A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to Evaluate the Safety and Efficacy of FMX103 1.5% Topical Minocycline Foam Compared to Vehicle in the Treatment of Facial Papulopustular Rosacea (FX2016-11)
Phase: PHASE3
Conditions: Facial Papulopustular Rosacea
Sponsor: Vyne Therapeutics Inc.

A Randomized, Multicenter, Double-blind, Vehicle-
controlled Study to Evaluate the Safety and Efficacy of 
FMX103 1.5% Topical Minocycline Foam Compared to 
Vehicle in the Treatment of Facial Papulopustular Rosacea 
(FX2016-11) 
ClinicalTrials.gov Identifier: NCT03142451 
Final Protocol, Version 3.0 (Amendment 2), dated 12-May-2017 
Final Protocol, Version 2.0 (Amendment 1), dated 06-Mar-2017 
Final Protocol, Version 1.0, dated 20-Jan-2017  

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CLINICAL PROTOCOL 
Title Page 
Study Title: 
A Randomized, Multicenter, Double-blind, Vehicle-
controlled Study to Evaluate the Safety and Efficacy of 
FMX103 1.5% Topical Minocycline Foam Compared to 
Vehicle in the Treatment of Facial Papulopustular Rosacea 
(FX2016-11) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-11 
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: 
12 May 2017 
Version of Protocol: 
Version 3 (Amendment 2) 
Supercedes: 
Version 2, issued 06 Mar 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. 
 
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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: 
A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to 
Evaluate the Safety and Efficacy of FMX103 1.5% Topical 
Minocycline Foam Compared to Vehicle in the Treatment of Facial 
Papulopustular Rosacea (Study FX2016-11) 
Protocol No: 
FX2016-11 
Study Centers: 
Multicenter (approximately 40 sites in the USA) 
Publication (reference): 
None 
Phase of Development: 
3 
Objectives: 
Primary Objectives: 
• 
To determine the efficacy of FMX103 1.5% minocycline foam 
applied topically once daily for 12 weeks in the treatment of 
rosacea. 
• 
To evaluate the safety of topical minocycline foam applied 
once daily for 12 weeks. 
Study Design and 
Methods: 
This is a randomized, multicenter, double-blind, vehicle-controlled, 
2-arm study to evaluate the safety and efficacy of FMX103 topical 
foam containing 1.5% minocycline compared to vehicle, in the 
treatment of subjects with moderate-to-severe facial papulopustular 
rosacea. Qualified subjects will be randomized in a 2:1 ratio 
(active:vehicle) to receive 1 of the following 2 treatments: 
• 
FMX103 minocycline foam 1.5% 
• 
Vehicle foam 
Subjects will be assigned to 1 of 2 treatments according to the 
randomization schedule, stratified by investigational site. Subjects will 
apply (or have applied) the study drug topically once daily for 12 weeks 
as directed. Subjects will be advised to use the study drug at 
approximately the same time each day. Both the Investigator and 
subject will be blinded to the study drug identity. 
Subjects will return for visits at Weeks 2, 4, 8, and 12. Efficacy 
evaluations (inflammatory lesion counts and Investigator’s Global 
Assessment [IGA] score) will be performed at Weeks 4, 8, and 12 
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during the study. 
Number of Subjects 
(planned): 
The planned enrollment is approximately 750 male and female subjects. 
Subjects will be randomly assigned to the two treatment groups, 
FMX103 1.5% and vehicle, in a 2:1 ratio, respectively. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years with a clinical 
diagnosis of moderate to severe facial papulopustular rosacea, defined 
as the presence of: 
• 
At least 15 and not more than 75 inflammatory facial lesions 
(ie, papules/pustules), and 
• 
An IGA of rosacea severity of moderate or severe using the 
following scale: 
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 
• 
Current or history of erythema and/or flushing 
Subjects must be willing to minimize external factors that might trigger 
rosacea flare-ups (eg, spicy foods, thermally hot foods and drinks, hot 
environments, prolonged sun exposure, strong winds, and alcoholic 
beverages). 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, once daily to 
the face, for 12 weeks. 
Reference Therapy: 
Vehicle foam. Topical application, once daily to the face, for 12 weeks. 
Study Duration: 
Subject participation in the study will be up to 18 weeks:  up to 6 weeks 
for Screening and Day 0/Baseline, and 12 weeks of study treatment. A 
safety follow-up telephone call will be conducted 4 weeks after 
completion of study treatment for only those subjects that do not 
participate in study FX2016-13 (Open label study) and who presented 
with either new or on-going adverse events at Visit 5/Week 12 (Final 
Visit). 
Endpoints and Outcomes: 
 
 
 
 
Efficacy Evaluations 
The co-primary efficacy parameters, include inflammatory lesion 
counts and IGA, will be evaluated at Day 0/Baseline and at Weeks 4, 8, 
and 12 (Final Visit). The Subject Global Assessment will be performed 
at Weeks 2, 4, 8, and 12 (Final Visit). The subject satisfaction 
questionnaire will be assessed at Week 12 (Final Visit) only. 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner), physical examinations, vital signs, clinical laboratory tests, 
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 and local signs and symptoms assessments (including erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, 
itching, peeling/desquamation, and hyperpigmentation) scores. 
Statistical Methods: 
The primary population for efficacy analysis will be the intent-to-treat 
(ITT) population, using multiple imputations to impute missing values. 
Supportive efficacy analyses will be conducted on the per-protocol (PP) 
population, with no imputation for missing values. 
The co-primary efficacy endpoints will be the dichotomized IGA score 
where treatment success is defined as at least a 2-step improvement 
resulting in a 0 (clear) or 1 (almost clear) score at Week 12 compared to 
Day 0/Baseline and the absolute change in inflammatory lesion count at 
Week 12 compared to Day 0/Baseline. 
The key secondary endpoints will be analyzed hierarchically: 
• 
Dichotomized IGA score where treatment success is defined as 
a 2-step improvement in score at Week 12 compared to Day 
0/Baseline. 
• 
Percent change in inflammatory lesion count at Week 12 
compared to Day 0/Baseline. 
Continuous efficacy endpoints will be analyzed using analysis of 
covariance (ANCOVA). Dichotomized efficacy endpoints will be 
analyzed using the Cochran-Mantel-Haenszel (CMH) test. 
The tolerability and safety of topical minocycline foam applied daily 
for 12 weeks will be evaluated using summary statistics and individual 
subject data listings. 
The active treatment group will be tested against vehicle at the 0.05 
two-sided level of significance. No statistical tests will be performed 
for any of the safety assessments. 
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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 ............................................................................................................................12 
5 
INVESTIGATIONAL PLAN ..................................................................................................................12 
5.1 
OVERALL STUDY DESIGN ................................................................................................................12 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................13 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................15 
7.1 
SCREENING VISIT .............................................................................................................................17 
7.2 
VISIT 1, DAY 0/BASELINE VISIT.......................................................................................................17 
7.3 
EARLY FOLLOW-UP, WEEK 1 (±3 DAYS) .........................................................................................18 
7.4 
VISIT 2, WEEK 2 (±3 DAYS) .............................................................................................................18 
7.5 
VISIT 3, WEEK 4 (±3 DAYS) .............................................................................................................18 
7.6 
VISIT 4, WEEK 8 (±3 DAYS) .............................................................................................................19 
7.7 
VISIT 5, WEEK 12 (-3/+5 DAYS) / FINAL VISIT OR EARLY TERMINATION .........................................20 
7.8 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................20 
8 
STUDY TREATMENTS ..........................................................................................................................21 
8.1 
TREATMENTS ADMINISTERED ..........................................................................................................21 
8.1.1 
Dosing Instructions ........................................................................................................21 
8.1.2 
Manufacturer ..................................................................................................................21 
8.1.3 
Labeling of Study Drug ..................................................................................................21 
8.1.4 
Storage of Study Drug ....................................................................................................22 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................22 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................23 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................23 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................23 
8.6 
BLINDING  ........................................................................................................................................23 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................24 
8.8 
USE OF CONTRACEPTION .................................................................................................................24 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................25 
9 
EFFICACY ASSESSMENTS ..................................................................................................................25 
9.1 
CO-PRIMARY EFFICACY ASSESSMENTS ...........................................................................................25 
9.1.1 
Lesion Counts.................................................................................................................25 
9.1.2 
Investigator Global Assessment .....................................................................................26 
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9.2 
SECONDARY AND TERTIARY EFFICACY ASSESSMENTS ....................................................................26 
9.2.1 
Percent Change in Inflammatory Lesion Counts ............................................................26 
9.2.2 
Interim Change in Inflammatory Lesion Counts ............................................................26 
9.2.3 
Subject Global Assessment ............................................................................................26 
9.2.4 
Subject Satisfaction Questionnaire .................................................................................26 
9.3 
PHOTOGRAPHY ................................................................................................................................26 
10 
SAFETY ASSESSMENTS .......................................................................................................................27 
10.1 
MEDICAL/SURGICAL HISTORY .........................................................................................................27 
10.2 
MEDICATION HISTORY.....................................................................................................................27 
10.3 
CONCOMITANT MEDICATIONS .........................................................................................................27 
10.4 
VITAL SIGNS ....................................................................................................................................27 
10.5 
PHYSICAL EXAMINATION .................................................................................................................27 
10.6 
CLINICAL LABORATORY TESTS........................................................................................................27 
10.6.1 
Urine Pregnancy Test .....................................................................................................28 
10.6.2 
Sample Collection, Storage, and Shipping .....................................................................28 
10.7 
OTHER SAFETY MEASUREMENTS .....................................................................................................28 
10.7.1 
Local Signs and Symptoms Assessments .......................................................................28 
10.7.1.1 Erythema (Clinical Erythema Assessment Scale) .........................................29 
10.7.1.2 Telangiectasia ................................................................................................29 
10.7.1.3 Burning/Stinging ...........................................................................................29 
10.7.1.4 Flushing/Blushing .........................................................................................30 
10.7.1.5 Dryness/Xerosis ............................................................................................30 
10.7.1.6 Itching ...........................................................................................................30 
10.7.1.7 Peeling/Desquamation ...................................................................................30 
10.7.1.8 Hyperpigmentation ........................................................................................30 
10.8 
ADVERSE EVENTS ............................................................................................................................31 
10.8.1 
Method of Determining Adverse Events ........................................................................31 
10.8.2 
Adverse Event Definitions .............................................................................................31 
10.8.2.1 Adverse Events ..............................................................................................31 
10.8.2.2 Serious Adverse Events .................................................................................32 
10.8.2.3 Severity of Adverse Events ...........................................................................32 
10.8.2.4 Relationship of Adverse Events to Study Treatments ...................................33 
10.8.2.5 Adverse Events Expectedness .......................................................................33 
10.8.3 
Reporting Adverse Events ..............................................................................................33 
10.8.4 
Adverse Event Follow-up ...............................................................................................33 
10.8.4.1 Pregnancy Reporting .....................................................................................34 
10.8.5 
Clinically Significantly Abnormal Laboratory Results ..................................................34 
10.9 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................34 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................34 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................34 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................35 
11.3 
ANALYSIS POPULATIONS .................................................................................................................35 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND DAY 0/BASELINE CHARACTERISTICS ......................36 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................36 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................37 
11.5.2 
Secondary Efficacy Endpoints .......................................................................................37 
11.5.3 
Tertiary Efficacy Endpoints ...........................................................................................37 
11.6 
SAFETY ENDPOINTS .........................................................................................................................38 
11.6.1 
Adverse Events ...............................................................................................................38 
11.6.2 
Vital Signs and Physical Examinations ..........................................................................38 
11.6.3 
Clinical Laboratory Results ............................................................................................38 
11.7 
INTERIM ANALYSIS ..........................................................................................................................39 
12 
STUDY MANAGEMENT .......................................................................................................................39 
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12.1 
MONITORING ...................................................................................................................................39 
12.2 
PROTOCOL AMENDMENTS................................................................................................................39 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................40 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................40 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................40 
12.6 
PUBLICATION POLICY ......................................................................................................................41 
13 
ETHICS .....................................................................................................................................................41 
13.1 
CONDUCT OF THE STUDY .................................................................................................................41 
13.2 
INSTITUTIONAL REVIEW BOARDS (IRB) ..........................................................................................41 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................41 
13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................42 
13.5 
RECORDS RETENTION ......................................................................................................................42 
13.6 
FINANCING .......................................................................................................................................42 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................43 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................43 
16 
REFERENCE LIST .................................................................................................................................43 
17 
STUDY AMENDMENTS ........................................................................................................................43 
17.1 
AMENDMENT 1, EFFECTIVE MARCH 6TH, 2017 ..................................................................................44 
17.2 
AMENDMENT 2, EFFECTIVE MAY 12TH, 2017 ....................................................................................50 
APPENDIX 1:  SUBJECT GLOBAL ASSESSMENT QUESTIONNAIRE ..................................................55 
APPENDIX 2:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................56 
APPENDIX 3: ACKNOWLEDGMENT OF RECEIPT AND REVIEW OF PROTOCOL .........................57 
 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-11 ........................... 16 
Table 2 
Study Drug Kits and Treatments – Study FX2016-11 ................................................... 21 
Table 3 
IGA Scale for Rosacea – Study FX2016-11 ................................................................... 26 
Table 4 
Clinical Laboratory Tests – Study FX2016-11 .............................................................. 28 
Table 5 
Sample Size Calculations Based on IGA Scores after 12 Weeks of Treatment in Phase 2 
Study FX2015-10 ........................................................................................................... 35 
 
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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 
BOCF 
Baseline observation carried forward 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
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 System 
ITT 
Intent-to-treat (population) 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed effects model for repeated measures 
OC 
Observed cases 
OTC 
Over-the-counter 
PP 
Per-protocol (population) 
PT 
Preferred term 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
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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 
 
