Conditions: Acne Vulgaris
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1110
Healthy volunteers: no

Brief summary:
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing Tazarotene Cream 0.1% to TAZORAC® (Tazarotene) Cream 0.1% and Both Active Treatments to a Vehicle Control in the Treatment of Acne Vulgaris

Detailed description:

Arms:
arm 1: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.) arm 2: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) arm 3: Placebo (Vehicle of test product) (Fougera Pharmaceuticals Inc.)

Interventions: intervention 1: Tazarotene Cream 0.1% intervention 2: Tazorac® intervention 3: Placebo
Intervention descriptions: intervention 1: Tazarotene Cream 0.1% applied to cover the affected areas of the face once daily for 84 +/- 4 days. intervention 2: Tazorac® applied to cover the affected areas of the face once daily for 84 +/- 4 days. intervention 3: Placebo (vehicle of the test product) applied to cover the affected areas of the face once daily for 84 +/- 4 days.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 1 of 70 
1.0 TITLE PAGE 
Protocol Title: 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-
Group Study Comparing Tazarotene Cream 0.1% to TAZORAC® 
(Tazarotene) Cream 0.1% and Both Active Treatments to a Vehicle Control 
in the Treatment of Acne Vulgaris 
Investigational Product: 
Tazarotene Cream 0.1% 
Population: 
Study Design: 
Sponsor: 
Protocol Number: 
: 
Protocol Date: 
Protocol History: 
Approximately 1110 males and non-pregnant females, 12-40 years of age, 
with acne vulgaris  
A multi-center, double-blind, randomized, vehicle-controlled, parallel-
group bioequivalence study with clinical endpoints comparing Tazarotene 
Cream 0.1% to TAZORAC® (tazarotene) Cream, 0.1% and both active 
treatments to a vehicle control in the treatment of acne vulgaris 
Fougera Pharmaceuticals Inc. 
0454-01-01 / NCT02886715
 
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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 2 of 70 
 
 
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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 3 of 70 
 
 
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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 4 of 70 
 
 
PRINCIPAL INVESTIGATOR’S SIGNATURE 
 
I agree to conduct protocol 0454-01-01 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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 5 of 70 
 
 
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 ......................................................................................................................... 19 
7.0 LIST OF ABBREVIATIONS AND TERMS ....................................................................................... 20 
8.0 INTRODUCTION ................................................................................................................................ 21 
8.1 Disease Being Treated ...................................................................................................................... 21 
8.2 Availability and Efficacy of Already Approved Therapies .............................................................. 21 
8.3 Scientific and Statistical Considerations ........................................................................................... 21 
8.4 Justification for use of Placebo ......................................................................................................... 22 
8.5 Risks and Benefits ............................................................................................................................. 22 
9.0 STUDY OBJECTIVES ......................................................................................................................... 23 
10.0 INVESTIGATIONAL PLAN ............................................................................................................. 23 
10.1 Study Design and Plan Description ................................................................................................ 23 
10.2 Selection of Study Design ............................................................................................................... 24 
10.3 Selection of Study Population ......................................................................................................... 24 
10.3.1 Inclusion Criteria...................................................................................................................... 24 
10.3.2 Exclusion Criteria .................................................................................................................... 26 
10.3.3 Restrictions During the Study .................................................................................................. 28 
10.3.4 Withdrawal of Subjects from the Study ................................................................................... 29 
10.3.5 Early Termination .................................................................................................................... 30 
10.4 Treatments....................................................................................................................................... 30 
10.4.1 Treatments Administration ...................................................................................................... 30 
10.4.2 Identity of IP ............................................................................................................................ 31 
10.4.3 Study Blind .............................................................................................................................. 31 
10.4.4 IP Shipment, Retention and Storage ........................................................................................ 33 
10.4.5 Method of Assigning Subjects to Treatment Groups ............................................................... 34 
10.4.6 Compliance .............................................................................................................................. 35 
10.5 Study Conduct ................................................................................................................................. 35 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 6 of 70 
 
 
10.5.1 Visit 1 (Day -14 to Day 1): Screening and Baseline Evaluation .............................................. 35 
10.5.2 Visit 2 (Day 28 ± 4 days): Interim Visit ................................................................................... 37 
10.5.3 Visit 3: (Day 56 ± 4 days): Interim Visit ................................................................................. 37 
10.5.4 Visit 4: (Day 85 ± 4 days) End of Study Visit or Early Termination....................................... 38 
10.6 Study Procedures ............................................................................................................................ 39 
10.6.1 Informed Consent and/or Assent .............................................................................................. 39 
10.6.2 Demographics .......................................................................................................................... 39 
10.6.3 Medical History........................................................................................................................ 39 
10.6.4 Pregnancy Test ......................................................................................................................... 39 
10.6.5 Vital Signs ................................................................................................................................ 39 
10.6.6 Concomitant Medication .......................................................................................................... 39 
10.6.7 IGA .......................................................................................................................................... 40 
10.6.8 Lesion Counts .......................................................................................................................... 40 
10.6.9 Application Site Reactions ....................................................................................................... 40 
10.6.10 Inclusion and Exclusion Criteria Review ............................................................................... 40 
10.6.11 Randomization ....................................................................................................................... 41 
10.6.12 Dispensing IP ......................................................................................................................... 41 
10.6.13 Returning IP ........................................................................................................................... 41 
10.6.14 Subject Dosing Instructions and Diary .................................................................................. 41 
10.6.15 Standardized Cleanser and Sunscreen .................................................................................... 42 
10.6.16 Health Status/AEs .................................................................................................................. 42 
10.7 AEs/ SAEs ...................................................................................................................................... 42 
10.7.1 Definitions ................................................................................................................................ 42 
10.7.2 Severity of AEs ........................................................................................................................ 43 
10.7.3 Relationship to the IP ............................................................................................................... 43 
10.7.4 AE Documentation ................................................................................................................... 44 
10.7.5 SAE Reporting ......................................................................................................................... 45 
10.7.6 Pregnancies .............................................................................................................................. 47 
10.7.7 Quality Complaints .................................................................................................................. 48 
 48 
10.7.9 Reconciliation .......................................................................................................................... 48 
11.0 STATISTICAL METHODS ............................................................................................................... 49 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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11.1 Statistical Plan ................................................................................................................................. 49 
11.2 Sample Size Determination ............................................................................................................. 49 
11.3 Study Populations ........................................................................................................................... 50 
11.3.1 PP Population ........................................................................................................................... 50 
11.3.2 Modified Intent-to-Treat (mITT) Population ........................................................................... 50 
11.3.3 Safety Populations.................................................................................................................... 51 
11.4 Baseline Comparability ................................................................................................................... 51 
11.5 Efficacy Endpoints .......................................................................................................................... 51 
11.6 Primary Endpoint Analysis ............................................................................................................. 52 
11.7 Secondary Endpoint Analysis ......................................................................................................... 52 
11.8 Treatment-by-Site Interaction and Pooling of Clinical Sites .......................................................... 53 
11.9 Safety Analysis ............................................................................................................................... 53 
12.0 REGULATORY OBLIGATIONS ...................................................................................................... 54 
12.1 Institutional Review Board ............................................................................................................. 54 
12.2 Subject Confidentiality ................................................................................................................... 54 
12.3 Study Documentation ...................................................................................................................... 55 
12.3.1 Protocol .................................................................................................................................... 55 
12.3.2 Informed Consent/ Assent ........................................................................................................ 55 
12.3.3 Protocol and Informed Consent Changes ................................................................................. 55 
12.3.4 Source Documents and Case Report Forms ............................................................................. 56 
12.3.5 Drug Accountability ................................................................................................................. 56 
12.3.6 Drug Storage ............................................................................................................................ 57 
12.3.7 Retention of Reserve Samples ................................................................................................. 57 
12.3.8 Return of Clinical Supplies ...................................................................................................... 57 
12.3.9 Pregnancy and Breastfeeding ................................................................................................... 58 
12.3.10 Reporting Safety Information to the IRB ............................................................................... 59 
12.3.11 Record Retention.................................................................................................................... 59 
12.3.12 Study Monitoring and Auditing ............................................................................................. 60 
12.3.13 Confidentiality, Use of Information and Publication ............................................................. 62 
12.3.14 End of the Trial ...................................................................................................................... 63 
12.3.15 Clinical Study Report ............................................................................................................. 63 
12.3.16 Termination of the Study ....................................................................................................... 64 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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 65 
14.0 APPENDICES .................................................................................................................................... 66 
14.1 APPENDIX A: Investigator’s Global Assessment for Acne Vulgaris ........................................... 66 
14.2 APPENDIX B: Application Site Reactions .................................................................................... 67 
14.3 APPENDIX C: Definition of Terms ............................................................................................... 68 
14.4 APPENDIX D: TAZORAC® (tazarotene) Cream, 0.1% ® Product Insert ...................................... 69 
14.5 APPENDIX E: Amendments to the Protocol ................................................................................. 70 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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5.0 SYNOPSIS 
 
Protocol Number 
0454-01-01 
Title 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-
Group Study Comparing Tazarotene Cream 0.1% to TAZORAC® (tazarotene) 
Cream 0.1% and Both Active Treatments to a Vehicle Control in the Treatment 
of Acne Vulgaris 
Objectives 
1. Evaluate the therapeutic equivalence of the Test product, Tazarotene Cream 
0.1% (Fougera Pharmaceuticals Inc.) to the Reference product, 
TAZORAC® (tazarotene) Cream 0.1% (Allergan, Inc.) in the treatment of 
acne vulgaris. 
2. Demonstrate the superiority of the efficacy of the Test and Reference 
(active) products over that of the Placebo in the treatment of acne vulgaris. 
3. Compare the safety of the Test, Reference and Placebo products in the 
treatment of acne vulgaris. 
Sponsor 
Fougera Pharmaceuticals Inc. 
Investigational 
Products 
• 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.) 
• 
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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) to the face. Subjects 
will be instructed to gently clean the face with the provided mild non-
medicated cleanser (e.g., Dove® Sensitive Skin or similar), pat dry and then 
apply a thin layer of the product to cover all of the affected skin areas, avoiding 
contact with the eyes, eyelids and mouth. Hands should be washed before and 
after each application.  
Study Period 
84 days (12 weeks) ± 4 days 
Treatment 
Randomization 
2: 2: 1 (Test: Reference: Placebo) 
Subject 
Populations 
Approximately 1110 male and non-pregnant female subjects, 12 to 40 years of 
age inclusive, who meet all of the inclusion criteria and none of the exclusion 
criteria, will be enrolled in order to obtain 
 subjects in the modified Intent-
to-Treat (mITT) population and 
 subjects in the Per-Protocol (PP) 
population. 
The primary inclusion criteria are: 
• 
Clinical diagnosis of acne vulgaris 
• 
On the face, > 25 non-inflammatory lesions (i.e., open and closed 
comedones) AND > 20 inflammatory lesions (i.e., papules and 
pustules) AND < 2 nodulocystic lesions (i.e., nodules and cysts) 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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• 
Investigator’s Global Assessment (IGA) of acne severity Grade 2, 3 or 
4 
Study Design 
A multi-center, double-blind, randomized, vehicle-controlled, parallel-group 
bioequivalence study with clinical endpoints comparing Tazarotene Cream 
0.1% to TAZORAC® (tazarotene) Cream, 0.1% and both active treatments to 
a vehicle control in the treatment of acne vulgaris. 
Investigative Sites 
Approximately 25 sites in the United States 
Study Conduct 
Eligible subjects will be randomized in a 2:2:1 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 the first dose on the evening of 
Day 1 and then continue to apply a thin layer once daily, in the evening, to the 
affected areas on the face until the evening before End of Study, 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 co-primary endpoints, percent change from Baseline in the 
inflammatory (papules and pustules) and non-inflammatory (open and closed 
comedones) lesion counts, are to be evaluated at the Week 12 visit (Day 85 ± 4, 
End of Study).  
Inclusion Criteria 
1. Healthy male or non-pregnant, non-lactating female, ≥ 12 and ≤ 40 years 
of age with a clinical diagnosis of acne vulgaris. 
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 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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 facial acne with: ≥ 25 non-inflammatory lesions (i.e., open and 
closed comedones) AND ≥ 20 inflammatory lesions (i.e., papules and 
pustules), AND ≤ 2 nodulocystic lesions (i.e., nodules and cysts). 
6. Have an IGA of acne severity Grade of 2, 3 or 4 (see Appendix A). 
7. 
 
