An Open-Label Study to Evaluate the Long-Term Safety of Topical Administration of FMX103 for 40 Weeks in the Treatment of Moderate to Severe Facial Papulopustular Rosacea (Study FX2016-13)
Phase: PHASE3
Conditions: Papulopustular Rosacea
Sponsor: Vyne Therapeutics Inc.

 
 
 
 
 
 
 
 
 
 
 
 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
 
ClinicalTrials.gov Identifier: NCT03276936 
 
 
 
Date of Protocol: 22 June 2017 

Privileged and Confidential 
Clinical Protocol:  Version 2 
1 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
CLINICAL PROTOCOL 
Title Page 
Study Title: 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-13 
Product: 
FMX103 1.5% minocycline foam 
Indication Studied: 
Papulopustular Rosacea 
Study Phase: 
3 
Sponsor’s Signatory: 
GCP Statement: 
This study will be conducted in accordance with Good 
Clinical Practice. Essential documents will be archived 
according to CPMP/ICH/135/95 
Date of Protocol: 
22 June 2017 
Version of Protocol 
Version 2 (Amendment 1) 
Supercedes: 
Version 1, issued 06 March 2017 
Prepared by: 
The Write Company, LLC 
Confidentiality Statement 
This document is the property of Foamix Pharmaceuticals, Inc., and is confidential and proprietary.  The information 
contained herein is believed to be accurate and complete as of the date of preparation.  The contents may not be used, 
divulged, published or otherwise disclosed without the expressed consent of Foamix Pharmaceuticals, Inc. 
2 of 83
PPD

Privileged and Confidential 
Clinical Protocol:  Version 2 
3 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Synopsis 
Name of 
Sponsor/Company: 
Foamix Pharmaceuticals, 
Inc. 
Individual Study Table Referring to 
Part of the Dossier: 
(For National Authority 
Use Only) 
Name of Finished Product: 
FMX103 
Volume: 
Name of Active 
Ingredient: 
Minocycline hydrochloride 
Page: 
Title of Study: 
An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate 
to Severe Facial Papulopustular Rosacea (Study FX2016-13) 
Protocol No: 
FX2016-13 
Study Centers: 
Multicenter (approximately 80 sites in the USA) 
Publication (reference): 
None 
Primary Objective: 
The primary objective is to show that open-label extended treatment 
with FMX103 1.5%, for up to an additional 40 weeks, is safe and well 
tolerated. 
Study Design and 
Methods: 
This is an open-label, multicenter, 40-week extension study to evaluate 
the long-term safety, tolerability, and efficacy of FMX103 1.5% topical 
foam in the treatment of moderate-to-severe facial papulopustular 
rosacea. Subjects entering this study will have recently participated in 1 
of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy 
studies (FX2016-11 and FX2016-12). Subjects must demonstrate that 
they are eligible to continue into Study FX2016-13 based in part on 
safety evaluations performed at Visit 5/Week 12 (Final Visit) of one of 
the previous double-blind studies. In addition, the subject’s 
Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final 
Visit) should not have worsened relative to the subject’s IGA at Day 
0/Baseline of one of the previous double-blind studies. 
At the completion of Visit 5/Week 12 (Final Visit) in Study FX2016-11 
or Study FX2016-12, subjects may be invited to continue into this 
open-label study for an additional 40 weeks of open-label treatment. A 
minimum of 400 subjects will be enrolled into from Studies FX2016-11 
and FX2016-12. Subjects who elect to continue into this open-label 
study will receive supplies of active FMX103 1.5% minocycline foam. 
Treatment during the open-label study will be guided by each subject’s 
clinical response. The Investigator may elect to suspend treatment if 
there is clinical improvement or resolution of rosacea. Even if the 
treatment is suspended temporarily, the subject will continue in the 
study and will attend all scheduled clinic visits. If at any time the 
rosacea recurs or worsens, treatment may be resumed. 
4 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 2 
4 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
Subjects may be discontinued from the study at any time if their disease 
becomes refractory or they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as 
Visit 5/Week 12 (Final Visit) of either Study FX2016-11 or 
Study FX2016-12. Subsequent visits for this open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and 
efficacy evaluations will be performed. Week 40 is the Final Visit 
(Visit 7) of this study. A safety follow-up telephone call will occur 4 
weeks after Final Visit (Visit 7). 
Number of Subjects 
(planned): 
The planned minimum enrollment is a minimum of 400 male and 
female subjects who were previously enrolled in Study FX2016-11 or 
Study FX2016-12. The sample size is intended to ensure that at least 
300 subjects continue to self-administer the study drug as needed for at 
least 6 months and 100 subjects continue for at least 1 year (ie, 
combined duration of treatment between the double-blind and open-
label studies). The number of subjects at each site will be determined 
by the rate of recruitment in Studies FX2016-11 and FX2016-12. No 
statistical rationale for subject number is provided. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years, who had a 
clinical diagnosis of moderate to severe facial papulopustular rosacea at 
the start of the previous double-blind study who completed 12 weeks of 
double-blind treatment in Study FX2016-11 or Study FX2016-12;  are 
willing to continue on open-label treatment with FMX103 in the current 
study and do not have a worsening of disease, determined by IGA, at 
Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment 
of the previous study. 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, self-
administered dosing as needed, for up to 40 weeks. 
Reference Therapy: 
Not applicable. 
Study Duration: 
Subject participation in the study will be up to 44 weeks.  
Endpoints and Outcomes: 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner); clinical laboratory tests; vital signs; physical examinations; 
and local signs and symptom assessments of the skin at the application 
sites (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation scores). 
Efficacy Evaluations 
The efficacy parameters will include inflammatory lesion counts and 
IGA at Baseline and at Weeks 4, 10, 16, 22, 28, 34, and 40 (Final 
Visit). 
5 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 2 
5 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
Statistical Methods: 
The All-Treated population, defined as all subjects who use the study 
drug at least once, will be used for all analyses. Missing data will not be 
imputed. All analyses will be based on observed data. The primary 
endpoints are the absolute change in the inflammatory lesion count 
compared to Baseline and the dichotomized IGA score, where success 
is defined as a 2-step improvement resulting in a 0 (clear) or 1 (almost 
clear) score at Week 40 compared to Baseline. The secondary endpoints 
of change from Baseline of Study FX2016-11 and Study FX2016-12 to 
each visit in inflammatory lesion count, IGA treatment success and a 
Subject Satisfaction Questionnaire administered at Visit 7 
(Week 40/Final Visit) will also be summarized.  
No statistical tests will be performed for any of the endpoints. 
The safety and tolerability safety of topical minocycline foam applied 
as needed for an additional 40 weeks will be evaluated using summary 
statistics and individual subject data listings. No statistical tests will be 
performed for any of the safety assessments. 
6 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 2 
6 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
Table of Contents 
Page 
TITLE PAGE ........................................................................................................................................................ 1 
SIGNATURE PAGE ............................................................................................................................................ 2 
SYNOPSIS............................................................................................................................................................. 3 
TABLE OF CONTENTS ..................................................................................................................................... 6 
LIST OF TABLES ................................................................................................................................................ 8 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................................................... 9 
2 
STUDY ADMINISTRATIVE STRUCTURE ........................................................................................10 
3 
INTRODUCTION ....................................................................................................................................11 
4 
STUDY OBJECTIVES ............................................................................................................................11 
4.1 
PRIMARY OBJECTIVE .......................................................................................................................11 
5 
INVESTIGATIONAL PLAN ..................................................................................................................11 
5.1 
OVERALL STUDY DESIGN ................................................................................................................11 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................12 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................13 
7.1 
BASELINE (ALSO VISIT 5/WEEK 12 [FINAL VISIT] OF PREVIOUS DOUBLE-BLIND STUDY) .................16 
7.2 
VISITS 1 THROUGH 6, WEEKS 4, 10, 16, 22, 28, AND 34 (±5 DAYS) ..................................................16 
7.3 
VISIT 7, WEEK 40/FINAL VISIT (±5 DAYS) OR EARLY TERMINATION ...............................................17 
7.4 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................17 
8 
STUDY TREATMENTS ..........................................................................................................................18 
8.1 
TREATMENT ADMINISTERED ............................................................................................................18 
8.1.1 
Dosing Instructions ........................................................................................................18 
8.1.2 
Manufacturer ..................................................................................................................18 
8.1.3 
Labeling of Study Drug ..................................................................................................19 
8.1.4 
Storage of Study Drug ....................................................................................................19 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................19 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................20 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................20 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................20 
8.6 
BLINDING  ........................................................................................................................................20 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................20 
8.8 
USE OF CONTRACEPTION .................................................................................................................21 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................21 
9 
EFFICACY ASSESSMENTS ..................................................................................................................22 
9.1 
PRIMARY EFFICACY ASSESSMENTS..................................................................................................22 
9.1.1 
Lesion Counts.................................................................................................................22 
9.1.2 
Investigator Global Assessment .....................................................................................22 
9.2 
SECONDARY EFFICACY ASSESSMENTS .............................................................................................22 
9.2.1 
Subject Satisfaction Questionnaire .................................................................................22 
10 
SAFETY ASSESSMENTS .......................................................................................................................23 
7 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
7 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
10.1 
CONCOMITANT MEDICATIONS .........................................................................................................23 
10.2 
VITAL SIGNS ....................................................................................................................................23 
10.3 
PHYSICAL EXAMINATION .................................................................................................................23 
10.4 
CLINICAL LABORATORY TESTS........................................................................................................23 
10.4.1 
Urine Pregnancy Test .....................................................................................................24 
10.4.2 
Sample Collection, Storage, and Shipping .....................................................................24 
10.5 
OTHER SAFETY MEASUREMENTS .....................................................................................................24 
10.5.1 
Local Signs and Symptom Assessments ........................................................................24 
10.5.1.1 Erythema (Clinical Erythema Assessment Scale) .........................................25 
10.5.1.2 Telangiectasia ................................................................................................25 
10.5.1.3 Burning/Stinging ...........................................................................................25 
10.5.1.4 Flushing/Blushing .........................................................................................26 
10.5.1.5 Dryness/Xerosis ............................................................................................26 
10.5.1.6 Itching ...........................................................................................................26 
10.5.1.7 Peeling/Desquamation ...................................................................................26 
10.5.1.8 Hyperpigmentation ........................................................................................26 
10.6 
ADVERSE EVENTS ............................................................................................................................27 
10.6.1 
Method of Determining Adverse Events ........................................................................27 
10.6.2 
Adverse Event Definitions .............................................................................................27 
10.6.2.1 Adverse Events ..............................................................................................27 
10.6.2.2 Serious Adverse Events .................................................................................28 
10.6.2.3 Severity of Adverse Events ...........................................................................28 
10.6.2.4 Relationship of Adverse Events to Study Treatments ...................................29 
10.6.2.5 Adverse Events Expectedness .......................................................................29 
10.6.3 
Reporting Adverse Events ..............................................................................................29 
10.6.4 
Adverse Event Follow-up ...............................................................................................29 
10.6.4.1 Pregnancy Reporting .....................................................................................30 
10.6.5 
Clinically Significantly Abnormal Laboratory Results ..................................................30 
10.7 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................30 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................30 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................30 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................31 
11.3 
ANALYSIS POPULATIONS .................................................................................................................31 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND BASELINE CHARACTERISTICS .................................31 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................31 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................31 
11.5.2 
Secondary Efficacy Endpoint .........................................................................................31 
11.6 
SAFETY ENDPOINTS .........................................................................................................................32 
11.6.1 
Adverse Events ...............................................................................................................32 
11.6.2 
Local Signs and Symptoms Assessments .......................................................................32 
11.6.3 
Clinical Laboratory Results ............................................................................................33 
11.7 
INTERIM ANALYSIS ..........................................................................................................................33 
12 
STUDY MANAGEMENT .......................................................................................................................33 
12.1 
MONITORING ...................................................................................................................................33 
12.2 
PROTOCOL AMENDMENTS................................................................................................................33 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................34 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................34 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................35 
12.6 
PUBLICATION POLICY ......................................................................................................................35 
13 
ETHICS .....................................................................................................................................................35 
13.1 
CONDUCT OF THE STUDY .................................................................................................................35 
13.2 
INSTITUTIONAL REVIEW BOARDS ....................................................................................................35 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................35 
8 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 2 
8 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................36 
13.5 
RECORDS RETENTION ......................................................................................................................36 
13.6 
FINANCING .......................................................................................................................................36 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................37 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................37 
16 
REFERENCE LIST .................................................................................................................................37 
17 
STUDY AMENDMENTS ........................................................................................................................37 
17.1 
AMENDMENT 1, EFFECTIVE JUNE 22ND, 2017 ..................................................................................38 
APPENDIX 1:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................43 
APPENDIX 2: ACKNOWLEDGMENT OF RECEIPT AND REVIEW OF PROTOCOL .........................44 
 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 ........................... 15 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 ..................................................... 18 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 ................................................................... 22 
Table 4 
Clinical Laboratory Tests – Study FX2016-13 .............................................................. 24 
 
9 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 2 
9 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Abbreviation/Term 
Definition 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartic acid transaminase 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
FV 
Final Visit 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed cases 
OTC 
Over-the-counter 
PT 
Preferred term 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
10 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 2 
11 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and eyes. It is a syndrome of 
undetermined etiology characterized by both vascular and papulopustular components involving 
the face and occasionally the neck and upper trunk. Clinical findings are usually limited to the 
sun exposed areas of the face and chest and include mid-facial erythema, telangiectasia, papules 
and pustules, and sebaceous gland hypertrophy. Rosacea is characterized by episodic flushing of 
affected areas, which may be associated with consumption of alcohol, hot drinks, or spicy foods. 
During inflammatory episodes, affected areas of the skin, primarily the convexities of the face, 
develop swelling, papules, and pustules. 
Rosacea occurs most commonly in adult life, between the ages of 30 and 60 years. It is very 
common in the United States (US) and Europe. Ocular involvement occurs in more than 50% of 
patients. 
Mainstays of treatment for papulopustular rosacea are the oral tetracyclines: doxycycline and 
minocycline. Systemic doxycycline (Oracea®, doxycycline 40 mg capsules) is approved. Topical 
treatments for rosacea include metronidazole, azelaic acid, and brimonidine tartrate. 
Minocycline hydrochloride is an established broad-spectrum antibiotic that is used orally “off-
label” in the treatment of papulopustular rosacea. Foamix has developed a topical minocycline 
foam product that is being evaluated for the treatment of papulopustular rosacea. The study 
medication FMX103 (minocycline HCl 1.5% foam) facilitates easy application and even 
distribution of the agent, thereby improving treatment convenience. 
The efficacy and safety of FMX103 have been established in a Phase 2 study in 232 adult 
subjects with moderate to severe papulopustular rosacea (Study FX2015-10). 
The purpose of this Phase 3 open-label extension study is to evaluate the long-term safety, 
tolerability, and efficacy of topical FMX103 1.5% (minocycline foam) during a 40-week period 
of self-administered dosing as needed in subjects with moderate to severe facial papulopustular 
rosacea who have previously participated in 1 of 2 Phase 3, 12-week, double-blind, 
vehicle-controlled safety and efficacy studies: Studies FX2016-11 and FX2016-12. 
4 
STUDY OBJECTIVES 
4.1 
Primary Objective 
The primary objective is to show that open-label extended treatment with FMX103 1.5%, for up 
to an additional 40 weeks, is safe and well tolerated.  
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is an open-label, multicenter, 40-week extension study to evaluate the long-term safety, 
tolerability, and efficacy of FMX103 1.5% topical foam in the treatment of moderate to severe 
facial papulopustular rosacea. Subjects will be eligible to enter this study upon successful 
12 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
12 of 44 
Final 
Protocol:  FX2016-13 
 