 
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3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and the eye. 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. 
Foamix has developed a topical minocycline foam product that is being evaluated for safety and 
efficacy in the treatment of rosacea. Minocycline hydrochloride is an established broad spectrum 
antibiotic that is used orally in the treatment of 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 has been evaluated in a Phase 2 study at two minocycline 
concentrations, 1.5% and 3%. The study included 232 subjects (males/females, aged ≥18 years) 
with moderate-to-severe papulopustular rosacea defined by the Investigator’s Global Assessment 
(IGA) score and with ≥12 inflammatory facial lesions (papules/pustules) at Day 0/Baseline. 
Subjects were treated with FMX103 1.5%, FMX103 3%, or vehicle foam, once daily for 12 
weeks. Efficacy and safety were evaluated at Weeks 2, 4, 8, and 12, with an additional safety 
follow-up visit at Week 16. The primary efficacy end point was the absolute change in 
inflammatory lesion count at Week 12. Other assessments included IGA improvement of ≥2 
grades and reaching an IGA score of “clear” or “almost clear” (IGA 0/1), clinical assessment of 
erythema, and safety and tolerability. 
At Week 12, both the 1.5% and 3% doses of FMX103 significantly reduced the number of 
papules and pustules vs. vehicle (both p<0.001, intent-to-treat [ITT] population). The mean 
reduction in lesion count from Day 0/Baseline was 21.1 for the FMX103 1.5% dose, 19.9 for the 
FMX103 3% dose, and 7.8 for the vehicle. The corresponding percent reductions were 61.4% 
and 55.5% for the 1.5% and 3% doses, respectively, and 29.7% for the vehicle. 
Both the 1.5% and 3% doses of FMX103 were statistically significantly better than vehicle in 
improving IGA scores by ≥2 grades at week 12 (p=0.002 and p=0.032, respectively). Both doses 
were also statistically significantly better than vehicle in achieving an IGA of “clear or almost 
clear” (score 0/1) at Week 12 (p=0.001 and p=0.041, respectively). Both FMX103 1.5% and 3% 
doses appeared to be generally safe and well-tolerated. Treatment-related dermal reactions were 
reported in 1 subject from the FMX103 1.5% dose group (considered mild) and in a few subjects 
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from the FMX103 3% dose group (mild, n=1; moderate, n=2; severe, n=1). No treatment-related 
systemic adverse events (AEs) were reported and discontinuation due to AEs (eczema, n=1; 
rosacea, n=1; burning sensation, n=1) was reported in 3 subjects in the FMX103 3% dose group. 
As a consequence of the above, the FMX103 1.5% dose concentration has been selected for 
further development. This Phase 3 study will further assess the safety and efficacy of topical 
minocycline HCl foam, 1.5%, applied once daily compared with vehicle foam for the treatment 
of moderate-to-severe papulopustular rosacea. 
4 
STUDY OBJECTIVES 
The primary objectives of the study are: 
• To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily 
for 12 weeks in the treatment of rosacea. 
• To evaluate the tolerability and safety of topical minocycline foam applied once daily for 12 
weeks. 
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy of FMX103 topical foam containing 1.5% minocycline compared to vehicle, 
in the treatment of subjects with moderate-to-severe facial papulopustular acne rosacea. 
Qualified subjects will be randomized in a 2:1 ratio (active:vehicle) to use once daily one of the 
following two treatments: 
• FMX103 minocycline foam 1.5% 
• Vehicle foam 
Subjects will be assigned to 1 of 2 treatments according to the randomization schedule, stratified 
by investigational site. Subjects will apply (or have applied) the study drug topically once daily 
for 12 weeks as directed. Subjects will be advised to use the study drug at approximately the 
same time each day about 1 hour before bedtime. Both the Investigator and subject will be 
blinded to the study drug identity.  
Subjects will return for visits at Weeks 2, 4, 8, and 12. Efficacy evaluations (inflammatory lesion 
counts [Section 9.1.1] and IGA score [Section 9.1.2]) will be performed at Weeks 4, 8, and 12 
during the study. Other assessments will be performed as described in Section 9 and Section 10. 
5.2 
Rationale for Study Design and Dose Selection 
A randomized, multicenter, double-blind, vehicle-controlled study design has been selected in 
order to assess the efficacy of the study drug. The subjects will be selected according to 
predefined entry criteria. The study treatment duration of 12 weeks is expected to be sufficient to 
show a treatment effect. 
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The concentration of minocycline in the composition was selected according to formulation 
integrity and stability considerations and based on the results of Phase 2 Study FX2015-10 
(described above in Section 3). 
Because of the mode of action of tetracycline drugs, the primary efficacy endpoints will be the 
effect on inflammatory lesion counts and IGA scores (Section 9). 
6 
STUDY POPULATION 
The study will randomize approximately 750 subjects to active or vehicle treatment (in a 2:1 
ratio) at approximately 40 sites in the US. 
6.1 
Inclusion Criteria 
Subjects can be included in the study if they meet all of the following inclusion criteria at the 
time of enrollment: 
1. Male or female ≥18 years-of-age. 
2. Moderate-to-severe rosacea (as per the IGA score; Table 3) on the proposed facial 
treatment area consisting of: 
a. At least 15 and not more than 75 facial papules and pustules, excluding lesions 
involving the eyes and scalp; 
b. No more than 2 nodules on the face. 
3. Presence of or history of erythema and/or flushing on the face. 
4. If a female 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. 
5. Willing to minimize external factors that might trigger rosacea flare-ups (eg, spicy foods, 
thermally hot foods and drinks, hot environments, prolonged sun exposure, strong winds, 
and alcoholic beverages). 
6. Subjects who use make-up must have used the same brands/types of make-up for a 
minimum period of 14 days prior to study entry and must agree to use the same make-up, 
brand/type, or frequency of use, throughout the study. 
7. Completed and signed an appropriately administered Informed Consent Form (ICF) prior 
to any study-related procedures. 
6.2 
Exclusion Criteria 
Subjects should be excluded from enrollment in the study for any of the following reasons: 
1. Woman who is pregnant, lactating, or planning to become pregnant during the study 
period. 
2. Presence of any skin condition on the face that would interfere with the diagnosis or 
assessment of rosacea. 
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3. Moderate or severe rhinophyma, dense telangiectasia (score 3, severe; Section 10.7.2.2), 
or plaque-like facial edema. 
4. Excessive facial hair (eg, beards, sideburns, moustaches, etc.) that would interfere with 
diagnosis or assessment of rosacea. 
5. History of hypersensitivity or allergy to minocycline, any other tetracycline, or of any 
other component of the formulation. 
6. Severe erythema, dryness, scaling, pruritus, stinging/burning, or edema. 
7. Active ocular rosacea (eg, conjunctivitis, blepharitis, or keratitis) of sufficient severity to 
require topical or systemic antibiotics. 
8. Use within 6 months prior to Day 0/Baseline of oral retinoids (eg, Accutane®) or 
therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are 
allowed). 
9. Initiation of use of estrogens or oral contraceptives less than 3 months prior to Day 
0/Baseline. 
10. Use within 1 month prior to Day 0/Baseline of: 
a. Topical retinoids to the face. 
b. Systemic antibiotics known to have an impact on the severity of facial rosacea 
(eg, containing tetracycline and its derivatives, erythromycin and its derivatives, 
sulfamethoxazole, or trimethoprim). Subjects requiring systemic antibiotics not 
known to affect rosacea will be considered on a case-by-case basis. 
c. Systemic corticosteroids (Note: intranasal and inhalational corticosteroids do not 
require a washout and maybe used throughout the trial if the subject is on a stable 
dose). 
11. Use within 2 weeks prior to Day 0/Baseline of: 
a. Topical corticosteroids. 
b. Topical antibiotics. 
c. Topical medications for rosacea (eg, metronidazole). 
12. Use of a sauna during the 2 weeks prior to Day 0/Baseline and during the study. 
13. Had wax epilation of the face within 2 weeks prior to Day 0/Baseline. 
14. Active bacterial folliculitis. 
15. Consumption of excessive alcohol, abuse of licit or illicit drugs, or a condition that, in the 
opinion of the Investigator, could compromise the subject’s ability to comply with study 
requirements. 
16. Participation in activities that involve excessive or prolonged exposure to sunlight or 
weather extremes, such as wind or cold. 
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17. Presence of any clinically significant condition or situation, other than the condition
being studied, that in the opinion of the Investigator would interfere with the study
evaluations or optimal participation in the study.
18. Participation in an investigational drug study (ie, subject has been treated with an
investigational drug) within 30 days prior to Day 0/Baseline. Subjects who are
participating in non-treatment studies such as observational studies or registry studies can
be considered for inclusion.
19. Previously enrolled in this study.
20. Prior laser therapy (for telangiectasia or other conditions), electrodessication, or
phototherapy (eg, ClearLight®) to the facial area within 180 days prior to Day 0/Baseline.
21. Prior cosmetic procedures (eg, facials) that may affect the efficacy and safety profile of
the investigational product within 14 days prior to Day 0/Baseline.
7 
STUDY PROCEDURES 
Potential subjects will be assessed for eligibility at Screening. During this visit, the purpose, 
timing, procedures, and risks of the study will be explained to the subject, including 
requirements for enrollment and participation in the study, medication restrictions during the 
study, and requirements for washout of certain medications that the subject may already be 
taking. 
The eligible subject who is willing to participate in the study will then sign an appropriately 
administered ICF prior to any study-related procedures being performed. 
Procedures at the Screening Visit will include obtaining blood and urine samples for clinical 
laboratory tests. The results of these tests must be no more than 45 days old at the time of the 
Day 0/Baseline Visit and randomization. 
If a subject who has agreed to participate in the study, has signed the ICF and is currently 
undergoing rosacea therapy identified in Exclusion Criteria 10 and 11, they must first enter a 
washout period (ie,1 month or 2 weeks, as specified in Exclusion Criteria 10 and 11, 
respectively) during the screening period.  Screening procedures are to be performed as defined 
in the Screening Visit (Section 7.1). 
The schedule of study assessments and procedures and the time point at which they will be 
performed during the study is presented in Table 1. If a subject prematurely withdraws from the 
study, the subject should return to the study site for an early termination visit during which all 
evaluations described under Final Visit 5/Week 12 must be performed. 
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Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-11 
Assessment or Procedure 
Screening 
Day 0 / 
Baseline0 
Visits/Early 
Follow-up 
Final 
Visitb 
Safety 
Follow-upf 
Visit 
1 
EF 
2 
3 
4 
5 
Week 
1 
2 
4 
8 
12 
Informed consent 
X 
Demographic data 
X 
Assign subject identification 
X 
Medical/surgical/medication history 
X 
Inclusion/exclusion criteria 
X 
X 
Physical examination, height, weightc 
X 
X 
Blood pressure/heart rated 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
X 
X 
Urine pregnancy test (females of 
childbearing potential only) 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
X 
X 
X 
Subject Global Assessment 
X 
X 
X 
X 
Subject Satisfaction Questionnaire 
X 
Local signs and symptoms 
assessmentse  
X 
X 
X 
X 
X 
X 
Photography† 
X 
X 
X 
X 
Randomization 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
Schedule/confirm next visit 
X 
X 
X 
X 
X 
X 
EF – Early Follow-up telephone call, no visit; † only for study centers participating in subject photography (Section 9.3) 
a.
Day 0/Baseline must occur within 45 days of Screening. Blood test results must not show clinically significant
abnormalities.
b.
If a subject prematurely withdraws from the study, all evaluations described under Visit 5/Week 12 (Final Visit)
must be performed at an Early Termination Visit.
c.
Height to be measured only at Day 0/Baseline.
d.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest.
e.
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.
f.
A safety follow-up telephone call will be made 4 weeks after Visit 5/Week 12 (Final Visit) for only those subjects
that do not participate in study FX2016-13 (Open label study) and presented with either new or on-going adverse
events at Visit 5/Week 12 (Final Visit).
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7.1 
Screening Visit 
• Obtain a signed and dated, written ICF prior to any study-related procedures. 
• Obtain demographic data. 
• Using the Interactive Response Technology System (IRT), assign the subject an identification 
number. 
• Obtain medical/surgical history (Section 10.1). 
• Obtain history of prior medication usage (including previous use of rosacea medications); 
record start and stop dates of any medications used in the last 3 months (Section 10.2). 
• Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria (Section 6.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Collect blood and urine samples for clinical laboratory tests and send to the central laboratory 
(Section 10.6.2). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
• Perform IGA (Section 9.1.2). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Schedule/confirm the next study visit. 
7.2 
Visit 1, Day 0/Baseline Visit 
• Confirm eligibility according to the inclusion (Section 6.1) and exclusion criteria 
(Section 6.2). 
• Perform physical examination including height and weight (Section 10.5). 
• Measure blood pressure and heart rate (Section 10.4). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
• Perform IGA (Section 9.1.2). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Randomize the subject using the IRT when all criteria have been met. 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
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• Dispense one kit (2 canisters) of study drug. 
• Dispense facial cleanser and moisturizer. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.3 
Early Follow-up, Week 1 (±3 Days) 
An early follow-up telephone call will be made 1 week after Visit 1, Day 0/Baseline. 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Confirm that subject continues to use only the provided facial cleanser and moisturizer. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.4 
Visit 2, Week 2 (±3 Days) 
• Measure blood pressure and heart rate (Section 10.4). 
• Have the subject complete the Subject Global Assessment (Section 9.2.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Confirm that subject continues to use only the provided facial cleanser and moisturizer. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Perform drug accountability to assess compliance (Section 8.2). 
• Collect used study canister (if applicable). 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.5 
Visit 3, Week 4 (±3 Days) 
• Measure blood pressure and heart rate (Section 10.4). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
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• Perform IGA (Section 9.1.2). 
• Have the subject complete the Subject Global Assessment (Section 9.2.3). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Perform drug accountability to assess compliance (Section 8.2). 
• Collect used study drug canister (if applicable). 
• Dispense one kit (2 canisters) of study drug. 
• Confirm that subject continues to use only the provided facial cleanser and moisturizer and 
dispense additional quantities as required. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.6 
Visit 4, Week 8 (±3 Days) 
• Measure blood pressure and heart rate (Section 10.4). 
• 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 9.2.3). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Perform drug accountability to assess compliance (Section 8.2). 
• Collect used study drug canister (if applicable). 
• Dispense one kit (2 canisters) of study drug. 
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• Confirm that subject continues to use only the provided facial cleanser and moisturizer and 
dispense additional quantities as required. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.7 
Visit 5, Week 12 (-3/+5 days) / Final Visit or Early Termination 
• Perform physical examination including weight (Section 10.5). 
• Measure blood pressure and heart rate (Section 10.4). 
• Collect blood and urine samples for clinical laboratory tests and send to the central laboratory 
(Section 10.6.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
• Perform IGA (Section 9.1.2). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Have the subject complete the Subject Global Assessment (Section 9.2.3). 
• Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.4). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Collect all used and full study drug canisters. 
• Perform drug accountability to assess compliance and record the date of the last dose 
(Section 8.2). 
• Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 5/Week 12 (Final 
Visit) date (±5 days) only for subjects that will not participate in study FX2016-13 (Open 
label study) (Section 7.9) and presented with either new or on-going adverse events at Visit 
5/Week 12 (Final Visit). 
7.8 
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 5/Week 12 (Final Visit) for 
only those subjects that do not participate in study FX2016-13 (Open label study) and presented 
with either new or on-going adverse events at Visit 5/Week 12 (Final Visit). Follow up on these 
adverse events and any new concomitant medications will be recorded. 
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8 
STUDY TREATMENTS 
This study will include FMX103 minocycline foam 1.5% and vehicle foam. 
8.1 
Treatments Administered 
The description of study drug kits and treatments is shown below in Table 2. 
Table 2 
Study Drug Kits and Treatments – Study FX2016-11 
Dosage form description: 
Foam containing minocycline HCl 1.5% or vehicle foam 
Package description: 
Canisters, each containing 35 g of the clinical trial supply foam 
Daily dose: 
Once daily application of a sufficient amount of foam to cover the entire face. 
Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% active) 
or 0.0 mg (vehicle) of minocycline. 
Cumulative maximal dose for 
dosing (12 weeks): 
630 mg (1.5%) minocycline 
Dispensing: 
Kits consisting of 2 canisters, each canister containing 35 g of FMX103 
minocycline formulation, 1.5%, or vehicle dispensed at Visit 1 (Day 
0/Baseline), Visit 3 (Week 4), and Visit 4 (Week 8).  
8.1.1 
Dosing Instructions 
The dosing regimen will be the same for both treatment groups. 
Study drug kits containing 2 canisters of investigational drug will be dispensed at Visit 1 (Day 
0/Baseline), Visit 3 (Week 4), and Visit 4 (Week 8).  
After shaking the canister well, a small amount of study drug (about ½ gram or a cherry-sized 
amount) should be expressed from the canister onto the finger tips and then applied as a thin 
layer over all areas of the face. Additional drug may be used as needed to ensure the entire face is 
treated.  
Study drug should be applied at approximately the same time each day, about 1 hour before 
bedtime. 
8.1.2 
Manufacturer 
The manufacturer of the investigational product is ASM Aerosol-Service AG, Moehlin, 
Switzerland. 
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 
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• 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% and vehicle canisters must be stored at 2°C – 8°C until being dispensed to the 
subject. Subsequently, they 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 use of the study drug. The Investigator or 
designee will verify the contents of the drug shipment and confirm receipt of the study drug in 
the 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 regional regulatory authority 
inspection at any time. At the conclusion of the study, the Investigator must provide a copy of 
this record to the Sponsor and each canister that has been retrieved from a subject will be 
returned to the vendor to be weighed. 
Under no circumstances will the Investigator allow the investigational drugs to be used other 
than as directed by this protocol. Qualified study personnel must use the IRT to assign and 
dispense kits to the subjects. Reasons for digression from the expected dispensing regimen must 
also be recorded. 
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8.3 
Handling and Disposal of Study Drug 
The study drug must be protected from unauthorized access (eg, in a locked storage facility). 
Any unused, partially used, or empty bottles of study drug will be returned to the Sponsor or 
designee by the time of the site’s close-out visit. Receipt, distribution, and return of the study 
drug must be properly documented on forms provided by the Sponsor or designee. 
8.4 
Method of Assignment of Study Drug 
After pretreatment, clinical evaluations and all other Screening procedures have been completed, 
authorized site personnel will acknowledge that the applicable subject met all the specified 
inclusion criteria (Section 6.1) and none of the exclusion criteria (Section 6.2). Assignment to a 
treatment group will then follow a predetermined list of randomization numbers, with each 
successive number receiving 1 of the 2 treatments in random order. Authorized site personnel 
will use the IRT system to assign a kit number that corresponds to the randomization schedule. 
The kit box with the assigned kit number will be dispensed to the subject. 
The randomization code will be provided by Premier Research, Research Triangle Park, NC. 
8.5 
Selection and Timing of Doses in the Study 
The 1.5% concentration of minocycline has been shown to be effective compared to vehicle in a 
Phase 2 study in subjects with rosacea. The once-daily dosing regimen is appropriate given the 
pharmacokinetic characteristics of minocycline. 
8.6 
Blinding 
This is a double-blind study, with limited access to the randomization code. The randomization 
code will be held in confidence until after the study database is locked and a memo documenting 
the database lock has been issued. Every effort will be made to retain the integrity of the blind. 
When issued to the sites, the study drug will be identical in appearance for all subjects, 
regardless of treatment assignment. 
The treatment each subject receives will not be disclosed to the Investigator, study site personnel, 
subjects, monitors, or the Sponsor staff except as required for the purposes of conducting this 
study. 
In the event that emergency identification of study drug is required (eg, if the Investigator 
believes that the information is necessary to properly treat a subject with an AE), the study drug 
identity can be obtained by the Investigator through the IRT system. 
Before breaking the blind for a subject, the Investigator should determine that the information is 
necessary (ie, that it will alter the subject’s immediate course of treatment and will contribute to 
the management of the AE). In many cases, particularly when the emergency is clearly not 
related to study drug, the problem may be effectively managed by assuming that the subject is 
receiving active study drug without the need for unblinding. Every effort should be made to alert 
the medical monitor before requesting that the blind be broken. If this is not possible, the medical 
monitor should be immediately notified of the breaking of the blind. The Investigator will record 
the unblinding procedures in the subject’s source documents. 
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If unblinding is necessary, the subject will be withdrawn from the study and Early Termination 
Visit (ie, Visit 5 [Week 12]) assessments will be completed. 
8.7 
Prior/Concomitant Therapy 
As necessary, subjects should use the facial cleanser Cetaphil Gentile Skin Cleanser and the 
facial moisturizer Eucerin Daily Protection Broad Spectrum SPF30 Face Lotion. Both products 
will be provided by the Sponsor. Alternative, non-medicated cleansers or moisturizers may be 
used if agreed to by the Sponsor. 
The use of or change in the dose of any and all concomitant medications, either prescription or 
over-the-counter (OTC), during the study will be recorded. The reason for use or change of dose 
of a concomitant therapy may need to be reported as an AE. Therapies (medication and non-
medication therapies) not restricted by the protocol may be used. Non-prohibited chronic 
therapies being used at Day 0/Baseline may be continued. If a female subject 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 study. 
If a subject is taking anticoagulant therapy, the subject should be advised that they may require a 
downward adjustment of their anticoagulant dosage. 
All topical or systemic medications listed in the exclusion criteria are prohibited during this 
study. Similarly, no other topical medications are permitted to be used on the face during this 
period. 
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 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 listed below 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: 
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• 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 kits (empty/used/unused) at the appropriate visits. The study site personnel will question the 
subject on the history of 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 
Co-Primary Efficacy Assessments 
The co-primary efficacy assessments will include the inflammatory lesion counts and the IGA of 
severity of disease. Lesion counts, IGA, and other efficacy evaluations 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 will be performed at Screening and Visit 1 (Day 0/Baseline) to confirm eligibility, and 
again at Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12/Final Visit). 
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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 will be performed at Screening and Visit 1 (Day 0/Baseline) to confirm 
eligibility, and again at Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-11 
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 
Percent Change in Inflammatory Lesion Counts 
The percent change in inflammatory lesion counts at Visit 5 (Week 12/Final Visit) compared to 
Visit 1 (Day 0/Baseline) will be evaluated. 
9.2.2 
Interim Change in Inflammatory Lesion Counts 
The absolute 
 change in inflammatory lesion counts at Visit 3 (Week 4) and Visit 4 
(Week 8) compared to Visit 1 (Day 0/Baseline) will be evaluated. 
9.2.3 
Subject Global Assessment 
This score will be obtained from the subject at Visit 2 (Week 2), Visit 3 (Week 4), Visit 4 (Week 
8), and Visit 5 (Week 12/Final Visit) using the questionnaire in Appendix 1. 
9.2.4 
Subject Satisfaction Questionnaire 
A subject satisfaction questionnaire (Appendix 2) will be administered at Visit 5 (Week 12/Final 
Visit). 
9.3 
Photography 
Photography will be performed at selected study centers only. Study centers should refer to their 
specific Clinical Trial Agreement to confirm participation. 
Photography of the full face will be performed at Day 0/Baseline and at Weeks 4, 8, and 12 using 
recognized methods. The equipment and techniques for this photography and for archiving the 
images are described in the Study Manual. Photographs will be reviewed at the site and by the 
sponsor for quality. Photographs will not be used to assess the lesion counts or the IGA, but will 
be archived to be available for subsequent review, if required, by the sponsor, auditors, or the 
FDA. 
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10 
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
physical examinations, the monitoring of vital signs, AEs (volunteered, observed, and elicited by 
general questioning in a non-suggestive manner), clinical laboratory tests, and local signs and 
symptoms assessments (including erythema, telangiectasia, burning/stinging, flushing/blushing, 
dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) scores. 
10.1 
Medical/Surgical History 
A complete medical and surgical history will be obtained at Screening, which will include the 
following:  diseases of the head, ears, eyes, nose and throat; respiratory diseases; cardiovascular 
diseases; gastrointestinal diseases; hepatic diseases; genitourinary diseases; musculoskeletal 
diseases; endocrine diseases; neurological diseases; psychiatric diseases; skin diseases; allergies; 
hematological diseases; and other abnormalities. 
10.2 
Medication History 
A history of medication usage (including previous use of rosacea medications and non-
medication therapies) will be recorded at Screening. The start and stop dates of previous use of 
medications in the last 3 months will be recorded. 
10.3 
Concomitant Medications 
All topical or systemic medications listed in the exclusion criteria are prohibited. No other 
topical medications are permitted to be used on the face. All medication that the subject is 
currently taking or any change in medication or dosage since the last visit will be documented 
throughout the study. The use of or change in the dose of any and all concomitant medication, 
either prescription or OTC, during the study will be recorded. The reason for use or change of 
dose of a concomitant therapy may need to be reported as an AE. 
10.4 
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all post-Day 0/Baseline 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. 
10.5 
Physical Examination 
A complete physical examination (excluding the genitourinary examination) will be performed. 
Weight will be recorded at the Visit 1 (Day 0/Baseline) and Visit 5 (Week 12/Final Visit). Height 
will be measured at Visit 1 (Day 0/Baseline) only. 
10.6 
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at the Screening Visit and 
Visit 5 (Week 12/Final Visit). All clinical laboratory tests will be performed at a central 
laboratory. Table 4 presents the specific clinical laboratory tests to be evaluated. 
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Please refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples. 
Table 4 
Clinical Laboratory Tests – Study FX2016-11 
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 
 