 
 
 
 
8. 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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. Females taking hormonal contraceptives or oral estrogen for less than three 
months before Visit 1 and those that plan to change the dosage regimen 
during the course of the study. 
3. Has more than 2 facial nodulocystic lesions (i.e., nodules or cysts). Any 
nodules or cysts present will be documented but not included in the 
inflammatory or non-inflammatory lesion count for analysis. 
4. 
 
5. Presence of any skin condition that would interfere with the diagnosis or 
assessment of acne vulgaris (e.g., on the face: rosacea, dermatitis, 
psoriasis, squamous cell carcinoma, eczema, acneiform eruptions caused 
by medications, steroid acne, steroid folliculitis, bacterial folliculitis). 
6. Has excessive facial hair, such as beards, sideburns, moustaches, etc., that 
would interfere with the diagnosis or assessment of acne. 
7. 
 
 
8. Has active facial sunburn and/or peeling due to sunburn or subjects who 
will be exposed to excessive sunlight during the study. 
9. 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. 
10. 
 
 
 
 
 
 
 
11. History of acne that has been unresponsive to tazarotene and/or other 
retinoids. 
12. Use within 6 months before Baseline of oral isotretinoin (Accutane®), oral 
retinoids (e.g., Soriatane®), or therapeutic vitamin A supplements greater 
than 10,000 units/day (multivitamins are allowed). 
13. Use of the following on the face within 1 month before Baseline or during 
the study: 
• 
Cryodestruction or chemodestruction 
• 
Dermabrasion 
• 
Photodynamic therapy 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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• 
Acne surgery 
• 
Intralesional steroids 
• 
X-ray therapy 
14. Use of the following within 1 month before Baseline: 
• 
Spironolactone 
• 
Systemic steroids (The occasional use of inhaled, intranasal or 
ophthalmic corticosteroids for the management of acute and 
temporary conditions (e.g., allergic rhinitis) and the use of oral 
acetaminophen for the management of common aches (e.g., 
headache, menstrual cramps) will be allowed throughout the study 
to the extent that is acceptable to the Investigator.) 
• 
Systemic antibiotics 
• 
Systemic anti-inflammatory agents (The use of low dose aspirin 
for prophylactic use is allowed, provided that the regimen has been 
stable for at least 3 months before Baseline and will remain 
constant throughout the study.) 
• 
Systemic treatment for acne vulgaris (other than oral retinoids that 
require a 6 month washout), including anti-androgens 
15. Use of the following on the face within 2 weeks before Baseline: 
• 
Topical steroids 
• 
Topical retinoids 
• 
Topical zinc 
• 
Topical acne treatments (including over-the-counter (OTC) 
preparations) 
• 
Topical anti-inflammatory agents (including salicylic acid) 
• 
Topical antibiotics 
16. Use of the following on the face within 1 week before Baseline: 
• 
Phototherapy devices for acne 
 
• 
 
• 
 
17. Inability to understand the protocol requirements, instructions and study-
related restrictions, the nature, scope and possible consequences of the 
clinical study. 
18. Receipt of any drug and/or IP as part of a research study within the 30 days 
before Baseline. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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19. 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. 
20. Previous participation in this study. 
21. Employees of the Investigator or research center or their immediate family 
members. 
Efficacy Endpoints Primary Efficacy Endpoints 
The two co-primary efficacy endpoints are (1) the percent change from 
Baseline to Week 12 in the inflammatory (papules/pustules) lesion counts and 
(2) the percent change from Baseline to Week 12 in the non-inflammatory 
(open and closed comedones) lesion counts. 
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is the proportion of subjects who are 
considered a Clinical Success at Week 12, as defined by an IGA score that is 
at least 2 grades less than the Baseline assessment. That is, at Week 12, subjects 
with an IGA score of 4 at Baseline must achieve a score of 0, 1 or 2, subjects 
with an IGA score of 3 at Baseline must achieve a score of 0 or 1, and subjects 
with an IGA score of 2 at Baseline must achieve a score of 0 to be considered 
a Clinical Success. 
A Clinical Failure is defined as an IGA score at Week 12 that is the same, 
higher or one grade lower than the Baseline IGA. Subjects who are 
discontinued due to lack of treatment effect or worsening condition will be 
considered Clinical Failures. 
Measures 
The following scale will be used for evaluation of Baseline disease severity 
and treatment effect. 
IGA for Acne Vulgaris 
 
Grade 
Description 
0 
Clear skin with no inflammatory or non-inflammatory 
lesions 
1 
Almost clear; rare non-inflammatory lesions with no more 
than one small inflammatory lesion 
2 
Mild severity; greater than Grade 1; some non-
inflammatory lesions with no more than a few 
inflammatory lesions (papules/pustules only, no nodular 
lesions) 
3 
Moderate severity; greater than Grade 2; up to many non-
inflammatory lesions and may have some inflammatory 
lesions, but no more than one small nodular lesion 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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4 
Severe; greater than Grade 3; up to many non-
inflammatory lesions and may have some 
inflammatory lesions, but no more than a few 
nodular lesions 
5 
Greater than Grade 4 
Patients with a Baseline IGA score of 2, 3 or 4 will be enrolled in the study. 
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 each treatment’s mean percent change from Baseline 
to Week 12 in the number of inflamed and non-inflamed lesions. 
The statistical analyses will involve Analysis of Variance (ANOVA) with 
terms for treatment and site as fixed effects in the model. 
Primary Endpoint Analysis 
Therapeutic Equivalence Analysis 
The primary measure of therapeutic equivalence will be evaluated using 
the PP population, with results in the mITT population being supportive. 
Under the assumptions of normally distributed data, the adjusted 90% 
confidence interval will be calculated for the Test/Reference ratio of the 
mean percent change from Baseline in inflammatory and non-
inflammatory lesion counts using an iterative procedure similar to Fieller’s 
method. ANOVA with treatment and site as fixed effects in the model will 
be conducted on the mean percent change from Baseline to Week 12 in the 
inflammatory (papules/pustules) lesion counts and non-inflammatory 
(open and closed comedones) lesion counts. If the adjusted 90% 
confidence intervals for the least-squares mean Test/Reference ratios are 
within 80-125% for both co-primary endpoints, then therapeutic 
equivalence of the Test to Reference product will be considered to have 
been demonstrated. 
To declare therapeutic equivalence of the Test product to the Reference 
product, therapeutic equivalence must be demonstrated for only the 
primary endpoints in the PP population. 
Superiority to Placebo Analysis 
The primary measure of superiority will be evaluated using the mITT 
population, using 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 is concluded if these treatments’ mean percent changes from 
Baseline in inflamed and non-inflamed lesion counts at Week 12 are 
statistically superior to that of the Placebo at the 5% significance level (p 
< 0.05, two-sided). The superiority of Test and Reference treatments over 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 16 of 70 
 
 
the Placebo will be evaluated in the same ANOVA model for Test vs. 
Placebo and Reference vs. Placebo. 
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. 
Secondary Endpoint Analysis 
The PP population will be used for analysis of therapeutic equivalence and 
the mITT population will be used for analyses of superiority. 
Therapeutic Equivalence Analysis 
For the proportion of Clinical Success, if the 90% confidence interval (with 
Yates’ Correction factor) of the difference between the proportion of 
subjects considered a Clinical Success in the Test and the Reference 
product groups at Week 12 is contained within -20% to +20%, then 
therapeutic equivalence of the Test to Reference product will be 
considered supported for the secondary endpoint. 
Superiority to Placebo Analysis 
The analyses for superiority will be conducted using the mITT population 
and LOCF. For the determination of superiority, the proportion of subjects 
considered a Clinical Success at Week 12 in the Test and Reference 
product groups will each be compared to the proportion of subjects 
considered as Clinical Success in the Placebo group. 
If the proportion of subjects showing Clinical Success in the Test and 
Reference groups is statistically significantly greater (p < 0.05; using 
Cochran-Mantel-Haenszel exact test stratified by clinical site) than the 
Clinical Success seen in the Placebo group then superiority will be 
concluded. 
A summary table with frequency and percentage of the proportion of 
Clinical Success by treatment group will be presented. 
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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 17 of 70 
 
 
Signs and symptoms of acne vulgaris 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. The electronic case report forms for the study can allow for 
reporting by Investigators of lesion worsening beyond Grade 4 with treatment. 
It is recommended that enrollment of acne vulgaris subjects not include 
subjects with nodulocystic acne. Subjects who worsen beyond Grade 4 will be 
described in the safety evaluation. 
Sample Size 
Determination 
For the primary endpoint analysis (percent change from Baseline at Week 12 
(Study Day 85 ± 4 days) in inflammatory and non- inflammatory lesion count), 
sample size is estimated for therapeutic equivalence of the Test to the 
Reference product and superiority of each of the active treatments groups over 
Placebo. As no variability data were available for TAZORAC® cream, 0.1%, 
the sample size estimations are based on data reported in the 
 
 
Sample size 
calculations were performed using 
. 
In the PP population, the mean percent reduction in inflammatory lesion count 
in the Reference treatment group at Week 12 is expected to be approximately 
, with a standard deviation (SD) of 
 (coefficient of variation of 
). The mean percent reduction in non-inflammatory lesion count in the 
Reference treatment group at Week 12 is expected to be approximately 
 
with a SD of 
 (coefficient of variation of 
). Based on these numbers, 
a sample size of 
 subjects per active treatment group in the PP population 
will provide approximately 
 power to demonstrate that the adjusted 90% 
confidence interval for the T/R ratio of least-squares treatment means for the 
primary endpoint is contained within the pre-defined equivalence limits [80%, 
125%], if the true ratio is 
 and assuming 
 correlation between inflamed 
and non-inflamed lesion counts. 
In the mITT population, the mean percent reduction in inflammatory and non-
inflammatory lesion counts in the Placebo group is expected to be 
approximately 
 (
, SD) and 
 (
, SD), respectively. With a 
conversion rate of 
 from the mITT to the PP population, 
 subjects in 
each active group and 
 subjects in the Placebo group are required in the 
mITT population for the superiority analyses. This sample size will ensure 
sufficient power 
 to show a difference at p < 0.05 (two-sided) between 
each active treatment group and the Placebo group for each endpoint, assuming 
 correlation between the inflamed and non-inflamed lesion counts and 
 
correlation between the two superiority tests for each endpoint. Under the 
above assumptions, the overall study power to demonstrate therapeutic 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 18 of 70 
 
 
equivalence and superiority for the primary endpoint is estimated to be at least 
. To allow for approximately 
 subjects who may 
drop out from the study or are otherwise non-evaluable, up to 1110 subjects 
will be enrolled (444 in each active group and 222 in the Placebo group). 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 19 of 70 
 