Date:  22 June 2017 
completion of 1 of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy Phase 3 studies 
(FX2016-11 and FX2016-12) and if they meet all of the entry criteria.  
At the completion of Visit 5/Week 12 (Final Visit, or FV) in Study FX2016-11 or Study FX2016-
12, subjects who meet entry criteria will be invited to continue into this open-label study for an 
additional 40 weeks of treatment. A minimum of 400 subjects from Studies FX2016-11 and 
FX2016-12 will be enrolled into open-label Study FX2016-13. Subsequent enrollment of 
additional subjects will be considered as necessary to meet regulatory requirements. Subjects 
who elect to continue into this open-label study will receive supplies of active FMX103 1.5% 
minocycline foam. 
Treatment during the open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all facial areas if there is clinical 
improvement or resolution of the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the study and will attend all 
scheduled clinic visits. If at any time their rosacea recurs or worsens, treatment of the affected 
areas may be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as Visit 5/Week 12 (Final Visit) of 
either Study FX2016-11 or Study FX2016-12. Subsequent visits for the open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and efficacy evaluations will be 
performed. Week 40 is the Final Visit (Visit 7) of this study. 
Safety and efficacy evaluations will be performed as shown in Table 1. 
5.2
Rationale for Study Design and Dose Selection 
Chronic exposure in an open-label design is appropriate to evaluate the safety of long-term use. 
The omission of a control group is appropriate. Subjects will be selected according to pre-
defined entry criteria from 2 pivotal, Phase 3, randomized, multicenter, double-blind, vehicle-
controlled, 12-week studies. The open-label study treatment duration of 40 weeks will thus result 
in a total treatment duration of 52 weeks, adequate for chronic exposure. 
This open-label extension study is necessary to obtain safety information about the long-term use 
of FMX103 1.5% to treat facial papulopustular rosacea because of its chronic nature. The study 
design is expected to provide sufficient safety information to fulfill the International Conference 
on Harmonization (ICH) E1 guideline. 
The concentration of minocycline (1.5%) was selected according to formulation integrity and 
stability considerations and based on the results of the Phase 2 Study FX2015-10. 
6
STUDY POPULATION 
The study population will be comprised of subjects who have completed Study FX2016-11 or 
Study FX2016-12 and have agreed and are eligible to continue into this 40-week open-label 
extension study. A minimum of 400 subjects will be enrolled at approximately 80 sites in the US. 
All subjects will receive active treatment with FMX103 1.5% minocycline foam. 
13 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
13 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
6.1
Inclusion Criteria 
Subjects will be included in the study if they meet all of the following inclusion criteria at the 
time of enrollment: 
1. Healthy male or non-pregnant females, aged ≥18 years, who had a clinical diagnosis of
moderate to severe facial papulopustular rosacea at the start of the previous double-blind
study (Study FX2016-11 or Study FX2016-12).
2. Have completed and signed an appropriately administered informed consent form (ICF)
prior to any study-related procedures.
3. Have completed 12 weeks of treatment in either Study FX2016-11 or Study FX2016-12.
4. Have not had a worsening of disease, determined by the Investigator’s Global Assessment
(IGA), at Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment in Study
FX2016-11 or Study FX2016-12.
5. Are willing to continue on open-label treatment with FMX103 as described in this
protocol.
6. If a woman of child-bearing potential, have a negative urine pregnancy test and agree to
use an effective method of contraception (Section 8.8). A sterile sexual partner is NOT
considered an adequate form of birth control.
7. If a woman of child-bearing potential is using an oral contraceptive product, she should
have been on the same product for at least 3 months and she should continue using the
same or equivalent product for the duration of the of the study.
6.2 
Exclusion Criteria 
Subjects will be excluded from enrollment in the study for any of the following reasons: 
1. Women who are pregnant, lactating, or planning to become pregnant during the study.
2. Have a new systemic disease or condition, including an ongoing AE that might interfere
with the conduct of the study or the interpretation of results.
3. Have developed a condition that would have been exclusionary for Study FX2016-11 or
Study FX2016-12, including pseudomembranous colitis, antibiotic-associated colitis,
hepatitis, liver damage, renal impairment, drug addiction, or alcohol abuse.
4. Have abnormal laboratory values at the Final Visit (Week 12) of Study FX2016-11 or
Study FX2016-12 that are considered clinically significant. Subjects are permitted to
enroll in the study whilst laboratory results for Final Visit (Week 12) for Study FX2016-11
or Study FX2016-12 are pending receipt.
5. Are unable to fully comply with the study requirements.
7
STUDY PROCEDURES 
The schedule of study assessments and procedures is presented in Table 1. If a subject withdraws 
from the study prematurely, he or she should return to the study site for an early termination 
14 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
14 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
visit, during which all evaluations described under Visit 7/Week 40 (Final Visit) should be 
performed. 
15 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
15 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 
Assessment or Procedure 
Baselinea 
Visits 
Final 
Visitb 
Safety 
Follow-upc 
Study Visit 
(FV of 
previous 
DB Study) 
1 
2 
3 
4 
5 
6 
7 
N/A 
Study Week 
(Week since beginning of 
previous DB study) 
1 
(12) 
4 
(16) 
10 
(22) 
16 
(28) 
22 
(34) 
28 
(40) 
34 
(46) 
40 
(52) 
44 
(56) 
Informed consent 
X 
Record subject identificationd 
X 
Inclusion/exclusion criteria 
X 
Physical examination (including 
weight) 
X 
X 
Blood pressure/heart ratee 
X 
X 
X 
X 
X 
X 
X 
X 
Blood/urine samples for clinical 
laboratory tests 
X 
X 
X 
Urine pregnancy testf 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global 
Assessment 
Xg 
X 
X 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
Questionnaire 
X 
Local signs and symptom 
assessmentsh 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
X 
X 
X 
X 
Review application instructions 
X 
X 
X 
X 
X 
X 
X 
Schedule/confirm next visit or 
call (for safety follow-up only) 
X 
X 
X 
X 
X 
X 
X 
X 
DB = double-blind; FV = final visit; N/A = not applicable, no visit 
a.
Baseline for the study will be conducted at the same time as Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12. All 
assessments performed at Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12 should not be repeated but should be 
recorded as the same assessments at Baseline for this study.
b.
If a subject withdraws from the study prematurely, all evaluations described under Visit 7/Week 40 (Final Visit) should be performed.
c.
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit). 
d.
Previously assigned subject identification from Study FX2016-11 or Study FX2016-12 will be used in this study.
e.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest. 
f.
A urine pregnancy test will be done at the study site at every visit for all subjects of childbearing potential; home pregnancy tests will be 
dispensed at each visit, if needed, and will be performed at least monthly or whenever there is a suspicion of pregnancy (eg, a missed 
menstrual period). 
g.
The subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final Visit) should not have worsened relative to the subject’s
IGA at Day 0/Baseline of one of the previous double-blind studies. 
h.
The severity of each of the following local rosacea signs/symptoms will be measured:  erythema, telangiectasia, burning/stinging,
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. 
16 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
16 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
7.1
Baseline (also Visit 5/Week 12 [Final Visit] of previous double-blind study) 
•
Obtain a signed and dated ICF.
•
Record subject identification from Study FX2016-11 or Study FX2016-12.
•
Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria
(Section 6.2).
•
Record physical examination results, including weight, from Final Visit (Section 10.3).
•
Record blood pressure and heart rate results from Final Visit (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform IGA (Section 9.1.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Review application instructions to confirm that the subject continues to use the study drug
properly.
•
Dispense 1 study drug kits (ie, 2 canisters) of FMX103 1.5%.
•
Dispense facial cleanser and moisturizer.
•
Schedule/confirm the next study visit.
7.2
Visits 1 through 6, Weeks 4, 10, 16, 22, 28, and 34 (±5 days) 
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit as needed (Section 10.4.1).
•
At Visit 3 (Week 16) only – Collect blood and urine samples for clinical laboratory tests
and send to the central laboratory (Section 10.4.2).
•
Perform IGA (Section 9.1.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
17 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
17 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
•
Review application instructions to confirm that the subject continues to use study drug
properly.
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Dispense 2 study drug kits (ie, 4 canisters) of FMX103 1.5% if required.
•
Confirm that subject continues to use only the provided facial cleanser and moisturizer
and dispense additional quantities as required.
•
Schedule/confirm the next study visit.
7.3
Visit 7, Week 40/Final Visit (±5 days) or Early Termination 
•
Perform physical examination, including weight (Section 10.3).
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform IGA (Section 9.1.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.2).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 7/Week 40 if
required (Section 7.4).
7.4
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit). 
Follow up on adverse events and any new concomitant medications will be recorded. 
18 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
18 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
8 
STUDY TREATMENTS 
This is an open-label study; all subjects will receive FMX103 1.5% minocycline foam. 
8.1 
Treatment Administered 
The description of study drug kits and treatment is shown in Table 2. 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 
Dosage form description: 
Foam containing minocycline HCl 1.5% 
Package description: 
2 canisters of FMX103 1.5%, each canister containing 35 g of the clinical 
trial supply foam 
Daily dose: 
As needed application of a sufficient amount of foam to cover the whole face. 
Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% active) 
of minocycline. 
Cumulative maximal dose over 
40 weeks: 
Up to approximately 2100 mg of minocycline assuming application of 0.5 g 
of FMX103 1.5% foam once daily to the face for 280 days. 
Dispensing: 
Up to 2 kits consisting of 2 canisters/kit (ie, 4 canisters total) dispensed at 
Baseline and Visits 1-6 (Weeks 4-34). Up to a total of 14 kits (28 canisters) 
dispensed to the subject for the study.   
8.1.1
Dosing Instructions 
At enrollment, subjects will receive supplies of active FMX103 1.5% minocycline foam. 
Up to 2 study drug kits consisting of 2 canisters/kit (ie, 4 canisters total of investigational drug) 
will be dispensed at Baseline and Visits 1 through 6 (Weeks 4 through 34). Subjects will be 
instructed to express a small amount of study drug from the canister onto the finger tips and then 
apply as a thin layer over the whole face. Additional drug may be used as needed to assure the 
entire face is treated. Sufficient product will be dispensed at each visit to allow continuation of 
treatment as required. 
Study drug should be applied at approximately the same time each day, about 1 hour before 
bedtime. 
Treatment during this open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment if there is clinical improvement or resolution of 
rosacea. Even if treatment is suspended temporarily, the subject will continue in the study and 
will attend all scheduled clinic visits. If at any time the rosacea recurs or worsens, treatment may 
be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
8.1.2
Manufacturer 
The manufacturer of the investigational product is
 