10.6.1 
Urine Pregnancy Test 
A urine pregnancy test will be performed on all females of childbearing potential at the 
Screening Visit, Visit 1 (Day 0/Baseline), Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 
12/Final Visit) or when a subject prematurely withdraws from the study. 
10.6.2 
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. 
10.7 
Other Safety Measurements 
10.7.1 
Local Signs and Symptoms Assessments 
The severity of each of the following local signs and symptoms will be measured at Screening, 
Visit 1 (Day 0/Baseline), and at each study visit:  erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. The 
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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 adverse events, unless a sign/symptom is 
believed to have been related to the study medication or is the reason for discontinuation from 
the study. 
10.7.1.1 
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 
10.7.1.2 
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 
10.7.1.3 
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 
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10.7.1.4 
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 
10.7.1.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
• 0 = None 
• 1 = Mild 
• 2 = Moderate 
• 3 = Severe 
10.7.1.6 
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 
10.7.1.7 
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 
10.7.1.8 
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 
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10.8 
Adverse Events 
10.8.1 
Method of Determining Adverse Events 
Safety assessments will include recording adverse events reported spontaneously by the subject 
or observed by the Investigator. AEs will be recorded at each visit on the appropriate 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 10.8.4) 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 10.8.2 and Section 10.8.3, 
respectively. 
10.8.2 
Adverse Event Definitions 
10.8.2.1 
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 
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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. 
10.8.2.2 
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. 
10.8.2.3 
Severity of Adverse Events 
Severity of an AE refers to the extent to which an AE 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.
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10.8.2.4 
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to 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.
10.8.2.5 
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. 
10.8.3 
Reporting Adverse Events 
Adverse events that occur from the time of informed consent/assent through 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 or 
designee 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 or designee. Any pertinent follow-up information should be provided in a similar 
manner. Contact information is provided below: 
10.8.4 
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until resolution or stabilization (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, stabilized, or no longer serious enough to warrant follow-up. 
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 resolved or stabilized. 
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10.8.4.1 
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 Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of laboratory pregnancy testing 
are available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
A urine pregnancy test will be performed on all females of childbearing potential as described in 
Section 10.6.1. 
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, missed or late menstrual 
period). 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 laboratory 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. 
10.8.5 
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be so flagged 
when reported to the site. The Investigator will determine which out-of-range laboratory test 
results should be characterized as clinically significant and will so 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. 
10.9 
Appropriateness of Safety Measurement 
The safety assessments to be utilized 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 (SAP) will be finalized prior to breaking of the study blind. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated, but the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. All hypothesis testing will be conducted 
using two-sided tests with a 0.05 level of significance. 
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11.2 
Determination of Sample Size 
In the Phase 2 Study FX2015-10, the proportion of subjects with an IGA score of 0 or 1 after 
 of treatment was 
 in the FMX103 1.5% dose group compared to 
 for the 
vehicle dose group. Table 5 provides alternate assumptions on this primary response criterion 
with corresponding implications on sample size. Power was set to 90% and a type-1 error was set 
to a two-sided test with a 0.05 level of significance. Sample size was calculated based on 
Fisher’s Exact test. 
Table 5 
Sample Size Calculations Based on IGA Scores after 
 of 
Treatment in Phase 2 Study FX2015-10 
Vehicle IGA (Score 0,1) 
FMX103 1.5% IGA (Score 0,1) 
Sample Size (Vehicle, Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assuming a 
 dropout rate, 500 subjects receiving FMX103 and 250 subjects receiving 
vehicle will provide at least 90% power for a statistically significant difference on an IGA score 
of 0 or 1. 
For the co-primary endpoint of change from Day 0/Baseline to 
 in inflammatory lesion 
count, in the Phase 2 study the FMX103 1.5% dose group had a mean reduction of 
 lesions 
whereas the vehicle had a mean reduction of 
 lesions. The standard deviation was 
. For a 
90% power, 
 and 
 subjects in the FMX103 1.5% and vehicle groups, respectively, will be 
needed. Therefore, the sample size needed to provide at least 90% power for both co-primary 
endpoints is 
 and 
 subjects in the FMX103 1.5% and vehicle groups, respectively. 
11.3 
Analysis Populations 
The following populations will be defined for analysis: 
• Intent-to-Treat (ITT) population:  all randomized subjects. 
• Per-Protocol (PP) population:  defined as the subset of the ITT population without any 
protocol deviations that may have an impact on the efficacy assessments. Subjects to be 
included in the PP population will be determined by the Sponsor/CRO prior to the unblinding 
of the study. 
Subjects may be included in the PP population if all of the following are met: 
o 
Have met all inclusion/exclusion criteria 
o 
Have not administered any interfering concomitant medications 
o 
Were not subject to a randomization error 
o 
Completed treatment through Week 12 
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o 
Were greater than 80% compliant with study medication where % compliance is 
defined as: 
% Compliance = 100 x (expected treatment duration in days minus # days a dose was missed) / 
(expected treatment duration in days) 
• Safety Population:  all randomized subjects who use any study product. Subjects who have 
no post-Day 0/Baseline assessments will be included in the Safety population unless all 
dispensed study drug is returned unused. 
The ITT population will be the primary population for efficacy analysis. The PP population will 
be secondary for the co-primary endpoints only. The Safety population will be used for the 
analyses of safety endpoints. 
All efficacy analyses will be conducted according to the randomized treatment assignment; all 
safety analyses will be conducted according to the treatment actually received. 
11.4 
Subject Accounting, Demographics, and Day 0/Baseline Characteristics 
Demographics, Day 0/Baseline characteristics, and prior and concomitant medications will be 
summarized by treatment. Study completion status and reasons for discontinuation will also be 
displayed by treatment. 
Medical and surgical history will only be presented in the listings. 
11.5 
Efficacy Endpoints 
The primary population for all efficacy analyses will be the ITT population. For the analyses of 
the co-primary and secondary efficacy endpoints based on the ITT population, a variety of 
methods will be used to impute missing data, including multiple imputation (MI), last-
observation-carried forward (LOCF), and Day 0/Baseline observation carried forward (BOCF). 
MI will be the primary imputation method. Sensitivity analyses using LOCF and BOCF will be 
performed only on the co-primary efficacy endpoints to assess the robustness of alternate 
imputation assumptions. For the continuous efficacy measure, a mixed effects model for repeated 
measures (MMRM) analysis will also be conducted as a sensitivity analysis. All supportive 
analyses using the PP population will use the Observed-Cases (OC) approach, that is there will 
be no imputation for missing data at any time point. No other imputations will be made unless 
otherwise specified. 
For all efficacy analyses, subjects will be analyzed according to the treatment group to which 
they were randomized. 
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11.5.1 
Primary Efficacy Endpoints 
The co-primary efficacy endpoints are: 
• The absolute change in the inflammatory lesion count at Week 12 compared to Day 
0/Baseline. 
• The dichotomized IGA score where treatment success is defined as at least a 2-step 
improvement resulting in a 0 (clear) or 1 (almost clear) score at Week 12 compared to Day 
0/Baseline. 
The null hypothesis of the equality of the FMX103 1.5% and vehicle means for absolute change 
from Day 0/Baseline to Week 12 in the inflammatory lesion count and the equality of IGA 
success rates at Week 12 will each be tested at a two-sided 0.05 level of significance. Change 
from Day 0/Baseline in inflammatory lesion count will be analyzed using an analysis of 
covariance (ANCOVA), with treatment as a main effect, Day 0/Baseline inflammatory lesion 
count as a covariate, and investigational site as a blocking factor. An investigation site-by-
treatment interaction term will be included in the ANCOVA model to test for homogeneity 
among investigational sites. 
The dichotomized IGA will be analyzed using the Cochran-Mantel-Haenszel (CMH) test, 
stratified by investigational site. For dichotomized IGA, the investigational site-by-treatment 
interaction will be assessed with the Breslow-Day test. Investigational site-by-treatment 
interaction will be tested at a two-sided 0.1 level, and if significant will be further explored 
through the examination of descriptive statistics by individual (non-pooled) investigative sites.  
For analysis purposes, all investigative sites with fewer than 8 randomized subjects will be 
combined into a single pooled site. If a resulting pooled site still has fewer than 10 randomized 
subjects, then this pooled site will be further combined with the smallest unpooled site. This 
pooling process will continue until there are at least 8 randomized subjects in each pooled site. 
11.5.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
• The dichotomized IGA score where success is defined as a 2-step improvement in score at 
Week 12 compared to Day 0/Baseline. 
• The percent change in inflammatory lesion count at Week 12 compared to Day 0/Baseline. 
• The absolute change from Day 0/Baseline in the inflammatory lesion count and IGA 
treatment success at the interim visit at Week 8. 
• The absolute change from Day 0/Baseline in the inflammatory lesion count and IGA 
treatment success at the interim visit at Week 4. 
Secondary efficacy endpoints will be treated sequentially in the order listed above, at a 0.05 level 
of significance, only if the co-primary efficacy endpoints are significant. 
11.5.3 
 
 
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• 
 
• 
 
11.6 
Safety Endpoints 
Safety endpoints will be reported on the Safety population. Subjects will be reported according 
to the treatment they actually received. Safety assessment will be based on descriptive statistics 
and individual 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 
pre-treatment, or worsen relative to the pre-treatment 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 for each treatment group. At each level of 
summarization, a subject will be counted only once if he/she reported one or more events. The 
severity of TEAEs and relationship to study drug will be summarized in a similar manner. For 
summaries of relationship to 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. 
TEAEs, vital signs, and clinical laboratory measurements will be summarized by treatment group 
using descriptive statistics. For vital signs, change from Day 0/Baseline values will also be 
summarized. For all safety variables, subject data listings will be provided. 
Local signs and symptoms 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 10.7.2. 
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 prematurely withdraw from the study 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 
Day 0/Baseline and at each post-Day 0/Baseline time point. Changes from Day 0/Baseline will 
also be summarized. Day 0/Baseline is defined as the last non-missing value prior to the first 
dose of study drug. 
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 
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(normal), or above the laboratory range (high) at Day 0/Baseline with the number of subjects 
with low, normal, or high values at the Final Visit. Day 0/Baseline is defined as the last non-
missing value prior to the first dose of study drug. 
A listing of subjects with pre-treatment and 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 immediately notify the Sponsor 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 GCP-ICH, and their 
agreement with the source data. The monitor will also verify the correct use of the study drug. At 
a 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. 
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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 the IRB’s 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 
Withdrawn subjects are those who do not complete all evaluations and procedures outlined in the 
protocol. Subjects who discontinue taking study drug for any reason must also be withdrawn 
from the study. 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 10.8.4. 
• 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 stabilized 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/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, relocation of subject, etc. If a 
subject becomes pregnant during the study, the subject will be withdrawn from the study and 
followed through conclusion of the pregnancy. 
If a subject is withdrawn from the study following the start of study drug, all Visit 5 
(Week 12/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 
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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, which will make reasonable 
efforts to assure that the results are published in a peer-reviewed journal. As some of the 
information concerning the investigational product and development activities at the Sponsor 
may be of a strictly confidential 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 (IRB) 
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/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/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 their 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/she has informed the subject about the study 
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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 ensures 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 and assent 
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 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. 
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14 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and 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 (CQA) Department 
may conduct periodic audits of the study processes, including, but not limited to, auditing the 
clinical site, laboratories, vendors and CROs, the clinical database, and the final study report. 
15 
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, electronic case report forms (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 
FX2016-11. 
Section 17.1 describes the changes made to Protocol FX2016-11 Version 1 issued January 20, 
2017, via Amendment 1 effective March 6th, 2017. 
Section 17.2 describes the changes made to Protocol FX2016-11 Version 2 issued March 6th, 
2017, via Amendment 2 effective May 12th, 2017. 
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17.1 
Amendment 1, effective March 6th, 2017 
The following is the summary of the changes that were made to Protocol FX2016-11 Version 1 
issued January 20, 2017. 
Content changes:  
New or changed text is bolded. 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis (Study 
Centers); Sect. 6 
Study Population 
…approximately 30 
sites…  
…approximately 40 sites… 
Number of study 
centers adjusted to 
account for larger study 
sample size. 
Sect. 11.2 
Determination of 
Sample Size; Table 
5 Sample Size 
Calculations Based 
on IGA Scores 
after 
 of 
Treatment in Phase 
2 Study FX2015-
10 and text  
 
…
... 
…
... 
Typographic error. 
Sect. 11.2 
Determination of 
Sample Size; Table 
5 and text  
 
New text inserted in Table 
5. 
Vehicle IGA (Score 0,1): 
; FMX103 1.5% IGA 
(Score 0,1): 
; 
Sample Size (Vehicle, 
Active): 
 
Study sample size 
calculation based on an 
assumed 
 reduction 
in effect difference 
between active and 
vehicle, relative to 
Study FX2015-10 
FMX103 1.5% IGA 
(Score 0,1) v’s Vehicle 
IGA (Score 0,1) 
observed difference. 
As above. 
Assuming a 
 dropout 
rate, 
 subjects 
receiving FMX103 and 
 subjects… 
Assuming a 
 dropout 
rate, 
 subjects receiving 
FMX103 and 
 
subjects… 
Corrected for larger 
study sample size. 
As above. 
Therefore, the sample size 
needed to provide 90% 
power for both co-primary 
endpoints is 
 and 
 
subjects… 
Therefore, the sample size 
needed to provide at least 
90% power for both co-
primary endpoints is 
 
and 
 subjects… 
Corrected for larger 
study sample size. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis 
(Statistical 
Methods); Sect. 
11.5.1 Primary 
Efficacy Endpoints 
…treatment success is 
defined as a 2-step 
improvement… 
…treatment success is 
defined as at least a 2-step 
improvement… 
Clarification of 
treatment success 
criteria. 
Synopsis (Number 
of Subjects 
(planned); Sect. 6 
Study Population 
…approximately 450 
subjects… 
…approximately 600 
subjects… 
Corrected for larger 
study sample size. 
Sect. 7.2 Visit 1, 
Day 0/Baseline 
Visit 
New text. 
Dispense facial cleanser 
and moisturizer. 
Clarification of the 
need to dispense 
cleanser and 
moisturizer at Day 
0/Baseline. 
Sect. 7.4 
• Confirm that subject 
continues to use only 
the provided facial 
cleanser. 
• 
Confirm that subject 
continues to use only 
the provided facial 
cleanser and 
moisturizer. 
Reflecting the addition 
of moisturizer. 
Sect. 7.5 and 7.6 
• Confirm that subject 
continues to use only 
the provided facial 
cleanser. 
• 
Confirm that subject 
continues to use only 
the provided facial 
cleanser and 
moisturizer and 
dispense additional 
quantities as required. 
Clarification of cleanser 
and moisturizer re-
supply to subjects. 
Sect. 8.7 
Prior/Concomitant 
Therapy 
• Subjects should use 
the facial cleanser 
Cetaphil Gentle Skin 
Cleanser (which will 
be provided by the 
Sponsor). An 
alternative, non-
medicated cleanser 
may be used if agreed 
to by the Sponsor. 
• 
As necessary, subjects 
should use the facial 
cleanser Cetaphil 
Gentle Skin Cleanser 
and the facial 
moisturizer Eucerin 
Daily Protection Broad 
Spectrum SPF30 Face 
Lotion. Both products 
will be provided by 
the Sponsor. 
Alternative non-
medicated cleansers 
or moisturizers may 
be used if agreed to by 
the Sponsor. 
Addition of a SPF-
containing moisturizer 
to support a positive 
skin care regimen 
during the study. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis, 
Endpoints and 
Outcomes;   
The efficacy parameters 
will include inflammatory 
lesion counts, IGA at Day 
0/Baseline and at Weeks 
4, 8, and 12 (Final Visit), 
and the subject global 
assessment and 
satisfaction questionnaire 
at the Final Visit. 
The co-primary efficacy 
parameters, include 
inflammatory lesion counts 
and IGA, will be evaluated 
at Day 0/Baseline and at 
Weeks 4, 8, and 12 (Final 
Visit). The Subject Global 
Assessment will be 
performed at Weeks 2, 4, 8, 
and 12 (Final Visit). The 
subject satisfaction 
questionnaire will be 
assessed at Week 12 (Final 
Visit) only. 
Addition of more 
frequent subject global 
assessments to be 
conducted at each post-
Day 0/Baseline visit. 
Table 1 Schedule 
of Study 
Assessments and 
Procedures – Study 
FX2016-11: 
Subject Global 
Assessment 
Subject Global 
Assessment at Week 12 
(Final Visit) only. 
Additional Subject Global 
Assessments added at 
Weeks 2, 4, and 8. 
Addition of more 
frequent subject global 
assessments to be 
conducted at each post-
Day 0/Baseline visit. 
Sect. 7.4; 7.5 and 
7.6 
New text. 
Have the subject complete 
the Subject Global 
Assessment (Section 9.2.3) 
As above. 
Sect. 9.2.3 
This score will be 
obtained from the subject 
at Visit 7 (Week 12/Final 
Visit) using the 
questionnaire in Appendix 
1. 
This score will be 
obtained from the subject 
at Visit 2 (Week 2), Visit 3 
(Week 4), Visit 4 (Week 
8), and Visit 5 (Week 
12/Final Visit) using the 
questionnaire in Appendix 
1. 
As above. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Sect. 6.2 Exclusion 
Criteria 23 
Screening 
electrocardiogram (ECG) 
that reveals a QTcF >500 
msec. 
Text removed. 
A review of Solodyn® 
product labelling and 
an assessment of the 
safety and 
pharmacokinetics of 
minocycline when 
topically applied as 
FMX101 (4% 
minocycline HCl foam) 
to moderate-to-severe 
acne vulgaris subjects 
under maximum use 
conditions (4g per day 
for 21 days) warrants 
the removal of  ECG 
assessments at Day 
0/Baseline as it has 
been determined by the 
Sponsor as being an 
unnecessary procedure. 
Table 1 Schedule 
of Study 
Assessments and 
Procedures – Study 
FX2016-11 
Electrocardiogram 
Text removed. 
As above. 
Sect. 7.1 Screening 
Visit 
Perform 12-lead ECG 
(Section 10.7.1) 
Text removed. 
As above. 
Sect. 10.7.1 
Electrocardiograms 
A standard 12-lead ECG 
will be performed at 
Screening only. Subjects 
will be supine and at rest 
for at least 10 minutes 
before measurement. 
Subjects will have their 
participation discontinued 
if an ECG reveals a 
QTcF>500msec (see 
Exclusion Criterion 23). 
Text removed. 
As above. 
Global change 
Visit schedule has been 
adjusted from Visit 1 (Day 
0/Baseline); Visit 2 (Week 
1); Visit 3 (Week 4); Visit 
4 (Week 6); Visit 5 (Week 
8); Visit 6 (Week 10) and 
Visit 7 (Week 12/Final 
Visit) 
New schedule is Visit 1 
(Day 0/Baseline); Early 
Follow-up (Week 1); Visit 
2 (Week 2); Visit 3 (Week 
4); Visit 4 (Week 8) and 
Visit 5 (Week 12/Final 
Visit) 
To remove unnecessary 
study visits. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Sect. 7.3 Early 
Follow-up, Week 1 
(±3 Days) 
New text. 
7.3 Early Follow-up, 
Week 1 (±3 Days) 
An early follow-up 
telephone call will be 
made 1 week after Visit 1, 
Day 0/Baseline. 
Record concomitant 
medications (Section 8.7). 
Record Aes (Section 10.8). 
Confirm that subject 
continues to use only the 
provided facial cleanser 
and moisturizer. 
Review application 
instructions to confirm 
that the subject continues 
to use the study drug as 
directed. 
Schedule/confirm the next 
study visit and remind 
subject to avoid 
overexposure to sunlight 
and to use the same make-
up brand/type, or 
frequency of use, 
throughout the study as 
applicable. 
To support early 
contact with subjects to 
address outstanding 
questions and reinforce 
study instructions. 
Sect. 7.7 Visit 5, 
Week 12 (-3/+5 
days) / Final Visit 
or Early 
Termination 
Schedule/confirm a safety 
follow-up telephone call 4 
weeks from Visit 7/Week 
12 (Final Visit) date (±5 
days) for subjects that will 
not participate in study 
FX2015-13 (Open label 
study) (Section 7.9). 
Schedule/confirm a safety 
follow-up telephone call 4 
weeks from Visit 5/Week 
12 (Final Visit) date (±5 
days) only for subjects that 
will not participate in study 
FX2015-13 (Open label 
study) (Section 7.9) and 
presented with either new 
or on-going adverse 
events at Visit 5/Week 12 
(Final Visit). 
Clarification of Safety 
Follow telephone call 
requirements. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Sect. 7.8 Safety 
Follow-Up ((±5 
days) 
A safety follow-up 
telephone call will be 
made 4 weeks after Visit 
7/Week 12 (Final Visit) 
for only those subjects 
that do not participate in 
study FX2015-13 (Open 
label study). Follow up on 
existing and any new 
concomitant medications 
and adverse events will be 
recorded. 
A safety follow-up 
telephone call will be made 
4 weeks after Visit 5/Week 
12 (Final Visit) for only 
those subjects that do not 
participate in study 
FX2015-13 (Open label 
study) and presented with 
either new or on-going 
adverse events at Visit 
5/Week 12 (Final Visit). 
Follow up on these adverse 
events and any new 
concomitant medications 
will be recorded. 
Clarification of AE 
reporting requirements. 
Synopsis, 
Diagnosis and 
Main Criteria for 
Inclusion 
At least 12 and not more 
than 50 inflammatory 
facial lesions (ie, 
papules/pustules),… 
At least 15 and not more 
than 75 inflammatory facial 
lesions (ie, 
papules/pustules),… 
Change inflammatory 
lesion count range in 
the inclusion criteria 
from 12-50 to 15-75. 
Sect. 6.1 Inclusion 
Criteria 
a. At least 12 and not 
more than 50 facial 
papules and pustules… 
a. At least 15 and not more 
than 75 facial papules and 
pustules… 
As above. 
Table 2 Study 
Drug Kits and 
Treatments – 
Study FX2016-11 
Additional kits of 
2 canisters may be 
dispensed at other visits if 
required. 
Text removed. 
Redundant text due to 
change in visit schedule 
Sect. 8.1.1 Dosing 
Instructions 
Additional kits will be 
available for dispensing at 
other visits (ie, Visits 4 
and 6) to ensure enough 
product is available for 
daily dosing. 
Text removed. 
As above. 
Sect. 12.2 Protocol 
Amendments 
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 
Text removed. 
Misplaced text / 
repetition. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Appendix 3 
New text. 
Addition of investigator 
acknowledgement of 
protocol review and receipt. 
Investigator 
confirmation of review 
and receipt of study 
protocol. 
 