 
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/Assent 
X‡ 
 
 
 
Medical History/ 
Demographics 
X‡ 
 
 
 
Pregnancy Test†  
X‡ 
X 
X 
X 
Vital Signs 
X
‡ 
 
 
X 
Lesion Counts 
X
‡ 
X 
X 
X 
Investigator’s Global 
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 through the evening for 84 days (Day 1 to Day 84) 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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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7.0 LIST OF ABBREVIATIONS AND TERMS 
ADaM 
Analysis Dataset Model 
OTC 
Over-The-Counter 
ADR 
Adverse Drug Reaction 
PD 
Protocol Deviation 
AE 
Adverse Event 
PP 
Per-Protocol 
ANOVA 
Analysis of Variance 
RLD 
Reference Listed Drug 
C 
Celsius 
SADR 
Serious Adverse Drug 
Reaction 
CDER 
Center for Drug Evaluation and 
Research 
SAE  
Serious Adverse Event 
CDISC 
Clinical Data Interchange 
Consortium 
SAP 
Statistical Analysis Plan 
CFR 
Code of Federal Regulations 
SAS 
Statistical Analysis Software 
CI 
Confidence Interval 
SD 
Standard Deviation 
cm 
Centimeter 
SDTM 
Study Data Tabulation Model 
CRO  
Clinical Research Organization 
 
 
eCRF 
electronic Case Report Form 
 
 
eCTD 
electronic Common Technical 
Document 
 
 
F 
Fahrenheit 
 
 
FDA  
Food and Drug Administration 
 
 
g 
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 
Last Observation Carried Forward 
 
 
LPPV 
Local Person for Pharmacovigilence 
 
 
MedDRA 
Medical Dictionary for Regulatory 
Activities 
 
 
mg 
Milligram 
 
 
mITT 
modified Intent-to-Treat 
 
 
ml 
milliliter 
 
 
NDA  
New Drug Application 
 
 
OGD 
Office of Generic Drugs 
 
 
OHRP 
Office of Human Rights Protection 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 21 of 70 
 
 
8.0 INTRODUCTION 
8.1 Disease Being Treated 
Acne vulgaris is a dermatological condition that is characterized by increased sebum production in skin, 
proliferation of Propionibacterium acnes and epithelial desquamation. Although most common in 
teenagers and young adults, it can be a chronic condition that continues throughout adulthood. It is 
estimated that at least 75% of the adolescent and adult population will show some signs of acne during 
their lives.2-5 In the United States, acne is the most common reason for dermatologist consultation. 
Though signs and symptoms of acne are cosmetically embarrassing and socially stressful, the risk of 
serious medical complications arising from acne is low. 
The clinical appearance of acne can range from very mild (a few comedones on the face) to very severe 
(large cysts and nodules on the face, chest and back). Subjects selected for this study are considered to 
have facial acne with ≥ 25 non-inflammatory facial lesions (open and closed comedones), ≥ 20 
inflammatory facial lesions (papules and pustules), ≤ 2 facial nodulocystic lesions and an Investigator’s 
Global Assessment (IGA) grade of 2, 3 or 4. 
8.2 Availability and Efficacy of Already Approved Therapies 
Treatment of acne depends on the severity of the condition, previous treatment regimens and personal 
preference of the subject. There are a number of different therapies currently available for the treatment 
of acne. For mild cases, good skin hygiene and over-the-counter (OTC) anti-bacterial washes and scrubs 
have been shown to control the signs and symptoms. Retinoids, antimicrobials and antibiotics are the 
mainstay of topical acne therapy. Such treatments are active at application sites, and they can prevent 
new lesions.6 In severe cases, oral antibiotics or retinoids may also be considered if the benefits 
outweigh the potential risks to the subject. 
Tazarotene is one of a class of drugs known as the acetylenic retinoids. Retinoids, such as tazarotene, 
are the core of topical therapy for acne because they are comedolytic and resolve the precursor 
microcomedone lesion. The main target of acne treatment is the microcomedone.6,7 Tazarotene may 
also have direct and indirect activity against inflammatory acne. In skin grafts, tazarotene inhibits the 
expression of a presumed pro-inflammatory marker, migration inhibitory factor related protein type 8 
(MRP8), suggesting a direct anti-inflammatory effect. In addition to its effects on the precursor 
microcomedone lesion, tazarotene allows aeration and release of accumulated sebum by clearing 
obstructed follicles. This makes the follicles a less hospitable environment for P. acnes and indirectly 
halts the progression to inflammatory acne.8 
8.3 Scientific and Statistical Considerations 
Tazarotene has low systemic absorption and rapid elimination from semi-solid topical formulations of 
TAZORAC® with mean peak plasma concentrations of tazarotenic acid of 0.10 ng/mL observed on 
Day 15 following once daily application of tazarotene cream, 0.1% to the face of subjects with facial 
acne vulgaris.9 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 
efficacy can be considered.10-12 Based on the low systemic bioavailability of tazarotene from the topical 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 22 of 70 
 
 
cream product, a comparative clinical safety and efficacy study is considered the most appropriate 
method to evaluate the therapeutic equivalence of two tazarotene topical cream, 0.1% 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.16,17 
Eligible subjects will have a 20% chance of being randomized to Placebo (2:2:1 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 and Human Services, has issued a 
detailed guidebook to Institutional Review Boards (IRBs) that includes discussion on the use of 
placebos in clinical studies.18 
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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 23 of 70 
 
 
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 
investigational site’s 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 0.1% (Fougera 
Pharmaceuticals Inc.) to the Reference product, TAZORAC® (tazarotene) Cream 0.1% (Allergan, 
Inc.) in the treatment of acne vulgaris. 
2. Demonstrate the superiority of the efficacy of the Test and Reference (active) products over that of 
the Placebo in the treatment of acne vulgaris. 
3. Compare the safety of the Test, Reference and Placebo products in the treatment of acne vulgaris. 
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 0.1% (Fougera 
Pharmaceuticals Inc.) compared to the FDA Reference Listed Drug (RLD) TAZORAC® (tazarotene) 
Cream, 0.1% (Allergan) in subjects with a clinical diagnosis of acne vulgaris. Additionally, both the 
Test product and Reference (i.e., the RLD) product will be tested for superiority to a Placebo. Subjects 
with confirmed facial acne vulgaris will apply the investigational product (IP) once daily, in the 
evening, for 84 days ± 4 days (12 weeks). 
Before any study-specific procedures are performed, all subjects will read and sign the IRB-approved 
ICF. For a subject considered to be a minor in the state he/she is screened, the parent or legal guardian 
will be required to sign the ICF and the subject will sign an IRB-approved “assent to participate” form, 
as applicable. 
Each site will develop an individualized recruitment plan to collectively enroll approximately 1110 
eligible subjects, ≥ 12 to ≤ 40 years of age, with a clinical diagnosis of acne vulgaris and meeting the 
inclusion/exclusion criteria. Subjects will be randomized to one of the three IPs as follows: 
• 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.) 
• 
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
• 
Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 24 of 70 
 
 
At Visit 1, eligible subjects will be randomized to the Test, Reference or Placebo product in a 2:2:1 
ratio using 
, which is an interactive response technology (IRT) system provided by the IRT 
provider. Study subjects will be provided with 
 of IP. At Visit 2 and/or Visit 3, subjects 
who continue to be eligible for continuation in the study can be dispensed another 
 of 
investigational product, as needed, based on the amount of IP remaining from the tube previously 
dispensed. Further, any empty tubes will be collect 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 up to 
 will be needed 
to dose the subject for the treatment period. Additional tubes beyond the initial 
 will only be 
dispensed if the initial supply is lost and/or significantly damaged (i.e., becomes punctured) and 
warrants replacement. 
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 a thin layer (2 mg/cm2) of the product once daily, in the evening, 
through the evening before Visit 4 (Day 85 ± 4). 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 
analyses of interest are (1) the mean percent change from Baseline to Week 12 in the inflammatory 
(papules/pustules) lesion counts and (2) the mean percent change from Baseline to Week 12 in the non-
inflammatory (open and closed comedones) lesion counts. The secondary analysis is the proportion of 
subjects who are considered a Clinical Success at Week 12, as defined by an IGA score that is at least 
2 grades less than the Baseline assessment. A Clinical Failure is defined as an IGA score that is the 
same, higher or one grade lower than the Baseline IGA at Week 12 (Appendix A). 
10.2 Selection of Study Design 
This protocol is designed based on studies conducted as a part of the 
 
and the FDA draft guidance for tazarotene cream, 0.1%, released in June, 2011.19 
Statistical analyses of the clinical data will be based on recommendations in the FDA Guidances or 
communications with the Office of Generic Drugs (OGD)/FDA.11,20 
10.3 Selection of Study Population 
10.3.1 Inclusion Criteria 
1. Healthy male or non-pregnant, non-lactating female, ≥ 12 and ≤ 40 years of age with a clinical 
diagnosis of acne vulgaris. 
2. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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 facial acne with: ≥ 25 non-inflammatory lesions (i.e., open and closed comedones) AND 
≥ 20 inflammatory lesions (i.e., papules and pustules), AND ≤ 2 nodulocystic lesions (i.e., 
nodules and cysts). 
6. Have an IGA of acne severity Grade of 2, 3 or 4 (see Appendix A). 
7. 
 
 
 
 
8. 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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. Females taking hormonal contraceptives or oral estrogen for less than three months before Visit 
1 and those that plan to change the dosage regimen during the course of the study. 
3. Has more than 2 facial nodulocystic lesions (i.e., nodules or cysts). Any nodules or cysts 
present will be documented but not included in the inflammatory or non-inflammatory lesion 
count for analysis. 
4. 
 
 
5. Presence of any skin condition that would interfere with the diagnosis or assessment of acne 
vulgaris (e.g., on the face: rosacea, dermatitis, psoriasis, squamous cell carcinoma, eczema, 
acneform eruptions caused by medications, steroid acne, steroid folliculitis, bacterial 
folliculitis). 
6. Has excessive facial hair, such as beards, sideburns, moustaches, etc., that would interfere with 
the diagnosis or assessment of acne. 
7. 
 
8. Has active facial sunburn and/or peeling due to sunburn or subjects who will be exposed to 
excessive sunlight during the study. 
9. 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. 
10. 
 