 
19 of 83
CCI

Privileged and Confidential 
Clinical Protocol:  Version 2 
19 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
8.1.3
Labeling of Study Drug 
The Sponsor or designee will label study drug supplies according to the requirements of the 
Code of Federal Regulations (21CFR§ 210, Subpart G-Packaging & Labeling Control). 
The labels of the investigational (test) product will contain appropriate information as required 
by regional regulatory authorities and include, as needed, the following information: 
•
Name and address of the Sponsor
•
Protocol number
•
Product name/dosage form/mode of administration
•
Kit Number/Canister Number
•
Site number/Subject number
•
Name and address of manufacturer
•
Date of manufacture
•
Lot/batch number
•
Canister contents
•
Storage conditions
•
Caution statements, as follow:
o
“New Drug – Limited by Federal Law to Investigational Use”
o
“Flammable”
o
“Shake well before use”
o
“Keep out of the reach of children”
The composition, pharmaceutical quality, batch number, and expiration date of the 
investigational (test) product will be traceable via the kit number. 
8.1.4
Storage of Study Drug 
FMX103 1.5% canisters must be stored at 2°C – 8°C until being dispensed to the subject. 
Subsequently, the canisters must be stored at 20°C – 25°C (refer to USP Controlled Room 
Temperature). The Investigator will be responsible for the suitable storage of the investigational 
product in compliance with the storage instructions and must restrict access to the study 
personnel only. 
8.2
Study Drug Accountability 
The Investigator will have overall responsibility for the study drug. The Investigator or designee 
will verify the contents of the drug shipment and confirm receipt of the study drug in the 
Interactive Response Technology (IRT) system. In addition, an accurate study drug dispensing 
record that specifies the date and amount dispensed to each subject must be kept. This inventory 
record must be available for inspection by representatives of the Sponsor and is subject to 
20 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
21 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
If a subject is taking anticoagulant therapy, he or she should be advised that a downward 
adjustment of their anticoagulant dose may be required. 
See the FMX103 investigator’s brochure (IB) for information about tetracyclines and possible 
drug-drug interactions. 
8.8
Use of Contraception 
Tetracycline-class antibiotics can cause fetal harm when administered to a pregnant woman. 
Tetracycline-class antibiotics used during tooth development (last half of pregnancy, infancy, and 
childhood to the age of 8 years) may cause permanent discoloration of teeth (yellow-gray-
brown). 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. Females of childbearing potential include any female who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation/occlusion, or bilateral oophorectomy) or who is not postmenopausal (defined as 
amenorrhea >12 consecutive months). Females of childbearing potential must have a negative 
urine pregnancy test and, if they are sexually active or become sexually active during the study, 
must use an effective method of birth control such as those in the follow list during the course of 
the study. The following is not an all-inclusive list; the subject must discuss with the Investigator 
the most appropriate form of birth control: 
•
Hormonal methods
o
Oral contraceptives – (Oral antibiotics may lessen the effectiveness of oral
contraceptives. Therefore, a second form of birth control must be utilized in
subjects using oral contraceptives.)
o
Implant
o
Injection
o
Transdermal patch
o
Intravaginal ring
•
Intrauterine device (hormonal or non-hormonal)
•
Barrier methods
o
Condom (male or female) with spermicide
o
Diaphragm with spermicide
•
Complete abstinence
8.9
Treatment Compliance 
Each subject is to be instructed on the importance of following the dosing schedule and returning 
all study drug kits (empty/used/unused) at the appropriate visits. The study site personnel will 
22 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
22 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
question each subject on study drug use since the last visit. A subject who deviates significantly 
from the prescribed dosage will be counseled. 
9
EFFICACY ASSESSMENTS 
Every attempt must be made to ensure the same evaluator performs the efficacy evaluations for a 
particular subject throughout the study; when this is not possible, another approved evaluator 
may perform the evaluations. Following are the methods and scales that will be used to measure 
each of the efficacy parameters to be performed. 
9.1
Primary Efficacy Assessments 
The efficacy assessments will include the inflammatory lesion counts and the IGA of severity of 
disease and will be performed by the Investigator/evaluator. 
9.1.1
Lesion Counts 
The number of papules, pustules, and nodules will be counted and the numbers recorded. Facial 
area lesion counts will be made for the forehead, left and right cheeks, nose, and chin. The lesion 
counts performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will 
constitute the Baseline value for this study. Lesion counts will be repeated at Visit 1 (Week 4), 
Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), 
and Visit 7 (Week 40/Final Visit). 
9.1.2
Investigator Global Assessment 
The Investigator will also assess the global severity of rosacea using the IGA scale as described 
in Table 3. The IGA performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) will constitute the Baseline value for this study. Assessment will be repeated 
at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), 
Visit 6 (Week 34), and Visit 7 (Week 40/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 
Score 
Grade 
Description 
0 
Clear 
No inflammatory papules or pustules 
1 
Almost clear 
Few inflammatory papules or pustules 
2 
Mild 
Several inflammatory papules or pustules 
3 
Moderate 
Moderate number of inflammatory papules or pustules and no nodules 
4 
Severe 
Many inflammatory papules or pustules, and up to 2 nodules 
9.2
Secondary Efficacy Assessments 
9.2.1
Subject Satisfaction Questionnaire 
A Subject Satisfaction Questionnaire (Appendix 1) will be administered at Visit 7 
(Week 40/Final Visit). 
23 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
23 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
10
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
the monitoring of AEs (volunteered, observed, and elicited by general questioning in a non-
suggestive manner), clinical laboratory tests, vital signs, physical examinations, and local signs 
and symptom assessments (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) 
scores. 
10.1
Concomitant Medications 
All medications that the subject is currently taking or any change in medication or dosage since 
the last visit will be documented throughout the study. The reason for use or change of dose of a 
concomitant therapy may need to be reported as an AE. 
10.2
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all visits. All BP measurements will be 
made using a sphygmomanometer with an appropriate cuff size for the individual subject. 
Measurements will be taken while the subject is seated after at least 5 minutes at rest. 
10.3
Physical Examination 
A complete physical examination (excluding the genitourinary examination), including body 
weight, will be performed at Baseline (ie, Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) and at Visit 7 (Week 40/Final Visit). 
10.4
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at Baseline (ie, Visit 5/Week 12 
[Final Visit] in Study FX2016-11 or Study FX2016-12) and at Visit 3 (Week 16) and Visit 7 
(Week 40/Final Visit). All clinical laboratory tests will be analyzed by a central laboratory. 
Table 4 presents the specific clinical laboratory tests to be evaluated. 
Please refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples. 
24 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
24 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Table 4 
Clinical Laboratory Tests – Study FX2016-13 
Hematology 
Urinalysis 
Serum chemistry 
Hematocrit 
Hemoglobin 
Platelet count 
Red blood cell (RBC) 
count 
White blood cell (WBC) 
count with differential 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes esterase 
pH 
Protein 
Specific gravity 
Urine pregnancy test performed at the site 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase 
Aspartic acid transaminase (AST) 
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Creatinine kinase 
Gamma glutamyl transferase (GGT) 
Globulin 
Glucose 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (if elevated obtain 
direct bilirubin) 
Total protein 
Uric acid 
10.4.1
Urine Pregnancy Test 
A urine pregnancy test will be performed at the study site on all females of childbearing potential 
at all study visits and when a subject withdraws from the study prematurely. In addition, home 
pregnancy tests will be dispensed at each study visit to all female subjects of a childbearing 
potential and will be performed at least monthly and whenever there is a suspicion of pregnancy 
(eg, a missed or late menstrual period). 
10.4.2
Sample Collection, Storage, and Shipping 
Sample collection kits, requisition slips, and shipping boxes will be supplied by the central 
laboratory. Sample collection procedures and shipping instructions will be detailed in the 
laboratory manual. Study sites must be equipped to store the samples according to the laboratory 
manual procedures before shipping to the central laboratory. 
10.5
Other Safety Measurements 
10.5.1
Local Signs and Symptom Assessments 
Local signs and symptom assessments of the skin at the application sites measured at 
Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will constitute Baseline 
values for this study.  Assessments will be repeated at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 
(Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), and Visit 7 (Week 40/Final 
Visit). The following local signs and symptoms will be measured:  erythema, telangiectasia, 
25 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
25 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
burning/stinging, flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation. The score for signs will be determined by the Investigator and must represent 
the subject’s condition at the time of the evaluation; the score for symptoms (ie, burning/stinging, 
flushing/blushing) should be scored based on the subject’s symptoms reported for the previous 
3 days. 
These signs/symptoms should not be included as AEs, unless a sign/symptom is believed to have 
been related to the study drug or is the reason for discontinuation from the study. 
10.5.1.1
Erythema (Clinical Erythema Assessment Scale) 
Erythema of the face will be graded according to the following scale: 
•
0 = clear skin/no signs of erythema
•
1 = almost clear of erythema, slight redness
•
2 = mild erythema, definite redness
•
3 = moderate erythema, marked redness
•
4 = severe erythema, fiery redness
10.5.1.2 
Telangiectasia 
The severity of facial telangiectasia will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  scattered telangiectasia
•
2 = Moderate:  numerous telangiectasia
•
3 = Severe:  dense telangiectasia forming sprays of vessels
10.5.1.3 
Burning/Stinging 
The severity of facial burning/stinging will be graded according to the following scale: 
•
0 = None:  no warm or burning sensation
•
1 = Mild:  slight warm tingling/stinging sensation; not really bothersome
•
2 = Moderate:  constant or intermittent warm tingling/stinging sensation that is somewhat
bothersome
•
3 = Severe:  bothersome warm to hot tingling/stinging sensation
26 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
26 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
10.5.1.4 
Flushing/Blushing 
The severity of facial flushing/blushing will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic episodes lasting for a few moments to several minutes
•
2 = Moderate:  intermittent episodes lasting for greater than 30 minutes
•
3 = Severe:  almost constant episodes lasting for several hours
10.5.1.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
•
0 = None
•
1 = Mild
•
2 = Moderate
•
3 = Severe
10.5.1.6 
Itching 
The severity of facial itching will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic itching lasting for a few moments to several minutes
•
2 = Moderate:  intermittent itching lasting for greater than 30 minutes
•
3 = Severe:  almost constant, intense itching lasting for several hours
10.5.1.7 
Peeling/Desquamation 
The severity of facial peeling/desquamation will be graded according to the following scale: 
•
0 = No peeling
•
1 = Mild:  small, scattered areas of scaling/flaking
•
2 = Moderate:  larger, contiguous areas of scaling/flaking
•
3 = Severe:  pronounced flaking/shedding scales covering entire application area
10.5.1.8 
Hyperpigmentation 
The severity of facial skin hyperpigmentation will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  few scattered, small areas of light hyperpigmentation
•
2 = Moderate:  larger or more intense areas of hyperpigmentation
•
3 = Severe:  intense, extensive hyperpigmentation
27 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
27 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
10.6
Adverse Events 
10.6.1
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator. Adverse events will be recorded at each visit on the appropriate case report 
form (CRF). Every attempt should be made to describe the AE in terms of a diagnosis. If a clear 
diagnosis has been made, individual signs and symptoms will not be recorded unless they 
represent atypical or extreme manifestations of the diagnosis, in which case they should be 
reported as separate events. If a clear diagnosis cannot be established, each sign and symptom 
must be recorded separately. 
Subjects should be asked whether, since the time of the last observation or visit, they had any of 
the following: 
•
Experienced any changes in well-being
•
Used any new medications
•
Changed medication regimens (both prescription and OTC)
•
Were admitted to a hospital or had any accidents
•
Developed unusual headaches or changes in vision
With exception to the above, all questions should be of a general nature and should not suggest 
symptoms. 
When an AE is suspected, all relevant evaluations will be performed and appropriate treatment 
provided. Additional follow-up will be done as necessary (Section 10.6.4) and recorded in the 
subject’s source documents, and the results will be provided to the Sponsor. 
For AE definitions and reporting requirements, refer to Section 10.6.2 and Section 10.6.3, 
respectively. 
10.6.2
Adverse Event Definitions 
10.6.2.1
Adverse Events 
An AE is any unfavorable or unintended sign, symptom, or disease that appears or worsens in a 
subject after the subject signs the ICF for a clinical study. 
Examples of what may be considered an AE include any of the following: 
•
A new illness.
•
An exacerbation of a sign or symptom of an underlying condition or of a concomitant
illness unrelated to participation in the clinical study or an effect of the study drug or
comparator drug.
No causal relationship with the study drug is implied by the use of the term “adverse event.” An 
exacerbation of a pre-existing condition/illness is defined as a more frequent occurrence or as an 
increase in the severity of the pre-existing condition/illness during the study. Planned or elective 
28 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
28 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
surgical procedures for pre-existing conditions that have not worsened are not AEs. However, 
any complication that occurs during a planned or elective surgery is an AE (Note:  If the event 
meets the criteria for a serious adverse event [SAE], such as an extended hospitalization, it will 
be considered an SAE). Conditions leading to unplanned surgical procedures may also be AEs. 
10.6.2.2
Serious Adverse Events 
A serious adverse event (SAE) is any AE that: 
•
Results in death.
•
Is life-threatening.
(Note:  The term “life-threatening” refers to any AE that, as it occurs, puts the subject at
immediate risk of death. It does not refer to an AE that hypothetically might have caused
death if it were more severe.)
•
Results in hospitalization or prolongation of current hospitalization (not including
hospitalization for a pre-existing condition that has not increased in severity or frequency
from the subject’s underlying medical condition prior to entry into the study).
•
Results in persistent or significant disability/incapacity.
•
Is a congenital anomaly/birth defect in the offspring of a subject.
•
Is another serious (important medical events) event.
(Note:  Important medical events may not be immediately life-threatening or result in
death or hospitalization but may be considered serious when, based upon appropriate
medical judgment, they may jeopardize the subject or require medical or surgical
intervention to prevent one of the outcomes listed above. Examples of such medical
events include allergic bronchospasm requiring intensive treatment in an emergency room
or at home; blood dyscrasias or convulsions that do not result in inpatient hospitalization;
or development of drug dependency or drug abuse.)
SAEs will be reported by the Sponsor to the regulatory authorities as required. 
10.6.2.3
Severity of Adverse Events 
The severity of an AE refers to the extent to which it affects the subject’s daily activities and 
differs from “serious”, which is a regulatory classification. Severity will be categorized 
according to the following criteria: 
•
Mild:  The symptom has a negligible effect or no impairing effect on the subject’s normal
function.
•
Moderate:  The symptom impairs the subject’s normal function to some extent.
•
Severe:  The symptom has an obvious, significantly impairing effect on the subject’s
normal function.
29 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
29 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
10.6.2.4
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to the study drug and will be categorized according 
to the following criteria: 
•
Unlikely:  There is no medical evidence to suggest that the AE may be related to study
drug usage, or there is another more probable medical explanation.
•
Possible:  There is medical evidence to suggest that there is a reasonable possibility that
the AE may be related to study drug usage. However, other medical explanations cannot
be excluded as a possible cause.
•
Probable:  There is strong medical evidence to suggest that the AE is related to study
drug usage.
10.6.2.5
Adverse Events Expectedness 
Expected AEs are defined as those described in the FMX103 IB. If an event increases in intensity 
or severity from that described in the IB, it will be considered unexpected. 
10.6.3
Reporting Adverse Events 
Adverse events that occur from the time of informed consent completion of the last study visit 
should be reported. Any AE that the Investigator becomes aware of that occurs within 30 days of 
study completion or withdrawal should also be reported. 
Any SAEs occurring in a subject receiving study drug must be reported to the Sponsor within 
24 hours of the site being informed of the event, even if the event does not appear to be drug 
related. The report must be done by faxing the completed SAE Report Form to the Sponsor. Any 
pertinent follow-up information should be provided in a similar manner. Contact information is 
provided below: 
Foamix Pharmaceuticals Inc./Premier Research 
Pharmacovigilance 
Phone:  +1 215-282-5434 
Fax:  +1 215-972-8765 
Email:  globalPv-US@premier-research.com 
10.6.4
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until they resolve or the subject stabilizes (in the opinion of the Investigator), or for 30 
days, whichever is shorter. Investigators and the Sponsor will decide if longer follow-up is 
appropriate on a case-by-case basis. Subjects who experience any clinically significant AE will 
remain under medical supervision until the Investigator or the Sponsor’s medical monitor deems 
the AE to be resolved, the subject is stable, or the event is no longer serious enough to warrant 
follow-up. 
30 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
30 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Laboratory values that are abnormal and not assessed as AEs may be followed at the discretion 
of the Investigator or the Sponsor’s medical monitor until they resolve or the subject is stable. 
10.6.4.1
Pregnancy Reporting 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. The ICF that the subject signs must document this discussion. 
If a subject or an Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of site pregnancy testing are 
available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
Urine pregnancy tests will be performed on all females of childbearing potential as described in 
Section 10.4.1. 
During the study, all female subjects of childbearing potential should be instructed to contact the 
Investigator immediately if they suspect they might be pregnant (eg, positive home pregnancy 
test [Section 10.4.1], missed or late menstrual period, etc.). If a subject or Investigator suspects 
that the subject may be pregnant at any time before or during the study, the study drug must be 
withheld until the results of site pregnancy testing are available. The Sponsor and site monitor 
must be notified and relevant information collected on the appropriate form. If pregnancy is 