17.2 
Amendment 2, effective May 12th, 2017 
The following is the summary of the changes that were made to Protocol FX2016-11 Version 2 
issued March 06, 2017. 
Content changes:  
New or changed text is bolded. 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis, Sect. 5.1 
Overall Study 
Design 
Subjects will be assigned 
to 1 of 2 treatments 
according to the 
randomization schedule. 
Subjects will be assigned to 
1 of 2 treatments according 
to the randomization 
schedule, stratified by 
investigational site. 
Addition of clarifying 
text. 
Synopsis, Number 
of Subjects 
(planned), Sect. 6 
Study Population 
…approximately 600… 
…approximately 750… 
Adjustment in relation 
to a new sample size 
calculation. 
Sect. 6.1 Inclusion 
Criteria 
Subjects were included in 
the study if they met… 
Subjects can be included in 
the study if they meet all… 
Typographical error. 
Sect. 6.2 Exclusion 
Criteria 
Subjects were excluded 
from enrollment… 
Subjects should be 
excluded from enrollment 
As above. 
Sect. 6.2 Exclusion 
Criterion 4 
An active nodule on the 
face >5 mm in diameter. 
Text removed. 
Exclusion criterion 
inconsistent with IGA 
grade 4 inclusion 
criterion. 
Sect. 7 Study 
Procedures 
… Exclusion Criteria 11 
and 12, they must first 
enter…as specified in 
Exclusion Criteria 11 and 
12, respectively)… 
…Exclusion Criteria 10 and 
11, they must first 
enter…as specified in 
Exclusion Criteria 10 and 
11, respectively)… 
Reference changed due 
to renumbering of 
exclusion criteria due to 
the above omission. 
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Revision 
Rationale 
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New Text 
Sect. 7 Study 
Procedures 
…they must first enter a 
washout period (ie,1 
month or 2 weeks, as 
specified in Exclusion 
Criteria 10 and 11, 
respectively) before 
beginning the screening 
procedures.   
…they must first enter a 
washout period (ie,1 month 
or 2 weeks, as specified in 
Exclusion Criteria 10 and 
11, respectively) during 
the screening period.  
Screening procedures are 
to be performed as 
defined in the schedule of 
events Table 1. 
Clarification that prior 
medication wash-out 
can occur during the 
screening period. 
Table 1 Schedule 
of Study 
Assessments and 
Procedures, Sect. 
7.4 Visit 2, Week 2 
(±3 Days), Sect. 
8.1.1 Dosing 
Instructions 
Procedure to dispense 
study drug at Visit 2. 
Procedure removed.  
Unnecessary dispensing 
occasion. 
Synopsis, Study 
Duration, Sect. 7.7, 
Sect. 7.8, Table 1f 
…FX2015-13… 
…FX2016-13… 
Incorrect study 
reference. 
Table 2 
…25 g… 
…35 g… 
Correction of canister 
content weight. 
Table 2 
Once daily application of 
a sufficient amount of 
foam to cover the 
involved area. 
Once daily application of a 
sufficient amount of foam 
to cover the entire face. 
Adjustment of 
application instructions 
to align with that 
conducted during Phase 
2 study (FX2015-10). 
Sect. 8.1.1 Dosing 
Instructions 
…over all involved areas 
of the face. Additional 
drug may be used as 
needed to assure the entire 
involved area… 
…over all areas of the 
face. Additional drug may 
be used as needed to ensure 
the entire face is treated… 
As above. 
Sect. 5.1 Overall 
Study Design, 
Sect. 8.1.1 Dosing 
Instructions 
Study drug should be 
applied at approximately 
the same time each day, 
preferably in the evening 
about 1 hour before 
bedtime. 
Study drug should be 
applied at approximately 
the same time each day, 
about 1 hour before 
bedtime. 
Removal of evening 
application preference 
to reflect subjects with 
different sleep patterns 
e.g. shift workers. 
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New Text 
Sect. 11.2 
Determination of 
Sample Size and 
Table 5 Sample 
Size Calculations 
Based on IGA 
Scores after 
 
Weeks of 
Treatment in Phase 
2 Study FX2015-
10 
N/A. 
Simplification of Table 5 
and inclusion of new 
sample size calculations. 
Sponsor has elected to 
increase the sample size 
based on additional 
scenarios covering the 
Phase 2 study data 
(FX2015-10). 
Sect. 9.3 
Photography 
New text. 
Photography will be 
performed at selected 
study centers only. Study 
centers should refer to 
their specific Clinical 
Trial Agreement to 
confirm participation. 
Clarification that not all 
study centers will 
participate in subject 
photography. 
Table 1 Schedule 
of Study 
Assessments and 
Procedures 
New table footer 
† only for study centers 
participating in subject 
photography (Section 9.3). 
As above. 
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Revision 
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New Text 
Sect. 11.3 Analysis 
Populations 
Subjects may be excluded 
from the PP population if 
any of the following are 
met: 
Failure to meet 
inclusion/exclusion 
criteria 
Have administered any 
interfering concomitant 
medications 
Have not, in the opinion 
of the Investigator, been 
compliant with the 
treatment regimen (eg, 
reported frequent missed 
doses) 
Randomization error 
Prior to breaking the 
blind, additional criteria 
for exclusion from the PP 
population may be 
included to accommodate 
for unforeseen events that 
occurred during the 
conduct of the study. 
Subjects may be included 
in the PP population if all 
of the following are met: 
Have met all 
inclusion/exclusion 
criteria 
Have not administered 
any interfering 
concomitant medications 
Were not subject to a 
randomization error 
Completed treatment 
through Week 12 
Were greater than 80% 
compliant with study 
medication where % 
compliance is defined as: 
% Compliance = 100 x 
(expected treatment 
duration in days minus # 
days a dose was missed) / 
(expected treatment 
duration in days) 
Request by FDA to 
clarify the Per Protocol 
population. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Sect. 11.5.1 
Primary Efficacy 
Endpoints 
The dichotomized IGA 
will be analyzed using the 
Cochran-Mantel-Haenszel 
(CMH) test, stratified by 
investigational site. 
An investigation site-by-
treatment interaction 
term will be included in 
the ANCOVA model to 
test for homogeneity 
among investigational 
sites. 
The dichotomized IGA will 
be analyzed using the 
Cochran-Mantel-Haenszel 
(CMH) test, stratified by 
investigational site. For 
dichotomized IGA, the 
investigational site-by-
treatment interaction will 
be assessed with the 
Breslow-Day test. 
Investigational site-by-
treatment interaction will 
be tested at a two-sided 
0.1 level, and if significant 
will be further explored 
through the examination 
of descriptive statistics by 
individual (non-pooled) 
investigative sites.  
For analysis purposes, all 
investigative sites with 
fewer than 8 randomized 
subjects will be combined 
into a single pooled site. If 
a resulting pooled site still 
has fewer than 10 
randomized subjects, then 
this pooled site will be 
further combined with the 
smallest unpooled site. 
This pooling process will 
continue until there are at 
least 8 randomized 
subjects in each pooled 
site. 
Request by FDA to 
clarify the statistical 
approach for pooled 
site and site interaction 
analysis. 
 
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APPENDIX 1:  Subject Global Assessment Questionnaire 
Question:  “Considering your rosacea just before starting treatment and considering your 
condition today, indicate the change you have experienced according to the scale below”: 
 
• 5 = Much better than prior to treatment 
• 4 = Slightly better than prior to treatment 
• 3 = Same as prior to treatment 
• 2 = Slightly worse than prior to treatment 
• 1 = Much worse than prior to treatment 
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APPENDIX 2:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 5 (Week 12 / Final Visit): 
 
1. How satisfied are you with this product in treating your rosacea? 
2. How satisfied are you with how easy this product is to use? 
3. How satisfied are you with this product compared to other products you have previously 
used for rosacea, such as gels and creams? 
4. How satisfied are you with how this product feels on your skin after treatment? 
5. How satisfied are you with the odor of this product after treatment? 
6. How satisfied are you with the color of this product after treatment? 
7. Overall, how satisfied are you with this product? 
8. Overall, how likely are you to recommend this product to a friend? 
 
Answers to Questions 1 through 7 will be selected from the following: 
• 1 = Very Satisfied 
• 2 = Satisfied 
• 3 = Somewhat Satisfied 
• 4 = Dissatisfied 
• 5 = Very Dissatisfied 
 
The answer to Question 8 will be selected from the following: 
• 1 = Very Likely 
• 2 = Likely 
• 3 = Somewhat Likely 
• 4 = Unlikely 
• 5 = Very Unlikely 
 
 
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APPENDIX 3: Acknowledgment Of Receipt And Review Of 
Protocol 
 
 
Protocol Number: FX2016-11, Version 3 
 
Protocol Title: A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to Evaluate 
the Safety and Efficacy of FMX103 1.5% Topical Minocycline Foam Compared to Vehicle in 
the Treatment of Facial Papulopustular Rosacea (FX2016-11) 
 
 
I hereby acknowledge receipt and review of the following Protocol: 
 
 
1. Version 3, dated May 12th, 2017 
 
 
 
 
 
 
Principal Investigator Name (Print) 
 
 
 
 
 
Principal Investigator Signature 
Date of Signature  
 
(DD MMM YYYY) 
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CLINICAL PROTOCOL 
Title Page 
Study Title: 
A Randomized, Multicenter, Double-blind, Vehicle-
controlled Study to Evaluate the Safety and Efficacy of 
FMX103 1.5% Topical Minocycline Foam Compared to 
Vehicle in the Treatment of Facial Papulopustular Rosacea 
(FX2016-11) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-11 
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: 
Version 2 (Amendment 1) 
Supercedes: 
Version 1, issued 20 Jan 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. 
 
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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: 
A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to 
Evaluate the Safety and Efficacy of FMX103 1.5% Topical 
Minocycline Foam Compared to Vehicle in the Treatment of Facial 
Papulopustular Rosacea (Study FX2016-11) 
Protocol No: 
FX2016-11 
Study Centers: 
Multicenter (approximately 40 sites in the USA) 
Publication (reference): 
None 
Phase of Development: 
3 
Objectives: 
Primary Objectives: 
• 
To determine the efficacy of FMX103 1.5% minocycline foam 
applied topically once daily for 12 weeks in the treatment of 
rosacea. 
• 
To evaluate the safety of topical minocycline foam applied 
once daily for 12 weeks. 
Study Design and 
Methods: 
This is a randomized, multicenter, double-blind, vehicle-controlled, 
2-arm study to evaluate the safety and efficacy of FMX103 topical 
foam containing 1.5% minocycline compared to vehicle, in the 
treatment of subjects with moderate-to-severe facial papulopustular 
rosacea. Qualified subjects will be randomized in a 2:1 ratio 
(active:vehicle) to receive 1 of the following 2 treatments: 
• 
FMX103 minocycline foam 1.5% 
• 
Vehicle foam 
Subjects will be assigned to 1 of 2 treatments according to the 
randomization schedule. Subjects will apply (or have applied) the study 
drug topically once daily for 12 weeks as directed. Subjects will be 
advised to use the study drug at approximately the same time each day. 
Both the Investigator and subject will be blinded to the study drug 
identity. 
Subjects will return for visits at Weeks 2, 4, 8, and 12. Efficacy 
evaluations (inflammatory lesion counts and Investigator’s Global 
Assessment [IGA] score) will be performed at Weeks 4, 8, and 12 
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during the study. 
Number of Subjects 
(planned): 
The planned enrollment is approximately 600 male and female subjects. 
Subjects will be randomly assigned to the two treatment groups, 
FMX103 1.5% and vehicle, in a 2:1 ratio, respectively. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years with a clinical 
diagnosis of moderate to severe facial papulopustular rosacea, defined 
as the presence of: 
• 
At least 15 and not more than 75 inflammatory facial lesions 
(ie, papules/pustules), and 
• 
An IGA of rosacea severity of moderate or severe using the 
following scale: 
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 
• 
Current or history of erythema and/or flushing 
Subjects must be willing to minimize external factors that might trigger 
rosacea flare-ups (eg, spicy foods, thermally hot foods and drinks, hot 
environments, prolonged sun exposure, strong winds, and alcoholic 
beverages). 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, once daily to 
the face, for 12 weeks. 
Reference Therapy: 
Vehicle foam. Topical application, once daily to the face, for 12 weeks. 
Study Duration: 
Subject participation in the study will be up to 18 weeks:  up to 6 weeks 
for Screening and Day 0/Baseline, and 12 weeks of study treatment. A 
safety follow-up telephone call will be conducted 4 weeks after 
completion of study treatment for only those subjects that do not 
participate in study FX2015-13 (Open label study) and who presented 
with either new or on-going adverse events at Visit 5/Week 12 (Final 
Visit). 
Endpoints and Outcomes: 
 
 
 
 
Efficacy Evaluations 
The co-primary efficacy parameters, include inflammatory lesion 
counts and IGA, will be evaluated at Day 0/Baseline and at Weeks 4, 8, 
and 12 (Final Visit). The Subject Global Assessment will be performed 
at Weeks 2, 4, 8, and 12 (Final Visit). The subject satisfaction 
questionnaire will be assessed at Week 12 (Final Visit) only. 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner), physical examinations, vital signs, clinical laboratory tests, 
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 and local signs and symptoms assessments (including erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, 
itching, peeling/desquamation, and hyperpigmentation) scores. 
Statistical Methods: 
The primary population for efficacy analysis will be the intent-to-treat 
(ITT) population, using multiple imputations to impute missing values. 
Supportive efficacy analyses will be conducted on the per-protocol (PP) 
population, with no imputation for missing values. 
The co-primary efficacy endpoints will be the dichotomized IGA score 
where treatment success is defined as at least a 2-step improvement 
resulting in a 0 (clear) or 1 (almost clear) score at Week 12 compared to 
Day 0/Baseline and the absolute change in inflammatory lesion count at 
Week 12 compared to Day 0/Baseline. 
The key secondary endpoints will be analyzed hierarchically: 
• 
Dichotomized IGA score where treatment success is defined as 
a 2-step improvement in score at Week 12 compared to Day 
0/Baseline. 
• 
Percent change in inflammatory lesion count at Week 12 
compared to Day 0/Baseline. 
Continuous efficacy endpoints will be analyzed using analysis of 
covariance (ANCOVA). Dichotomized efficacy endpoints will be 
analyzed using the Cochran-Mantel-Haenszel (CMH) test. 
The tolerability and safety of topical minocycline foam applied daily 
for 12 weeks will be evaluated using summary statistics and individual 
subject data listings. 
The active treatment group will be tested against vehicle at the 0.05 
two-sided level of significance. No statistical tests will be performed 
for any of the safety assessments. 
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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 ............................................................................................................................12 
5 
INVESTIGATIONAL PLAN ..................................................................................................................12 
5.1 
OVERALL STUDY DESIGN ................................................................................................................12 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................13 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................15 
7.1 
SCREENING VISIT .............................................................................................................................17 
7.2 
VISIT 1, DAY 0/BASELINE VISIT.......................................................................................................17 
7.3 
EARLY FOLLOW-UP, WEEK 1 (±3 DAYS) .........................................................................................18 
7.4 
VISIT 2, WEEK 2 (±3 DAYS) .............................................................................................................18 
7.5 
VISIT 3, WEEK 4 (±3 DAYS) .............................................................................................................18 
7.6 
VISIT 4, WEEK 8 (±3 DAYS) .............................................................................................................19 
7.7 
VISIT 5, WEEK 12 (-3/+5 DAYS) / FINAL VISIT OR EARLY TERMINATION .........................................20 
7.8 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................20 
8 
STUDY TREATMENTS ..........................................................................................................................21 
8.1 
TREATMENTS ADMINISTERED ..........................................................................................................21 
8.1.1 
Dosing Instructions ........................................................................................................21 
8.1.2 
Manufacturer ..................................................................................................................21 
8.1.3 
Labeling of Study Drug ..................................................................................................21 
8.1.4 
Storage of Study Drug ....................................................................................................22 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................22 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................23 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................23 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................23 
8.6 
BLINDING  ........................................................................................................................................23 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................24 
8.8 
USE OF CONTRACEPTION .................................................................................................................24 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................25 
9 
EFFICACY ASSESSMENTS ..................................................................................................................25 
9.1 
CO-PRIMARY EFFICACY ASSESSMENTS ...........................................................................................25 
9.1.1 
Lesion Counts.................................................................................................................25 
9.1.2 
Investigator Global Assessment .....................................................................................26 
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9.2 
SECONDARY AND TERTIARY EFFICACY ASSESSMENTS ....................................................................26 
9.2.1 
Percent Change in Inflammatory Lesion Counts ............................................................26 
9.2.2 
Interim Change in Inflammatory Lesion Counts ............................................................26 
9.2.3 
Subject Global Assessment ............................................................................................26 
9.2.4 
Subject Satisfaction Questionnaire .................................................................................26 
9.3 
PHOTOGRAPHY ................................................................................................................................26 
10 
SAFETY ASSESSMENTS .......................................................................................................................27 
10.1 
MEDICAL/SURGICAL HISTORY .........................................................................................................27 
10.2 
MEDICATION HISTORY.....................................................................................................................27 
10.3 
CONCOMITANT MEDICATIONS .........................................................................................................27 
10.4 
VITAL SIGNS ....................................................................................................................................27 
10.5 
PHYSICAL EXAMINATION .................................................................................................................27 
10.6 
CLINICAL LABORATORY TESTS........................................................................................................27 
10.6.1 
Urine Pregnancy Test .....................................................................................................28 
10.6.2 
Sample Collection, Storage, and Shipping .....................................................................28 
10.7 
OTHER SAFETY MEASUREMENTS .....................................................................................................28 
10.7.1 
Local Signs and Symptoms Assessments .......................................................................28 
10.7.1.1 Erythema (Clinical Erythema Assessment Scale) .........................................29 
10.7.1.2 Telangiectasia ................................................................................................29 
10.7.1.3 Burning/Stinging ...........................................................................................29 
10.7.1.4 Flushing/Blushing .........................................................................................30 
10.7.1.5 Dryness/Xerosis ............................................................................................30 
10.7.1.6 Itching ...........................................................................................................30 
10.7.1.7 Peeling/Desquamation ...................................................................................30 
10.7.1.8 Hyperpigmentation ........................................................................................30 
10.8 
ADVERSE EVENTS ............................................................................................................................31 
10.8.1 
Method of Determining Adverse Events ........................................................................31 
10.8.2 
Adverse Event Definitions .............................................................................................31 
10.8.2.1 Adverse Events ..............................................................................................31 
10.8.2.2 Serious Adverse Events .................................................................................32 
10.8.2.3 Severity of Adverse Events ...........................................................................32 
10.8.2.4 Relationship of Adverse Events to Study Treatments ...................................32 
10.8.2.5 Adverse Events Expectedness .......................................................................33 
10.8.3 
Reporting Adverse Events ..............................................................................................33 
10.8.4 
Adverse Event Follow-up ...............................................................................................33 
10.8.4.1 Pregnancy Reporting .....................................................................................34 
10.8.5 
Clinically Significantly Abnormal Laboratory Results ..................................................34 
10.9 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................34 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................34 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................34 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................35 
11.3 
ANALYSIS POPULATIONS .................................................................................................................35 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND DAY 0/BASELINE CHARACTERISTICS ......................36 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................36 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................37 
11.5.2 
Secondary Efficacy Endpoints .......................................................................................37 
11.5.3 
Tertiary Efficacy Endpoints ...........................................................................................37 
11.6 
SAFETY ENDPOINTS .........................................................................................................................37 
11.6.1 
Adverse Events ...............................................................................................................38 
11.6.2 
Vital Signs and Physical Examinations ..........................................................................38 
11.6.3 
Clinical Laboratory Results ............................................................................................38 
11.7 
INTERIM ANALYSIS ..........................................................................................................................38 
12 
STUDY MANAGEMENT .......................................................................................................................39 
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12.1 
MONITORING ...................................................................................................................................39 
12.2 
PROTOCOL AMENDMENTS................................................................................................................39 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................39 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................40 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................40 
12.6 
PUBLICATION POLICY ......................................................................................................................40 
13 
ETHICS .....................................................................................................................................................41 
13.1 
CONDUCT OF THE STUDY .................................................................................................................41 
13.2 
INSTITUTIONAL REVIEW BOARDS (IRB) ..........................................................................................41 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................41 
13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................41 
13.5 
RECORDS RETENTION ......................................................................................................................42 
13.6 
FINANCING .......................................................................................................................................42 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................42 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................43 
16 
REFERENCE LIST .................................................................................................................................43 
17 
STUDY AMENDMENTS ........................................................................................................................43 
17.1 
AMENDMENT 1, EFFECTIVE MARCH 6TH, 2017 ................................................................................43 
APPENDIX 1:  SUBJECT GLOBAL ASSESSMENT QUESTIONNAIRE ..................................................51 
APPENDIX 2:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................52 
APPENDIX 3: ACKNOWLEDGMENT OF RECEIPT AND REVIEW OF PROTOCOL .........................53 
 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-11 ........................... 16 
Table 2 
Study Drug Kits and Treatments – Study FX2016-11 ................................................... 21 
Table 3 
IGA Scale for Rosacea – Study FX2016-11 ................................................................... 26 
Table 4 
Clinical Laboratory Tests – Study FX2016-11 .............................................................. 28 
Table 5 
Sample Size Calculations Based on IGA Scores after 12 Weeks of Treatment in Phase 2 
Study FX2015-10 ........................................................................................................... 35 
 
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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 
BOCF 
Baseline observation carried forward 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
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 System 
ITT 
Intent-to-treat (population) 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed effects model for repeated measures 
OC 
Observed cases 
OTC 
Over-the-counter 
PP 
Per-protocol (population) 
PT 
Preferred term 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
2 
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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 
 