 
 
 
 
11. History of acne that has been unresponsive to tazarotene and/or other retinoids. 
12. Use within 6 months before Baseline of oral isotretinoin (Accutane®), oral retinoids (e.g., 
Soriatane®), or therapeutic vitamin A supplements greater than 10,000 units/day (multivitamins 
are allowed). 
13. Use of the following on the face within 1 month before Baseline: 
• 
Cryodestruction or chemodestruction 
• 
Dermabrasion 
• 
Photodynamic therapy 
• 
Acne surgery 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 27 of 70 
 
 
• 
Intralesional steroids 
• 
X-ray therapy 
14. Use of the following within 1 month before Baseline: 
• 
Spironolactone 
• 
Systemic steroids 
 
 
 
 
 
• 
Systemic antibiotics 
• 
Systemic anti-inflammatory agents 
 
 
• 
Systemic treatment for acne vulgaris (other than oral retinoids that require a 6 month 
washout), including anti-androgens 
15. Use of the following on the face within 2 weeks before Baseline: 
• 
Topical steroids 
• 
Topical retinoids 
• 
Topical zinc 
• 
Topical acne treatments (including OTC preparations) 
• 
Topical anti-inflammatory agents 
 
• 
Topical antibiotics 
16. Use of the following on the face within 1 week before Baseline: 
• 
Phototherapy devices for acne 
 
• 
 
• 
17. Inability to understand the protocol requirements, instructions and study-related restrictions, 
the nature, scope and possible consequences of the clinical study. 
18. Receipt of any drug and/or IP as part of a research study within the 30 days before Baseline. 
19. Subjects who consume excessive amounts of alcohol, abuse drugs, or have any condition that 
would, in the Investigator’s opinion, compromise compliance with this protocol. 
20. Previous participation in this study. 
21. Employees of the Investigator or research center or their immediate family members. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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 on the face: 
o Cryodestruction or chemodestruction 
o Dermabrasion 
o Photodynamic therapy 
o Acne surgery 
o Intralesional steroids 
o X-ray therapy 
• 
Topical products applied to the face other than the IP and the study-provided sunscreen 
and cleanser. Prohibited products include: 
o Moisturizers 
o New brands of make-up 
o Creams, ointments, lotions or powders 
o Medicated cleansers/soaps 
o Medicated shaving products 
o Adhesive strips 
o Any topical product for the treatment of acne applied to the face other than the IP. 
• 
The use of tanning booths, sun lamps, non-prescription ultraviolet light sources or 
excessive sun exposure 
• 
Phototherapy 
• 
Spironolactone 
• 
Oral retinoids, therapeutic vitamin A supplements of greater than 10,000 units/day 
(multivitamins are allowed) or other systemic treatment for acne vulgaris 
• 
Photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, 
sulfonamides) 
• 
Systemic (i.e., oral or injectable) antibiotics 
• 
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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 29 of 70 
 
 
 
 
• 
Anti-pruritics including anti-histamines within 24 hours of study visits 
• 
Any systemic product for the treatment of acne 
• 
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 the study-provided 
sunscreen of at least SPF 15 on the face (as needed). Subjects should not allow the IP to come in 
contact with the eyes, eyelids or mouth, should not use the IP on skin that has eczema, and to always 
wash hands thoroughly after application of IP. 
Subjects will be questioned about all prescription and 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 and/or assent 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 
• 
Significant adverse event (AE) that could affect the safety of the subject or the validity of the 
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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 30 of 70 
 
 
• 
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. In case of 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 a worsening condition and require alternate or supplemental 
therapy for the treatment of acne 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 
(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). 
At Visit 2 and/or Visit 3, subjects who continue to be eligible for continuation in the study can be 
dispensed a 
 
 of IP, as needed, based on the amount of IP remaining from the 
tube 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]). 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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) during their menstrual 
period. 
 
 
 
 
Subjects will be instructed to gently wash the face with the provided mild non-medicated cleanser 
(e.g., Dove® Sensitive Skin or similar), pat dry and then apply a thin layer (2 mg/cm2) of the product 
to the affected areas of the face, avoiding contact with the eyes, eyelids and mouth. 
Subjects will be instructed to apply the IP 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. Subjects 
will then continue to apply a thin layer (2 mg/cm2) of the IP once daily, in the evening, through the 
evening before their final visit for a total of 84 days ± 4 days. There will be no application of the 
product on the day of the End of Study visit. 
Subjects will also be instructed not to apply the IP to cuts, abrasions, eczematous skin and 
sunburned skin and not to use “waxing” as a depilatory method on skin treated with the IP. 
Based on an approximate 
 of cream should be sufficient 
to last for the full duration of the study (84 days ± 4 days). Subject kits will each contain 
 
of IP and will be randomized using 
. If a subject requires additional IP beyond 
 
in order to complete dosing in the study (i.e., tube lost, all IP used between visits or tube 
significantly damaged [became punctured]), an additional kit of investigational product may be 
assigned to the subject using 
. 
 
 
 
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 0.1% (Fougera Pharmaceuticals Inc.) 
• 
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
• 
Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
10.4.3 Study Blind 
The sponsor, contract research organization (CRO), Investigator, staff at the study site, study 
monitors, and data analysis/management personnel will be blinded to the subject’s treatment 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 32 of 70 
 
 
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 
 The 
 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 Pharmacovigilience 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 
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: 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 33 of 70 
 
 
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 IPs 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.
 
 
 
 
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. 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 34 of 70 
 
 
 
 
 
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.21 
10.4.5 Method of Assigning Subjects to Treatment Groups 
The IP will be randomized, packaged and blinded by 
 
 
. 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 packaged 
 
There will be 
 in each kit box.
 
 
 
Should the subject’s tube become significantly damaged (i.e., punctured 
and/or leaking) or if the subject should use an entire tube or lose a full and/or partially full tube of 
IP that is needed in order to complete the standard dosing regimen, an additional kit may be 
assigned to the subject using 
. Therefore it is estimated that the majority of subjects will 
require 
 
 of study product, while a minority of subjects will require dispensing of 
 due to a lost tube or complete use of both dispensed tubes 
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 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 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 35 of 70 
 
 
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 the kit box number in the subject’s source documentation and drug 
dispensing log. The 
 will then dispense 
. 
 
 
 At Visits 2, 3 and/or Unscheduled Visit, 
additional IP may be dispensed to the subject, as needed. 
 
 
If an additional kit is required at either of these visits, the subject 
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 and/or their parent/caregiver 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 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/Assent: Subjects who are willing to comply with study procedures will 
read, understand and sign the IRB-approved informed consent and/or assent, as appropriate. 
For a subject considered to be a minor in the state he/she is screened, the parent or legal 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 36 of 70 
 
 
guardian will be required to sign the ICF and the subject will sign an IRB-approved “assent to 
participate” form, as applicable. 
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 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. 
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 B. 
6. Investigator’s Global Assessment: A Medical Investigator (MD, DO, CRNP or PA) will 
confirm the diagnosis of acne vulgaris and will perform a severity rating according to the IGA 
to determine the severity of the acne. See Appendix A. 
7. Lesion Count: A validated/qualified staff will perform the count of inflammatory lesions (i.e., 
papules and pustules), non-inflammatory lesions (i.e., open and closed comedones) and 
nodulocystic lesions (i.e., nodules and cysts). 
8. Inclusion/Exclusion Criteria Review: Confirm the subject meets all inclusion criteria and 
none of the exclusion criteria. 
9. Randomization: Eligible subjects selected for enrollment will be assigned a randomization 
number using 
. 
10. 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 
. The site will also dispense study supplies (i.e., cleanser and 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. 
11. 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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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 acne. See Appendix A. 
4. Lesion Count: A validated/qualified staff will perform count of inflammatory lesions (i.e., 
papules and pustules), non-inflammatory lesions (i.e., open and closed comedones) and 
nodulocystic lesions (i.e., nodules and cysts). 
5. Application Site Reactions: A Medical Investigator will evaluate any Application Site 
Reactions since the last visit. See Appendix B. 
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, re-dispense the tube to the subject. The subject should be dispensed enough IP to 
complete all required doses until Visit 3. 
 
 
 Record any lost or significantly damaged (i.e., 
punctured) IP. 
8. Dispense Supplies, Subject Instructions and Diary: Dispense study supplies (i.e., cleanser 
and/or 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. 
10.5.3 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 acne. See Appendix A. 
4. Lesion Count: A validated/qualified staff will perform count of inflammatory lesions (i.e., 
papules and pustules), non-inflammatory lesions (i.e., open and closed comedones) and 
nodulocystic lesions (i.e., nodules and cysts). 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 38 of 70 
 
 
5. Application Site Reactions: A Medical Investigator will evaluate any Application Site 
Reactions since the last visit. See Appendix B. 
6. Collect and Review Subject’s Diary: Collect the diary from the subject and review for 
compliance with the protocol requirements. 
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, re-dispense the tube to the subject. The subject should be dispensed enough IP to 
complete all required doses until Visit 4.
 
 
 Record any lost IP or significantly damaged (i.e., 
punctured). 
8. Dispense Supplies, Subject Instructions and Diary: Dispense study supplies (i.e., cleanser 
and/or 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 acne. See Appendix A. 
5. Lesion Count: A validated/qualified staff will perform count of inflammatory lesions (i.e., 
papules and pustules), non-inflammatory lesions (i.e., open and closed comedones) and 
nodulocystic lesions (i.e., nodules and cysts). 
6. Application Site Reactions: A Medical Investigator will evaluate any Application Site 
Reactions since the last visit. See Appendix B. 
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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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10.6 Study Procedures 
10.6.1 Informed Consent and/or Assent 
At Visit 1, before performing any study-related procedures the study subject must sign the IRB-
approved ICF. For a subject considered to be a minor in the state he/she is screened, the parent or 
legal guardian will be required to sign the ICF and the subject will sign an IRB-approved “assent 
to participate” form, as applicable. Both the consent and assent forms 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 informed consent themselves or having their parent/legal 
guardian conduct on their behalf. If the consent and/or assent are required in any 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 will 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 acne 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 the subject 
must 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. 
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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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 IGA 
At Visit 1, a Medical Investigator (MD, DO, CRNP or PA) should document a confirmed diagnosis 
of acne vulgaris. 
At each visit, a Medical Investigator will perform an acne severity rating according to the IGA (see 
Appendix A). At Visit 1, the IGA must be a score 2, 3 or 4 for the subject to be eligible for inclusion. 
At Visit 4 (or Early Termination), the IGA score will be used to evaluate the secondary endpoint 
which is the proportion of subject considered a Clinical Success, with Clinical Success defined as 
an IGA score that is at least 2 grades less than the Baseline assessment. 
 
The IGA is a static scale and no reference to previous scores for the subject should be made during 
this assessment. 
10.6.8 Lesion Counts 
At each visit the number of inflammatory lesions (i.e., papules and pustules), non-inflammatory 
lesions (i.e., open and closed comedones) and nodulocystic lesions (i.e., nodules and cysts) on the 
facial area, including the nose, will be counted and recorded. Counts of each lesion type (i.e., 
inflammatory, non-inflammatory and nodulocystic) should be reported separately in the source and 
electronic case report form (eCRF). Definitions of these terms are listed in Appendix C. 
Lesion counts should only be conducted by those individuals who have successfully completed the 
lesion count validation. Wherever possible, the same individual should attempt to perform all lesion 
counts at all visits for an individual subject. 
At Visit 4 (or Early Termination), the lesion counts for the inflammatory and the non-inflammatory 
lesions will be used to evaluate the primary endpoints of percent change in inflammatory lesion 
counts and percent change in non-inflammatory lesion counts. 
10.6.9 Application Site Reactions 
At Visit 1, the Investigator will grade the individual signs and symptoms per Appendix B. This will 
serve as a baseline for subsequent assessments of application site reactions. At Visits 2, 3 and 4, 
the Medical 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 B. Reactions will be documented in source documents for each subject. 
10.6.10 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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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10.6.11 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). 
10.6.12 Dispensing IP 
An 
 will dispense an initial supply of IP at Visit 1, and will resupply the 
subject at Visit 2, 3 or an Unscheduled Visit, as needed. The subject will initially be dispensed 
 
 of IP. When the subject returns for Visits 2 and 3, the amount of IP remaining will be assessed. 
If a tube still contains significant product, the tube will be re-dispensed to the subject. If an 
additional tube is required, the tube should be pulled from the allocated kit box. Enough IP should 
be dispensed so that the subject can complete all required doses until the next scheduled visit.  
 