confirmed, the subject must be withdrawn from the study and the Sponsor and site monitor 
notified. Additional relevant information about the confirmed pregnancy will be recorded on the 
appropriate form(s); pregnancy will not be captured as an AE. 
The subject should be followed until the outcome of the pregnancy is known. 
10.6.5
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be flagged when 
reported to the site. The Investigator will determine which out-of-range laboratory test results 
should be characterized as clinically significant and annotate the laboratory report. If a clinically 
significant laboratory abnormality requires treatment or is the reason for a subject being 
discontinued from the study, the abnormal result must also be classified as an AE. 
10.7
Appropriateness of Safety Measurement 
The safety assessments to be used in this study are standard safety measures in clinical trials. 
11
STATISTICAL DESIGN AND ANALYSIS 
11.1
Statistical Analysis Plan 
A detailed statistical analysis plan will be finalized prior to database lock. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated; however, the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
31 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
31 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. 
11.2
Determination of Sample Size 
The planned minimum enrollment is 400 male and female subjects who were previously enrolled 
in Study FX2016-11 or Study FX2016-12. The sample size is intended to ensure that at least 300 
subjects continue to self-administer the study drug as needed for at least 6 months and 100 
subjects continue for at least 1 year (ie, combined duration of treatment between the double-blind 
and open-label studies). The number of subjects at each site will be determined by the rate of 
recruitment in Studies FX2016-11 and FX2016-12. No statistical rationale for subject number is 
provided. 
11.3
Analysis Populations 
The following populations are defined for analysis: 
•
The All-Treated population:  all subjects who use study drug at least once. This population
will be used for safety and efficacy analyses.
11.4
Subject Accounting, Demographics, and Baseline Characteristics 
Demographics, baseline characteristics, medical and surgical history (FX2016-11 and 
FX2016-12) and prior and concomitant medications will be summarized. Study completion 
status and reasons for discontinuation will also be displayed. 
11.5
Efficacy Endpoints 
11.5.1
Primary Efficacy Endpoints 
The primary efficacy endpoints are: 
•
The absolute change in the inflammatory lesion count at Week 40 compared to Baseline.
•
The dichotomized IGA score where success is defined as a 2-step improvement resulting
in a 0 (clear) or 1 (almost clear) score at Week 40 compared to Baseline.
For the efficacy analyses, Baseline will be defined as Day 0/Baseline of the initial double-blind 
study, ie either Study FX2016-11 or Study FX2016-12. The changes from Baseline of Studies 
FX2016-11 and FX2016-12 to Week 40 of this study for each of the primary endpoints will be 
calculated. Descriptive statistics (number of subjects, mean, median, standard error, coefficient 
of variation, minimum and maximum) for each variable will be presented for each visit and for 
the changes from Baseline. No hypothesis testing will be performed. 
11.5.2
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
•
The absolute change from Day 0/Baseline in the inflammatory lesion count at Weeks 4,
10, 16, 22, 28 and 34.
32 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
32 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
•
The dichotomized IGA score where success is defined as a 2-step improvement resulting
in a 0 (clear) or 1 (almost clear) score at Weeks 4, 10, 16, 22, 28 and 34 compared to Day
0/Baseline.
•
The percent change in inflammatory lesion count at Weeks 4, 10, 16, 22, 28 and 34
compared to Day 0/Baseline.
•
The Subject Satisfaction Questionnaire administered at Visit 7 (Week 40/Final Visit).
11.6
Safety Endpoints 
Safety endpoints will be reported on the All Treated population. Safety assessments will be 
summarized in tables using descriptive statistics and in individual by-subject listings. No 
statistical tests will be performed for any of the safety assessments. For the safety analyses, 
Baseline will be defined as Day 0/Baseline of the initial double-blind study, ie either Study 
FX2016-11 or Study FX2016-12. 
Treatment-emergent AEs (TEAEs) will be defined as events that emerge having been absent 
prior to enrollment in this study or worsen relative to the pre-enrollment state. Summaries of AEs 
will be limited to TEAEs. The number and percentage of subjects reporting events under each 
System Organ Class (SOC) and preferred term (PT) will be summarized. At each level of 
summarization, a subject will be counted only once if he or she reported one or more events. The 
severity of TEAEs and relationship to the study drug will be summarized in a similar manner. 
For summaries of relationship to the study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE severity, a subject will be classified according to 
the highest severity. All TEAEs continuing, but not worsening, after enrollment in this study will 
also be tabulated. 
Treatment-emergent AEs, vital signs, physical examination assessments and clinical laboratory 
measurements will be summarized using descriptive statistics. For vital signs, change from 
Baseline values will also be summarized. For all safety variables, subject data listings will be 
provided. 
11.6.1
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to SOC and PT. 
Summaries of SAEs and subjects who withdraw from the study prematurely due to AEs will be 
presented. 
11.6.2
Local Signs and Symptoms Assessments 
Local signs and symptom assessments will include active assessments of erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, itching, 
peeling/desquamation, and hyperpigmentation using the scales described under Section 10.5.1. 
Local signs and symptom assessments will be summarized using descriptive statistics at Baseline 
and at each post-Baseline time point. Changes from Baseline will also be summarized. 
33 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
33 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
11.6.3
Clinical Laboratory Results 
Shift tables for each clinical laboratory test will cross-tabulate the number of subjects with values 
below the laboratory reference range (low), values within the laboratory reference range 
(normal), or above the laboratory range (high) at Baseline with the number of subjects with low, 
normal, or high values at the Final Visit.  
A listing of subjects with treatment-emergent clinically significant abnormal laboratory values 
will be presented for each treatment group. Clinical significance is based on the Investigator’s 
judgment. 
11.7
Interim Analysis 
No interim analysis is planned. 
12
STUDY MANAGEMENT 
12.1
Monitoring 
The Investigator will be responsible for preparing and maintaining adequate and accurate source 
documents (medical records, raw data collection forms, etc.) designed to record all observations 
and other pertinent data for each subject treated with the study drug. The Investigator will allow 
representatives of the Sponsor, contract designees, authorized regulatory authority inspectors, 
and the institutional review board (IRB) to have direct access to all documents pertaining to the 
study. The Investigator is to notify the Sponsor immediately of any regulatory authority 
inspections. The Investigator will be informed about the outcome of any Sponsor audit. 
This study will be monitored regularly, by or under supervision of a monitor from the Sponsor. 
The frequency of monitoring visits will be agreed upon by the Sponsor’s representative and the 
study site. 
Monitoring visits will take place on a regular basis according to the enrollment rate and number 
of subjects enrolled at each investigational site. During these visits, the monitor will check the 
completion of the CRF entries, compliance with the study protocol and with Good Clinical 
Practice (GCP)-ICH, and their agreement with the source data. The monitor will also verify the 
correct use of the study drug. At the final visit, the monitor will check all remaining material, 
including the remaining quantities of the study drug, and will organize their return to the Sponsor 
or designee. At each visit, the Investigator and staff will be expected to cooperate with the 
Sponsor’s representative(s) for the purposes of review and verification of protocol compliance, 
AE reporting, CRFs, source documents, clinical supplies and inventory records, and any 
additional records as may have been previously arranged between the Investigator and the 
Sponsor’s representative(s). 
The Investigator and/or other designated study personnel are expected to contact the Sponsor’s 
clinical research associate, as needed, regarding study concerns and/or questions. Contact 
information is provided in the Study Reference Manual for the site. 
12.2
Protocol Amendments 
The Sponsor may propose to amend this protocol at any time. 
34 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
34 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
No change to the protocol will be implemented until the Sponsor and the IRB have reviewed and 
approved the amendment. 
12.3
Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the IRB-approved protocol 
(intentional or unintentional). All deviations are to be documented at the site and reported to the 
IRB according to their guidelines. 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety. All such procedures must have written documentation and be 
promptly reported to the Sponsor and IRB. 
12.4
Withdrawal of Subjects 
Subjects or Investigators may choose to discontinue a subject’s participation in the study at any 
time. Subjects may be withdrawn from the study because of any of the following: 
•
Adverse Event:  An AE that in the opinion of the Investigator or Sponsor suggests that 
continued participation in the study is not in the subject’s best interest for safety reasons. 
All AEs that are present when the subject withdraws from the study will be followed as 
described in Section 10.6.4.
•
Abnormal Laboratory Result:  Any clinically significant laboratory abnormality that 
requires withdrawal of the subject from the study should be considered an AE leading to 
withdrawal. If possible, laboratory tests will be repeated for any results that were 
clinically significantly abnormal until the abnormality is resolved or the subject is stable 
to the satisfaction of the Investigator in consultation with the medical monitor.
•
Lost to Follow-up:  Confirmed at minimum by two phone calls and a traceable letter 
without answer.
•
Subject Request:  Subject requests, for any reason (eg, AE), to be withdrawn or 
withdraws his or her consent.
•
Protocol Deviation:  A subject may be withdrawn from the study at the discretion of the 
Investigator or Sponsor due to poor compliance with protocol requirements that may 
compromise the study results or subject safety.
•
Other:  Other reasons include but are not limited to Investigator decision that it is in the 
subject’s best interest to be withdrawn, administrative reasons, subject’s relocation, etc. If 
a subject becomes pregnant during the study, she will be withdrawn from the study and 
followed through conclusion of the pregnancy (Section 10.6.4.1). 
If a subject is withdrawn from the study following the start of study drug, all Visit 7 
(Week 40/Final Visit) assessments should be completed. Subjects withdrawn from the study will 
not be replaced. 
35 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
35 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
12.5
Termination of the Study 
The study may be terminated at any time at the request of the Sponsor or a regulatory authority, 
with proper and timely notification of all parties concerned. The IRB will be informed promptly 
and the Sponsor or the Investigator will supply reason(s) for the termination or suspension, as 
specified by the applicable regulatory requirements. Otherwise, the study is considered 
terminated upon completion of all subject treatments and evaluations. 
12.6
Publication Policy 
The data obtained in this study are the property of the Sponsor, who will make reasonable efforts 
to assure that the results are published in a peer-reviewed journal. Since some of the information 
concerning the investigational product and development activities at the Sponsor may be strictly 
confidential in nature, any manuscript or other presentation of data must first be reviewed by the 
Sponsor before its submission. 
13
ETHICS 
13.1
Conduct of the Study 
This study will be conducted in accordance with the ICH Harmonized Tripartite Guideline for 
GCP, 1997; the US Title 21 CFR parts 50, 56, and 312; and the ethical principles that have their 
origin in the Declaration of Helsinki. The study will not begin until all of the requirements of the 
appropriate regulatory authorities have been fulfilled. 
13.2
Institutional Review Boards 
This protocol (and any changes), all consent forms, and subject consent procedures must be 
reviewed and approved by a properly constituted IRB. The information presented to the IRB at 
the time initial approval is sought must include any plans for subject recruitment that involve 
advertising or other direct contact with potential subjects outside of the physician-subject 
relationship. A letter of approval issued by the IRB must be sent to the Sponsor prior to initiation 
of the study. Any changes made to the protocol must be approved by the IRB prior to 
implementation, except where needed to eliminate a potential imminent safety hazard to the 
subjects. In this case, immediate implementation may take place followed by IRB approval. 
Review and approval by the IRB for continuation of the study must take place at least once a 
year. 
13.3
Written Informed Consent 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential benefits and risks of participation to each 
subject prior to his or her entry into the study (ie, before examinations and procedures associated 
with selection for the study are initiated). Each subject will have ample opportunity to ask 
questions and will be informed about the right to withdraw from the study at any time without 
any disadvantage and without having to provide reasons for this decision. 
Following this informative discussion, the subject will be asked if he or she is willing to sign a 
statement of informed consent. Only subjects who voluntarily sign the ICF may enter the study. 
36 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
36 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
The ICF must be reviewed and approved by the Sponsor and the IRB prior to use. 
The original signed ICF will remain in the Investigator’s files. The Investigator or designee will 
indicate in each subject’s source documents that he or she has informed the subject about the 
study and its procedures, the subject has signed and dated the ICF, and the subject has been given 
a copy of the documents. The Investigator or designee will inform subjects of any new 
information that may be relevant to the subject’s willingness to continue in the study. 
13.4
Subject Confidentiality 
The Sponsor will ensure that the following have permission to review all study-related 
documents:  monitor, auditor, IRB, and regulatory authorities. The subject’s identity and 
study-related records will remain confidential throughout the duration of the study data 
collection and reporting process. 
The investigative site assigns a unique subject identification code to each potential study subject. 
The identification code protects the subject’s identity and is used in lieu of the subject’s name 
when reporting subject data. The data will always maintain the confidentiality of the subject. 
The Investigator or designee will review the subject data, which will be referenced using the 
subject identifier. At the conclusion of the study, the data obtained may be presented to regional 
regulatory authorities but the subject’s identity will not be revealed. In addition, if any clinical 
data obtained from the study is published in scientific journals or presented at scientific meetings 
the subject’s identity will not be revealed. 
13.5
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, source 
documentation corresponding to all information contained in the CRFs, signed ICF forms, 
relevant correspondence, and all other supporting documentation) until at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years after the formal 
discontinuation of clinical development of the investigational product. These documents should 
be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted. Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same time period. Custody of the records may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies. Written notice of 
transfer must be submitted to the Sponsor. The Investigator must contact the Sponsor prior to 
disposing of any study records. 
13.6
Financing 
Funding for this study will be agreed upon between the Investigator and the Sponsor and will be 
confirmed in writing before the study starts. 
Completion of Financial Disclosure Forms will be required before the study starts. Any additions 
to the primary site personnel will necessitate the completion of new Financial Disclosure Forms. 
37 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
37 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
This information will also be collected at site closure and 1 year after the completion of the 
study. 
14
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and the Investigator will take all steps possible to ensure the accuracy, consistency, 
completeness, and reliability of the data, including participating in an Investigator meeting 
and/or site initiation visit, routine site monitoring, review of CRFs against source documents, and 
quality control checks. 
In addition, a representative from the Sponsor’s Clinical Quality Assurance Department may 
conduct periodic audits of the study processes, including, but not limited to, auditing the clinical 
site, laboratories, vendors and contract research organizations CROs, the clinical database, and 
the final study report. 
15
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, eCRFs developed through a validated, Electronic 
Records/Electronic Signatures-compliant platform (US Title 21 CFR Part 11). Foamix Clinical 
Data Management department or designee will create the eCRFs and corresponding clinical 
database based on the final protocol. 
All site personnel who will be using this system will receive formal training on the system, after 
which each person will be issued a unique username and password. Only the person who owns 
the username and password will enter the system using that username and password. For data 
security reasons and to be in compliance with regulatory guidelines, usernames and passwords 
are not transferable. 
The Investigator is responsible for all data entered via the remote data capture (RDC) system 
eCRFs and must confirm the accuracy of the data by electronically approving (signing) the 
eCRFs. This responsibility includes the timely completion and accuracy of the data entered into 
the eCRFs by their site personnel as well as the review and approval of some data entered 
directly into the database (eg, clinical laboratory results) by an external vendor. The Sponsor will 
review the database to identify data errors or inconsistencies, which will be posted in the RDC 
system as queries for resolution. In addition, the Sponsor may make obvious corrections to the 
data in the database (eg, obvious errors in dates) and so inform the Investigator without issuing a 
query to the site. 
16
REFERENCE LIST 
Not applicable. 
17
STUDY AMENDMENTS 
This section describes the amendment(s) that have been made to the protocol for Study 
FX2016-13. 
Section 17.1 describes the changes made to Protocol FX2016-13 Version 1 issued March 6th, 
2017, via Amendment 1 effective June 22nd, 2017. 
38 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
38 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
17.1 
Amendment 1, effective June 22nd, 2017 
The following is the summary of the changes that were made to Protocol FX2016-11 Version 1 
issued March 6th, 2017. 
Content changes:  
New or changed text is bolded. 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Section 2 Study 
Administrative 
Structure 
Premier Research 
Removal of 
study team 
member due to 
retirement.  
Synopsis 
(Statistical 
Methods) 
Change from baseline of 
Study FX2016-11 and 
Study FX2016-12 to each 
visit from inflammatory 
lesion count and IGA 
will also be summarized. 
The secondary endpoint 
is the Subject 
Satisfaction 
Questionnaire 
administered at Visit 7 
(Week 40/Final Visit). 
The secondary endpoints of 
change from Baseline of 
Study FX2016-11 and 
Study FX2016-12 to each 
visit  in inflammatory 
lesion count, IGA 
treatment success and a 
Subject Satisfaction 
Questionnaire administered 
at Visit 7 
(Week 40/Final Visit) will 
also be summarized. 
Clarification of 
study secondary 
efficacy 
endpoints and 
their statistical 
treatment. 
Section 6.3 
Exclusion 
Criteria 4 
None. 
Subjects are permitted to 
enroll in the study whilst 
laboratory results for 
Final Visit (Week 12) for 
Study FX2016-11 or 
Study FX2016-12 are 
pending receipt. 
Clarification of 
subject study 
qualification 
status while 
laboratory 
results are 
pending receipt. 
39 of 83
PPD