 
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3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and the eye. 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. 
Foamix has developed a topical minocycline foam product that is being evaluated for safety and 
efficacy in the treatment of rosacea. Minocycline hydrochloride is an established broad spectrum 
antibiotic that is used orally in the treatment of 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 has been evaluated in a Phase 2 study at two minocycline 
concentrations, 1.5% and 3%. The study included 232 subjects (males/females, aged ≥18 years) 
with moderate-to-severe papulopustular rosacea defined by the Investigator’s Global Assessment 
(IGA) score and with ≥12 inflammatory facial lesions (papules/pustules) at Day 0/Baseline. 
Subjects were treated with FMX103 1.5%, FMX103 3%, or vehicle foam, once daily for 12 
weeks. Efficacy and safety were evaluated at Weeks 2, 4, 8, and 12, with an additional safety 
follow-up visit at Week 16. The primary efficacy end point was the absolute change in 
inflammatory lesion count at Week 12. Other assessments included IGA improvement of ≥2 
grades and reaching an IGA score of “clear” or “almost clear” (IGA 0/1), clinical assessment of 
erythema, and safety and tolerability. 
At Week 12, both the 1.5% and 3% doses of FMX103 significantly reduced the number of 
papules and pustules vs. vehicle (both p<0.001, intent-to-treat [ITT] population). The mean 
reduction in lesion count from Day 0/Baseline was 21.1 for the FMX103 1.5% dose, 19.9 for the 
FMX103 3% dose, and 7.8 for the vehicle. The corresponding percent reductions were 61.4% 
and 55.5% for the 1.5% and 3% doses, respectively, and 29.7% for the vehicle. 
Both the 1.5% and 3% doses of FMX103 were statistically significantly better than vehicle in 
improving IGA scores by ≥2 grades at week 12 (p=0.002 and p=0.032, respectively). Both doses 
were also statistically significantly better than vehicle in achieving an IGA of “clear or almost 
clear” (score 0/1) at Week 12 (p=0.001 and p=0.041, respectively). Both FMX103 1.5% and 3% 
doses appeared to be generally safe and well-tolerated. Treatment-related dermal reactions were 
reported in 1 subject from the FMX103 1.5% dose group (considered mild) and in a few subjects 
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from the FMX103 3% dose group (mild, n=1; moderate, n=2; severe, n=1). No treatment-related 
systemic adverse events (AEs) were reported and discontinuation due to AEs (eczema, n=1; 
rosacea, n=1; burning sensation, n=1) was reported in 3 subjects in the FMX103 3% dose group. 
As a consequence of the above, the FMX103 1.5% dose concentration has been selected for 
further development. This Phase 3 study will further assess the safety and efficacy of topical 
minocycline HCl foam, 1.5%, applied once daily compared with vehicle foam for the treatment 
of moderate-to-severe papulopustular rosacea. 
4 
STUDY OBJECTIVES 
The primary objectives of the study are: 
• To determine the efficacy of FMX103 1.5% minocycline foam applied topically once daily 
for 12 weeks in the treatment of rosacea. 
• To evaluate the tolerability and safety of topical minocycline foam applied once daily for 12 
weeks. 
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy of FMX103 topical foam containing 1.5% minocycline compared to vehicle, 
in the treatment of subjects with moderate-to-severe facial papulopustular acne rosacea. 
Qualified subjects will be randomized in a 2:1 ratio (active:vehicle) to use once daily one of the 
following two treatments: 
• FMX103 minocycline foam 1.5% 
• Vehicle foam 
Subjects will be assigned to 1 of 2 treatments according to the randomization schedule. Subjects 
will apply (or have applied) the study drug topically once daily for 12 weeks as directed. 
Subjects will be advised to use the study drug at approximately the same time each day, 
preferably in the evening about 1 hour before bedtime. Both the Investigator and subject will be 
blinded to the study drug identity.  
Subjects will return for visits at Weeks 2, 4, 8, and 12. Efficacy evaluations (inflammatory lesion 
counts [Section 9.1.1] and IGA score [Section 9.1.2]) will be performed at Weeks 4, 8, and 12 
during the study. Other assessments will be performed as described in Section 9 and Section 10. 
5.2 
Rationale for Study Design and Dose Selection 
A randomized, multicenter, double-blind, vehicle-controlled study design has been selected in 
order to assess the efficacy of the study drug. The subjects will be selected according to 
predefined entry criteria. The study treatment duration of 12 weeks is expected to be sufficient to 
show a treatment effect. 
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The concentration of minocycline in the composition was selected according to formulation 
integrity and stability considerations and based on the results of Phase 2 Study FX2015-10 
(described above in Section 3). 
Because of the mode of action of tetracycline drugs, the primary efficacy endpoints will be the 
effect on inflammatory lesion counts and IGA scores (Section 9). 
6 
STUDY POPULATION 
The study will randomize approximately 600 subjects to active or vehicle treatment (in a 2:1 
ratio) at approximately 40 sites in the US. 
6.1 
Inclusion Criteria 
Subjects were included in the study if they met all of the following inclusion criteria at the time 
of enrollment: 
1. Male or female ≥18 years-of-age. 
2. Moderate-to-severe rosacea (as per the IGA score; Table 3) on the proposed facial 
treatment area consisting of: 
a. At least 15 and not more than 75 facial papules and pustules, excluding lesions 
involving the eyes and scalp; 
b. No more than 2 nodules on the face. 
3. Presence of or history of erythema and/or flushing on the face. 
4. If a female 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. 
5. Willing to minimize external factors that might trigger rosacea flare-ups (eg, spicy foods, 
thermally hot foods and drinks, hot environments, prolonged sun exposure, strong winds, 
and alcoholic beverages). 
6. Subjects who use make-up must have used the same brands/types of make-up for a 
minimum period of 14 days prior to study entry and must agree to use the same make-up, 
brand/type, or frequency of use, throughout the study. 
7. Completed and signed an appropriately administered Informed Consent Form (ICF) prior 
to any study-related procedures. 
6.2 
Exclusion Criteria 
Subjects were excluded from enrollment in the study for any of the following reasons: 
1. Woman who is pregnant, lactating, or planning to become pregnant during the study 
period. 
2. Presence of any skin condition on the face that would interfere with the diagnosis or 
assessment of rosacea. 
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3. Moderate or severe rhinophyma, dense telangiectasia (score 3, severe; Section 10.7.2.2), 
or plaque-like facial edema. 
4. An active nodule on the face >5 mm in diameter. 
5. Excessive facial hair (eg, beards, sideburns, moustaches, etc.) that would interfere with 
diagnosis or assessment of rosacea. 
6. History of hypersensitivity or allergy to minocycline, any other tetracycline, or of any 
other component of the formulation. 
7. Severe erythema, dryness, scaling, pruritus, stinging/burning, or edema. 
8. Active ocular rosacea (eg, conjunctivitis, blepharitis, or keratitis) of sufficient severity to 
require topical or systemic antibiotics. 
9. Use within 6 months prior to Day 0/Baseline of oral retinoids (eg, Accutane®) or 
therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are 
allowed). 
10. Initiation of use of estrogens or oral contraceptives less than 3 months prior to Day 
0/Baseline. 
11. Use within 1 month prior to Day 0/Baseline of: 
a. Topical retinoids to the face. 
b. Systemic antibiotics known to have an impact on the severity of facial rosacea 
(eg, containing tetracycline and its derivatives, erythromycin and its derivatives, 
sulfamethoxazole, or trimethoprim). Subjects requiring systemic antibiotics not 
known to affect rosacea will be considered on a case-by-case basis. 
c. Systemic corticosteroids (Note: intranasal and inhalational corticosteroids do not 
require a washout and maybe used throughout the trial if the subject is on a stable 
dose). 
12. Use within 2 weeks prior to Day 0/Baseline of: 
a. Topical corticosteroids. 
b. Topical antibiotics. 
c. Topical medications for rosacea (eg, metronidazole). 
13. Use of a sauna during the 2 weeks prior to Day 0/Baseline and during the study. 
14. Had wax epilation of the face within 2 weeks prior to Day 0/Baseline. 
15. Active bacterial folliculitis. 
16. Consumption of excessive alcohol, abuse of licit or illicit drugs, or a condition that, in the 
opinion of the Investigator, could compromise the subject’s ability to comply with study 
requirements. 
17. Participation in activities that involve excessive or prolonged exposure to sunlight or 
weather extremes, such as wind or cold. 
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18. Presence of any clinically significant condition or situation, other than the condition 
being studied, that in the opinion of the Investigator would interfere with the study 
evaluations or optimal participation in the study. 
19. Participation in an investigational drug study (ie, subject has been treated with an 
investigational drug) within 30 days prior to Day 0/Baseline. Subjects who are 
participating in non-treatment studies such as observational studies or registry studies can 
be considered for inclusion. 
20. Previously enrolled in this study. 
21. Prior laser therapy (for telangiectasia or other conditions), electrodessication, or 
phototherapy (eg, ClearLight®) to the facial area within 180 days prior to Day 0/Baseline. 
22. Prior cosmetic procedures (eg, facials) that may affect the efficacy and safety profile of 
the investigational product within 14 days prior to Day 0/Baseline. 
7 
STUDY PROCEDURES 
Potential subjects will be assessed for eligibility at Screening. During this visit, the purpose, 
timing, procedures, and risks of the study will be explained to the subject, including 
requirements for enrollment and participation in the study, medication restrictions during the 
study, and requirements for washout of certain medications that the subject may already be 
taking. 
The eligible subject who is willing to participate in the study will then sign an appropriately 
administered ICF prior to any study-related procedures being performed. 
Procedures at the Screening Visit will include obtaining blood and urine samples for clinical 
laboratory tests. The results of these tests must be no more than 45 days old at the time of the 
Day 0/Baseline Visit and randomization. 
If a subject who has agreed to participate in the study and signed the ICF is currently undergoing 
rosacea therapy identified in Exclusion Criteria 11 and 12, they must first enter a washout period 
(ie,1 month or 2 weeks, as specified in Exclusion Criteria 11 and 12, respectively) before 
beginning the screening procedures. 
The schedule of study assessments and procedures and the time point at which they will be 
performed during the study is presented in Table 1. If a subject prematurely withdraws from the 
study, the subject should return to the study site for an early termination visit during which all 
evaluations described under Final Visit 5/Week 12 must be performed. 
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Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-11 
Assessment or Procedure 
Screening 
Day 0 / 
Baseline0 
Visits/Early 
Follow-up 
Final 
Visitb 
Safety 
Follow-upf 
Visit 
1 
EF 
2 
3 
4 
5 
Week 
1 
2 
4 
8 
12 
Informed consent 
X 
Demographic data 
X 
Assign subject identification 
X 
Medical/surgical/medication history 
X 
Inclusion/exclusion criteria 
X 
X 
Physical examination, height, weightc 
X 
X 
Blood pressure/heart rated 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
X 
X 
Urine pregnancy test (females of 
childbearing potential only) 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
X 
X 
X 
Subject Global Assessment 
X 
X 
X 
X 
Subject Satisfaction Questionnaire 
X 
Local signs and 
symptoms assessmentse  
X 
X 
X 
X 
X 
X 
Photography 
X 
X 
X 
X 
Randomization 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
X 
Schedule/confirm next visit 
X 
X 
X 
X 
X 
X 
EF – Early Follow-up telephone call, no visit 
a.
Day 0/Baseline must occur within 45 days of Screening. Blood test results must not show clinically significant
abnormalities.
b.
If a subject prematurely withdraws from the study, all evaluations described under Visit 5/Week 12 (Final Visit)
must be performed at an Early Termination Visit.
c.
Height to be measured only at Day 0/Baseline.
d.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest.
e.
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.
f.
A safety follow-up telephone call will be made 4 weeks after Visit 5/Week 12 (Final Visit) for only those subjects
that do not participate in study FX2015-13 (Open label study) and presented with either new or on-going adverse
events at Visit 5/Week 12 (Final Visit).
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7.1 
Screening Visit 
• Obtain a signed and dated, written ICF prior to any study-related procedures. 
• Obtain demographic data. 
• Using the Interactive Response Technology System (IRT), assign the subject an identification 
number. 
• Obtain medical/surgical history (Section 10.1). 
• Obtain history of prior medication usage (including previous use of rosacea medications); 
record start and stop dates of any medications used in the last 3 months (Section 10.2). 
• Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria (Section 6.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Collect blood and urine samples for clinical laboratory tests and send to the central laboratory 
(Section 10.6.2). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
• Perform IGA (Section 9.1.2). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Schedule/confirm the next study visit. 
7.2 
Visit 1, Day 0/Baseline Visit 
• Confirm eligibility according to the inclusion (Section 6.1) and exclusion criteria 
(Section 6.2). 
• Perform physical examination including height and weight (Section 10.5). 
• Measure blood pressure and heart rate (Section 10.4). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
• Perform IGA (Section 9.1.2). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Randomize the subject using the IRT when all criteria have been met. 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Dispense one kit (2 canisters) of study drug. 
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• Dispense facial cleanser and moisturizer. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.3 
Early Follow-up, Week 1 (±3 Days) 
An early follow-up telephone call will be made 1 week after Visit 1, Day 0/Baseline. 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Confirm that subject continues to use only the provided facial cleanser and moisturizer. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.4 
Visit 2, Week 2 (±3 Days) 
• Measure blood pressure and heart rate (Section 10.4). 
• Have the subject complete the Subject Global Assessment (Section 9.2.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Confirm that subject continues to use only the provided facial cleanser and moisturizer. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Perform drug accountability to assess compliance (Section 8.2). 
• Collect used study canister (if applicable). 
• Dispense one kit (2 canisters) of study drug. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.5 
Visit 3, Week 4 (±3 Days) 
• Measure blood pressure and heart rate (Section 10.4). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
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• Perform IGA (Section 9.1.2). 
• Have the subject complete the Subject Global Assessment (Section 9.2.3). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Perform drug accountability to assess compliance (Section 8.2). 
• Collect used study drug canister (if applicable). 
• Dispense one kit (2 canisters) of study drug. 
• Confirm that subject continues to use only the provided facial cleanser and moisturizer and 
dispense additional quantities as required. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.6 
Visit 4, Week 8 (±3 Days) 
• Measure blood pressure and heart rate (Section 10.4). 
• 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 9.2.3). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Perform drug accountability to assess compliance (Section 8.2). 
• Collect used study drug canister (if applicable). 
• Dispense one kit (2 canisters) of study drug. 
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• Confirm that subject continues to use only the provided facial cleanser and moisturizer and 
dispense additional quantities as required. 
• Review application instructions to confirm that the subject continues to use the study drug as 
directed. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to sunlight 
and to use the same make-up brand/type, or frequency of use, throughout the study as 
applicable. 
7.7 
Visit 5, Week 12 (-3/+5 days) / Final Visit or Early Termination 
• Perform physical examination including weight (Section 10.5). 
• Measure blood pressure and heart rate (Section 10.4). 
• Collect blood and urine samples for clinical laboratory tests and send to the central laboratory 
(Section 10.6.2). 
• Collect a urine sample from female subjects of childbearing potential for a urine pregnancy 
test (Section 10.6.1). 
• Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
• Perform IGA (Section 9.1.2). 
• Perform photography (Section 9.3). 
• Perform local signs and symptoms assessments (Section 10.7.2). 
• Have the subject complete the Subject Global Assessment (Section 9.2.3). 
• Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.4). 
• Record concomitant medications (Section 8.7). 
• Record AEs (Section 10.8). 
• Collect all used and full study drug canisters. 
• Perform drug accountability to assess compliance and record the date of the last dose 
(Section 8.2). 
• Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 5/Week 12 (Final 
Visit) date (±5 days) only for subjects that will not participate in study FX2015-13 (Open 
label study) (Section 7.9) and presented with either new or on-going adverse events at Visit 
5/Week 12 (Final Visit). 
7.8 
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 5/Week 12 (Final Visit) for 
only those subjects that do not participate in study FX2015-13 (Open label study) and presented 
with either new or on-going adverse events at Visit 5/Week 12 (Final Visit). Follow up on these 
adverse events and any new concomitant medications will be recorded. 
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8 
STUDY TREATMENTS 
This study will include FMX103 minocycline foam 1.5% and vehicle foam. 
8.1 
Treatments Administered 
The description of study drug kits and treatments is shown below in Table 2. 
Table 2 
Study Drug Kits and Treatments – Study FX2016-11 
Dosage form description: 
Foam containing minocycline HCl 1.5% or vehicle foam 
Package description: 
Canisters, each containing 25 g of the clinical trial supply foam 
Daily dose: 
Once daily 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) or 0.0 mg (vehicle) of minocycline. 
Cumulative maximal dose for 
dosing (12 weeks): 
630 mg (1.5%) minocycline 
Dispensing: 
Kits consisting of 2 canisters, each canister containing 25 g of FMX103 
minocycline formulation, 1.5%, or vehicle dispensed at Visit 1 (Day 
0/Baseline), Visit 2 (Week 2), Visit 3 (Week 4), and Visit 4 (Week 8).  
8.1.1 
Dosing Instructions 
The dosing regimen will be the same for both treatment groups. 
Study drug kits containing 2 canisters of investigational drug will be dispensed at Visit 1 (Day 
0/Baseline), Visit 2 (Week 2), Visit 3 (Week 4), and Visit 4 (Week 8).  
After shaking the canister well, a small amount of study drug (about ½ gram or a cherry-sized 
amount) should be expressed from the canister onto the finger tips and then applied as a thin 
layer over all involved areas of the face. Additional drug may be used as needed to assure the 
entire involved area is treated.  
Study drug should be applied at approximately the same time each day, preferably in the evening 
about 1 hour before bedtime. 
8.1.2 
Manufacturer 
The manufacturer of the investigational product is ASM Aerosol-Service AG, Moehlin, 
Switzerland. 
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 
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• 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% and vehicle canisters must be stored at 2°C – 8°C until being dispensed to the 
subject. Subsequently, they 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 use of the study drug. The Investigator or 
designee will verify the contents of the drug shipment and confirm receipt of the study drug in 
the 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 regional regulatory authority 
inspection at any time. At the conclusion of the study, the Investigator must provide a copy of 
this record to the Sponsor and each canister that has been retrieved from a subject will be 
returned to the vendor to be weighed. 
Under no circumstances will the Investigator allow the investigational drugs to be used other 
than as directed by this protocol. Qualified study personnel must use the IRT to assign and 
dispense kits to the subjects. Reasons for digression from the expected dispensing regimen must 
also be recorded. 
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8.3 
Handling and Disposal of Study Drug 
The study drug must be protected from unauthorized access (eg, in a locked storage facility). 
Any unused, partially used, or empty bottles of study drug will be returned to the Sponsor or 
designee by the time of the site’s close-out visit. Receipt, distribution, and return of the study 
drug must be properly documented on forms provided by the Sponsor or designee. 
8.4 
Method of Assignment of Study Drug 
After pretreatment clinical evaluations and all other Screening procedures have been completed, 
authorized site personnel will acknowledge that the applicable subject met all the specified 
inclusion criteria (Section 6.1) and none of the exclusion criteria (Section 6.2). Assignment to a 
treatment group will then follow a predetermined list of randomization numbers, with each 
successive number receiving 1 of the 2 treatments in random order. Authorized site personnel 
will use the IRT system to assign a kit number that corresponds to the randomization schedule. 
The kit box with the assigned kit number will be dispensed to the subject. 
The randomization code will be provided by Premier Research, Research Triangle Park, NC. 
8.5 
Selection and Timing of Doses in the Study 
The 1.5% concentration of minocycline has been shown to be effective compared to vehicle in a 
Phase 2 study in subjects with rosacea. The once-daily dosing regimen is appropriate given the 
pharmacokinetic characteristics of minocycline. 
8.6 
Blinding 
This is a double-blind study, with limited access to the randomization code. The randomization 
code will be held in confidence until after the study database is locked and a memo documenting 
the database lock has been issued. Every effort will be made to retain the integrity of the blind. 
When issued to the sites, the study drug will be identical in appearance for all subjects, 
regardless of treatment assignment. 
The treatment each subject receives will not be disclosed to the Investigator, study site personnel, 
subjects, monitors, or the Sponsor staff except as required for the purposes of conducting this 
study. 
In the event that emergency identification of study drug is required (eg, if the Investigator 
believes that the information is necessary to properly treat a subject with an AE), the study drug 
identity can be obtained by the Investigator through the IRT system. 
Before breaking the blind for a subject, the Investigator should determine that the information is 
necessary (ie, that it will alter the subject’s immediate course of treatment and will contribute to 
the management of the AE). In many cases, particularly when the emergency is clearly not 
related to study drug, the problem may be effectively managed by assuming that the subject is 
receiving active study drug without the need for unblinding. Every effort should be made to alert 
the medical monitor before requesting that the blind be broken. If this is not possible, the medical 
monitor should be immediately notified of the breaking of the blind. The Investigator will record 
the unblinding procedures in the subject’s source documents. 
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If unblinding is necessary, the subject will be withdrawn from the study and Early Termination 
Visit (ie, Visit 5 [Week 12]) assessments will be completed. 
8.7 
Prior/Concomitant Therapy 
As necessary, subjects should use the facial cleanser Cetaphil Gentile Skin Cleanser and the 
facial moisturizer Eucerin Daily Protection Broad Spectrum SPF30 Face Lotion. Both products 
will be provided by the Sponsor. Alternative, non-medicated cleansers or moisturizers may be 
used if agreed to by the Sponsor. 
The use of or change in the dose of any and all concomitant medications, either prescription or 
over-the-counter (OTC), during the study will be recorded. The reason for use or change of dose 
of a concomitant therapy may need to be reported as an AE. Therapies (medication and non-
medication therapies) not restricted by the protocol may be used. Non-prohibited chronic 
therapies being used at Day 0/Baseline may be continued. If a female subject 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 study. 
If a subject is taking anticoagulant therapy, the subject should be advised that they may require a 
downward adjustment of their anticoagulant dosage. 
All topical or systemic medications listed in the exclusion criteria are prohibited during this 
study. Similarly, no other topical medications are permitted to be used on the face during this 
period. 
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 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 listed below 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: 
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• 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 kits (empty/used/unused) at the appropriate visits. The study site personnel will question the 
subject on the history of 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 
Co-Primary Efficacy Assessments 
The co-primary efficacy assessments will include the inflammatory lesion counts and the IGA of 
severity of disease. Lesion counts, IGA, and other efficacy evaluations 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 will be performed at Screening and Visit 1 (Day 0/Baseline) to confirm eligibility, and 
again at Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12/Final Visit). 
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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 will be performed at Screening and Visit 1 (Day 0/Baseline) to confirm 
eligibility, and again at Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-11 
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 
Percent Change in Inflammatory Lesion Counts 
The percent change in inflammatory lesion counts at Visit 5 (Week 12/Final Visit) compared to 
Visit 1 (Day 0/Baseline) will be evaluated. 
9.2.2 
Interim Change in Inflammatory Lesion Counts 
The absolute 
 change in inflammatory lesion counts at Visit 3 (Week 4) and Visit 4 
(Week 8) compared to Visit 1 (Day 0/Baseline) will be evaluated. 
9.2.3 
Subject Global Assessment 
This score will be obtained from the subject at Visit 2 (Week 2), Visit 3 (Week 4), Visit 4 (Week 
8), and Visit 5 (Week 12/Final Visit) using the questionnaire in Appendix 1. 
9.2.4 
Subject Satisfaction Questionnaire 
A subject satisfaction questionnaire (Appendix 2) will be administered at Visit 5 (Week 12/Final 
Visit). 
9.3 
Photography 
Photography of the full face will be performed at Day 0/Baseline and at Weeks 4, 8, and 12 using 
recognized methods. The equipment and techniques for this photography and for archiving the 
images are described in the Study Manual. Photographs will be reviewed at the site and by the 
sponsor for quality. Photographs will not be used to assess the lesion counts or the IGA, but will 
be archived to be available for subsequent review, if required, by the sponsor, auditors, or the 
FDA. 
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10 
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
physical examinations, the monitoring of vital signs, AEs (volunteered, observed, and elicited by 
general questioning in a non-suggestive manner), clinical laboratory tests, and local signs and 
symptoms assessments (including erythema, telangiectasia, burning/stinging, flushing/blushing, 
dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) scores. 
10.1 
Medical/Surgical History 
A complete medical and surgical history will be obtained at Screening, which will include the 
following:  diseases of the head, ears, eyes, nose and throat; respiratory diseases; cardiovascular 
diseases; gastrointestinal diseases; hepatic diseases; genitourinary diseases; musculoskeletal 
diseases; endocrine diseases; neurological diseases; psychiatric diseases; skin diseases; allergies; 
hematological diseases; and other abnormalities. 
10.2 
Medication History 
A history of medication usage (including previous use of rosacea medications and non-
medication therapies) will be recorded at Screening. The start and stop dates of previous use of 
medications in the last 3 months will be recorded. 
10.3 
Concomitant Medications 
All topical or systemic medications listed in the exclusion criteria are prohibited. No other 
topical medications are permitted to be used on the face. All medication that the subject is 
currently taking or any change in medication or dosage since the last visit will be documented 
throughout the study. The use of or change in the dose of any and all concomitant medication, 
either prescription or OTC, during the study will be recorded. The reason for use or change of 
dose of a concomitant therapy may need to be reported as an AE. 
10.4 
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all post-Day 0/Baseline 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. 
10.5 
Physical Examination 
A complete physical examination (excluding the genitourinary examination) will be performed. 
Weight will be recorded at the Visit 1 (Day 0/Baseline) and Visit 5 (Week 12/Final Visit). Height 
will be measured at Visit 1 (Day 0/Baseline) only. 
10.6 
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at the Screening Visit and 
Visit 5 (Week 12/Final Visit). All clinical laboratory tests will be performed at a central 
laboratory. Table 4 presents the specific clinical laboratory tests to be evaluated. 
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Please refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples. 
Table 4 
Clinical Laboratory Tests – Study FX2016-11 
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 
 