 
 
 The 
 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 
 
 
10.6.13 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. 
Any observed tube unblinding will be reported to the CRO and sponsor immediately. 
10.6.14 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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 42 of 70 
 
 
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. 
10.6.15 Standardized Cleanser and Sunscreen 
Along with the IP at Visit 1, the subject will be provided with standardized mild non-medicated 
cleanser (Dove Sensitive Skin or similar) and 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 mild non-medicated cleanser and/or 
sunscreen is needed during the study, additional can be dispensed at Visits 2, 3 or an Unscheduled 
Visit. 
10.6.16 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 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 
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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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• 
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 on the informed consent. The common 
side effects will be discussed with the subjects 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). 
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 AEs 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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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, 
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 an IP causality assessment “IP not yet administered”. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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Adverse events occurring after first dosing 
The Investigator should follow all AEs that occurred from first dosing and during the course of the 
study to the last visit for the subject, at which point the outcome assessment will be documented in 
the CRF. 
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 [SADRs]), 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. 
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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 46 of 70 
 
 
LPPV, Sandoz (United States) 
Name: 
 
 
Email:
 
Fax: 
 
 
CRO Contacts 
 
Cell Phone:
 
Phone: 
 
Fax: 
 
Email:
 
 
 
 
Phone: 
 
Fax:
 
Email: 
 
Sponsor Contacts 
 
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 Reaction [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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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 
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. 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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. 
 
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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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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. 
 
 
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 
For the primary endpoint analysis (percent change from Baseline at Week 12 (Study Day 85 ± 4 days) 
in inflammatory and non- inflammatory lesion count), the sample size is estimated for therapeutic 
equivalence of the Test to the Reference product and superiority of each of the active treatments groups 
over Placebo. As no variability data were available for TAZORAC® Cream, 0.1%, the sample size 
estimations are based on data reported in the 
 
 
 Sample size calculations were performed using 
 
In the PP population, the mean percent reduction in inflammatory lesion count in the Reference 
treatment group at Week 12 is expected to be approximately 
, with a SD of 
 (coefficient 
of variation of 
). The mean percent reduction in non-inflammatory lesion count in the Reference 
treatment group at Week 12 is expected to be approximately 
, with a SD of 
 (coefficient of 
variation of 
). Based on these numbers, a sample size of 
 subjects per active treatment group in 
the PP population will provide approximately 
 power to demonstrate that the adjusted 90% 
confidence interval for the T/R ratio of least-squares treatment means for the primary endpoint is 
contained within the pre-defined equivalence limits [80%, 125%], if the true ratio is 
 and 
assuming 
 correlation between inflamed and non-inflamed lesion counts. 
In the mITT population, the mean percent reduction in inflammatory and non-inflammatory lesion 
counts in the Placebo group is expected to be approximately 
 SD) and 
 SD), 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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respectively. With a conversion rate of 
 from the mITT to the PP population, 
 subjects in each 
active group and 
 subjects in the Placebo group are required in the mITT population for the 
superiority analyses. This sample size will ensure sufficient power 
 to show a difference at p < 
0.05 (two-sided) between each active treatment group and the Placebo group for each endpoint, 
assuming 
 correlation between the inflamed and non-inflamed lesion counts and 
 correlation 
between the two superiority tests for each endpoint. Under the above assumptions, the overall study 
power to demonstrate therapeutic equivalence and superiority for the primary endpoint is estimated to 
be at least 
. To allow for approximately
 subjects who may drop out from 
the study or are otherwise non-evaluable, up to 1110 subjects will be enrolled (444 in each active group 
and 222 in the Placebo group). 
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 
 
 
 
 
 
 
 
 
 
 
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. 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
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11.3.3 Safety Populations 
All subjects who are randomized and received 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 number of inflammatory lesions (i.e., papules and pustules) 
o Baseline number of non-inflammatory lesions (i.e., open and closed comedones) 
o Baseline number of nodulocystic lesions (i.e., nodules and cysts) 
o Baseline IGA score 
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 
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 Endpoints 
The two co-primary efficacy endpoints are (1) the percent change from Baseline to Week 12 in the 
inflammatory (papules/pustules) lesion counts and (2) the percent change from Baseline to Week 12 in 
the non-inflammatory (open and closed comedones) lesion counts. 
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is the proportion of subjects who are considered a Clinical Success at 
Week 12, as defined by an IGA score that is at least 2 grades less than the Baseline assessment. That 
is, at Week 12, subjects with an IGA score of 4 at Baseline must achieve a score of 0, 1 or 2, subjects 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 52 of 70 
 
 
with an IGA score of 3 at Baseline must achieve a score of 0 or 1, and subjects with an IGA score of 2 
at Baseline must achieve a score of 0 to be considered a Clinical Success. 
A Clinical Failure is defined as an IGA score at Week 12 that is the same, higher or one grade lower 
than the Baseline IGA. Subjects who are discontinued due to lack of treatment effect or worsening 
condition will be considered Clinical Failures. 
11.6 Primary Endpoint Analysis 
Therapeutic Equivalence Analysis 
The primary measure of therapeutic equivalence will be evaluated using the PP population, with results 
in the mITT population being supportive. Under the assumptions of normally distributed data, the 
adjusted 90% confidence interval will be calculated for the Test/Reference ratio of the mean percent 
change from Baseline in inflammatory and non-inflammatory lesion counts using an iterative procedure 
similar to Fieller’s method. ANOVA with treatment and site as fixed effects in the model will be 
conducted on the mean percent change from Baseline to Week 12 in the inflammatory 
(papules/pustules) lesion counts and non-inflammatory (open and closed comedones) lesion counts. If 
the adjusted 90% confidence intervals for the least-squares mean Test/Reference ratios are within 80-
125% for both co-primary endpoints, then therapeutic equivalence of the Test to Reference product will 
be considered to have been demonstrated. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary endpoints in the PP population. 
Superiority to Placebo Analysis 
The primary measure of superiority will be evaluated using the mITT population, using 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 is concluded if these treatments’ mean percent changes 
from Baseline in inflamed and non-inflamed lesion counts at Week 12 are statistically superior to that 
of the Placebo at the 5% significance level (p < 0.05, two-sided). The superiority of Test and Reference 
treatments over the Placebo will be evaluated in the same ANOVA model for Test vs. Placebo and 
Reference vs. Placebo. 
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. 
11.7 Secondary Endpoint Analysis 
The PP population will be used for analysis of therapeutic equivalence and the mITT population will 
be used for analyses of superiority. 
Therapeutic Equivalence Analysis 
For the proportion of Clinical Success, if the 90% confidence interval (with Yates’ Correction factor) 
of the difference between the proportion of subjects considered a Clinical Success in the Test and the 
Reference product groups at Week 12 is contained within -20% to +20%, then therapeutic equivalence 
of the Test to Reference product will be considered supported for the secondary endpoint. 
Superiority to Placebo Analysis 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 53 of 70 
 
 
The analyses for superiority will be conducted using the mITT population and LOCF. For the 
determination of superiority, the proportion of subjects considered a Clinical Success at Week 12 in the 
Test and Reference product groups will each be compared to the proportion of subjects considered as 
Clinical Success in the Placebo group. 
If the proportion of subjects showing Clinical Success in the Test and Reference groups is statistically 
significantly greater (p < 0.05; using Cochran-Mantel-Haenszel exact test stratified by clinical site) 
than the Clinical Success seen in the Placebo group then superiority will be concluded. 
A summary table with frequency and percentage of the proportion of Clinical Success by treatment 
group will be presented. 
11.8 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 in the ANOVA 
model for evaluations involving the primary efficacy endpoint. 
 
If no 
treatment-by-site interaction is identified with the primary endpoint then no adjustment will be made 
to any efficacy analysis and treatment-by site interaction will not be included as a term in the statistical 
models for evaluating therapeutic equivalence and superiority. 
11.9 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 acne vulgaris 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 subjects who received randomized IP will be included in the comparative safety analysis. The eCRF 
for the study can allow for reporting by Investigators of lesion worsening beyond Grade 4 with 
treatment. It is recommended that enrollment of acne vulgaris subjects not include subjects with 
nodulocystic acne. Subjects who worsen beyond Grade 4 will be described in the safety evaluation. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 54 of 70 
 
 
12.0 REGULATORY OBLIGATIONS 
12.1 Institutional Review Board 
The study protocol, informed consent/assent form, 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 
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 
visit. 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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 55 of 70 
 
 
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 (GCPs) 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 2013.10,22-24 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 FDA Form 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. 
12.3.2 Informed Consent/ Assent 
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. Subjects who are considered minors 
in the state where they are screened will be asked to sign an “assent to participate” form, written in 
language appropriate for children, as applicable. The minor’s parent or legal guardian will sign the 
ICF. A copy of the ICF and Assent (when applicable) 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 
informed consent/assent forms 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 and Assent amendments/revisions, along with 
letters noting IRB approval, will be submitted to the sponsor. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 56 of 70 
 
 
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 eCRF, 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 
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 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 57 of 70 
 
 
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.” 
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: 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 58 of 70 
 
 
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 
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. 
Female subjects of childbearing potential must have been using and must agree to continue to use 
accepted methods of birth control, throughout the study. These include: 
• 
Total abstinence with a documented second acceptable method of birth control should the 
subject become sexually active 
• 
Intrauterine Device 
• 
Double-barrier method (such as condom plus diaphragm with spermicide) 
• 
Oral, transdermal, injected or implanted non-hormonal or hormonal contraceptive, 
throughout the study (i.e., Norplant®, Depo-Provera®). If the female is using a hormonal 
contraceptive, the same product must be taken for 3 months before Visit 1. 
NOTE: A sterile sexual partner is not considered an adequate form of birth control. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 59 of 70 
 
 
Subjects who report that they have become pregnant during the study or have a positive pregnancy 
test at Visits 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 
 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 
 
 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 
LPPV 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.25 
12.3.11 Record Retention 
The study will be conducted according to GCPs 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. 
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, Assent Forms 
• 
All Logs and Forms 
• 
Monitoring Reports and Letters 
• 
Correspondence 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 60 of 70 
 
 
Regulations require the Investigator to 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. 
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, 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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 61 of 70 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 62 of 70 
 
 
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, 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 63 of 70 
 
 
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 used IP must be collected. The Investigator can, at their discretion, discuss alternative 
treatments with the subject. 
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 electronic common technical 
document (eCTD) and ICH formatting standards and guidelines.26 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. 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 64 of 70 
 
 
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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 65 of 70 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 66 of 70 
 
 
14.0 APPENDICES 
14.1 APPENDIX A: Investigator’s Global Assessment for Acne Vulgaris 
To be eligible for participation in the study a subject must have a Baseline IGA score of 2, 3 or 4. 
Grade 
Description 
0 
Clear skin with no inflammatory or non-inflammatory lesions 
1 
Almost clear; rare non-inflammatory lesions with no more than one small 
inflammatory lesion 
2 
Mild severity; greater than Grade 1; some non-inflammatory lesions with 
no more than a few inflammatory lesions (papules/pustules only, no 
nodular lesions) 
3 
Moderate severity; greater than Grade 2; up to many non-inflammatory 
lesions and may have some inflammatory lesions, but no more than one 
small nodular lesion 
4 
Severe; greater than Grade 3; up to many non-inflammatory lesions 
and may have some inflammatory lesions, but no more than a few 
nodular lesions 
5 
Greater than Grade 4 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 67 of 70 
 
 
14.2 APPENDIX B: 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 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 68 of 70 
 