Privileged and Confidential 
Clinical Protocol:  Version 2 
39 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Table 1 Schedule 
of Study 
Assessments and 
Procedures – 
Study FX2016-
13, Footnote f 
A urine pregnancy test 
will be done at the study 
site at every visit for all 
subjects of childbearing 
potential; home 
pregnancy tests will be 
dispensed at each visit 
and will be performed at 
least monthly or 
whenever there is a 
suspicion of pregnancy 
(eg, a missed period). 
A urine pregnancy test will 
be done at the study site at 
every visit for all subjects 
of childbearing potential; 
home pregnancy tests will 
be dispensed at each visit, 
if needed, and will be 
performed at least monthly 
or whenever there is a 
suspicion of pregnancy (eg, 
a missed menstrual 
period). 
Home pregnancy 
tests will be 
dispensed as 
needed and not 
necessarily at 
every visit. 
Section 7.1 
Baseline (also 
Visit 5/Week 12 
[Final Visit] of 
previous double-
blind study) 
Have the subject 
complete the Subject 
Global Assessment 
(Section 9.2.1). 
Have the subject 
complete the Subject 
Satisfaction 
Questionnaire (Section 
9.2.2). 
Text removed. 
Typographical 
error. 
Section 7.2 
Visits 1 through 
6, Weeks 4, 10, 
16, 22, 28, and 
34 (±5 days) 
…and dispense a home 
pregnancy test kit 
(Section 10.4.1). 
…and dispense a home 
pregnancy test kit as 
needed (Section 10.4.1). 
Home pregnancy 
tests will be 
dispensed as 
needed and not 
necessarily at 
every visit. 
Section 7.2 
Visits 1 through 
6, Weeks 4, 10, 
16, 22, 28, and 
34 (±5 days) 
Dispense a home 
pregnancy test kit 
(Section 10.4.1). 
Text removed. 
Repetition from 
previous bullet-
point. 
40 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
40 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis (Study 
Design and 
Methods), Table 
1 footnote c., 
Section 7.4 
Safety Follow-up 
(±5 days).  
A safety follow-up 
telephone call will be 
made 4 weeks after Visit 
7/Week 40 (Final Visit) 
for only those subjects 
who presented with 
either new or on-going 
adverse events at Visit 
7/Week 40 (Final Visit). 
Follow up on these 
adverse events… 
A safety follow-up 
telephone call will be made 
4 weeks after Visit 7/Week 
40. Follow up on adverse
events…
Removal of 
qualifiers for 
safety follow-up. 
Synopsis (Study 
Design and 
Methods), Table 
2, Section 8.1.1 
Dosing 
Instructions 
…involved areas (of the 
face)… 
…whole (entire) face… 
Alignment with 
treatment area 
text within 
FX2016-11 and 
FX2016-12. 
Table 2, Section 
8.1.1 Dosing 
Instructions 
…canister containing 
25 g of the clinical… 
canister containing 35 g of 
the clinical… 
Correction of 
unit pack size. 
Section 8.1.1 
Dosing 
Instructions 
None. 
Study drug should be 
applied at approximately 
the same time each day, 
about 1 hour before 
bedtime. 
Alignment with 
treatment 
application text 
within FX2016-
11 and FX2016-
12. 
41 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
41 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Section 11.5.2 
Secondary 
Efficacy 
Endpoints 
New text. 
The secondary efficacy 
endpoints are: 
The absolute change from 
Day 0/Baseline in the 
inflammatory lesion 
count at Weeks 4, 10, 16, 
22, 28 and 34. 
The dichotomized IGA 
score where success is 
defined as a 2-step 
improvement resulting in 
a 0 (clear) or 1 (almost 
clear) score at Weeks 4, 
10, 16, 22, 28 and 34 
compared to Day 
0/Baseline. 
The percent change in 
inflammatory lesion 
count at Weeks 4, 10, 16, 
22, 28 and 34 compared 
to Day 0/Baseline. 
Addition of 
secondary 
efficacy 
endpoints. 
Section 11.6 
Safety Endpoints New text. 
For the safety analyses, 
Baseline will be defined 
as Day 0/Baseline of the 
initial double-blind study, 
ie either Study FX2016-11 
or Study FX2016-12. 
Clarification of 
Baseline 
timepoint for 
safety analyses. 
Section 11.6 
Safety Endpoints 
Treatment-emergent AEs, 
vital signs, and clinical 
laboratory 
measurements… 
Treatment-emergent AEs, 
vital signs, physical 
examination assessments 
and clinical laboratory 
measurements… 
Section 
incorrectly 
placed. 
42 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
42 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Section 11.6 
Safety Endpoints 
Local signs and symptom 
assessments will include 
active assessments of 
erythema, telangiectasia, 
burning/stinging, 
flushing/blushing, 
dryness/xerosis, itching, 
peeling/desquamation, 
and hyperpigmentation 
using the scales 
described under Section 
10.5.1. 
Text removed to Section 
11.6.2. 
As above. 
Section 11.6.2 
Local Signs and 
Symptoms 
Assessments 
Vital sign and physical 
examination parameters 
will be summarized using 
descriptive statistics at 
Baseline and at each 
post-Baseline timepoint. 
Changes from Baseline 
will also be summarized. 
Local signs and symptom 
assessments will include 
active assessments of 
erythema, telangiectasia, 
burning/stinging, 
flushing/blushing, 
dryness/xerosis, itching, 
peeling/desquamation, and 
hyperpigmentation using 
the scales described under 
Section 10.5.1. 
As above. 
Section 11.6.3 
Baseline is defined as the 
last non-missing value 
prior to enrollment in this 
study. 
Text removed. 
Baseline has 
been defined 
within Section 
11.6. 
43 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
43 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
APPENDIX 1:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 7 (Week 40/Final Visit): 
1.
How satisfied are you with how easy this product is to use?
2. How satisfied are you with how this product feels on your skin after treatment?
3. How satisfied are you with the odor of this product after treatment?
4. How satisfied are you with the color of this product after treatment?
5. How satisfied are you with the ease of application of the product to your skin?
6. How satisfied are you with the ease in which this product fits into your daily routine?
7. How satisfied are you with this product compared to other products you have previously
used for rosacea, such as gels and creams?
8. Overall, how likely are you to use this product with other rosacea treatments?
9. Overall, how likely are you to recommend this product to a friend?
10. Overall, how satisfied are you with this product?
Answers to Questions 1 through 9 will be selected from the following: 
•
1 = Very Satisfied
•
2 = Satisfied
•
3 = Somewhat Satisfied
•
4 = Dissatisfied
•
5 = Very Dissatisfied
The answer to Questions 10 and 11 will be selected from the following: 
•
1 = Very Likely
•
2 = Likely
•
3 = Somewhat Likely
•
4 = Unlikely
•
5 = Very Unlikely
44 of 83