10.6.1 
Urine Pregnancy Test 
A urine pregnancy test will be performed on all females of childbearing potential at the 
Screening Visit, Visit 1 (Day 0/Baseline), Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 
12/Final Visit) or when a subject prematurely withdraws from the study. 
10.6.2 
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. 
10.7 
Other Safety Measurements 
10.7.1 
Local Signs and Symptoms Assessments 
The severity of each of the following local signs and symptoms will be measured at Screening, 
Visit 1 (Day 0/Baseline), and at each study visit:  erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. The 
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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 medication or is the reason for discontinuation from the study. 
10.7.1.1 
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 
10.7.1.2 
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 
10.7.1.3 
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 
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10.7.1.4 
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 
10.7.1.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
• 0 = None 
• 1 = Mild 
• 2 = Moderate 
• 3 = Severe 
10.7.1.6 
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 
10.7.1.7 
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 
10.7.1.8 
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 
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10.8 
Adverse Events 
10.8.1 
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator. AEs will be recorded at each visit on the appropriate 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 10.8.4) 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 10.8.2 and Section 10.8.3, 
respectively. 
10.8.2 
Adverse Event Definitions 
10.8.2.1 
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 
surgical procedures for pre-existing conditions that have not worsened are not AEs. However, 
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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. 
10.8.2.2 
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. 
10.8.2.3 
Severity of Adverse Events 
Severity of an AE refers to the extent to which an AE 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.
10.8.2.4 
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to study drug and will be categorized according to 
the following criteria: 
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•
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.
10.8.2.5 
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. 
10.8.3 
Reporting Adverse Events 
Adverse events that occur from the time of informed consent/assent through 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 or 
designee 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 or designee. Any pertinent follow-up information should be provided in a similar 
manner. Contact information is provided below: 
10.8.4 
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until resolution or stabilization (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, stabilized, or no longer serious enough to warrant follow-up. 
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 resolved or stabilized. 
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10.8.4.1 
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 Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of laboratory pregnancy testing 
are available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
A urine pregnancy test will be performed on all females of childbearing potential as described in 
Section 10.6.1. 
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, missed or late menstrual 
period). 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 laboratory 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. 
10.8.5 
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be so flagged 
when reported to the site. The Investigator will determine which out-of-range laboratory test 
results should be characterized as clinically significant and will so 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. 
10.9 
Appropriateness of Safety Measurement 
The safety assessments to be utilized 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 (SAP) will be finalized prior to breaking of the study blind. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated, but the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. All hypothesis testing will be conducted 
using two-sided tests with a 0.05 level of significance. 
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11.2 
Determination of Sample Size 
In the Phase 2 Study FX2015-10, the proportion of subjects with an IGA score of 0 or 1 after 
 of treatment was 
 in the FMX103 1.5% dose group compared to 
 for the 
vehicle dose group. Table 5 provides alternate assumptions on this primary response criterion 
with corresponding implications on sample size. Power was set to 90% and a type-1 error was set 
to a two-sided test with a 0.05 level of significance. Sample size was calculated based on 
Fisher’s Exact test. 
Table 5 
Sample Size Calculations Based on IGA Scores after 
 of 
Treatment in Phase 2 Study FX2015-10 
Vehicle IGA (Score 0,1) 
FMX103 1.5% IGA (Score 0,1) 
Sample Size (Vehicle, Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assuming a 
 dropout rate, 400 subjects receiving FMX103 and 200 subjects receiving 
vehicle will provide at least 90% power for a statistically significant difference on an IGA score 
of 0 or 1. 
For the co-primary endpoint of change from Day 0/Baseline to 
 in inflammatory lesion 
count, in the Phase 2 study the FMX103 1.5% dose group had a mean reduction of 
 lesions 
whereas the vehicle had a mean reduction of 
 lesions. The standard deviation was 
. For a 
90% power, 
 and 
 subjects in the FMX103 1.5% and vehicle groups, respectively, will be 
needed. Therefore, the sample size needed to provide at least 90% power for both co-primary 
endpoints is 
 and 
 subjects in the FMX103 1.5% and vehicle groups, respectively. 
11.3 
Analysis Populations 
The following populations will be defined for analysis: 
• Intent-to-Treat (ITT) population:  all randomized subjects. 
• Per-Protocol (PP) population:  defined as the subset of the ITT population without any 
protocol deviations that may have an impact on the efficacy assessments. Subjects to be 
included in the PP population will be determined by the Sponsor/CRO prior to the unblinding 
of the study. 
Subjects may be excluded from the PP population if any of the following are met: 
o Failure to meet inclusion/exclusion criteria 
o Have administered any interfering concomitant medications 
o Have not, in the opinion of the Investigator, been compliant with the treatment 
regimen (eg, reported frequent missed doses) 
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o Randomization error 
Prior to breaking the blind, additional criteria for exclusion from the PP population may 
be included to accommodate for unforeseen events that occurred during the conduct of 
the study. 
• Safety Population:  all randomized subjects who use any study product. Subjects who have 
no post-Day 0/Baseline assessments will be included in the Safety population unless all 
dispensed study drug is returned unused. 
The ITT population will be the primary population for efficacy analysis. The PP population will 
be secondary for the co-primary endpoints only. The Safety population will be used for the 
analyses of safety endpoints. 
All efficacy analyses will be conducted according to the randomized treatment assignment; all 
safety analyses will be conducted according to the treatment actually received. 
11.4 
Subject Accounting, Demographics, and Day 0/Baseline Characteristics 
Demographics, Day 0/Baseline characteristics, and prior and concomitant medications will be 
summarized by treatment. Study completion status and reasons for discontinuation will also be 
displayed by treatment. 
Medical and surgical history will only be presented in the listings. 
11.5 
Efficacy Endpoints 
The primary population for all efficacy analyses will be the ITT population. For the analyses of 
the co-primary and secondary efficacy endpoints based on the ITT population, a variety of 
methods will be used to impute missing data, including multiple imputation (MI), last-
observation-carried forward (LOCF), and Day 0/Baseline observation carried forward (BOCF). 
MI will be the primary imputation method. Sensitivity analyses using LOCF and BOCF will be 
performed only on the co-primary efficacy endpoints to assess the robustness of alternate 
imputation assumptions. For the continuous efficacy measure, a mixed effects model for repeated 
measures (MMRM) analysis will also be conducted as a sensitivity analysis. All supportive 
analyses using the PP population will use the Observed-Cases (OC) approach, that is there will 
be no imputation for missing data at any time point. No other imputations will be made unless 
otherwise specified. 
For all efficacy analyses, subjects will be analyzed according to the treatment group to which 
they were randomized. 
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11.5.1 
Primary Efficacy Endpoints 
The co-primary efficacy endpoints are: 
• The absolute change in the inflammatory lesion count at Week 12 compared to Day 
0/Baseline. 
• The dichotomized IGA score where treatment success is defined as at least a 2-step 
improvement resulting in a 0 (clear) or 1 (almost clear) score at Week 12 compared to Day 
0/Baseline. 
The null hypothesis of the equality of the FMX103 1.5% and vehicle means for absolute change 
from Day 0/Baseline to Week 12 in the inflammatory lesion count and the equality of IGA 
success rates at Week 12 will each be tested at a two-sided 0.05 level of significance. Change 
from Day 0/Baseline in inflammatory lesion count will be analyzed using an analysis of 
covariance (ANCOVA), with treatment as a main effect, Day 0/Baseline inflammatory lesion 
count as a covariate, and investigational site as a blocking factor. Investigational site-by-
treatment interaction will be tested at a two-sided 0.1 level, and if significant, will be further 
explored. The dichotomized IGA will be analyzed using the Cochran-Mantel-Haenszel (CMH) 
test, stratified by investigational site. 
11.5.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
• The dichotomized IGA score where success is defined as a 2-step improvement in score at 
Week 12 compared to Day 0/Baseline. 
• The percent change in inflammatory lesion count at Week 12 compared to Day 0/Baseline. 
• The absolute change from Day 0/Baseline in the inflammatory lesion count and IGA 
treatment success at the interim visit at Week 8. 
• The absolute change from Day 0/Baseline in the inflammatory lesion count and IGA 
treatment success at the interim visit at Week 4. 
Secondary efficacy endpoints will be treated sequentially in the order listed above, at a 0.05 level 
of significance, only if the co-primary efficacy endpoints are significant. 
11.5.3 
 
 
• 
 
• 
 
11.6 
Safety Endpoints 
Safety endpoints will be reported on the Safety population. Subjects will be reported according 
to the treatment they actually received. Safety assessment will be based on descriptive statistics 
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and individual 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 
pre-treatment, or worsen relative to the pre-treatment 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 for each treatment group. At each level of 
summarization, a subject will be counted only once if he/she reported one or more events. The 
severity of TEAEs and relationship to study drug will be summarized in a similar manner. For 
summaries of relationship to 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. 
TEAEs, vital signs, and clinical laboratory measurements will be summarized by treatment group 
using descriptive statistics. For vital signs, change from Day 0/Baseline values will also be 
summarized. For all safety variables, subject data listings will be provided. 
Local signs and symptoms 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 10.7.2. 
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 prematurely withdraw from the study 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 
Day 0/Baseline and at each post-Day 0/Baseline time point. Changes from Day 0/Baseline will 
also be summarized. Day 0/Baseline is defined as the last non-missing value prior to the first 
dose of study drug. 
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 Day 0/Baseline with the number of subjects 
with low, normal, or high values at the Final Visit. Day 0/Baseline is defined as the last non-
missing value prior to the first dose of study drug. 
A listing of subjects with pre-treatment and 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. 
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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 immediately notify the Sponsor 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 GCP-ICH, and their 
agreement with the source data. The monitor will also verify the correct use of the study drug. At 
a 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 the IRB’s 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. 
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12.4 
Withdrawal of Subjects 
Withdrawn subjects are those who do not complete all evaluations and procedures outlined in the 
protocol. Subjects who discontinue taking study drug for any reason must also be withdrawn 
from the study. 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 10.8.4. 
• 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 stabilized 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/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, relocation of subject, etc. If a 
subject becomes pregnant during the study, the subject will be withdrawn from the study and 
followed through conclusion of the pregnancy. 
If a subject is withdrawn from the study following the start of study drug, all Visit 5 
(Week 12/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. 
12.6 
Publication Policy 
The data obtained in this study are the property of the Sponsor, which will make reasonable 
efforts to assure that the results are published in a peer-reviewed journal. As some of the 
information concerning the investigational product and development activities at the Sponsor 
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may be of a strictly confidential 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 (IRB) 
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/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/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 their 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/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 ensures 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 
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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 and assent 
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 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 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 (CQA) Department 
may conduct periodic audits of the study processes, including, but not limited to, auditing the 
clinical site, laboratories, vendors and CROs, the clinical database, and the final study report. 
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15 
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, electronic case report forms (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 
FX2016-11. 
Section 17.1 describes the changes made to Protocol FX2016-11 Version 1 issued January 20, 
2017, via Amendment 1 effective March 6th, 2017. 
17.1 
Amendment 1, effective March 6th, 2017 
The following is the summary of the changes that were made to Protocol FX2016-11 Version 1 
issued January 20, 2017. 
Content changes:  
New or changed text is bolded. 
 
 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis (Study 
Centers); Sect. 6 
Study Population 
…approximately 30 
sites…  
…approximately 40 sites… 
Number of study 
centers adjusted to 
account for larger study 
sample size. 
Sect. 11.2 
Determination of 
Sample Size; Table 
5 Sample Size 
Calculations Based 
on IGA Scores 
after 
 of 
Treatment in Phase 
2 Study FX2015-
10 and text  
 
…
... 
…
... 
Typographic error. 
Sect. 11.2 
Determination of 
Sample Size; Table 
5 and text  
 
New text inserted in 
Table 5. 
Vehicle IGA (Score 0,1): 
; FMX103 1.5% IGA 
(Score 0,1): 
; Sample 
Size (Vehicle, Active): 
 
 
Study sample size 
calculation based on an 
assumed 
 reduction 
in effect difference 
between active and 
vehicle, relative to 
Study FX2015-10 
FMX103 1.5% IGA 
(Score 0,1) v’s Vehicle 
IGA (Score 0,1) 
observed difference. 
As above. 
Assuming a 
 
dropout rate, 
 
subjects receiving 
FMX103 and 
 
subjects… 
Assuming a 
 dropout rate, 
 subjects receiving 
FMX103 and 
 subjects… 
Corrected for larger 
study sample size. 
As above. 
Therefore, the sample 
size needed to provide 
90% power for both co-
primary endpoints is 
 and 
 subjects… 
Therefore, the sample size 
needed to provide at least 
90% power for both co-
primary endpoints is 
 and 
 subjects… 
Corrected for larger 
study sample size. 
Synopsis 
(Statistical 
Methods); Sect. 
11.5.1 Primary 
Efficacy Endpoints 
…treatment success is 
defined as a 2-step 
improvement… 
…treatment success is defined 
as at least a 2-step 
improvement… 
Clarification of 
treatment success 
criteria. 
Synopsis (Number 
of Subjects 
(planned); Sect. 6 
Study Population 
…approximately 450 
subjects… 
…approximately 600 
subjects… 
Corrected for larger 
study sample size. 
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CCI
CCI
CCI
CCI
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CCI
CCI
CCI
CCI
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Sect. 7.2 Visit 1, 
Day 0/Baseline 
Visit 
New text. 
Dispense facial cleanser and 
moisturizer. 
Clarification of the 
need to dispense 
cleanser and 
moisturizer at Day 
0/Baseline. 
Sect. 7.4 
• Confirm that subject 
continues to use 
only the provided 
facial cleanser. 
• 
Confirm that subject 
continues to use only the 
provided facial cleanser 
and moisturizer. 
Reflecting the addition 
of moisturizer. 
Sect. 7.5 and 7.6 
• Confirm that subject 
continues to use 
only the provided 
facial cleanser. 
• 
Confirm that subject 
continues to use only the 
provided facial cleanser 
and moisturizer and 
dispense additional 
quantities as required. 
Clarification of cleanser 
and moisturizer re-
supply to subjects. 
Sect. 8.7 
Prior/Concomitant 
Therapy 
• Subjects should use 
the facial cleanser 
Cetaphil Gentle 
Skin Cleanser 
(which will be 
provided by the 
Sponsor). An 
alternative, non-
medicated cleanser 
may be used if 
agreed to by the 
Sponsor. 
• 
As necessary, subjects 
should use the facial 
cleanser Cetaphil Gentle 
Skin Cleanser and the 
facial moisturizer 
Eucerin Daily Protection 
Broad Spectrum SPF30 
Face Lotion. Both 
products will be 
provided by the Sponsor. 
Alternative non-
medicated cleansers or 
moisturizers may be 
used if agreed to by the 
Sponsor. 
Addition of a SPF-
containing moisturizer 
to support a positive 
skin care regimen 
during the study. 
Synopsis, 
Endpoints and 
Outcomes;   
The efficacy parameters 
will include 
inflammatory lesion 
counts, IGA at Day 
0/Baseline and at 
Weeks 4, 8, and 12 
(Final Visit), and the 
subject global 
assessment and 
satisfaction 
questionnaire at the 
Final Visit. 
The co-primary efficacy 
parameters, include 
inflammatory lesion counts 
and IGA, will be evaluated at 
Day 0/Baseline and at Weeks 
4, 8, and 12 (Final Visit). The 
Subject Global Assessment 
will be performed at Weeks 2, 
4, 8, and 12 (Final Visit). The 
subject satisfaction 
questionnaire will be assessed 
at Week 12 (Final Visit) only. 
Addition of more 
frequent subject global 
assessments to be 
conducted at each post-
Day 0/Baseline visit. 
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Table 1 Schedule 
of Study 
Assessments and 
Procedures – Study 
FX2016-11: 
Subject Global 
Assessment 
Subject Global 
Assessment at Week 12 
(Final Visit) only. 
Additional Subject Global 
Assessments added at Weeks 
2, 4, and 8. 
Addition of more 
frequent subject global 
assessments to be 
conducted at each post-
Day 0/Baseline visit. 
Sect. 7.4; 7.5 and 
7.6 
New text. 
Have the subject complete 
the Subject Global 
Assessment (Section 9.2.3) 
As above. 
Sect. 9.2.3 
This score will be 
obtained from the 
subject at Visit 7 (Week 
12/Final Visit) using 
the questionnaire in 
Appendix 1. 
This score will be obtained 
from the subject at Visit 2 
(Week 2), Visit 3 (Week 4), 
Visit 4 (Week 8), and Visit 5 
(Week 12/Final Visit) using 
the questionnaire in 
Appendix 1. 
As above. 
Sect. 6.2 Exclusion 
Criteria 23 
Screening 
electrocardiogram 
(ECG) that reveals a 
QTcF >500 msec. 
Text removed. 
A review of Solodyn® 
product labelling and 
an assessment of the 
safety and 
pharmacokinetics of 
minocycline when 
topically applied as 
FMX101 (4% 
minocycline HCl foam) 
to moderate-to-severe 
acne vulgaris subjects 
under maximum use 
conditions (4g per day 
for 21 days) warrants 
the removal of  ECG 
assessments at Day 
0/Baseline as it has 
been determined by the 
Sponsor as being an 
unnecessary procedure. 
Table 1 Schedule 
of Study 
Assessments and 
Procedures – Study 
FX2016-11 
Electrocardiogram 
Text removed. 
As above. 
Sect. 7.1 Screening 
Visit 
Perform 12-lead ECG 
(Section 10.7.1) 
Text removed. 
As above. 
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New Text 
Sect. 10.7.1 
Electrocardiograms 
A standard 12-lead 
ECG will be performed 
at Screening only. 
Subjects will be supine 
and at rest for at least 
10 minutes before 
measurement. Subjects 
will have their 
participation 
discontinued if an ECG 
reveals a 
QTcF>500msec (see 
Exclusion Criterion 
23). 
Text removed. 
As above. 
Global change 
Visit schedule has been 
adjusted from Visit 1 
(Day 0/Baseline); Visit 
2 (Week 1); Visit 3 
(Week 4); Visit 4 
(Week 6); Visit 5 
(Week 8); Visit 6 
(Week 10) and Visit 7 
(Week 12/Final Visit) 
New schedule is Visit 1 (Day 
0/Baseline); Early Follow-up 
(Week 1); Visit 2 (Week 2); 
Visit 3 (Week 4); Visit 4 
(Week 8) and Visit 5 (Week 
12/Final Visit) 
To remove unnecessary 
study visits. 
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Sect. 7.3 Early 
Follow-up, Week 1 
(±3 Days) 
New text. 
7.3 Early Follow-up, Week 1 
(±3 Days) 
An early follow-up telephone 
call will be made 1 week 
after Visit 1, Day 0/Baseline. 
Record concomitant 
medications (Section 8.7). 
Record AEs (Section 10.8). 
Confirm that subject 
continues to use only the 
provided facial cleanser and 
moisturizer. 
Review application 
instructions to confirm that 
the subject continues to use 
the study drug as directed. 
Schedule/confirm the next 
study visit and remind 
subject to avoid 
overexposure to sunlight and 
to use the same make-up 
brand/type, or frequency of 
use, throughout the study as 
applicable. 
To support early 
contact with subjects to 
address outstanding 
questions and reinforce 
study instructions. 
Sect. 7.7 Visit 5, 
Week 12 (-3/+5 
days) / Final Visit 
or Early 
Termination 
Schedule/confirm a 
safety follow-up 
telephone call 4 weeks 
from Visit 7/Week 12 
(Final Visit) date (±5 
days) for subjects that 
will not participate in 
study FX2015-13 
(Open label study) 
(Section 7.9). 
Schedule/confirm a safety 
follow-up telephone call 4 
weeks from Visit 5/Week 12 
(Final Visit) date (±5 days) 
only for subjects that will not 
participate in study FX2015-
13 (Open label study) (Section 
7.9) and presented with 
either new or on-going 
adverse events at Visit 
5/Week 12 (Final Visit). 
Clarification of Safety 
Follow telephone call 
requirements. 
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Sect. 7.8 Safety 
Follow-Up ((±5 
days) 
A safety follow-up 
telephone call will be 
made 4 weeks after 
Visit 7/Week 12 (Final 
Visit) for only those 
subjects that do not 
participate in study 
FX2015-13 (Open label 
study). Follow up on 
existing and any new 
concomitant 
medications and 
adverse events will be 
recorded. 
A safety follow-up telephone 
call will be made 4 weeks 
after Visit 5/Week 12 (Final 
Visit) for only those subjects 
that do not participate in study 
FX2015-13 (Open label study) 
and presented with either 
new or on-going adverse 
events at Visit 5/Week 12 
(Final Visit). Follow up on 
these adverse events and any 
new concomitant medications 
will be recorded. 
Clarification of AE 
reporting requirements. 
Synopsis, 
Diagnosis and 
Main Criteria for 
Inclusion 
At least 12 and not 
more than 50 
inflammatory facial 
lesions (ie, 
papules/pustules),… 
At least 15 and not more than 
75 inflammatory facial lesions 
(ie, papules/pustules),… 
Change inflammatory 
lesion count range in 
the inclusion criteria 
from 12-50 to 15-75. 
Sect. 6.1 Inclusion 
Criteria 
a. At least 12 and not 
more than 50 facial 
papules and pustules… 
a. At least 15 and not more 
than 75 facial papules and 
pustules… 
As above. 
Table 2 Study 
Drug Kits and 
Treatments – 
Study FX2016-11 
Additional kits of 
2 canisters may be 
dispensed at other visits 
if required. 
Text removed. 
Redundant text due to 
change in visit schedule 
Sect. 8.1.1 Dosing 
Instructions 
Additional kits will be 
available for dispensing 
at other visits (ie, Visits 
4 and 6) to ensure 
enough product is 
available for daily 
dosing. 
Text removed. 
As above. 
Sect. 12.2 Protocol 
Amendments 
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 
Text removed. 
Misplaced text / 
repetition. 
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Rationale 
Old Text 
New Text 
Appendix 3 
New text. 
Addition of investigator 
acknowledgement of protocol 
review and receipt. 
Investigator 
confirmation of review 
and receipt of study 
protocol. 
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APPENDIX 1:  Subject Global Assessment Questionnaire 
Question:  “Considering your rosacea just before starting treatment and considering your 
condition today, indicate the change you have experienced according to the scale below”: 
 
• 5 = Much better than prior to treatment 
• 4 = Slightly better than prior to treatment 
• 3 = Same as prior to treatment 
• 2 = Slightly worse than prior to treatment 
• 1 = Much worse than prior to treatment 
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APPENDIX 2:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 5 (Week 12 / Final Visit): 
 
1. How satisfied are you with this product in treating your rosacea? 
2. How satisfied are you with how easy this product is to use? 
3. How satisfied are you with this product compared to other products you have previously 
used for rosacea, such as gels and creams? 
4. How satisfied are you with how this product feels on your skin after treatment? 
5. How satisfied are you with the odor of this product after treatment? 
6. How satisfied are you with the color of this product after treatment? 
7. Overall, how satisfied are you with this product? 
8. Overall, how likely are you to recommend this product to a friend? 
 
