
Slight but definite elevation of plaque above normal skin level; may 
have up to moderate erythema (red coloration); fine scales with some 
lesions partially covered 
3 
Moderate 
Moderate elevation with rounded or sloped edges to plaque; moderate 
erythema (red coloration); somewhat coarse scales with most lesions 
partially covered 
4 
Severe 
Marked elevation with hard, sharp edges to plaque; severe erythema 
(very red coloration); coarse, thick scales with virtually all lesions 
covered and a rough surface 
5 
Very 
Severe 
Very marked elevation with very hard, sharp edges to plaque; very 
severe erythema (extreme red coloration); very coarse, thick scales with 
all lesions covered and a very rough surface 
To be eligible for participation in the study a subject must have a Baseline IGA score of 3, 4 or 5. 
A subject shall be considered a “treatment success” if he/she has an IGA score of 0, 1 or 2 within 
the treatment area at the Week 12 visit. 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.05%                                       Protocol / 
 0453-01-01/
 
 
4/26/2017                    Fougera Pharmaceuticals Inc.             
        Page 61 of 62                                               
 
APPENDIX B: Psoriasis Area Severity Index at the Target Lesion Site 
 
Score 
Grade 
Erythema 
Scaling 
Plaque Elevation 
0 
Clear 
No evidence of 
erythema 
No evidence of 
scaling 
No evidence of plaques 
above normal skin level 
1 
Almost 
Clear 
Pink discoloration, 
minimal erythema 
Occasional fine 
scales hardly 
noticeable 
Slight, just discernible 
elevation above normal 
skin level 
2 
Mild 
Light red coloration 
Slight but definite 
roughness, fine scale 
present, no cracking 
Discernible elevation 
above normal skin level 
upon examination, but 
not pronounced 
3 
Moderate Moderate redness, 
but not dark 
Moderate roughness, 
somewhat coarse 
scaling 
Definite plaque 
formation with 
rounded/sloped edges to 
plaque 
4 
Severe 
Dark red coloration 
Marked roughness, 
coarse/thick scaling, 
cracking may be 
evident 
Marked elevation with 
hard, distinct edges to 
plaque 
5 
Very 
Severe 
Very dark red 
coloration with 
induration present 
Very thick scales 
covering extensive 
area, severe 
cracking/fissures may 
be evident 
Very marked elevation, 
very hard and sharp 
edges to plaque 
To be eligible for participation in the study a subject must have a minimum plaque elevation of at 
least moderate severity (score ≥ 3) at the target lesion site. The most severe lesion at Baseline 
should be identified as the target lesion. 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.05%                                       Protocol / 
 0453-01-01/
 
 
4/26/2017                    Fougera Pharmaceuticals Inc.             
        Page 62 of 62                                               
 
APPENDIX C: Application Site Reactions 
The following application site reactions will be evaluated at each visit based on the scale 
provided below: 
 
Signs and Symptoms: 
Erythema 
Dryness 
Burning/Stinging 
Erosion 
Edema 
Pain 
Itching 
 
Grading Scale: 
Severity 
Grade 
Absent 
0 
Mild 
1 (slight, barely perceptible) 
Moderate 2 (distinct presence) 
Severe 
3 (marked, intense)