 
14.3 APPENDIX C: Definition of Terms 
 
Papules: a small circumscribed, superficial, solid, inflamed elevation of the skin that does not contain 
pus 
Pustules: inflamed skin swelling full of pus 
Open Comedones: A Widely Dilated Orifice in Which the Pigmented Impaction (Sebum and Keratin) 
Is Visible at the Skin Surface, Commonly Known As Blackheads 
Closed Comedones: Opening Is not Widely Dilated and the Impaction (Containing Sebum and 
Keratin) Appears As a Small Flesh Colored Papule, Also Known As a Whitehead 
Nodules: an inflamed cyst or papule  
Cysts: similar to a nodule and often filled with pus 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 69 of 70 
 
 
14.4 APPENDIX D: TAZORAC® (tazarotene) Cream, 0.1% ® Product Insert 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study Comparing 
Tazarotene Cream 0.1% to TAZORAC® (tazarotene) Cream 0.1% and Both Active Treatments to a 
Vehicle Control in the Treatment of Acne Vulgaris 
 
Confidential  0454-01-01 Rev.2 12/22/2016  Fougera Pharmaceuticals Inc.  Page 70 of 70 
 
 
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 11.7 Updated Cochran-Mantel-Haenszel exact test in Superiority to Placebo Analysis 
 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN 
Tazarotene Cream 0.1% 
    Protocol / 
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           Page 1 of 64         
STATISTICAL ANALYSIS PLAN 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study 
Comparing Tazarotene Cream 0.1% to TAZORAC® (Tazarotene) Cream 0.1% and Both Active 
Treatments to a Vehicle Control in the Treatment of Acne Vulgaris 
Protocol Number:  0454-01-01 / NCT02886715
 
Sponsor: 
Fougera Pharmaceuticals Inc. 
60 Baylis Road 
Melville, New York, 11747 
Contract Research Organization: 
 
 
April 26, 2017 
Final Version 2.0 


  
 
STATISTICAL ANALYSIS PLAN 
 
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SAP FINAL VERSION APPROVALS 
 
 
 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Study 
Comparing Tazarotene Cream 0.1% to TAZORAC® (Tazarotene) Cream 0.1% and Both 
Active Treatments to a Vehicle Control in the Treatment of Acne Vulgaris 
         
 
 
 
 
Written By: 
 
Signature: _____________________________  
 
 
 
 
Date:_____________________ 
Reviewed By: 
 
Signature: ____________________________ 
 
 
 
 
    
 
 
 
 
 
Date:_____________________ 
Approved By: 
 
Signature: ____________________________  
 
 
 
 
 
 
 
Date:_____________________ 
 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
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Revision History 
VERSION 
DATE 
DESCRIPTION OF REVISIONS 
REVISED BY 
  
 


  
 
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List of Abbreviations and Definition of Terms 
ADaM  
 
Analysis Data Model  
AE 
 
 
Adverse Event 
ANOVA 
 
Analysis of Variance 
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 
F 
 
 
Fahrenheit 
FDA  
 
Food and Drug Administration 
GLM  
 
Generalized Linear Model 
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 
PD 
 
 
Protocol Deviation 
PP 
 
 
Per-Protocol 
PROC  
 
Procedure 
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 .................................................................................................... 14 
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 Efficacy Analyses ....................................................................................................................................... 15 
8.2.1 Primary Efficacy Analysis ....................................................................................................................... 15 
8.2.2 Secondary Efficacy Analyses .................................................................................................................. 16 
8.2.3 Treatment-by-Site Interaction and Pooling of Clinical Sites ................................................................... 18 
8.3 Safety Analysis ........................................................................................................................................... 18 
8.3.1 Adverse Events ........................................................................................................................................ 18 
8.3.2 Application Site Reactions ...................................................................................................................... 19 
8.3.3 Vital Signs ............................................................................................................................................... 19 
8.4 Multiple Comparisons ................................................................................................................................ 19 
8.5 Methods for Handling Missing Data .......................................................................................................... 19 
8.6 Interim Analyses ......................................................................................................................................... 20 
9. TABLE, LISTING AND FIGURE SHELLS ............................................................................................... 20 
T16.1.9.1 Summary of Discontinued Subjects  (Safety Population) .............................. 22 
T16.1.9.2 Summary of Protocol Deviations  (Safety Population) .................................. 23 
T16.1.9.3.1 Summary of Subjects Excluded from Efficacy Analysis ............................ 24 
T16.1.9.3.2 Summary of Subjects Included in Analysis Population by Study Center . 25 
T16.1.9.4.1 Summary of Demographic Data (Safety Population) ................................. 26 
T16.1.9.5.1 Summary of Demographic Data  (modified Intent-to-Treat Population) . 28 
T16.1.9.5.2 Summary of Baseline Parameters (modified Intent-to-Treat Population) 28 
T16.1.9.6.1 Summary of Demographic Data  (Per-Protocol Population) ..................... 28 
T16.1.9.6.2 Summary of Baseline Parameters (Per-Protocol Population) .................... 28 
T16.1.9.7.1 Descriptive Summary of Co-Primary Efficacy Endpoint  (Percent Change from 
Baseline in Inflammatory Lesion Count)  (Per-Protocol Population) ............. 29 
T16.1.9.7.2 Descriptive Summary of Co-Primary Efficacy Endpoint  (Percent Change from 
Baseline in Inflammatory Lesion Count)  (modified Intent-to-Treat Population)
 ................................................................................................................................ 30 
T16.1.9.8.1 Summary of Analysis Results of Co-Primary Efficacy Endpoint .............. 31 
T16.1.9.8.2 Summary of Supportive Analysis Results of Co-Primary Efficacy Endpoint
 ................................................................................................................................ 32 
T16.1.9.9.1 Descriptive Summary of Co-Primary Efficacy Endpoint  (Percent Change from 
Baseline in Non-Inflammatory Lesion Count)  (Per-Protocol Population) ..... 33 


  
 
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T16.1.9.9.2 Descriptive Summary of Co-Primary Efficacy Endpoint  (Percent Change from 
Baseline in Non-Inflammatory Lesion Count)  (modified Intent-to-Treat 
Population) ............................................................................................................ 34 
T16.1.9.10.1 Summary of Analysis Results of Co-Primary Efficacy Endpoint ............ 35 
T16.1.9.10.2 Summary of Supportive Analysis Results of Co-Primary Efficacy Endpoint
 ................................................................................................................................ 36 
T16.1.9.11 Summary of Analysis Results of Secondary Efficacy Endpoint ................. 37 
T16.1.9.12 Overall Summary of Adverse Events  (Safety Population) ......................... 38 
T16.1.9.13 Summary of Frequency of All Adverse Events by Body System  (Safety 
Population) ............................................................................................................ 39 
T16.1.9.14 Summary of Frequency for AEs Occurring in at Least 5% of Subjects by Body 
System (Safety Population) .................................................................................. 39 
T16.1.9.15 Summary of Frequency of All Adverse Events by Severity (Safety Population)
 ................................................................................................................................ 40 
T16.1.9.16 Summary of Frequency of All Adverse Events by Relationship  (Safety 
Population) ............................................................................................................ 41 
T16.1.9.17 Summary of Frequency of Serious Adverse Events  (Safety Population) .. 42 
T16.1.9.18 Summary of Application Site Reaction  (Safety Population) ...................... 43 
T16.1.9.19 Summary of Frequency of Application Site Reaction  (Safety Population)44 
T16.1.9.20 Summary of Vital Signs  (Safety Population) ............................................... 45 
L16.2.1 Listing of Discontinued Subjects ......................................................................... 46 
L16.2.2 Listing of Protocol Deviations ............................................................................. 47 
L16.2.3.1 Subjects Excluded from the Per-Protocol Population Data Set .................... 48 
L16.2.3.2 Subjects Excluded from the Modified Intent-to-Treat Data Set................... 49 
L16.2.4.1 Listing of Demographic Data ........................................................................... 50 
L16.2.4.2 Listing of Medical History ................................................................................ 51 
L16.2.4.3 Listing of Concomitant Medications ............................................................... 52 
L16.2.5.1 Listing of Visit Date Information ..................................................................... 53 
L16.2.5.2 Listing of Drug Administration ....................................................................... 54 
L16.2.6.1 Listing of Lesion Count..................................................................................... 55 
L16.2.6.2 Listing of Investigator Global Assessment ...................................................... 56 
L16.2.7.1 Listing of Adverse Events by Treatment Group ............................................ 57 
L16.2.7.2 Listing of Application Site Reactions .............................................................. 58 
L16.2.8.1 Listing of Pregnancy Test Results.................................................................... 59 
L16.2.8.2 Listing of Vital Signs ......................................................................................... 60 
APPENDIX A: Investigator’s Global Assessment for Acne Vulgaris ................................ 61 
APPENDIX B: Application Site Reactions ......................................................................... 62 
 
 63 


  
 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the final Clinical Study Protocol 0454-01-01 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 0454-01-01 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 
patient in this study. 
 
2. OBJECTIVES 
The objectives of this study are to: 
 
1. Evaluate the therapeutic equivalence of the Test product, Tazarotene Cream 0.1% (Fougera 
Pharmaceuticals Inc.) to the Reference product, TAZORAC® (tazarotene) Cream 0.1% 
(Allergan, Inc.) in the treatment of acne vulgaris. 
 
2. Demonstrate the superiority of the efficacy of the Test and Reference (active) products 
over that of the Placebo in the treatment of acne vulgaris. 
 
3. Compare the safety of the Test, Reference and Placebo products in the treatment of acne 
vulgaris. 
 
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 generic tazarotene cream 


  
 
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0.1% (Fougera Pharmaceuticals Inc.) compared to the FDA Reference Listed Drug (RLD) 
TAZORAC® (tazarotene) Cream, 0.1% (Allergan) in subjects with a clinical diagnosis of acne 
vulgaris. Additionally, both the Test product and Reference (i.e., the RLD) product will be tested 
for superiority to a Placebo. Subjects with confirmed facial acne vulgaris will apply the 
investigational product (IP) once daily, in the evening, for 84 days ± 4 days (12 weeks). 
Before any study-specific procedures are performed, all subjects will read and sign the IRB-
approved ICF. For a subject considered to be a minor in the state he/she is screened, the parent or 
legal guardian will be required to sign the ICF and the subject will sign an IRB-approved “assent 
to participate” form, as applicable. 
Each site will develop an individualized recruitment plan to collectively enroll approximately 1110 
eligible subjects, ≥ 12 to ≤ 40 years of age, with a clinical diagnosis of acne vulgaris and meeting 
the inclusion/exclusion criteria. Subjects will be randomized to one of the three IPs as follows: 
• Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.) 
• Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
• Placebo: Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
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: 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 2:2:1 
ratio using 
, which is an interactive response technology (IRT) system provided by the 
IRT provider. Study subjects will be provided with 
 of IP. At Visit 2 and/or Visit 
3, subjects who continue to be eligible for continuation in the study can be dispensed another 
 
 of investigational product, as needed, based on the amount of IP remaining from the 
tube previously dispensed. Further, any empty tubes will be collect 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 up to 
 will be needed to dose the subject for the treatment period. Additional tubes 
beyond the initial 
 will only be dispensed if the initial supply is lost and/or significantly 
damaged (i.e., becomes punctured) and warrants replacement. 


  
 
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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 a thin layer (2 mg/cm2) of the product once daily, in the 
evening, through the evening before Visit 4 (Day 85 ± 4). 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 two co-primary 
statistical analyses of interest are (1) the percent change from Baseline to Week 12 in the 
inflammatory (papules/pustules) lesion counts and (2) the percent change from Baseline to Week 
12 in the non-inflammatory (open and closed comedones) lesion counts. The secondary analysis 
is the proportion of subjects who are considered a Clinical Success at Week 12, as defined by an 
IGA score that is at least 2 grades less than the Baseline assessment. A Clinical Failure is defined 
as an IGA score that is the same, higher or one grade lower than the Baseline IGA at Week 12 
(Appendix A). 
 