Answers to Questions 1 through 7 will be selected from the following: 
• 1 = Very Satisfied 
• 2 = Satisfied 
• 3 = Somewhat Satisfied 
• 4 = Dissatisfied 
• 5 = Very Dissatisfied 
 
The answer to Question 8 will be selected from the following: 
• 1 = Very Likely 
• 2 = Likely 
• 3 = Somewhat Likely 
• 4 = Unlikely 
• 5 = Very Unlikely 
 
 
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APPENDIX 3: Acknowledgment Of Receipt And Review Of 
Protocol 
 
 
Protocol Number: FX2016-11, Version 2 
 
Protocol Title: A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to Evaluate 
the Safety and Efficacy of FMX103 1.5% Topical Minocycline Foam Compared to Vehicle in 
the Treatment of Facial Papulopustular Rosacea (FX2016-11) 
 
 
I hereby acknowledge receipt and review of the following Protocol: 
 
 
1. Version 2, dated March 6th, 2017 
 
 
 
 
 
 
Principal Investigator Name (Print) 
 
 
 
 
 
Principal Investigator Signature 
Date of Signature  
 
(DD MMM YYYY) 
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CLINICAL PROTOCOL 
Title Page 
Study Title: 
A Randomized, Multicenter, Double-blind, Vehicle-
controlled Study to Evaluate the Safety and Efficacy of 
FMX103 1.5% Topical Minocycline Foam Compared to 
Vehicle in the Treatment of Facial Papulopustular Rosacea 
(FX2016-11) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-11 
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: 
20 Jan 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. 
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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: 
A Randomized, Multicenter, Double-blind, Vehicle-controlled Study to 
Evaluate the Safety and Efficacy of FMX103 1.5% Topical 
Minocycline Foam Compared to Vehicle in the Treatment of Facial 
Papulopustular Rosacea (Study FX2016-11) 
Protocol No: 
FX2016-11 
Study Centers: 
Multicenter (approximately 30 sites in the USA) 
Publication (reference): 
None 
Phase of Development: 
3 
Objectives: 
Primary Objectives: 
 
To determine the efficacy of FMX103 1.5% minocycline foam 
applied topically once daily for 12 weeks in the treatment of 
rosacea. 
 
To evaluate the safety of topical minocycline foam applied 
once daily for 12 weeks. 
Study Design and 
Methods: 
This is a randomized, multicenter, double-blind, vehicle-controlled, 
2-arm study to evaluate the safety and efficacy of FMX103 topical 
foam containing 1.5% minocycline compared to vehicle, in the 
treatment of subjects with moderate-to-severe facial papulopustular 
rosacea. Qualified subjects will be randomized in a 2:1 ratio 
(active:vehicle) to receive 1 of the following 2 treatments: 
 
FMX103 minocycline foam 1.5% 
 
Vehicle foam 
Subjects will be assigned to 1 of 2 treatments according to the 
randomization schedule. Subjects will apply (or have applied) the study 
drug topically once daily for 12 weeks as directed. Subjects will be 
advised to use the study drug at approximately the same time each day. 
Both the Investigator and subject will be blinded to the study drug 
identity. 
Subjects will return for visits at Weeks 1, 4, 6, 8, 10, and 12. Efficacy 
evaluations (inflammatory lesion counts and Investigator’s Global 
Assessment [IGA] score) will be performed at Weeks 4, 8, and 12 
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during the study. 
Number of Subjects 
(planned): 
The planned enrollment is approximately 450 male and female subjects. 
Subjects will be randomly assigned to the two treatment groups, 
FMX103 1.5% and vehicle, in a 2:1 ratio, respectively. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years with a clinical 
diagnosis of moderate to severe facial papulopustular rosacea, defined 
as the presence of: 
 
At least 12 and not more than 50 inflammatory facial lesions 
(ie, papules/pustules), and 
 
An IGA of rosacea severity of moderate or severe using the 
following scale: 
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 
 
Current or history of erythema and/or flushing 
Subjects must be willing to minimize external factors that might trigger 
rosacea flare-ups (eg, spicy foods, thermally hot foods and drinks, hot 
environments, prolonged sun exposure, strong winds, and alcoholic 
beverages). 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, once daily to 
the face, for 12 weeks. 
Reference Therapy: 
Vehicle foam. Topical application, once daily to the face, for 12 weeks. 
Study Duration: 
Subject participation in the study will be up to 18 weeks:  up to 6 weeks 
for Screening and Day 0/Baseline, and 12 weeks of study treatment. A 
safety follow-up telephone call will be conducted 4 weeks after 
completion of study treatment for only those subjects that do not 
participate in study FX2015-13 (Open label study). 
Endpoints and Outcomes: 
 
 
 
 
 
Efficacy Evaluations 
The efficacy parameters will include inflammatory lesion counts, IGA 
at Day 0/Baseline and at Weeks 4, 8, and 12 (Final Visit), and the 
subject global assessment and satisfaction questionnaire at the Final 
Visit. 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner), physical examinations, vital signs, clinical laboratory tests, 
and local signs and symptoms assessments (including erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, 
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itching, peeling/desquamation, and hyperpigmentation) scores. 
Statistical Methods: 
The primary population for efficacy analysis will be the intent-to-treat 
(ITT) population, using multiple imputations to impute missing values. 
Supportive efficacy analyses will be conducted on the per-protocol (PP) 
population, with no imputation for missing values. 
The co-primary efficacy endpoints will be the dichotomized IGA score 
where treatment success is defined as a 2-step improvement resulting in 
a 0 (clear) or 1 (almost clear) score at Week 12 compared to Day 
0/Baseline and the absolute change in inflammatory lesion count at 
Week 12 compared to Day 0/Baseline. 
The key secondary endpoints will be analyzed hierarchically: 
 
Dichotomized IGA score where treatment success is defined as 
a 2-step improvement in score at Week 12 compared to Day 
0/Baseline. 
 
Percent change in inflammatory lesion count at Week 12 
compared to Day 0/Baseline. 
Continuous efficacy endpoints will be analyzed using analysis of 
covariance (ANCOVA). Dichotomized efficacy endpoints will be 
analyzed using the Cochran-Mantel-Haenszel (CMH) test. 
The tolerability and safety of topical minocycline foam applied daily 
for 12 weeks will be evaluated using summary statistics and individual 
subject data listings. 
The active treatment group will be tested against vehicle at the 0.05 
two-sided level of significance. No statistical tests will be performed 
for any of the safety assessments. 
 
 
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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 ............................................................................................................................12 
5 
INVESTIGATIONAL PLAN ..................................................................................................................12 
5.1 
OVERALL STUDY DESIGN ................................................................................................................12 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................13 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................15 
7.1 
SCREENING VISIT .............................................................................................................................17 
7.2 
VISIT 1, DAY 0/BASELINE VISIT.......................................................................................................17 
7.3 
VISIT 2, WEEK 1 (±3 DAYS) .............................................................................................................18 
7.4 
VISIT 3, WEEK 4 (±3 DAYS) .............................................................................................................18 
7.5 
VISIT 4, WEEK 6 (±3 DAYS) .............................................................................................................19 
7.6 
VISIT 5, WEEK 8 (±3 DAYS) .............................................................................................................19 
7.7 
VISIT 6, WEEK 10 (±3 DAYS) ...........................................................................................................20 
7.8 
VISIT 7, WEEK 12 (-3/+5 DAYS)/ FINAL OR EARLY TERMINATION ...................................................20 
7.9 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................21 
8 
STUDY TREATMENTS ..........................................................................................................................21 
8.1 
TREATMENTS ADMINISTERED ..........................................................................................................21 
8.1.1 
Dosing Instructions ........................................................................................................21 
8.1.2 
Manufacturer ..................................................................................................................22 
8.1.3 
Labeling of Study Drug ..................................................................................................22 
8.1.4 
Storage of Study Drug ....................................................................................................22 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................23 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................23 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................23 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................23 
8.6 
BLINDING 23 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................24 
8.8 
USE OF CONTRACEPTION .................................................................................................................24 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................25 
9 
EFFICACY ASSESSMENTS ..................................................................................................................25 
9.1 
CO-PRIMARY EFFICACY ASSESSMENTS ...........................................................................................26 
9.1.1 
Lesion Counts.................................................................................................................26 
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9.1.2 
Investigator Global Assessment .....................................................................................26 
9.2 
SECONDARY AND TERTIARY EFFICACY ASSESSMENTS ....................................................................26 
9.2.1 
Percent Change in Inflammatory Lesion Counts ............................................................26 
9.2.2 
Interim Change in Inflammatory Lesion Counts ............................................................26 
9.2.3 
Subject Global Assessment ............................................................................................26 
9.2.4 
Subject Satisfaction Questionnaire .................................................................................26 
9.3 
PHOTOGRAPHY ................................................................................................................................27 
10 
SAFETY ASSESSMENTS .......................................................................................................................27 
10.1 
MEDICAL/SURGICAL HISTORY .........................................................................................................27 
10.2 
MEDICATION HISTORY.....................................................................................................................27 
10.3 
CONCOMITANT MEDICATIONS .........................................................................................................27 
10.4 
VITAL SIGNS ....................................................................................................................................27 
10.5 
PHYSICAL EXAMINATION .................................................................................................................28 
10.6 
CLINICAL LABORATORY TESTS........................................................................................................28 
10.6.1 
Urine Pregnancy Test .....................................................................................................28 
10.6.2 
Sample Collection, Storage, and Shipping .....................................................................29 
10.7 
OTHER SAFETY MEASUREMENTS .....................................................................................................29 
10.7.1 
Electrocardiograms ........................................................................................................29 
10.7.2 
Local Signs and Symptoms Assessments .......................................................................29 
10.7.2.1 Erythema (Clinical Erythema Assessment Scale) .........................................29 
10.7.2.2 Telangiectasia ................................................................................................29 
10.7.2.3 Burning/Stinging ...........................................................................................30 
10.7.2.4 Flushing/Blushing .........................................................................................30 
10.7.2.5 Dryness/Xerosis ............................................................................................30 
10.7.2.6 Itching ...........................................................................................................30 
10.7.2.7 Peeling/Desquamation ...................................................................................30 
10.7.2.8 Hyperpigmentation ........................................................................................31 
10.8 
ADVERSE EVENTS ............................................................................................................................31 
10.8.1 
Method of Determining Adverse Events ........................................................................31 
10.8.2 
Adverse Event Definitions .............................................................................................31 
10.8.2.1 Adverse Events ..............................................................................................31 
10.8.2.2 Serious Adverse Events .................................................................................32 
10.8.2.3 Severity of Adverse Events ...........................................................................32 
10.8.2.4 Relationship of Adverse Events to Study Treatments ...................................33 
10.8.2.5 Adverse Events Expectedness .......................................................................33 
10.8.3 
Reporting Adverse Events ..............................................................................................33 
10.8.4 
Adverse Event Follow-up ...............................................................................................33 
10.8.4.1 Pregnancy Reporting .....................................................................................34 
10.8.5 
Clinically Significantly Abnormal Laboratory Results ..................................................34 
10.9 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................34 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................34 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................34 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................35 
11.3 
ANALYSIS POPULATIONS .................................................................................................................35 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND DAY 0/BASELINE CHARACTERISTICS ......................36 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................36 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................37 
11.5.2 
Secondary Efficacy Endpoints .......................................................................................37 
11.5.3 
Tertiary Efficacy Endpoints ...........................................................................................37 
11.6 
SAFETY ENDPOINTS .........................................................................................................................37 
11.6.1 
Adverse Events ...............................................................................................................38 
11.6.2 
Vital Signs and Physical Examinations ..........................................................................38 
11.6.3 
Clinical Laboratory Results ............................................................................................38 
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11.7 
INTERIM ANALYSIS ..........................................................................................................................38 
12 
STUDY MANAGEMENT .......................................................................................................................39 
12.1 
MONITORING ...................................................................................................................................39 
12.2 
PROTOCOL AMENDMENTS................................................................................................................39 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................39 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................40 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................40 
12.6 
PUBLICATION POLICY ......................................................................................................................41 
13 
ETHICS .....................................................................................................................................................41 
13.1 
CONDUCT OF THE STUDY .................................................................................................................41 
13.2 
INSTITUTIONAL REVIEW BOARDS (IRB) ..........................................................................................41 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................41 
13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................42 
13.5 
RECORDS RETENTION ......................................................................................................................42 
13.6 
FINANCING .......................................................................................................................................42 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................42 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................43 
16 
REFERENCE LIST .................................................................................................................................43 
APPENDIX 1:  SUBJECT GLOBAL ASSESSMENT QUESTIONNAIRE ..................................................44 
APPENDIX 2:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................45 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-11 ........................... 16 
Table 2 
Study Drug Kits and Treatments – Study FX2016-11 ................................................... 21 
Table 3 
IGA Scale for Rosacea – Study FX2016-11 ................................................................... 26 
Table 4 
Clinical Laboratory Tests – Study FX2016-11 .............................................................. 28 
Table 5 
Sample Size Calculations Based on IGA Scores after 12 Weeks of Treatment in Phase 2 
Study FX2015-10 ........................................................................................................... 35 
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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 
BOCF 
Baseline observation carried forward 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
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 System 
ITT 
Intent-to-treat (population) 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed effects model for repeated measures 
OC 
Observed cases 
OTC 
Over-the-counter 
PP 
Per-protocol (population) 
PT 
Preferred term 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
 
 
 
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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 
 
 
 
 
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3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and the eye. 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. 
Foamix has developed a topical minocycline foam product that is being evaluated for safety and 
efficacy in the treatment of rosacea. Minocycline hydrochloride is an established broad spectrum 
antibiotic that is used orally in the treatment of 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 has been evaluated in a Phase 2 study at two minocycline 
concentrations, 1.5% and 3%. The study included 232 subjects (males/females, aged ≥18 years) 
with moderate-to-severe papulopustular rosacea defined by the Investigator’s Global Assessment 
(IGA) score and with ≥12 inflammatory facial lesions (papules/pustules) at Day 0/Baseline. 
Subjects were treated with FMX103 1.5%, FMX103 3%, or vehicle foam, once daily for 12 
weeks. Efficacy and safety were evaluated at Weeks 2, 4, 8, and 12, with an additional safety 
follow-up visit at Week 16. The primary efficacy end point was the absolute change in 
inflammatory lesion count at Week 12. Other assessments included IGA improvement of ≥2 
grades and reaching an IGA score of “clear” or “almost clear” (IGA 0/1), clinical assessment of 
erythema, and safety and tolerability. 
At Week 12, both the 1.5% and 3% doses of FMX103 significantly reduced the number of 
papules and pustules vs. vehicle (both p<0.001, intent-to-treat [ITT] population). The mean 
reduction in lesion count from Day 0/Baseline was 21.1 for the FMX103 1.5% dose, 19.9 for the 
FMX103 3% dose, and 7.8 for the vehicle. The corresponding percent reductions were 61.4% 
and 55.5% for the 1.5% and 3% doses, respectively, and 29.7% for the vehicle. 
Both the 1.5% and 3% doses of FMX103 were statistically significantly better than vehicle in 
improving IGA scores by ≥2 grades at week 12 (p=0.002 and p=0.032, respectively). Both doses 
were also statistically significantly better than vehicle in achieving an IGA of “clear or almost 
clear” (score 0/1) at Week 12 (p=0.001 and p=0.041, respectively). Both FMX103 1.5% and 3% 
doses appeared to be generally safe and well-tolerated. Treatment-related dermal reactions were 
reported in 1 subject from the FMX103 1.5% dose group (considered mild) and in a few subjects 
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from the FMX103 3% dose group (mild, n=1; moderate, n=2; severe, n=1). No treatment-related 
systemic adverse events (AEs) were reported and discontinuation due to AEs (eczema, n=1; 
rosacea, n=1; burning sensation, n=1) was reported in 3 subjects in the FMX103 3% dose group. 
As a consequence of the above, the FMX103 1.5% dose concentration has been selected for 
further development. This Phase 3 study will further assess the safety and efficacy of topical 
minocycline HCl foam, 1.5%, applied once daily compared with vehicle foam for the treatment 
of moderate-to-severe papulopustular rosacea. 
4 
STUDY OBJECTIVES 
The primary objectives of the study are: 
 To determine the efficacy of FMX103 1.5% minocycline foam applied topically once 
daily for 12 weeks in the treatment of rosacea. 
 To evaluate the tolerability and safety of topical minocycline foam applied once daily for 
12 weeks. 
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy of FMX103 topical foam containing 1.5% minocycline compared to vehicle, 
in the treatment of subjects with moderate-to-severe facial papulopustular acne rosacea. 
Qualified subjects will be randomized in a 2:1 ratio (active:vehicle) to use once daily one of the 
following two treatments: 
 FMX103 minocycline foam 1.5% 
 Vehicle foam 
Subjects will be assigned to 1 of 2 treatments according to the randomization schedule. Subjects 
will apply (or have applied) the study drug topically once daily for 12 weeks as directed. 
Subjects will be advised to use the study drug at approximately the same time each day, 
preferably in the evening about 1 hour before bedtime. Both the Investigator and subject will be 
blinded to the study drug identity.  
Subjects will return for visits at Weeks 1, 4, 6, 8, 10, and 12. Efficacy evaluations (inflammatory 
lesion counts [Section 9.1.1] and IGA score [Section 9.1.2]) will be performed at Weeks 4, 8, and 
12 during the study. Other assessments will be performed as described in Section 9 and 
Section 10. 
5.2 
Rationale for Study Design and Dose Selection 
A randomized, multicenter, double-blind, vehicle-controlled study design has been selected in 
order to assess the efficacy of the study drug. The subjects will be selected according to 
predefined entry criteria. The study treatment duration of 12 weeks is expected to be sufficient to 
show a treatment effect. 
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The concentration of minocycline in the composition was selected according to formulation 
integrity and stability considerations and based on the results of Phase 2 Study FX2015-10 
(described above in Section 3). 
Because of the mode of action of tetracycline drugs, the primary efficacy endpoints will be the 
effect on inflammatory lesion counts and IGA scores (Section 9). 
6 
STUDY POPULATION 
The study will randomize approximately 450 subjects to active or vehicle treatment (in a 2:1 
ratio) at approximately 30 sites in the US. 
6.1 
Inclusion Criteria 
Subjects were included in the study if they met all of the following inclusion criteria at the time 
of enrollment: 
1. Male or female ≥18 years-of-age. 
2. Moderate-to-severe rosacea (as per the IGA score; Table 3) on the proposed facial 
treatment area consisting of: 
a. At least 12 and not more than 50 facial papules and pustules, excluding lesions 
involving the eyes and scalp; 
b. No more than 2 nodules on the face. 
3. Presence of or history of erythema and/or flushing on the face. 
4. If a female 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. 
5. Willing to minimize external factors that might trigger rosacea flare-ups (eg, spicy foods, 
thermally hot foods and drinks, hot environments, prolonged sun exposure, strong winds, 
and alcoholic beverages). 
6. Subjects who use make-up must have used the same brands/types of make-up for a 
minimum period of 14 days prior to study entry and must agree to use the same make-up, 
brand/type, or frequency of use, throughout the study. 
7. Completed and signed an appropriately administered Informed Consent Form (ICF) prior 
to any study-related procedures. 
6.2 
Exclusion Criteria 
Subjects were excluded from enrollment in the study for any of the following reasons: 
1. Woman who is pregnant, lactating, or planning to become pregnant during the study 
period. 
2. Presence of any skin condition on the face that would interfere with the diagnosis or 
assessment of rosacea. 
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3. Moderate or severe rhinophyma, dense telangiectasia (score 3, severe; Section 10.7.2.2), 
or plaque-like facial edema. 
4. An active nodule on the face >5 mm in diameter. 
5. Excessive facial hair (eg, beards, sideburns, moustaches, etc.) that would interfere with 
diagnosis or assessment of rosacea. 
6. History of hypersensitivity or allergy to minocycline, any other tetracycline, or of any 
other component of the formulation. 
7. Severe erythema, dryness, scaling, pruritus, stinging/burning, or edema. 
8. Active ocular rosacea (eg, conjunctivitis, blepharitis, or keratitis) of sufficient severity to 
require topical or systemic antibiotics. 
9. Use within 6 months prior to Day 0/Baseline of oral retinoids (eg, Accutane®) or 
therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are 
allowed). 
10. Initiation of use of estrogens or oral contraceptives less than 3 months prior to Day 
0/Baseline. 
11. Use within 1 month prior to Day 0/Baseline of: 
a. Topical retinoids to the face. 
b. Systemic antibiotics known to have an impact on the severity of facial rosacea 
(eg, containing tetracycline and its derivatives, erythromycin and its derivatives, 
sulfamethoxazole, or trimethoprim). Subjects requiring systemic antibiotics not 
known to affect rosacea will be considered on a case-by-case basis. 
c. Systemic corticosteroids (Note: intranasal and inhalational corticosteroids do not 
require a washout and maybe used throughout the trial if the subject is on a stable 
dose). 
12. Use within 2 weeks prior to Day 0/Baseline of: 
a. Topical corticosteroids. 
b. Topical antibiotics. 
c. Topical medications for rosacea (eg, metronidazole). 
13. Use of a sauna during the 2 weeks prior to Day 0/Baseline and during the study. 
14. Had wax epilation of the face within 2 weeks prior to Day 0/Baseline. 
15. Active bacterial folliculitis. 
16. Consumption of excessive alcohol, abuse of licit or illicit drugs, or a condition that, in the 
opinion of the Investigator, could compromise the subject’s ability to comply with study 
requirements. 
17. Participation in activities that involve excessive or prolonged exposure to sunlight or 
weather extremes, such as wind or cold. 
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18. Presence of any clinically significant condition or situation, other than the condition 
being studied, that in the opinion of the Investigator would interfere with the study 
evaluations or optimal participation in the study. 
19. Participation in an investigational drug study (ie, subject has been treated with an 
investigational drug) within 30 days prior to Day 0/Baseline. Subjects who are 
participating in non-treatment studies such as observational studies or registry studies can 
be considered for inclusion. 
20. Previously enrolled in this study. 
21. Prior laser therapy (for telangiectasia or other conditions), electrodessication, or 
phototherapy (eg, ClearLight®) to the facial area within 180 days prior to Day 0/Baseline. 
22. Prior cosmetic procedures (eg, facials) that may affect the efficacy and safety profile of 
the investigational product within 14 days prior to Day 0/Baseline. 
23. Screening electrocardiogram (ECG) that reveals a QTcF >500 msec. 
7 
STUDY PROCEDURES 
Potential subjects will be assessed for eligibility at Screening. During this visit, the purpose, 
timing, procedures, and risks of the study will be explained to the subject, including 
requirements for enrollment and participation in the study, medication restrictions during the 
study, and requirements for washout of certain medications that the subject may already be 
taking. 
The eligible subject who is willing to participate in the study will then sign an appropriately 
administered ICF prior to any study-related procedures being performed. 
Procedures at the Screening Visit will include obtaining blood and urine samples for clinical 
laboratory tests. The results of these tests must be no more than 45 days old at the time of the 
Day 0/Baseline Visit and randomization. 
If a subject who has agreed to participate in the study and signed the ICF is currently undergoing 
rosacea therapy identified in Exclusion Criteria 11 and 12, they must first enter a washout period 
(ie,1 month or 2 weeks, as specified in Exclusion Criteria 11 and 12, respectively) before 
beginning the screening procedures. 
The schedule of study assessments and procedures and the time point at which they will be 
performed during the study is presented in Table 1. If a subject prematurely withdraws from the 
study, the subject should return to the study site for an early termination visit during which all 
evaluations described under Final Visit 7/Week 12 must be performed. 
 