Privileged and Confidential 
Clinical Protocol:  Version 2 
44 of 44 
Final 
Protocol:  FX2016-13 
Date:  22 June 2017 
APPENDIX 2: Acknowledgment Of Receipt And Review Of 
Protocol 
Protocol Number: FX2016-13, Version 2 
Protocol Title: An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate to Severe Facial 
Papulopustular Rosacea (Study FX2016-13) 
I hereby acknowledge receipt and review of the following Protocol: 
1. Version 2, dated June 22nd, 2017
Principal Investigator Name (Print) 
Principal Investigator Signature 
Date of Signature  
(DD MMM YYYY) 
45 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
1 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
CLINICAL PROTOCOL 
Title Page 
Study Title: 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-13 
Product: 
FMX103 1.5% minocycline foam 
Indication Studied: 
Papulopustular Rosacea 
Study Phase: 
3 
Sponsor’s Signatory: 
GCP Statement: 
This study will be conducted in accordance with Good 
Clinical Practice. Essential documents will be archived 
according to CPMP/ICH/135/95 
Date of Protocol: 
06 Mar 2017 
Version of Protocol 
1 
Supercedes: 
None 
Prepared by: 
The Write Company, LLC 
Confidentiality Statement 
This document is the property of Foamix Pharmaceuticals, Inc., and is confidential and proprietary.  The information 
contained herein is believed to be accurate and complete as of the date of preparation.  The contents may not be used, 
divulged, published or otherwise disclosed without the expressed consent of Foamix Pharmaceuticals, Inc. 
46 of 83
PPD

Privileged and Confidential 
Clinical Protocol:  Version 1 
3 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
Synopsis 
Name of 
Sponsor/Company: 
Foamix Pharmaceuticals, 
Inc. 
Individual Study Table Referring to 
Part of the Dossier: 
(For National Authority 
Use Only) 
Name of Finished Product: 
FMX103 
Volume: 
Name of Active 
Ingredient: 
Minocycline hydrochloride 
Page: 
Title of Study: 
An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate 
to Severe Facial Papulopustular Rosacea (Study FX2016-13) 
Protocol No: 
FX2016-13 
Study Centers: 
Multicenter (approximately 80 sites in the USA) 
Publication (reference): 
None 
Primary Objective: 
The primary objective is to show that open-label extended treatment 
with FMX103 1.5%, for up to an additional 40 weeks, is safe and well 
tolerated. 
Study Design and 
Methods: 
This is an open-label, multicenter, 40-week extension study to evaluate 
the long-term safety, tolerability, and efficacy of FMX103 1.5% topical 
foam in the treatment of moderate-to-severe facial papulopustular 
rosacea. Subjects entering this study will have recently participated in 1 
of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy 
studies (FX2016-11 and FX2016-12). At Baseline, subjects must 
demonstrate that they are eligible to continue into Study FX2016-13 
based in part on safety evaluations performed at Visit 5/Week 12 (Final 
Visit) of one of the previous double-blind studies. In addition, the 
subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 
(Final Visit) should not have worsened relative to the subject’s IGA at 
Day 0/Baseline of one of the previous double-blind studies. 
At the completion of Visit 5/Week 12 (Final Visit) in Study FX2016-11 
or Study FX2016-12, subjects may be invited to continue into this 
open-label study for an additional 40 weeks of open-label treatment. A 
minimum of 400 subjects will be enrolled into from Studies FX2016-11 
and FX2016-12. Subjects who elect to continue into this open-label 
study will receive supplies of active FMX103 1.5% minocycline foam. 
Treatment during the open-label study will be guided by each subject’s 
clinical response. The Investigator may elect to suspend treatment of 
some or all facial areas if there is clinical improvement or resolution of 
the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the 
study and will attend all scheduled clinic visits. If at any time the 
48 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
4 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
rosacea recurs or worsens, treatment of the affected areas may be 
resumed. 
Subjects may be discontinued from the study at any time if their disease 
becomes refractory or they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as 
Visit 5/Week 12 (Final Visit) of either Study FX2016-11 or 
Study FX2016-12. Subsequent visits for this open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and 
efficacy evaluations will be performed. Week 40 is the Final Visit 
(Visit 7) of this study. A safety follow-up telephone call will occur 4 
weeks after Final Visit (Visit 7) for only those subjects that present 
with new or on-going adverse events at Week 40 (Final Visit). 
Number of Subjects 
(planned): 
The planned minimum enrollment is a minimum of 400 male and 
female subjects who were previously enrolled in Study FX2016-11 or 
Study FX2016-12. The sample size is intended to ensure that at least 
300 subjects continue to self-administer the study drug as needed for at 
least 6 months and 100 subjects continue for at least 1 year (ie, 
combined duration of treatment between the double-blind and open-
label studies). The number of subjects at each site will be determined 
by the rate of recruitment in Studies FX2016-11 and FX2016-12. No 
statistical rationale for subject number is provided. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years, who had a 
clinical diagnosis of moderate to severe facial papulopustular rosacea at 
the start of the previous double-blind study who completed 12 weeks of 
double-blind treatment in Study FX2016-11 or Study FX2016-12;  are 
willing to continue on open-label treatment with FMX103 in the current 
study and do not have a worsening of disease, determined by IGA, at 
Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment 
of the previous study. 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, self-
administered dosing as needed, for up to 40 weeks. 
Reference Therapy: 
Not applicable. 
Study Duration: 
Subject participation in the study will be up to 44 weeks. 
Endpoints and Outcomes: 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner); clinical laboratory tests; vital signs; physical examinations; 
and local signs and symptom assessments of the skin at the application 
sites (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation scores). 
Efficacy Evaluations 
The efficacy parameters will include inflammatory lesion counts and 
IGA at Baseline and at Weeks 4, 10, 16, 22, 28, 34, and 40 (Final 
Visit). 
49 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
5 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
Statistical Methods: 
The All-Treated population, defined as all subjects who use the study 
drug at least once, will be used for all analyses. Missing data will not be 
imputed. All analyses will be based on observed data. The primary 
endpoints are the absolute change in the inflammatory lesion count 
compared to Baseline and the dichotomized IGA score, where success 
is defined as a 2-step improvement resulting in a 0 (clear) or 1 (almost 
clear) score at Week 40 compared to Baseline. Change from baseline of 
Study FX2016-11 and Study FX2016-12 to each visit from 
inflammatory lesion count and IGA will also be summarized. The 
secondary endpoint is the Subject Satisfaction Questionnaire 
administered at Visit 7 (Week 40/Final Visit). 
No statistical tests will be performed for any of the endpoints. 
The safety and tolerability safety of topical minocycline foam applied 
as needed for an additional 40 weeks will be evaluated using summary 
statistics and individual subject data listings. No statistical tests will be 
performed for any of the safety assessments. 
50 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
6 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
Table of Contents 
Page 
TITLE PAGE ........................................................................................................................................................ 1 
SIGNATURE PAGE ............................................................................................................................................ 2 
SYNOPSIS............................................................................................................................................................. 3 
TABLE OF CONTENTS ..................................................................................................................................... 6 
LIST OF TABLES ................................................................................................................................................ 8 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................................................... 9 
2 
STUDY ADMINISTRATIVE STRUCTURE ........................................................................................10 
3 
INTRODUCTION ....................................................................................................................................11 
4 
STUDY OBJECTIVES ............................................................................................................................11 
4.1 
PRIMARY OBJECTIVE .......................................................................................................................11 
5 
INVESTIGATIONAL PLAN ..................................................................................................................11 
5.1 
OVERALL STUDY DESIGN ................................................................................................................11 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................12 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................13 
7.1 
BASELINE (ALSO VISIT 5/WEEK 12 [FINAL VISIT] OF PREVIOUS DOUBLE-BLIND STUDY) .................15 
7.2 
VISITS 1 THROUGH 6, WEEKS 4, 10, 16, 22, 28, AND 34 (±5 DAYS) ..................................................15 
7.3 
VISIT 7, WEEK 40/FINAL VISIT (±5 DAYS) OR EARLY TERMINATION ...............................................16 
7.4 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................16 
8 
STUDY TREATMENTS ..........................................................................................................................17 
8.1 
TREATMENT ADMINISTERED ............................................................................................................17 
8.1.1 
Dosing Instructions ........................................................................................................17 
8.1.2 
Manufacturer ..................................................................................................................17 
8.1.3 
Labeling of Study Drug ..................................................................................................18 
8.1.4 
Storage of Study Drug ....................................................................................................18 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................18 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................19 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................19 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................19 
8.6 
BLINDING  ........................................................................................................................................19 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................19 
8.8 
USE OF CONTRACEPTION .................................................................................................................20 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................20 
9 
EFFICACY ASSESSMENTS ..................................................................................................................21 
9.1 
PRIMARY EFFICACY ASSESSMENTS..................................................................................................21 
9.1.1 
Lesion Counts.................................................................................................................21 
9.1.2 
Investigator Global Assessment .....................................................................................21 
9.2 
SECONDARY EFFICACY ASSESSMENTS .............................................................................................21 
9.2.1 
Subject Satisfaction Questionnaire .................................................................................21 
10 
SAFETY ASSESSMENTS .......................................................................................................................22 
51 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 1 
7 of 38 
Final 
Protocol:  FX2016-13 
 
Date:  06 Mar 2017 
10.1 
CONCOMITANT MEDICATIONS .........................................................................................................22 
10.2 
VITAL SIGNS ....................................................................................................................................22 
10.3 
PHYSICAL EXAMINATION .................................................................................................................22 
10.4 
CLINICAL LABORATORY TESTS........................................................................................................22 
10.4.1 
Urine Pregnancy Test .....................................................................................................23 
10.4.2 
Sample Collection, Storage, and Shipping .....................................................................23 
10.5 
OTHER SAFETY MEASUREMENTS .....................................................................................................23 
10.5.1 
Local Signs and Symptom Assessments ........................................................................23 
10.5.1.1 Erythema (Clinical Erythema Assessment Scale) .........................................24 
10.5.1.2 Telangiectasia ................................................................................................24 
10.5.1.3 Burning/Stinging ...........................................................................................24 
10.5.1.4 Flushing/Blushing .........................................................................................25 
10.5.1.5 Dryness/Xerosis ............................................................................................25 
10.5.1.6 Itching ...........................................................................................................25 
10.5.1.7 Peeling/Desquamation ...................................................................................25 
10.5.1.8 Hyperpigmentation ........................................................................................25 
10.6 
ADVERSE EVENTS ............................................................................................................................26 
10.6.1 
Method of Determining Adverse Events ........................................................................26 
10.6.2 
Adverse Event Definitions .............................................................................................26 
10.6.2.1 Adverse Events ..............................................................................................26 
10.6.2.2 Serious Adverse Events .................................................................................27 
10.6.2.3 Severity of Adverse Events ...........................................................................27 
10.6.2.4 Relationship of Adverse Events to Study Treatments ...................................28 
10.6.2.5 Adverse Events Expectedness .......................................................................28 
10.6.3 
Reporting Adverse Events ..............................................................................................28 
10.6.4 
Adverse Event Follow-up ...............................................................................................28 
10.6.4.1 Pregnancy Reporting .....................................................................................29 
10.6.5 
Clinically Significantly Abnormal Laboratory Results ..................................................29 
10.7 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................29 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................29 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................29 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................30 
11.3 
ANALYSIS POPULATIONS .................................................................................................................30 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND BASELINE CHARACTERISTICS .................................30 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................30 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................30 
11.5.2 
Secondary Efficacy Endpoint .........................................................................................30 
11.6 
SAFETY ENDPOINTS .........................................................................................................................31 
11.6.1 
Adverse Events ...............................................................................................................31 
11.6.2 
Vital Signs and Physical Examinations ..........................................................................31 
11.6.3 
Clinical Laboratory Results ............................................................................................31 
11.7 
INTERIM ANALYSIS ..........................................................................................................................32 
12 
STUDY MANAGEMENT .......................................................................................................................32 
12.1 
MONITORING ...................................................................................................................................32 
12.2 
PROTOCOL AMENDMENTS................................................................................................................32 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................32 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................33 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................33 
12.6 
PUBLICATION POLICY ......................................................................................................................34 
13 
ETHICS .....................................................................................................................................................34 
13.1 
CONDUCT OF THE STUDY .................................................................................................................34 
13.2 
INSTITUTIONAL REVIEW BOARDS ....................................................................................................34 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................34 
52 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 1 
8 of 38 
Final 
Protocol:  FX2016-13 
 
Date:  06 Mar 2017 
13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................35 
13.5 
RECORDS RETENTION ......................................................................................................................35 
13.6 
FINANCING .......................................................................................................................................35 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................35 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................36 
16 
REFERENCE LIST .................................................................................................................................36 
APPENDIX 1:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................37 
APPENDIX 2: ACKNOWLEDGMENT OF RECEIPT AND REVIEW OF PROTOCOL .........................38 
 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 ........................... 14 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 ..................................................... 17 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 ................................................................... 21 
Table 4 
Clinical Laboratory Tests – Study FX2016-13 .............................................................. 23 
 