  
 
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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/Assent 
X‡ 
 
 
 
Medical History/ 
Demographics 
X‡ 
 
 
 
Pregnancy Test†  
X‡ 
X 
X 
X 
Vital Signs 
X
‡ 
 
 
X 
Lesion Counts 
X
‡ 
X 
X 
X 
Investigator’s Global 
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 through the evening for 84 days (Day 1 to Day 84) 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 (percent change from Baseline at Week 12 (Study Day 85 ± 4 days) in 
inflammatory and non- inflammatory lesion counts), the sample size is estimated for therapeutic 
equivalence of the Test to the Reference product and superiority of each of the active treatments 
groups over Placebo. As no variability data were available for TAZORAC® Cream, 0.1%, the 
sample size estimations are based on data reported in the 
 
  


  
 
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In the PP population, the mean percent reduction in inflammatory lesion count in the Reference 
treatment group at Week 12 is expected to be approximately 
, with a SD of 
 
(coefficient of variation of 
). The mean percent reduction in non-inflammatory lesion count 
in the Reference treatment group at Week 12 is expected to be approximately 
, with a SD of 
 (coefficient of variation of 
). Based on these numbers, a sample size of 
 subjects per 
active treatment group in the PP population will provide approximately 
 power to demonstrate 
that the adjusted 90% confidence interval for the T/R ratio of least-squares treatment means for 
the primary endpoint is contained within the pre-defined equivalence limits [80%, 125%], if the 
true ratio is 
 and assuming 
 correlation between inflamed and non-inflamed lesion counts. 
In the mITT population, the mean percent reduction in inflammatory and non-inflammatory lesion 
counts in the Placebo group is expected to be approximately 
 (
, SD) and 
 (
, 
SD), respectively. With a conversion rate of 
 from the mITT to the PP population, 
 subjects 
in each active group and 
 subjects in the Placebo group are required in the mITT population 
for the superiority analyses. This sample size will ensure sufficient power 
 to show a 
difference at p < 0.05 (two-sided) between each active treatment group and the Placebo group for 
each endpoint, assuming 0% correlation between the inflamed and non-inflamed lesion counts and 
 correlation between the two superiority tests for each endpoint. Under the above assumptions, 
the overall study power to demonstrate therapeutic equivalence and superiority for the primary 
endpoint is estimated to be at least 
. To allow for approximately 
 
subjects who may drop out from the study or are otherwise non-evaluable, up to 1110 subjects will 
be enrolled (444 in each active group and 222 in the Placebo group). 
 
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) 
 
 
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 
The two co-primary efficacy endpoints are (1) the percent change from Baseline to Week 12 in the 
inflammatory (papules/pustules) lesion counts and (2) the percent change from Baseline to Week 
12 in the non-inflammatory (open and closed comedones) lesion counts. 
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is the proportion of subjects who are considered a Clinical 
Success at Week 12, as defined by an IGA score that is at least 2 grades less than the Baseline 
assessment. That is, at Week 12, subjects with an IGA score of 4 at Baseline must achieve a score 
of 0, 1 or 2, subjects with an IGA score of 3 at Baseline must achieve a score of 0 or 1, and subjects 
with an IGA score of 2 at Baseline must achieve a score of 0 to be considered a Clinical Success. 
A Clinical Failure is defined as an IGA score at Week 12 that is the same, higher or one grade 
lower than the Baseline IGA. Subjects who are discontinued due to lack of treatment effect or 
worsening condition will be considered Clinical Failures. 


  
 
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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 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 number of inflammatory lesions (i.e., papules and pustules) 
• Baseline number of non-inflammatory lesions (i.e., open and closed comedones) 
• Baseline number of nodulocystic lesions (i.e., nodules and cysts) 
• Baseline IGA score 
 
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 patient. 


  
 
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8.1.2 Medical History 
At Visit 1 subjects will be questioned about personal medical history including acne 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 patient. 
8.1.3 Concomitant Medications 
At Visit 1, subjects will be questioned about current and prior concomitant medication use over 
the previous 6 months. At Visit 2, Visit 3 and Visit 4 subjects will be questioned about ongoing or 
new concomitant medication use. 
All prior and concomitant medications taken since screening until the end of the study will be 
listed by treatment and patient.  
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 patient. 
8.2 Efficacy Analyses 
8.2.1 Primary Efficacy Analysis 
Therapeutic Bioequivalence Analysis 
The primary measure of therapeutic equivalence will be evaluated using the PP population, with 
results in the mITT population being supportive. 
 
The following Statistical Analysis Method is recommended by OGD for equivalence testing for a 
continuous variable:  
 
The compound hypothesis to be tested is:  
 
              𝐻𝐻0:  𝜇𝜇𝜇𝜇/𝜇𝜇𝜇𝜇< 𝜃𝜃1  𝑜𝑜𝑜𝑜  𝜇𝜇𝜇𝜇/𝜇𝜇𝜇𝜇> 𝜃𝜃2     versus   
 


  
 
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              𝐻𝐻𝐴𝐴:  𝜃𝜃1 ≤𝜇𝜇𝜇𝜇/𝜇𝜇𝜇𝜇≤𝜃𝜃2   
 
where    𝜇𝜇𝜇𝜇 = mean percent change from baseline of test treatment, and 
              𝜇𝜇𝜇𝜇 = mean percent change from baseline of reference treatment  
Under the assumptions of normally distributed data, the adjusted 90% confidence interval will be 
calculated for the Test/Reference ratio of the mean percent change from Baseline in inflammatory 
and non-inflammatory lesion counts using an iterative procedure similar to Fieller’s method. 
ANOVA with treatment and site as fixed effects in the model will be conducted on the mean 
percent change from Baseline to Week 12 in the inflammatory (papules/pustules) lesion counts 
and non-inflammatory (open and closed comedones) lesion counts. If the adjusted 90% confidence 
intervals for the least-squares mean Test/Reference ratios are within 80-125% for both co-primary 
endpoints, then therapeutic equivalence of the Test to Reference product will be considered to have 
been demonstrated. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary endpoints in the PP population. 
Superiority to Placebo Analysis 
The primary measure of superiority will be evaluated using the mITT population, using 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 is concluded if these treatments’ 
mean percent changes from Baseline in inflamed and non-inflamed lesion counts at Week 12 are 
statistically superior to that of the Placebo at the 5% significance level (p < 0.05, two-sided). The 
superiority of Test and Reference treatments over the Placebo will be evaluated in the same 
ANOVA model for Test vs. Placebo and Reference vs. Placebo. 
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. 
8.2.2 Secondary Efficacy Analyses 
The PP population will be used for analysis of therapeutic equivalence and the mITT population 
will be used for analyses of superiority. 
Therapeutic Bioequivalence Analysis 


  
 
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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   
 
 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 subjects considered as clinical success in test treatment group  
𝑛𝑛𝑅𝑅  =  sample size of reference treatment group  
𝑐𝑐𝑛𝑛𝑅𝑅=  number of subjects considered as clinical 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 Clinical Success, if the 90% confidence interval (with Yates’ Correction 
factor) of the difference between the proportion of subjects considered a Clinical Success in the 
Test and the Reference product groups at Week 12 is contained within -20% to +20%, then 
therapeutic equivalence of the Test to Reference product will be considered supported for the 
secondary endpoint. 
Superiority to Placebo Analysis 
The analyses for superiority will be conducted using the mITT population and LOCF.  
For the determination of superiority, the proportion of subjects considered a Clinical Success at 
Week 12 in the Test and Reference product groups will each be compared to the proportion of 


  
 
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subjects considered as Clinical Success in the Placebo group. 
If the proportion of subjects showing Clinical Success in the Test and Reference groups is 
statistically significantly greater (p < 0.05; using Cochran-Mantel-Haenszel exact test stratified by 
clinical site)) than the Clinical Success seen in the Placebo group then superiority will be 
concluded. 
A summary table with frequency and percentage of the proportion of Clinical Success by treatment 
group will be presented. 
8.2.3 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 in the 
ANOVA model for evaluations involving the primary efficacy endpoint. 
 
 
 
 
 If no treatment-by-site interaction is identified with the primary endpoint 
then no adjustment will be made to any efficacy analysis and treatment-by site interaction will not 
be included as a term in the statistical models for evaluating therapeutic equivalence and 
superiority. 
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 patient will be counted only once within each 
preferred term.   


  
 
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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 patient for local application site reactions 
based on the scale provided in Appendix B: 
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 patient’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 patient. 
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 


  
 
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data. Subjects with missing data will be excluded only from analyses for which data are not 
available, including denominators. 
Subjects discontinued early for reasons other than lack of treatment effect or worsening condition 
will be excluded from the PP population and included in the mITT population using 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 0.1%                                                          
 
Protocol / 
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Page 21 of 64                                                
 
 
 
 
 
 
 
 
 
 
 
 
 
TABLE, LISTING AND FIGURE SHELLS 
 
 
  
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
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4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 22 of 64                                                
 
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
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4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 23 of 64                                                
 
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
                               
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
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4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 24 of 64                                                
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol /
. 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 25 of 64                                                
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
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4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 26 of 64                                                
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 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
 
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 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 27 of 64                                                
T16.1.9.4.2 Summary of Baseline Parameters 
(Safety Population) 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
P-value 
Total Inflammatory Lesion Count 
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 Non-Inflammatory Lesion Count 
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 Nodulocystic Lesion Count 
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 
 
Investigator Global Assessment  
Clear 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
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%) 
 
           Note:  N= number of subjects in the treatment group;     n= number of subjects with data available;      % is based on N 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (Allergan, Inc.) 
Placebo:  Placebo (vehicle) Cream (Fougera Pharmaceuticals Inc.) 
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SAS\OUT                   Created on: ddmmmyy hh:mm                       Page 2 of 2 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 28 of 64                                                
 
 
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 0.1%                                                          
 
Protocol / 
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4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 29 of 64                                                
 
T16.1.9.7.1 Descriptive Summary of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Inflammatory Lesion Count)  
(Per-Protocol Population) 
 
 
 
 
Statistic 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
Overall 
(N = xxx) 
Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Week 12 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Percent Change from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
         N= number of subjects in the treatment group;     n= number of subjects with data available;      
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 30 of 64                                                
T16.1.9.7.2 Descriptive Summary of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Inflammatory Lesion Count)  
(modified Intent-to-Treat Population) 
 
 
 
 
Statistic 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
Overall 
(N = xxx) 
Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Week 12 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Percent Change from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
         N= number of subjects in the treatment group;     n= number of subjects with data available;      
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 31 of 64                                                
T16.1.9.8.1 Summary of Analysis Results of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Inflammatory Lesion Count between Treatment Groups) 
 
Equivalence: Per-Protocol Population 
 
Number of 
Subjects (N) 
Difference Between Treatments  
 
Treatment  
Group 
LSMeans 
Test-to-Reference 
Ratio 
90% CI Evaluation 
Test 
xxx 
xxx.x 
 
 
Reference 
xxx 
xxx.x 
xx.x 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Number of 
Subjects (N) 
 
LSMeans 
 
Treatment vs. Placebo 
Treatment  
Group 
Std Err 
LSMeans 
LSMeans 
Difference 
Std Err 
LSMeans 
Difference 
95% CI 
P-value 
Placebo  
xxx 
xxx.x 
xxx.x 
 
 
 