53 of 83

 
Privileged and Confidential 
 
Clinical Protocol:  Version 1 
9 of 38 
Final 
Protocol:  FX2016-13 
 
Date:  06 Mar 2017 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Abbreviation/Term 
Definition 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartic acid transaminase 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
FV 
Final Visit 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed cases 
OTC 
Over-the-counter 
PT 
Preferred term 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
54 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
10 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
2
STUDY ADMINISTRATIVE STRUCTURE 
Internal 
Name 
Affiliation / Address / 
Telephone Number 
Responsibility 
 
 
 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22 
Bridgewater, NJ 08807 
Sponsor 
 
 
 
External – Contract Research Organization (CRO) 
Name 
Affiliation / Address / 
Telephone Number 
Responsibility 
 
Premier Research 
Research Triangle Park 
One Park Drive, STE 150 
PO Box 13608 
Research Triangle Park, NC 27709 
Tel:  512-686-1256 
FMX103Medical@premier-
research.com 
Medical Monitor 
55 of 83
PPD
PPD
PPD
PPD
PPD
PPD
PPD

 
Privileged and Confidential 
 
Clinical Protocol:  Version 1 
11 of 38 
Final 
Protocol:  FX2016-13 
 
Date:  06 Mar 2017 
3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and eyes. It is a syndrome of 
undetermined etiology characterized by both vascular and papulopustular components involving 
the face and occasionally the neck and upper trunk. Clinical findings are usually limited to the 
sun exposed areas of the face and chest and include mid-facial erythema, telangiectasia, papules 
and pustules, and sebaceous gland hypertrophy. Rosacea is characterized by episodic flushing of 
affected areas, which may be associated with consumption of alcohol, hot drinks, or spicy foods. 
During inflammatory episodes, affected areas of the skin, primarily the convexities of the face, 
develop swelling, papules, and pustules. 
Rosacea occurs most commonly in adult life, between the ages of 30 and 60 years. It is very 
common in the United States (US) and Europe. Ocular involvement occurs in more than 50% of 
patients. 
Mainstays of treatment for papulopustular rosacea are the oral tetracyclines: doxycycline and 
minocycline. Systemic doxycycline (Oracea®, doxycycline 40 mg capsules) is approved. Topical 
treatments for rosacea include metronidazole, azelaic acid, and brimonidine tartrate. 
Minocycline hydrochloride is an established broad-spectrum antibiotic that is used orally “off-
label” in the treatment of papulopustular rosacea. Foamix has developed a topical minocycline 
foam product that is being evaluated for the treatment of papulopustular rosacea. The study 
medication FMX103 (minocycline HCl 1.5% foam) facilitates easy application and even 
distribution of the agent, thereby improving treatment convenience. 
The efficacy and safety of FMX103 have been established in a Phase 2 study in 232 adult 
subjects with moderate to severe papulopustular rosacea (Study FX2015-10). 
The purpose of this Phase 3 open-label extension study is to evaluate the long-term safety, 
tolerability, and efficacy of topical FMX103 1.5% (minocycline foam) during a 40-week period 
of self-administered dosing as needed in subjects with moderate to severe facial papulopustular 
rosacea who have previously participated in 1 of 2 Phase 3, 12-week, double-blind, 
vehicle-controlled safety and efficacy studies: Studies FX2016-11 and FX2016-12. 
4 
STUDY OBJECTIVES 
4.1 
Primary Objective 
The primary objective is to show that open-label extended treatment with FMX103 1.5%, for up 
to an additional 40 weeks, is safe and well tolerated.  
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is an open-label, multicenter, 40-week extension study to evaluate the long-term safety, 
tolerability, and efficacy of FMX103 1.5% topical foam in the treatment of moderate to severe 
facial papulopustular rosacea. Subjects will be eligible to enter this study upon successful 
56 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
12 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
completion of 1 of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy Phase 3 studies 
(FX2016-11 and FX2016-12) and if they meet all of the entry criteria.  
At the completion of Visit 5/Week 12 (Final Visit, or FV) in Study FX2016-11 or Study FX2016-
12, subjects who meet entry criteria will be invited to continue into this open-label study for an 
additional 40 weeks of treatment. A minimum of 400 subjects from Studies FX2016-11 and 
FX2016-12 will be enrolled into open-label Study FX2016-13. Subsequent enrollment of 
additional subjects will be considered as necessary to meet regulatory requirements. Subjects 
who elect to continue into this open-label study will receive supplies of active FMX103 1.5% 
minocycline foam. 
Treatment during the open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all facial areas if there is clinical 
improvement or resolution of the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the study and will attend all 
scheduled clinic visits. If at any time their rosacea recurs or worsens, treatment of the affected 
areas may be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as Visit 5/Week 12 (Final Visit) of 
either Study FX2016-11 or Study FX2016-12. Subsequent visits for the open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and efficacy evaluations will be 
performed. Week 40 is the Final Visit (Visit 7) of this study. 
Safety and efficacy evaluations will be performed as shown in Table 1. 
5.2
Rationale for Study Design and Dose Selection 
Chronic exposure in an open-label design is appropriate to evaluate the safety of long-term use. 
The omission of a control group is appropriate. Subjects will be selected according to pre-
defined entry criteria from 2 pivotal, Phase 3, randomized, multicenter, double-blind, vehicle-
controlled, 12-week studies. The open-label study treatment duration of 40 weeks will thus result 
in a total treatment duration of 52 weeks, adequate for chronic exposure. 
This open-label extension study is necessary to obtain safety information about the long-term use 
of FMX103 1.5% to treat facial papulopustular rosacea because of its chronic nature. The study 
design is expected to provide sufficient safety information to fulfill the International Conference 
on Harmonization (ICH) E1 guideline. 
The concentration of minocycline (1.5%) was selected according to formulation integrity and 
stability considerations and based on the results of the Phase 2 Study FX2015-10. 
6
STUDY POPULATION 
The study population will be comprised of subjects who have completed Study FX2016-11 or 
Study FX2016-12 and have agreed and are eligible to continue into this 40-week open-label 
extension study. A minimum of 400 subjects will be enrolled at approximately 80 sites in the US. 
All subjects will receive active treatment with FMX103 1.5% minocycline foam. 
57 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
13 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
6.1
Inclusion Criteria 
Subjects will be included in the study if they meet all of the following inclusion criteria at the 
time of enrollment: 
1. Healthy male or non-pregnant females, aged ≥18 years, who had a clinical diagnosis of
moderate to severe facial papulopustular rosacea at the start of the previous double-blind
study (Study FX2016-11 or Study FX2016-12).
2. Have completed and signed an appropriately administered informed consent form (ICF)
prior to any study-related procedures.
3. Have completed 12 weeks of treatment in either Study FX2016-11 or Study FX2016-12.
4. Have not had a worsening of disease, determined by the Investigator’s Global Assessment
(IGA), at Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment in Study
FX2016-11 or Study FX2016-12.
5. Are willing to continue on open-label treatment with FMX103 as described in this
protocol.
6. If a woman of child-bearing potential, have a negative urine pregnancy test and agree to
use an effective method of contraception (Section 8.8). A sterile sexual partner is NOT
considered an adequate form of birth control.
7. If a woman of child-bearing potential is using an oral contraceptive product, she should
have been on the same product for at least 3 months and she should continue using the
same or equivalent product for the duration of the of the study.
6.2 
Exclusion Criteria 
Subjects will be excluded from enrollment in the study for any of the following reasons: 
1. Women who are pregnant, lactating, or planning to become pregnant during the study.
2. Have a new systemic disease or condition, including an ongoing AE that might interfere
with the conduct of the study or the interpretation of results.
3. Have developed a condition that would have been exclusionary for Study FX2016-11 or
Study FX2016-12, including pseudomembranous colitis, antibiotic-associated colitis,
hepatitis, liver damage, renal impairment, drug addiction, or alcohol abuse.
4. Have abnormal laboratory values at the Final Visit (Week 12) of Study FX2016-11 or
Study FX2016-12 that are considered clinically significant.
5. Are unable to fully comply with the study requirements.
7
STUDY PROCEDURES 
The schedule of study assessments and procedures is presented in Table 1. If a subject withdraws 
from the study prematurely, he or she should return to the study site for an early termination 
visit, during which all evaluations described under Visit 7/Week 40 (Final Visit) should be 
performed. 
58 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
14 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 
Assessment or Procedure 
Baselinea 
Visits 
Final 
Visitb 
Safety 
Follow-upc 
Study Visit 
(FV of 
previous 
DB Study) 
1 
2 
3 
4 
5 
6 
7 
N/A 
Study Week 
(Week since beginning of 
previous DB study) 
1 
(12) 
4 
(16) 
10 
(22) 
16 
(28) 
22 
(34) 
28 
(40) 
34 
(46) 
40 
(52) 
44 
(56) 
Informed consent 
X 
Record subject identificationd 
X 
Inclusion/exclusion criteria 
X 
Physical examination (including 
weight) 
X 
X 
Blood pressure/heart ratee 
X 
X 
X 
X 
X 
X 
X 
X 
Blood/urine samples for clinical 
laboratory tests 
X 
X 
X 
Urine pregnancy testf 
X 
X 
X 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global 
Assessment 
Xg 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
Questionnaire 
X 
Local signs and symptom 
assessmentsh 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
X 
X 
X 
X 
Review application instructions 
X 
X 
X 
X 
X 
X 
X 
Schedule/confirm next visit or 
call (for safety follow-up only) 
X 
X 
X 
X 
X 
X 
X 
X 
DB = double-blind; FV = final visit; N/A = not applicable, no visit 
a.
Baseline for the study will be conducted at the same time as Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12. All 
assessments performed at Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12 should not be repeated but should be 
recorded as the same assessments at Baseline for this study.
b.
If a subject withdraws from the study prematurely, all evaluations described under Visit 7/Week 40 (Final Visit) should be performed.
c.
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit) for those subjects who presented with either 
new or on-going adverse events at Visit 7/Week 40 (Final Visit). 
d.
Previously assigned subject identification from Study FX2016-11 or Study FX2016-12 will be used in this study.
e.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest. 
f.
A urine pregnancy test will be done at the study site at every visit for all subjects of childbearing potential; home pregnancy tests will be 
dispensed at each visit and will be performed at least monthly or whenever there is a suspicion of pregnancy (eg, a missed period). 
g.
The subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final Visit) should not have worsened relative to the subject’s 
IGA at Day 0/Baseline of one of the previous double-blind studies. 
h.
The severity of each of the following local rosacea signs/symptoms will be measured:  erythema, telangiectasia, burning/stinging,
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. 
59 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
15 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
7.1
Baseline (also Visit 5/Week 12 [Final Visit] of previous double-blind study) 
•
Obtain a signed and dated ICF.
•
Record subject identification from Study FX2016-11 or Study FX2016-12.
•
Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria
(Section 6.2).
•
Record physical examination results, including weight, from Final Visit (Section 10.3).
•
Record blood pressure and heart rate results from Final Visit (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform IGA (Section 9.1.2).
•
Have the subject complete the Subject Global Assessment (Section 9.2.1).
•
Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.2).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Review application instructions to confirm that the subject continues to use the study drug
properly.
•
Dispense 2 study drug kits (ie, 4 canisters) of FMX103 1.5%.
•
Dispense facial cleanser and moisturizer.
•
Schedule/confirm the next study visit.
7.2
Visits 1 through 6, Weeks 4, 10, 16, 22, 28, and 34 (±5 days) 
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit (Section 10.4.1).
•
Dispense a home pregnancy test kit (Section 10.4.1).
•
At Visit 3 (Week 16) only – Collect blood and urine samples for clinical laboratory tests
and send to the central laboratory (Section 10.4.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform IGA (Section 9.1.2).
60 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
16 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Review application instructions to confirm that the subject continues to use study drug
properly.
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Dispense 2 study drug kits (ie, 4 canisters) of FMX103 1.5% if required.
•
Confirm that subject continues to use only the provided facial cleanser and moisturizer
and dispense additional quantities as required.
•
Schedule/confirm the next study visit.
7.3
Visit 7, Week 40/Final Visit (±5 days) or Early Termination 
•
Perform physical examination, including weight (Section 10.3).
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform IGA (Section 9.1.2).
•
Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.2).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 7/Week 40 if
required (Section 7.4).
7.4
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit) for 
only those subjects who presented with either new or on-going adverse events at Visit 7/Week 40 
61 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
17 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
(Final Visit). Follow up on these adverse events and any new concomitant medications will be 
recorded. 
8 
STUDY TREATMENTS 
This is an open-label study; all subjects will receive FMX103 1.5% minocycline foam. 
8.1 
Treatment Administered 
The description of study drug kits and treatment is shown in Table 2. 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 
Dosage form description: 
Foam containing minocycline HCl 1.5% 
Package description: 
2 canisters of FMX103 1.5%, each canister containing 25 g of the clinical 
trial supply foam 
Daily dose: 
As needed application of a sufficient amount of foam to cover the involved 
area. Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% 
active) of minocycline. 
Cumulative maximal dose over 
40 weeks: 
Up to approximately 2100 mg of minocycline assuming application of 0.5 g 
of FMX103 1.5% foam once daily to the face for 280 days. 
Dispensing: 
Up to 2 kits consisting of 2 canisters/kit (ie, 4 canisters total) dispensed at 
Baseline and Visits 1-6 (Weeks 4-34). Up to a total of 14 kits (28 canisters) 
dispensed to the subject for the study. 
8.1.1
Dosing Instructions 
At enrollment, subjects will receive supplies of active FMX103 1.5% minocycline foam. 
Up to 2 study drug kits consisting of 2 canisters/kit (ie, 4 canisters total of investigational drug) 
will be dispensed at Baseline and Visits 1 through 6 (Weeks 4 through 34). Subjects will be 
instructed to express a small amount of study drug from the canister onto the finger tips and then 
apply as a thin layer over all involved areas of the face as needed. Additional drug may be used 
as needed to assure the entire involved area is treated. Sufficient product will be dispensed at 
each visit to allow continuation of treatment as required. 
Treatment during this open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all facial areas if there is clinical 
improvement or resolution of the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the study and will attend all 
scheduled clinic visits. If at any time the rosacea recurs or worsens, treatment of the affected 
areas may be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
8.1.2
Manufacturer 
The manufacturer of the investigational product is
 