 
Test 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
Reference 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
              The 90% confidence interval for the test-to-reference ratio was calculated using a procedure similar to Fieller’s method. 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
  Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 32 of 64                                                
T16.1.9.8.2 Summary of Supportive Analysis Results of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Inflammatory Lesion Count between Treatment Groups) 
 
Equivalence: modified Intent-to-Treat Population 
 
Number of 
Subjects (N) 
Difference Between Treatments  
 
Treatment  
Group 
LSMeans 
Test-to-Reference 
Ratio 
90% CI Evaluation 
Test 
xxx 
xxx.x 
 
 
Reference 
xxx 
xxx.x 
xx.x 
xx.x – xx.x 
 
Superiority: Per-Protocol Population 
Number of 
Subjects (N) 
 
LSMeans 
 
Treatment vs. Placebo 
Treatment  
Group 
Std Err 
LSMeans 
LSMeans 
Difference 
Std Err 
LSMeans 
Difference 
95% CI 
P-value 
Placebo  
xxx 
xxx.x 
xxx.x 
 
 
 
 
Test 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
Reference 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
              The 90% confidence interval for the test-to-reference ratio was calculated using a procedure similar to Fieller’s method. 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
  Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 33 of 64                                                
T16.1.9.9.1 Descriptive Summary of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Non-Inflammatory Lesion Count)  
(Per-Protocol Population) 
 
 
 
 
Statistic 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
Overall 
(N = xxx) 
Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Week 12 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Percent Change from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
         N= number of subjects in the treatment group;     n= number of subjects with data available;      
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 34 of 64                                                
T16.1.9.9.2 Descriptive Summary of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Non-Inflammatory Lesion Count)  
(modified Intent-to-Treat Population) 
 
 
 
 
Statistic 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
Overall 
(N = xxx) 
Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Week 12 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
Percent Change from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
         N= number of subjects in the treatment group;     n= number of subjects with data available;      
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 35 of 64                                                
T16.1.9.10.1 Summary of Analysis Results of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Non-Inflammatory Lesion Count between Treatment Groups) 
 
Equivalence: Per-Protocol Population 
 
Number of 
Subjects (N) 
Difference Between Treatments  
 
Treatment  
Group 
LSMeans 
Test-to-Reference 
Ratio 
90% CI Evaluation 
Test 
xxx 
xxx.x 
 
 
Reference 
xxx 
xxx.x 
xx.x 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Number of 
Subjects (N) 
 
LSMeans 
 
Treatment vs. Placebo 
Treatment  
Group 
Std Err 
LSMeans 
LSMeans 
Difference 
Std Err 
LSMeans 
Difference 
95% CI 
P-value 
Placebo  
xxx 
xxx.x 
xxx.x 
 
 
 
 
Test 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
Reference 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
              The 90% confidence interval for the test-to-reference ratio was calculated using a procedure similar to Fieller’s method. 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
  Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 36 of 64                                                
 
T16.1.9.10.2 Summary of Supportive Analysis Results of Co-Primary Efficacy Endpoint  
(Percent Change from Baseline in Non-Inflammatory Lesion Count between Treatment Groups) 
 
Equivalence: modified Intent-to-Treat Population  
 
Number of 
Subjects (N) 
Difference Between Treatments  
 
Treatment  
Group 
LSMeans 
Test-to-Reference 
Ratio 
90% CI Evaluation 
Test 
xxx 
xxx.x 
 
 
Reference 
xxx 
xxx.x 
xx.x 
xx.x – xx.x 
 
Superiority: Per-Protocol Population 
Number of 
Subjects (N) 
 
LSMeans 
 
Treatment vs. Placebo 
Treatment  
Group 
Std Err 
LSMeans 
LSMeans 
Difference 
Std Err 
LSMeans 
Difference 
95% CI 
P-value 
Placebo  
xxx 
xxx.x 
xxx.x 
 
 
 
 
Test 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
Reference 
xxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xx.x – xx.x 
x.xxxx 
              The 90% confidence interval for the test-to-reference ratio was calculated using a procedure similar to Fieller’s method. 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
  Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 37 of 64                                                
T16.1.9.11 Summary of Analysis Results of Secondary Efficacy Endpoint  
(Proportion of Clinical Successes Between Treatment Groups) 
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 0.1% (Fougera Pharmaceuticals Inc.)  
        Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 38 of 64                                                
T16.1.9.12 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 39 of 64                                                
T16.1.9.13 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 
Patient 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 
 
T16.1.9.14 Summary of Frequency for AEs Occurring in at Least 5% of Subjects by Body System 
(Safety Population) 
 
 
 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 40 of 64                                                
T16.1.9.15 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 41 of 64                                                
T16.1.9.16 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 42 of 64                                                
T16.1.9.17 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 43 of 64                                                
 
T16.1.9.18 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 44 of 64                                                
T16.1.9.19 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 45 of 64                                                
T16.1.9.20 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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 46 of 64                                                
 
L16.2.1 Listing of Discontinued Subjects 
 
 Treatment 
 Group 
Patient 
Number 
Discontinuation 
Reason 
Population 
 Test 
xx - xxxx 
Withdrew Consent 
Safety 
 
xx - xxxx 
Lost to Follow-up 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 Reference 
 
 
 
 Placebo 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 47 of 64                                                
 
L16.2.2 Listing of Protocol Deviations 
 
Treatment  
Group 
Patient 
Number 
Protocol Deviation Summary 
Population 
Test 
xx - xxxx 
Outside Visit Window 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
Placebo 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 48 of 64                                                
 
L16.2.3.1 Subjects Excluded from the Per-Protocol Population Data Set 
 
Treatment 
Group 
Patient 
Number 
Exclusion 
Reason 
Test 
xx - xxxx 
Patient did not meet IE criterion. 
 
xx - xxxx 
Patient took prohibited medications 
 
 
 
 
 
 
 
Reference 
 
 
Placebo 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 49 of 64                                                
 
L16.2.3.2 Subjects Excluded from the Modified Intent-to-Treat Data Set 
 
Treatment 
Group 
Patient 
Number 
Exclusion 
Reason 
Test 
xx - xxxx 
Patient did not have at least one post-randomization evaluation 
 
xx - xxxx 
Patient did not have at least one post-randomization evaluation 
 
 
 
 
 
 
Reference 
 
 
Placebo 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 50 of 64                                                
 
L16.2.4.1 Listing of Demographic Data  
 
Treatment 
Group 
Patient 
Number 
 
Age 
 
Sex 
 
Ethnicity 
Race 
  Test 
xx - xxxx 
30 
Female 
Not Hispanic or Latino 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 51 of 64                                                
 
L16.2.4.2 Listing of Medical History 
 
Treatment 
Group 
Patient 
Number 
Category 
 
Reported Term 
 
Onset Date 
 
End Date 
 
Ongoing 
Test 
xx - xxxx 
Gynecologic 
Menopause 
2003 
2003 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 52 of 64                                                
 
L16.2.4.3 Listing of Concomitant Medications 
 
Test: Tazarotene Cream 0.1% 
 
Patient 
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\
SAS\OUT                   Created on: ddmmmyy hh:mm                           Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 53 of 64                                                
 
L16.2.5.1 Listing of Visit Date Information 
 
Treatment  
Group 
Patient 
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 54 of 64                                                
 
L16.2.5.2 Listing of Drug Administration 
 
Treatment  
Group 
Patient 
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 55 of 64                                                
 
L16.2.6.1 Listing of Lesion Count 
 
 
 
Treatment  
Group 
 
 
Patient 
Number 
Visit 
Total  
Inflammatory 
Lesion Count 
Total  
Non-Inflammatory 
Lesion Count 
Total  
Nodulocystic 
Lesion Count 
Percent Change  
from Baseline in  
Total Inflammatory  
Lesion Count 
Percent Change from  
Baseline in Total  
Non-Inflammatory 
 Lesion Count 
Test 
xx - xxxx 
1 
xx 
xx 
xx 
xx 
0.00 
 
 
2 
xx 
xx 
xx 
xx 
x.xx 
 
 
3 
xx 
xx 
xx 
xx 
x.xx 
 
 
4/ET 
xx 
xx 
xx 
xx 
x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 56 of 64                                                
 
L16.2.6.2 Listing of Investigator Global Assessment 
 
Treatment  
Group 
Patient 
Number 
Visit 
IGA 
 
Change from 
Baseline 
Success/ 
Failure 
Test 
xx - xxxx 
1 
xx 
0 
 
 
 
2 
xx 
xx 
 
 
 
3 
xx 
xx 
 
 
 
4/ET 
xx 
xx 
Success 
 
xx - xxxx 
1 
xx 
0 
 
 
 
2 
xx 
xx 
 
 
 
3 
xx 
xx 
 
 
 
4/ET 
xx 
xx 
Failure 
 
etc 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 57 of 64                                                
 
L16.2.7.1 Listing of Adverse Events by Treatment Group 
 
Test: Tazarotene Cream 0.1% 
 
 
 
Patient 
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\
SAS\OUT                   Created on: ddmmmyy hh:mm                       Page 1 of N 
 
 


 Fougera Pharmaceuticals Inc. 
 
 
 Tazarotene Cream 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 58 of 64                                                
 
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 0.1% (Fougera Pharmaceuticals Inc.)  
Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 59 of 64                                                
 
L16.2.8.1 Listing of Pregnancy Test Results 
 
Treatment  
Group 
Patient   
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 or  
Early Termination 
Test 
xx - xxxx 
Negative 
Negative 
Negative 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
          Test: Tazarotene Cream 0.1% (Fougera Pharmaceuticals Inc.)  
          Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                                          
 
Protocol / 
 0454-01-01/
 
 
 
4/26/2017   
                         Fougera Pharmaceuticals Inc.      
 
Page 60 of 64                                                
 
L16.2.8.2 Listing of Vital Signs 
 
Treatment 
Group 
Patient   
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 0.1% (Fougera Pharmaceuticals Inc.)  
     Reference: TAZORAC® (tazarotene) Cream, 0.1% (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 0.1%                                         Protocol / 
 0454-01-01/
 
 
4/26/2017                   Fougera Pharmaceuticals Inc.             
        Page 61 of 64                                               
 
APPENDIX A: Investigator’s Global Assessment for Acne Vulgaris 
  
 To be eligible for participation in the study a subject must have a Baseline IGA score of 2, 3 or 4. 
Grade 
Description 
0 
Clear skin with no inflammatory or non-inflammatory lesions 
1 
Almost clear; rare non-inflammatory lesions with no more than one 
small inflammatory lesion 
2 
Mild severity; greater than Grade 1; some non-inflammatory lesions 
with no more than a few inflammatory lesions (papules/pustules 
only, no nodular lesions) 
3 
Moderate severity; greater than Grade 2; up to many non-
inflammatory lesions and may have some inflammatory lesions, but 
no more than one small nodular lesion 
4 
Severe; greater than Grade 3; up to many non-inflammatory 
lesions and may have some inflammatory lesions, but no more 
than a few nodular lesions 
5 
Greater than Grade 4 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.1%                                         Protocol / 
 0454-01-01/
 
 
4/26/2017                   Fougera Pharmaceuticals Inc.             
        Page 62 of 64                                               
 
APPENDIX B: 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) 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.1%                                         Protocol / 
 0454-01-01/
 
4/26/2017                   Fougera Pharmaceuticals Inc.             
        Page 63 of 64                                               
 


 
STATISTICAL ANALYSIS PLAN 
 
Tazarotene Cream 0.1%                                         Protocol / 
 0454-01-01/
 
 
4/26/2017                   Fougera Pharmaceuticals Inc.             
        Page 64 of 64