 
62 of 83
CCI

Privileged and Confidential 
Clinical Protocol:  Version 1 
18 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
8.1.3
Labeling of Study Drug 
The Sponsor or designee will label study drug supplies according to the requirements of the 
Code of Federal Regulations (21CFR§ 210, Subpart G-Packaging & Labeling Control). 
The labels of the investigational (test) product will contain appropriate information as required 
by regional regulatory authorities and include, as needed, the following information: 
•
Name and address of the Sponsor
•
Protocol number
•
Product name/dosage form/mode of administration
•
Kit Number/Canister Number
•
Site number/Subject number
•
Name and address of manufacturer
•
Date of manufacture
•
Lot/batch number
•
Canister contents
•
Storage conditions
•
Caution statements, as follow:
o
“New Drug – Limited by Federal Law to Investigational Use”
o
“Flammable”
o
“Shake well before use”
o
“Keep out of the reach of children”
The composition, pharmaceutical quality, batch number, and expiration date of the 
investigational (test) product will be traceable via the kit number. 
8.1.4
Storage of Study Drug 
FMX103 1.5% canisters must be stored at 2°C – 8°C until being dispensed to the subject. 
Subsequently, the canisters must be stored at 20°C – 25°C (refer to USP Controlled Room 
Temperature). The Investigator will be responsible for the suitable storage of the investigational 
product in compliance with the storage instructions and must restrict access to the study 
personnel only. 
8.2
Study Drug Accountability 
The Investigator will have overall responsibility for the study drug. The Investigator or designee 
will verify the contents of the drug shipment and confirm receipt of the study drug in the 
Interactive Response Technology (IRT) system. In addition, an accurate study drug dispensing 
record that specifies the date and amount dispensed to each subject must be kept. This inventory 
record must be available for inspection by representatives of the Sponsor and is subject to 
63 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
20 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
If a subject is taking anticoagulant therapy, he or she should be advised that a downward 
adjustment of their anticoagulant dose may be required. 
See the FMX103 investigator’s brochure (IB) for information about tetracyclines and possible 
drug-drug interactions. 
8.8
Use of Contraception 
Tetracycline-class antibiotics can cause fetal harm when administered to a pregnant woman. 
Tetracycline-class antibiotics used during tooth development (last half of pregnancy, infancy, and 
childhood to the age of 8 years) may cause permanent discoloration of teeth (yellow-gray-
brown). 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. Females of childbearing potential include any female who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation/occlusion, or bilateral oophorectomy) or who is not postmenopausal (defined as 
amenorrhea >12 consecutive months). Females of childbearing potential must have a negative 
urine pregnancy test and, if they are sexually active or become sexually active during the study, 
must use an effective method of birth control such as those in the follow list during the course of 
the study. The following is not an all-inclusive list; the subject must discuss with the Investigator 
the most appropriate form of birth control: 
•
Hormonal methods
o
Oral contraceptives – (Oral antibiotics may lessen the effectiveness of oral
contraceptives. Therefore, a second form of birth control must be utilized in
subjects using oral contraceptives.)
o
Implant
o
Injection
o
Transdermal patch
o
Intravaginal ring
•
Intrauterine device (hormonal or non-hormonal)
•
Barrier methods
o
Condom (male or female) with spermicide
o
Diaphragm with spermicide
•
Complete abstinence
8.9
Treatment Compliance 
Each subject is to be instructed on the importance of following the dosing schedule and returning 
all study drug kits (empty/used/unused) at the appropriate visits. The study site personnel will 
65 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
21 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
question each subject on study drug use since the last visit. A subject who deviates significantly 
from the prescribed dosage will be counseled. 
9
EFFICACY ASSESSMENTS 
Every attempt must be made to ensure the same evaluator performs the efficacy evaluations for a 
particular subject throughout the study; when this is not possible, another approved evaluator 
may perform the evaluations. Following are the methods and scales that will be used to measure 
each of the efficacy parameters to be performed. 
9.1
Primary Efficacy Assessments 
The efficacy assessments will include the inflammatory lesion counts and the IGA of severity of 
disease and will be performed by the Investigator/evaluator. 
9.1.1
Lesion Counts 
The number of papules, pustules, and nodules will be counted and the numbers recorded. Facial 
area lesion counts will be made for the forehead, left and right cheeks, nose, and chin. The lesion 
counts performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will 
constitute the Baseline value for this study. Lesion counts will be repeated at Visit 1 (Week 4), 
Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), 
and Visit 7 (Week 40/Final Visit). 
9.1.2
Investigator Global Assessment 
The Investigator will also assess the global severity of rosacea using the IGA scale as described 
in Table 3. The IGA performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) will constitute the Baseline value for this study. Assessment will be repeated 
at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), 
Visit 6 (Week 34), and Visit 7 (Week 40/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 
Score 
Grade 
Description 
0 
Clear 
No inflammatory papules or pustules 
1 
Almost clear 
Few inflammatory papules or pustules 
2 
Mild 
Several inflammatory papules or pustules 
3 
Moderate 
Moderate number of inflammatory papules or pustules and no nodules 
4 
Severe 
Many inflammatory papules or pustules, and up to 2 nodules 
9.2
Secondary Efficacy Assessments 
9.2.1
Subject Satisfaction Questionnaire 
A Subject Satisfaction Questionnaire (Appendix 1) will be administered at Visit 7 
(Week 40/Final Visit). 
66 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
22 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
10
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
the monitoring of AEs (volunteered, observed, and elicited by general questioning in a non-
suggestive manner), clinical laboratory tests, vital signs, physical examinations, and local signs 
and symptom assessments (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) 
scores. 
10.1
Concomitant Medications 
All medications that the subject is currently taking or any change in medication or dosage since 
the last visit will be documented throughout the study. The reason for use or change of dose of a 
concomitant therapy may need to be reported as an AE. 
10.2
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all visits. All BP measurements will be 
made using a sphygmomanometer with an appropriate cuff size for the individual subject. 
Measurements will be taken while the subject is seated after at least 5 minutes at rest. 
10.3
Physical Examination 
A complete physical examination (excluding the genitourinary examination), including body 
weight, will be performed at Baseline (ie, Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) and at Visit 7 (Week 40/Final Visit). 
10.4
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at Baseline (ie, Visit 5/Week 12 
[Final Visit] in Study FX2016-11 or Study FX2016-12) and at Visit 3 (Week 16) and Visit 7 
(Week 40/Final Visit). All clinical laboratory tests will be analyzed by a central laboratory. 
Table 4 presents the specific clinical laboratory tests to be evaluated. 
Please refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples. 
67 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
23 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
Table 4 
Clinical Laboratory Tests – Study FX2016-13 
Hematology 
Urinalysis 
Serum chemistry 
Hematocrit 
Hemoglobin 
Platelet count 
Red blood cell (RBC) 
count 
White blood cell (WBC) 
count with differential 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes esterase 
pH 
Protein 
Specific gravity 
Urine pregnancy test performed at the site 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase 
Aspartic acid transaminase (AST) 
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Creatinine kinase 
Gamma glutamyl transferase (GGT) 
Globulin 
Glucose 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (if elevated obtain 
direct bilirubin) 
Total protein 
Uric acid 
10.4.1
Urine Pregnancy Test 
A urine pregnancy test will be performed at the study site on all females of childbearing potential 
at all study visits and when a subject withdraws from the study prematurely. In addition, home 
pregnancy tests will be dispensed at each study visit to all female subjects of a childbearing 
potential and will be performed at least monthly and whenever there is a suspicion of pregnancy 
(eg, a missed or late menstrual period). 
10.4.2
Sample Collection, Storage, and Shipping 
Sample collection kits, requisition slips, and shipping boxes will be supplied by the central 
laboratory. Sample collection procedures and shipping instructions will be detailed in the 
laboratory manual. Study sites must be equipped to store the samples according to the laboratory 
manual procedures before shipping to the central laboratory. 
10.5
Other Safety Measurements 
10.5.1
Local Signs and Symptom Assessments 
Local signs and symptom assessments of the skin at the application sites measured at 
Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will constitute Baseline 
values for this study.  Assessments will be repeated at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 
(Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), and Visit 7 (Week 40/Final 
Visit). The following local signs and symptoms will be measured:  erythema, telangiectasia, 
68 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
24 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
burning/stinging, flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation. The score for signs will be determined by the Investigator and must represent 
the subject’s condition at the time of the evaluation; the score for symptoms (ie, burning/stinging, 
flushing/blushing) should be scored based on the subject’s symptoms reported for the previous 
3 days. 
These signs/symptoms should not be included as AEs, unless a sign/symptom is believed to have 
been related to the study drug or is the reason for discontinuation from the study. 
10.5.1.1
Erythema (Clinical Erythema Assessment Scale) 
Erythema of the face will be graded according to the following scale: 
•
0 = clear skin/no signs of erythema
•
1 = almost clear of erythema, slight redness
•
2 = mild erythema, definite redness
•
3 = moderate erythema, marked redness
•
4 = severe erythema, fiery redness
10.5.1.2 
Telangiectasia 
The severity of facial telangiectasia will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  scattered telangiectasia
•
2 = Moderate:  numerous telangiectasia
•
3 = Severe:  dense telangiectasia forming sprays of vessels
10.5.1.3 
Burning/Stinging 
The severity of facial burning/stinging will be graded according to the following scale: 
•
0 = None:  no warm or burning sensation
•
1 = Mild:  slight warm tingling/stinging sensation; not really bothersome
•
2 = Moderate:  constant or intermittent warm tingling/stinging sensation that is somewhat
bothersome
•
3 = Severe:  bothersome warm to hot tingling/stinging sensation
69 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
25 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
10.5.1.4 
Flushing/Blushing 
The severity of facial flushing/blushing will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic episodes lasting for a few moments to several minutes
•
2 = Moderate:  intermittent episodes lasting for greater than 30 minutes
•
3 = Severe:  almost constant episodes lasting for several hours
10.5.1.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
•
0 = None
•
1 = Mild
•
2 = Moderate
•
3 = Severe
10.5.1.6 
Itching 
The severity of facial itching will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic itching lasting for a few moments to several minutes
•
2 = Moderate:  intermittent itching lasting for greater than 30 minutes
•
3 = Severe:  almost constant, intense itching lasting for several hours
10.5.1.7 
Peeling/Desquamation 
The severity of facial peeling/desquamation will be graded according to the following scale: 
•
0 = No peeling
•
1 = Mild:  small, scattered areas of scaling/flaking
•
2 = Moderate:  larger, contiguous areas of scaling/flaking
•
3 = Severe:  pronounced flaking/shedding scales covering entire application area
10.5.1.8 
Hyperpigmentation 
The severity of facial skin hyperpigmentation will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  few scattered, small areas of light hyperpigmentation
•
2 = Moderate:  larger or more intense areas of hyperpigmentation
•
3 = Severe:  intense, extensive hyperpigmentation
70 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
26 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
10.6
Adverse Events 
10.6.1
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator. Adverse events will be recorded at each visit on the appropriate case report 
form (CRF). Every attempt should be made to describe the AE in terms of a diagnosis. If a clear 
diagnosis has been made, individual signs and symptoms will not be recorded unless they 
represent atypical or extreme manifestations of the diagnosis, in which case they should be 
reported as separate events. If a clear diagnosis cannot be established, each sign and symptom 
must be recorded separately. 
Subjects should be asked whether, since the time of the last observation or visit, they had any of 
the following: 
•
Experienced any changes in well-being
•
Used any new medications
•
Changed medication regimens (both prescription and OTC)
•
Were admitted to a hospital or had any accidents
•
Developed unusual headaches or changes in vision
With exception to the above, all questions should be of a general nature and should not suggest 
symptoms. 
When an AE is suspected, all relevant evaluations will be performed and appropriate treatment 
provided. Additional follow-up will be done as necessary (Section 10.6.4) and recorded in the 
subject’s source documents, and the results will be provided to the Sponsor. 
For AE definitions and reporting requirements, refer to Section 10.6.2 and Section 10.6.3, 
respectively. 
10.6.2
Adverse Event Definitions 
10.6.2.1
Adverse Events 
An AE is any unfavorable or unintended sign, symptom, or disease that appears or worsens in a 
subject after the subject signs the ICF for a clinical study. 
Examples of what may be considered an AE include any of the following: 
•
A new illness.
•
An exacerbation of a sign or symptom of an underlying condition or of a concomitant
illness unrelated to participation in the clinical study or an effect of the study drug or
comparator drug.
No causal relationship with the study drug is implied by the use of the term “adverse event.” An 
exacerbation of a pre-existing condition/illness is defined as a more frequent occurrence or as an 
increase in the severity of the pre-existing condition/illness during the study. Planned or elective 
71 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
27 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
surgical procedures for pre-existing conditions that have not worsened are not AEs. However, 
any complication that occurs during a planned or elective surgery is an AE (Note:  If the event 
meets the criteria for a serious adverse event [SAE], such as an extended hospitalization, it will 
be considered an SAE). Conditions leading to unplanned surgical procedures may also be AEs. 
10.6.2.2
Serious Adverse Events 
A serious adverse event (SAE) is any AE that: 
•
Results in death.
•
Is life-threatening.
(Note:  The term “life-threatening” refers to any AE that, as it occurs, puts the subject at
immediate risk of death. It does not refer to an AE that hypothetically might have caused
death if it were more severe.)
•
Results in hospitalization or prolongation of current hospitalization (not including
hospitalization for a pre-existing condition that has not increased in severity or frequency
from the subject’s underlying medical condition prior to entry into the study).
•
Results in persistent or significant disability/incapacity.
•
Is a congenital anomaly/birth defect in the offspring of a subject.
•
Is another serious (important medical events) event.
(Note:  Important medical events may not be immediately life-threatening or result in
death or hospitalization but may be considered serious when, based upon appropriate
medical judgment, they may jeopardize the subject or require medical or surgical
intervention to prevent one of the outcomes listed above. Examples of such medical
events include allergic bronchospasm requiring intensive treatment in an emergency room
or at home; blood dyscrasias or convulsions that do not result in inpatient hospitalization;
or development of drug dependency or drug abuse.)
SAEs will be reported by the Sponsor to the regulatory authorities as required. 
10.6.2.3
Severity of Adverse Events 
The severity of an AE refers to the extent to which it affects the subject’s daily activities and 
differs from “serious”, which is a regulatory classification. Severity will be categorized 
according to the following criteria: 
•
Mild:  The symptom has a negligible effect or no impairing effect on the subject’s normal
function.
•
Moderate:  The symptom impairs the subject’s normal function to some extent.
•
Severe:  The symptom has an obvious, significantly impairing effect on the subject’s
normal function.
72 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
28 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
10.6.2.4
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to the study drug and will be categorized according 
to the following criteria: 
•
Unlikely:  There is no medical evidence to suggest that the AE may be related to study
drug usage, or there is another more probable medical explanation.
•
Possible:  There is medical evidence to suggest that there is a reasonable possibility that
the AE may be related to study drug usage. However, other medical explanations cannot
be excluded as a possible cause.
•
Probable:  There is strong medical evidence to suggest that the AE is related to study
drug usage.
10.6.2.5
Adverse Events Expectedness 
Expected AEs are defined as those described in the FMX103 IB. If an event increases in intensity 
or severity from that described in the IB, it will be considered unexpected. 
10.6.3
Reporting Adverse Events 
Adverse events that occur from the time of informed consent completion of the last study visit 
should be reported. Any AE that the Investigator becomes aware of that occurs within 30 days of 
study completion or withdrawal should also be reported. 
Any SAEs occurring in a subject receiving study drug must be reported to the Sponsor within 
24 hours of the site being informed of the event, even if the event does not appear to be drug 
related. The report must be done by faxing the completed SAE Report Form to the Sponsor. Any 
pertinent follow-up information should be provided in a similar manner. Contact information is 
provided below: 
Foamix Pharmaceuticals Inc./Premier Research 
Pharmacovigilance 
Phone:  +1 215-282-5434 
Fax:  +1 215-972-8765 
Email:  globalPv-US@premier-research.com 
10.6.4
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until they resolve or the subject stabilizes (in the opinion of the Investigator), or for 30 
days, whichever is shorter. Investigators and the Sponsor will decide if longer follow-up is 
appropriate on a case-by-case basis. Subjects who experience any clinically significant AE will 
remain under medical supervision until the Investigator or the Sponsor’s medical monitor deems 
the AE to be resolved, the subject is stable, or the event is no longer serious enough to warrant 
follow-up. 
73 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
29 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
Laboratory values that are abnormal and not assessed as AEs may be followed at the discretion 
of the Investigator or the Sponsor’s medical monitor until they resolve or the subject is stable. 
10.6.4.1
Pregnancy Reporting 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. The ICF that the subject signs must document this discussion. 
If a subject or an Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of site pregnancy testing are 
available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
Urine pregnancy tests will be performed on all females of childbearing potential as described in 
Section 10.4.1. 
During the study, all female subjects of childbearing potential should be instructed to contact the 
Investigator immediately if they suspect they might be pregnant (eg, positive home pregnancy 
test [Section 10.4.1], missed or late menstrual period, etc.). If a subject or Investigator suspects 
that the subject may be pregnant at any time before or during the study, the study drug must be 
withheld until the results of site pregnancy testing are available. The Sponsor and site monitor 
must be notified and relevant information collected on the appropriate form. If pregnancy is 
confirmed, the subject must be withdrawn from the study and the Sponsor and site monitor 
notified. Additional relevant information about the confirmed pregnancy will be recorded on the 
appropriate form(s); pregnancy will not be captured as an AE. 
The subject should be followed until the outcome of the pregnancy is known. 
10.6.5
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be flagged when 
reported to the site. The Investigator will determine which out-of-range laboratory test results 
should be characterized as clinically significant and annotate the laboratory report. If a clinically 
significant laboratory abnormality requires treatment or is the reason for a subject being 
discontinued from the study, the abnormal result must also be classified as an AE. 
10.7
Appropriateness of Safety Measurement 
The safety assessments to be used in this study are standard safety measures in clinical trials. 
11
STATISTICAL DESIGN AND ANALYSIS 
11.1
Statistical Analysis Plan 
A detailed statistical analysis plan will be finalized prior to database lock. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated; however, the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
74 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
30 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. 
11.2
Determination of Sample Size 
The planned minimum enrollment is 400 male and female subjects who were previously enrolled 
in Study FX2016-11 or Study FX2016-12. The sample size is intended to ensure that at least 300 
subjects continue to self-administer the study drug as needed for at least 6 months and 100 
subjects continue for at least 1 year (ie, combined duration of treatment between the double-blind 
and open-label studies). The number of subjects at each site will be determined by the rate of 
recruitment in Studies FX2016-11 and FX2016-12. No statistical rationale for subject number is 
provided. 
11.3
Analysis Populations 
The following populations are defined for analysis: 
•
The All-Treated population:  all subjects who use study drug at least once. This population
will be used for safety and efficacy analyses.
11.4
Subject Accounting, Demographics, and Baseline Characteristics 
Demographics, baseline characteristics, medical and surgical history (FX2016-11 and 
FX2016-12) and prior and concomitant medications will be summarized. Study completion 
status and reasons for discontinuation will also be displayed. 
11.5
Efficacy Endpoints 
11.5.1
Primary Efficacy Endpoints 
The primary efficacy endpoints are: 
•
The absolute change in the inflammatory lesion count at Week 40 compared to Baseline.
•
The dichotomized IGA score where success is defined as a 2-step improvement resulting
in a 0 (clear) or 1 (almost clear) score at Week 40 compared to Baseline.
For the efficacy analyses, Baseline will be defined as Day 0/Baseline of the initial double-blind 
study, ie either Study FX2016-11 or Study FX2016-12. The changes from Baseline of Studies 
FX2016-11 and FX2016-12 to Week 40 of this study for each of the primary endpoints will be 
calculated. Descriptive statistics (number of subjects, mean, median, standard error, coefficient 
of variation, minimum and maximum) for each variable will be presented for each visit and for 
the changes from Baseline. No hypothesis testing will be performed. 
11.5.2
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is: 
•
The Subject Satisfaction Questionnaire administered at Visit 7 (Week 40/Final Visit).
75 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
31 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
11.6
Safety Endpoints 
Safety endpoints will be reported on the All Treated population. Safety assessments will be 
summarized in tables using descriptive statistics and in individual by-subject listings. No 
statistical tests will be performed for any of the safety assessments. 
Treatment-emergent AEs (TEAEs) will be defined as events that emerge having been absent 
prior to enrollment in this study or worsen relative to the pre-enrollment state. Summaries of AEs 
will be limited to TEAEs. The number and percentage of subjects reporting events under each 
System Organ Class (SOC) and preferred term (PT) will be summarized. At each level of 
summarization, a subject will be counted only once if he or she reported one or more events. The 
severity of TEAEs and relationship to the study drug will be summarized in a similar manner. 
For summaries of relationship to the study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE severity, a subject will be classified according to 
the highest severity. All TEAEs continuing, but not worsening, after enrollment in this study will 
also be tabulated. 
Treatment-emergent AEs, vital signs, and clinical laboratory measurements will be summarized 
using descriptive statistics. For vital signs, change from Baseline values will also be summarized. 
For all safety variables, subject data listings will be provided. 
Local signs and symptom assessments will include active assessments of erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, itching, 
peeling/desquamation, and hyperpigmentation using the scales described under Section 10.5.1. 
11.6.1
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to SOC and PT. 
Summaries of SAEs and subjects who withdraw from the study prematurely due to AEs will be 
presented. 
11.6.2
Vital Signs and Physical Examinations 
Vital sign and physical examination parameters will be summarized using descriptive statistics at 
Baseline and at each post-Baseline time point. Changes from Baseline will also be summarized. 
11.6.3
Clinical Laboratory Results 
Shift tables for each clinical laboratory test will cross-tabulate the number of subjects with values 
below the laboratory reference range (low), values within the laboratory reference range 
(normal), or above the laboratory range (high) at Baseline with the number of subjects with low, 
normal, or high values at the Final Visit. Baseline is defined as the last non-missing value prior to 
enrollment in this study. 
A listing of subjects with treatment-emergent clinically significant abnormal laboratory values 
will be presented for each treatment group. Clinical significance is based on the Investigator’s 
judgment. 
76 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
32 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
11.7
Interim Analysis 
No interim analysis is planned. 
12
STUDY MANAGEMENT 
12.1
Monitoring 
The Investigator will be responsible for preparing and maintaining adequate and accurate source 
documents (medical records, raw data collection forms, etc.) designed to record all observations 
and other pertinent data for each subject treated with the study drug. The Investigator will allow 
representatives of the Sponsor, contract designees, authorized regulatory authority inspectors, 
and the institutional review board (IRB) to have direct access to all documents pertaining to the 
study. The Investigator is to notify the Sponsor immediately of any regulatory authority 
inspections. The Investigator will be informed about the outcome of any Sponsor audit. 
This study will be monitored regularly, by or under supervision of a monitor from the Sponsor. 
The frequency of monitoring visits will be agreed upon by the Sponsor’s representative and the 
study site. 
Monitoring visits will take place on a regular basis according to the enrollment rate and number 
of subjects enrolled at each investigational site. During these visits, the monitor will check the 
completion of the CRF entries, compliance with the study protocol and with Good Clinical 
Practice (GCP)-ICH, and their agreement with the source data. The monitor will also verify the 
correct use of the study drug. At the final visit, the monitor will check all remaining material, 
including the remaining quantities of the study drug, and will organize their return to the Sponsor 
or designee. At each visit, the Investigator and staff will be expected to cooperate with the 
Sponsor’s representative(s) for the purposes of review and verification of protocol compliance, 
AE reporting, CRFs, source documents, clinical supplies and inventory records, and any 
additional records as may have been previously arranged between the Investigator and the 
Sponsor’s representative(s). 
The Investigator and/or other designated study personnel are expected to contact the Sponsor’s 
clinical research associate, as needed, regarding study concerns and/or questions. Contact 
information is provided in the Study Reference Manual for the site. 
12.2
Protocol Amendments 
The Sponsor may propose to amend this protocol at any time. 
No change to the protocol will be implemented until the Sponsor and the IRB have reviewed and 
approved the amendment. 
12.3
Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the IRB-approved protocol 
(intentional or unintentional). All deviations are to be documented at the site and reported to the 
IRB according to their guidelines. 
77 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
33 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety. All such procedures must have written documentation and be 
promptly reported to the Sponsor and IRB. 
12.4
Withdrawal of Subjects 
Subjects or Investigators may choose to discontinue a subject’s participation in the study at any 
time. Subjects may be withdrawn from the study because of any of the following: 
•
Adverse Event:  An AE that in the opinion of the Investigator or Sponsor suggests that 
continued participation in the study is not in the subject’s best interest for safety reasons. 
All AEs that are present when the subject withdraws from the study will be followed as 
described in Section 10.6.4.
•
Abnormal Laboratory Result:  Any clinically significant laboratory abnormality that 
requires withdrawal of the subject from the study should be considered an AE leading to 
withdrawal. If possible, laboratory tests will be repeated for any results that were 
clinically significantly abnormal until the abnormality is resolved or the subject is stable 
to the satisfaction of the Investigator in consultation with the medical monitor.
•
Lost to Follow-up:  Confirmed at minimum by two phone calls and a traceable letter 
without answer.
•
Subject Request:  Subject requests, for any reason (eg, AE), to be withdrawn or 
withdraws his or her consent.
•
Protocol Deviation:  A subject may be withdrawn from the study at the discretion of the 
Investigator or Sponsor due to poor compliance with protocol requirements that may 
compromise the study results or subject safety.
•
Other:  Other reasons include but are not limited to Investigator decision that it is in the 
subject’s best interest to be withdrawn, administrative reasons, subject’s relocation, etc. If 
a subject becomes pregnant during the study, she will be withdrawn from the study and 
followed through conclusion of the pregnancy (Section 10.6.4.1). 
If a subject is withdrawn from the study following the start of study drug, all Visit 7 
(Week 40/Final Visit) assessments should be completed. Subjects withdrawn from the study will 
not be replaced. 
12.5
Termination of the Study 
The study may be terminated at any time at the request of the Sponsor or a regulatory authority, 
with proper and timely notification of all parties concerned. The IRB will be informed promptly 
and the Sponsor or the Investigator will supply reason(s) for the termination or suspension, as 
specified by the applicable regulatory requirements. Otherwise, the study is considered 
terminated upon completion of all subject treatments and evaluations. 
78 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
34 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
12.6
Publication Policy 
The data obtained in this study are the property of the Sponsor, who will make reasonable efforts 
to assure that the results are published in a peer-reviewed journal. Since some of the information 
concerning the investigational product and development activities at the Sponsor may be strictly 
confidential in nature, any manuscript or other presentation of data must first be reviewed by the 
Sponsor before its submission. 
13
ETHICS 
13.1
Conduct of the Study 
This study will be conducted in accordance with the ICH Harmonized Tripartite Guideline for 
GCP, 1997; the US Title 21 CFR parts 50, 56, and 312; and the ethical principles that have their 
origin in the Declaration of Helsinki. The study will not begin until all of the requirements of the 
appropriate regulatory authorities have been fulfilled. 
13.2
Institutional Review Boards 
This protocol (and any changes), all consent forms, and subject consent procedures must be 
reviewed and approved by a properly constituted IRB. The information presented to the IRB at 
the time initial approval is sought must include any plans for subject recruitment that involve 
advertising or other direct contact with potential subjects outside of the physician-subject 
relationship. A letter of approval issued by the IRB must be sent to the Sponsor prior to initiation 
of the study. Any changes made to the protocol must be approved by the IRB prior to 
implementation, except where needed to eliminate a potential imminent safety hazard to the 
subjects. In this case, immediate implementation may take place followed by IRB approval. 
Review and approval by the IRB for continuation of the study must take place at least once a 
year. 
13.3
Written Informed Consent 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential benefits and risks of participation to each 
subject prior to his or her entry into the study (ie, before examinations and procedures associated 
with selection for the study are initiated). Each subject will have ample opportunity to ask 
questions and will be informed about the right to withdraw from the study at any time without 
any disadvantage and without having to provide reasons for this decision. 
Following this informative discussion, the subject will be asked if he or she is willing to sign a 
statement of informed consent. Only subjects who voluntarily sign the ICF may enter the study. 
The ICF must be reviewed and approved by the Sponsor and the IRB prior to use. 
The original signed ICF will remain in the Investigator’s files. The Investigator or designee will 
indicate in each subject’s source documents that he or she has informed the subject about the 
study and its procedures, the subject has signed and dated the ICF, and the subject has been given 
a copy of the documents. The Investigator or designee will inform subjects of any new 
information that may be relevant to the subject’s willingness to continue in the study. 
79 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
35 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
13.4
Subject Confidentiality 
The Sponsor will ensure that the following have permission to review all study-related 
documents:  monitor, auditor, IRB, and regulatory authorities. The subject’s identity and 
study-related records will remain confidential throughout the duration of the study data 
collection and reporting process. 
The investigative site assigns a unique subject identification code to each potential study subject. 
The identification code protects the subject’s identity and is used in lieu of the subject’s name 
when reporting subject data. The data will always maintain the confidentiality of the subject. 
The Investigator or designee will review the subject data, which will be referenced using the 
subject identifier. At the conclusion of the study, the data obtained may be presented to regional 
regulatory authorities but the subject’s identity will not be revealed. In addition, if any clinical 
data obtained from the study is published in scientific journals or presented at scientific meetings 
the subject’s identity will not be revealed. 
13.5
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, source 
documentation corresponding to all information contained in the CRFs, signed ICF forms, 
relevant correspondence, and all other supporting documentation) until at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years after the formal 
discontinuation of clinical development of the investigational product. These documents should 
be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted. Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same time period. Custody of the records may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies. Written notice of 
transfer must be submitted to the Sponsor. The Investigator must contact the Sponsor prior to 
disposing of any study records. 
13.6
Financing 
Funding for this study will be agreed upon between the Investigator and the Sponsor and will be 
confirmed in writing before the study starts. 
Completion of Financial Disclosure Forms will be required before the study starts. Any additions 
to the primary site personnel will necessitate the completion of new Financial Disclosure Forms. 
This information will also be collected at site closure and 1 year after the completion of the 
study. 
14
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and the Investigator will take all steps possible to ensure the accuracy, consistency, 
completeness, and reliability of the data, including participating in an Investigator meeting 
and/or site initiation visit, routine site monitoring, review of CRFs against source documents, and 
quality control checks. 
80 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
36 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
In addition, a representative from the Sponsor’s Clinical Quality Assurance Department may 
conduct periodic audits of the study processes, including, but not limited to, auditing the clinical 
site, laboratories, vendors and contract research organizations CROs, the clinical database, and 
the final study report. 
15
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, eCRFs developed through a validated, Electronic 
Records/Electronic Signatures-compliant platform (US Title 21 CFR Part 11). Foamix Clinical 
Data Management department or designee will create the eCRFs and corresponding clinical 
database based on the final protocol. 
All site personnel who will be using this system will receive formal training on the system, after 
which each person will be issued a unique username and password. Only the person who owns 
the username and password will enter the system using that username and password. For data 
security reasons and to be in compliance with regulatory guidelines, usernames and passwords 
are not transferable. 
The Investigator is responsible for all data entered via the remote data capture (RDC) system 
eCRFs and must confirm the accuracy of the data by electronically approving (signing) the 
eCRFs. This responsibility includes the timely completion and accuracy of the data entered into 
the eCRFs by their site personnel as well as the review and approval of some data entered 
directly into the database (eg, clinical laboratory results) by an external vendor. The Sponsor will 
review the database to identify data errors or inconsistencies, which will be posted in the RDC 
system as queries for resolution. In addition, the Sponsor may make obvious corrections to the 
data in the database (eg, obvious errors in dates) and so inform the Investigator without issuing a 
query to the site. 
16
REFERENCE LIST 
Not applicable. 
81 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
37 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
APPENDIX 1:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 7 (Week 40/Final Visit): 
1.
How satisfied are you with how easy this product is to use?
2. How satisfied are you with how this product feels on your skin after treatment?
3. How satisfied are you with the odor of this product after treatment?
4. How satisfied are you with the color of this product after treatment?
5. How satisfied are you with the ease of application of the product to your skin?
6. How satisfied are you with the ease in which this product fits into your daily routine?
7. How satisfied are you with this product compared to other products you have previously
used for rosacea, such as gels and creams?
8. Overall, how likely are you to use this product with other rosacea treatments?
9. Overall, how likely are you to recommend this product to a friend?
10. Overall, how satisfied are you with this product?
Answers to Questions 1 through 9 will be selected from the following: 
•
1 = Very Satisfied
•
2 = Satisfied
•
3 = Somewhat Satisfied
•
4 = Dissatisfied
•
5 = Very Dissatisfied
The answer to Questions 10 and 11 will be selected from the following: 
•
1 = Very Likely
•
2 = Likely
•
3 = Somewhat Likely
•
4 = Unlikely
•
5 = Very Unlikely
82 of 83

Privileged and Confidential 
Clinical Protocol:  Version 1 
38 of 38 
Final 
Protocol:  FX2016-13 
Date:  06 Mar 2017 
APPENDIX 2: Acknowledgment Of Receipt And Review Of 
Protocol 
Protocol Number: FX2016-13, Version 1 
Protocol Title: An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate to Severe Facial 
Papulopustular Rosacea (Study FX2016-13) 
I hereby acknowledge receipt and review of the following Protocol: 
1. Version 1, dated March 6th, 2017
Principal Investigator Name (Print) 
Principal Investigator Signature 
Date of Signature  
(DD MMM YYYY) 
83 of 83