 
 
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Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-11 
Assessment or Procedure 
Screening 
Day 0 / 
Baselinea 
Visits 
Final 
Visitb 
Safety 
Follow-upg 
Visit 
1 
2 
3 
4 
5 
6 
7 
Week 
1 
4 
6 
8 
10 
12 
Informed consent 
X 
Demographic data 
X 
Assign subject identification 
X 
Medical/surgical/medication history 
X 
Inclusion/exclusion criteria 
X 
X 
Physical examination, height, weightc 
X 
X 
Electrocardiogram 
X 
Blood pressure/heart rated 
X 
X 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
X 
X 
Urine pregnancy test (females of 
childbearing potential only) 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
X 
X 
X 
Subject Global Assessment 
X 
Subject Satisfaction Questionnaire 
X 
Local signs and symptoms 
assessmentse  
X 
X 
X 
X 
X 
X 
X 
X 
Photography 
X 
X 
X 
X 
Randomization 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
Xf 
X 
Xf 
Schedule/confirm next visit 
X 
X 
X 
X 
X 
X 
X 
a.
Day 0/Baseline must occur within 45 days of Screening. Blood test results must not show clinically significant
abnormalities.
b.
If a subject prematurely withdraws from the study, all evaluations described under Visit 7/Week 12 (Final Visit) must be
performed at an Early Termination Visit.
c.
Height to be measured only at Day 0/Baseline.
d.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest.
e.
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.
f.
Dispense one kit (2 canisters) of study drug only if necessary at Visits 4 and 6.
g.
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 12 (Final Visit) for only those subjects that do
not participate in study FX2015-13 (Open label study).
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7.1 
Screening Visit 
 Obtain a signed and dated, written ICF prior to any study-related procedures. 
 Obtain demographic data. 
 Using the Interactive Response Technology System (IRT), assign the subject an 
identification number. 
 Obtain medical/surgical history (Section 10.1). 
 Obtain history of prior medication usage (including previous use of rosacea medications); 
record start and stop dates of any medications used in the last 3 months (Section 10.2). 
 Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria 
(Section 6.2). 
 Collect a urine sample from female subjects of childbearing potential for a urine 
pregnancy test (Section 10.6.1). 
 Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory (Section 10.6.2). 
 Perform 12-lead ECG (Section 10.7.1). 
 Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
 Perform IGA (Section 9.1.2). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Schedule/confirm the next study visit. 
7.2 
Visit 1, Day 0/Baseline Visit 
 Confirm eligibility according to the inclusion (Section 6.1) and exclusion criteria 
(Section 6.2). 
 Perform physical examination including height and weight (Section 10.5). 
 Measure blood pressure and heart rate (Section 10.4). 
 Collect a urine sample from female subjects of childbearing potential for a urine 
pregnancy test (Section 10.6.1). 
 Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
 Perform IGA (Section 9.1.2). 
 Perform photography (Section 9.3). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Randomize the subject using the IRT when all criteria have been met. 
 Record concomitant medications  (Section 8.7). 
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 Record AEs (Section 10.8). 
 Dispense one kit (2 canisters) of study drug. 
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight and to use the same make-up brand/type, or frequency of use, throughout the 
study as applicable. 
7.3 
Visit 2, Week 1 (±3 Days) 
 Measure blood pressure and heart rate (Section 10.4). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Record concomitant medications  (Section 8.7). 
 Record AEs (Section 10.8). 
 Confirm that subject continues to use only the provided facial cleanser. 
 Collect used study canister (if applicable). 
 Dispense one kit (2 canisters) of study drug. 
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight and to use the same make-up brand/type, or frequency of use, throughout the 
study as applicable. 
7.4 
Visit 3, Week 4 (±3 Days) 
 Measure blood pressure and heart rate (Section 10.4). 
 Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
 Perform IGA (Section 9.1.2). 
 Perform photography (Section 9.3). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Collect a urine sample from female subjects of childbearing potential for a urine 
pregnancy test (Section 10.6.1). 
 Record concomitant medications  (Section 8.7). 
 Record AEs (Section 10.8). 
 Perform drug accountability to assess compliance (Section 8.2). 
 Collect used study drug canister (if applicable). 
 Dispense one kit (2 canisters) of study drug. 
 Confirm that subject continues to use only the provided facial cleanser. 
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 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight and to use the same make-up brand/type, or frequency of use, throughout the 
study as applicable. 
7.5 
Visit 4, Week 6 (±3 Days) 
 Measure blood pressure and heart rate (Section 10.4). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Record concomitant medications (Section 8.7). 
 Record AEs (Section 10.8). 
 Collect used study drug canister (if applicable). 
 Dispense one kit (2 canisters) of study drug (if necessary). 
 Confirm that subject continues to use only the provided facial cleanser. 
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight and to use the same make-up brand/type, or frequency of use, throughout the 
study as applicable. 
7.6 
Visit 5, Week 8 (±3 Days) 
 Measure blood pressure and heart rate (Section 10.4). 
 Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
 Perform IGA (Section 9.1.2). 
 Perform photography (Section 9.3). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Collect a urine sample from female subjects of childbearing potential for a urine 
pregnancy test (Section 10.6.1). 
 Record concomitant medications (Section 8.7). 
 Record AEs (Section 10.8). 
 Perform drug accountability to assess compliance (Section 8.2). 
 Collect used study canister (if applicable). 
 Dispense one kit (2 canisters) of study drug. 
 Confirm that subject continues to use only the provided facial cleanser. 
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight and to use the same make-up brand/type, or frequency of use, throughout the 
study as applicable. 
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7.7 
Visit 6, Week 10 (±3 Days) 
 Measure blood pressure and heart rate (Section 10.4). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Record concomitant medications (Section 8.7). 
 Record AEs (Section 10.8). 
 Collect used study drug canister (if applicable). 
 Dispense one kit (2 canisters) of study drug (if necessary). 
 Confirm that subject continues to use only the provided facial cleanser. 
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight and to use the same make-up brand/type, or frequency of use, throughout the 
study as applicable. 
7.8 
Visit 7, Week 12 (-3/+5 days)/ Final or Early Termination 
 Perform physical examination including weight (Section 10.5). 
 Measure blood pressure and heart rate (Section 10.4). 
 Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory (Section 10.6.2). 
 Collect a urine sample from female subjects of childbearing potential for a urine 
pregnancy test (Section 10.6.1). 
 Perform facial lesion count of inflammatory lesions (Section 9.1.1). 
 Perform IGA (Section 9.1.2). 
 Perform photography (Section 9.3). 
 Perform local signs and symptoms assessments (Section 10.7.2). 
 Have the subject complete the Subject Global Assessment (Section 9.2.3). 
 Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.4). 
 Record concomitant medications (Section 8.7). 
 Record AEs (Section 10.8). 
 Collect all used and full study drug canisters. 
 Perform drug accountability to assess compliance and record the date of the last dose 
(Section 8.2). 
 Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 7/Week 12 (Final 
Visit) date (±5 days) for subjects that will not participate in study FX2015-13 (Open label 
study) (Section 7.9). 
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7.9 
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 12 (Final Visit) for 
only those subjects that do not participate in study FX2015-13 (Open label study). Follow up on 
existing and any new concomitant medications and adverse events will be recorded.   
8 
STUDY TREATMENTS 
This study will include FMX103 minocycline foam 1.5% and vehicle foam. 
8.1 
Treatments Administered 
The description of study drug kits and treatments is shown below in Table 2. 
Table 2 
Study Drug Kits and Treatments – Study FX2016-11 
Dosage form description: 
Foam containing minocycline HCl 1.5% or vehicle foam 
Package description: 
Canisters, each containing 25 g of the clinical trial supply foam 
Daily dose: 
Once daily 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) or 0.0 mg (vehicle) of minocycline. 
Cumulative maximal dose for 
dosing (12 weeks): 
630 mg (1.5%) minocycline 
Dispensing: 
Kits consisting of 2 canisters, each canister containing 25 g of FMX103 
minocycline formulation, 1.5%, or vehicle dispensed at Visit 1 (Day 
0/Baseline), Visit 2 (Week 1), Visit 3 (Week 4), and Visit 5 (Week 8). 
Additional kits of 2 canisters may be dispensed at other visits if required. 
 
8.1.1 
Dosing Instructions 
The dosing regimen will be the same for both treatment groups. 
Study drug kits containing 2 canisters of investigational drug will be dispensed at Visit 1 (Day 
0/Baseline), Visit 2 (Week 1), Visit 3 (Week 4), and Visit 5 (Week 8). Additional kits will be 
available for dispensing at other visits (ie, Visits 4 and 6) to ensure enough product is available 
for daily dosing. 
After shaking the canister well, a small amount of study drug (about ½ gram or a cherry-sized 
amount) should be expressed from the canister onto the finger tips and then applied as a thin 
layer over all involved areas of the face. Additional drug may be used as needed to assure the 
entire involved area is treated.  
Study drug should be applied at approximately the same time each day, preferably in the evening 
about 1 hour before bedtime. 
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8.1.2 
Manufacturer 
The manufacturer of the investigational product is ASM Aerosol-Service AG, Moehlin, 
Switzerland. 
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% and vehicle canisters must be stored at 2°C – 8°C until being dispensed to the 
subject. Subsequently, they 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. 
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8.2 
Study Drug Accountability 
The Investigator will have overall responsibility for the use of the study drug. The Investigator or 
designee will verify the contents of the drug shipment and confirm receipt of the study drug in 
the 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 regional regulatory authority 
inspection at any time. At the conclusion of the study, the Investigator must provide a copy of 
this record to the Sponsor and each canister that has been retrieved from a subject will be 
returned to the vendor to be weighed. 
Under no circumstances will the Investigator allow the investigational drugs to be used other 
than as directed by this protocol. Qualified study personnel must use the IRT to assign and 
dispense kits to the subjects. Reasons for digression from the expected dispensing regimen must 
also be recorded. 
8.3 
Handling and Disposal of Study Drug 
The study drug must be protected from unauthorized access (eg, in a locked storage facility). 
Any unused, partially used, or empty bottles of study drug will be returned to the Sponsor or 
designee by the time of the site’s close-out visit. Receipt, distribution, and return of the study 
drug must be properly documented on forms provided by the Sponsor or designee. 
8.4 
Method of Assignment of Study Drug 
After pretreatment clinical evaluations and all other Screening procedures have been completed, 
authorized site personnel will acknowledge that the applicable subject met all the specified 
inclusion criteria (Section 6.1) and none of the exclusion criteria (Section 6.2). Assignment to a 
treatment group will then follow a predetermined list of randomization numbers, with each 
successive number receiving 1 of the 2 treatments in random order. Authorized site personnel 
will use the IRT system to assign a kit number that corresponds to the randomization schedule. 
The kit box with the assigned kit number will be dispensed to the subject. 
The randomization code will be provided by Premier Research, Research Triangle Park, NC. 
8.5 
Selection and Timing of Doses in the Study 
The 1.5% concentration of minocycline has been shown to be effective compared to vehicle in a 
Phase 2 study in subjects with rosacea. The once-daily dosing regimen is appropriate given the 
pharmacokinetic characteristics of minocycline. 
8.6 
Blinding 
This is a double-blind study, with limited access to the randomization code. The randomization 
code will be held in confidence until after the study database is locked and a memo documenting 
the database lock has been issued. Every effort will be made to retain the integrity of the blind. 
When issued to the sites, the study drug will be identical in appearance for all subjects, 
regardless of treatment assignment. 
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The treatment each subject receives will not be disclosed to the Investigator, study site personnel, 
subjects, monitors, or the Sponsor staff except as required for the purposes of conducting this 
study. 
In the event that emergency identification of study drug is required (eg, if the Investigator 
believes that the information is necessary to properly treat a subject with an AE), the study drug 
identity can be obtained by the Investigator through the IRT system. 
Before breaking the blind for a subject, the Investigator should determine that the information is 
necessary (ie, that it will alter the subject’s immediate course of treatment and will contribute to 
the management of the AE). In many cases, particularly when the emergency is clearly not 
related to study drug, the problem may be effectively managed by assuming that the subject is 
receiving active study drug without the need for unblinding. Every effort should be made to alert 
the medical monitor before requesting that the blind be broken. If this is not possible, the medical 
monitor should be immediately notified of the breaking of the blind. The Investigator will record 
the unblinding procedures in the subject’s source documents. 
If unblinding is necessary, the subject will be withdrawn from the study and Early Termination 
Visit (ie, Visit 7 [Week 12]) assessments will be completed. 
8.7 
Prior/Concomitant Therapy 
Subjects should use the facial cleanser Cetaphil Gentle Skin Cleanser (which will be provided by 
the Sponsor). An alternative, non-medicated cleanser may be used if agreed to by the Sponsor. 
The use of or change in the dose of any and all concomitant medications, either prescription or 
over-the-counter (OTC), during the study will be recorded. The reason for use or change of dose 
of a concomitant therapy may need to be reported as an AE. Therapies (medication and non-
medication therapies) not restricted by the protocol may be used. Non-prohibited chronic 
therapies being used at Day 0/Baseline may be continued. If a female subject 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 study. 
If a subject is taking anticoagulant therapy, the subject should be advised that they may require a 
downward adjustment of their anticoagulant dosage. 
All topical or systemic medications listed in the exclusion criteria are prohibited during this 
study. Similarly, no other topical medications are permitted to be used on the face during this 
period. 
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). 
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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 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 listed below 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 kits (empty/used/unused) at the appropriate visits. The study site personnel will question the 
subject on the history of 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. 
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9.1 
Co-Primary Efficacy Assessments 
The co-primary efficacy assessments will include the inflammatory lesion counts and the IGA of 
severity of disease. Lesion counts, IGA, and other efficacy evaluations 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 will be performed at Screening and Visit 1 (Day 0/Baseline) to confirm eligibility, and 
again at Visit 3 (Week 4), Visit 5 (Week 8), and Visit 7 (Week 12/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 will be performed at Screening and Visit 1 (Day 0/Baseline) to confirm 
eligibility, and again at Visit 3 (Week 4), Visit 5 (Week 8), and Visit 7 (Week 12/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-11 
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 
Percent Change in Inflammatory Lesion Counts 
The percent change in inflammatory lesion counts at Visit 7 (Week 12/Final Visit) compared to 
Visit 1 (Day 0/Baseline) will be evaluated. 
9.2.2 
Interim Change in Inflammatory Lesion Counts 
The absolute 
 change in inflammatory lesion counts at Visit 3 (Week 4) and Visit 5 
(Week 8) compared to Visit 1 (Day 0/Baseline) will be evaluated. 
9.2.3 
Subject Global Assessment 
This score will be obtained from the subject at Visit 7 (Week 12/Final Visit) using the 
questionnaire in Appendix 1. 
9.2.4 
Subject Satisfaction Questionnaire 
A subject satisfaction questionnaire (Appendix 2) will be administered at Visit 7 (Week 12/Final 
Visit). 
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9.3 
Photography 
Photography of the full face will be performed at Day 0/Baseline and at Weeks 4, 8, and 12 using 
recognized methods. The equipment and techniques for this photography and for archiving the 
images are described in the Study Manual. Photographs will be reviewed at the site and by the 
sponsor for quality. Photographs will not be used to assess the lesion counts or the IGA, but will 
be archived to be available for subsequent review, if required, by the sponsor, auditors, or the 
FDA. 
10 
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
physical examinations, the monitoring of vital signs, AEs (volunteered, observed, and elicited by 
general questioning in a non-suggestive manner), clinical laboratory tests, and local signs and 
symptoms assessments (including erythema, telangiectasia, burning/stinging, flushing/blushing, 
dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) scores. 
10.1 
Medical/Surgical History 
A complete medical and surgical history will be obtained at Screening, which will include the 
following:  diseases of the head, ears, eyes, nose and throat; respiratory diseases; cardiovascular 
diseases; gastrointestinal diseases; hepatic diseases; genitourinary diseases; musculoskeletal 
diseases; endocrine diseases; neurological diseases; psychiatric diseases; skin diseases; allergies; 
hematological diseases; and other abnormalities. 
10.2 
Medication History 
A history of medication usage (including previous use of rosacea medications and non-
medication therapies) will be recorded at Screening. The start and stop dates of previous use of 
medications in the last 3 months will be recorded. 
10.3 
Concomitant Medications 
All topical or systemic medications listed in the exclusion criteria are prohibited. No other 
topical medications are permitted to be used on the face. All medication that the subject is 
currently taking or any change in medication or dosage since the last visit will be documented 
throughout the study. The use of or change in the dose of any and all concomitant medication, 
either prescription or OTC, during the study will be recorded. The reason for use or change of 
dose of a concomitant therapy may need to be reported as an AE. 
10.4 
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all post-Day 0/Baseline 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. 
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10.5 
Physical Examination 
A complete physical examination (excluding the genitourinary examination) will be performed. 
Weight will be recorded at the Visit 1 (Day 0/Baseline) and Visit 7 (Week 12/Final Visit). Height 
will be measured at Visit 1 (Day 0/Baseline) only. 
10.6 
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at the Screening Visit and 
Visit 7 (Week 12/Final Visit). All clinical laboratory tests will be performed at 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. 
Table 4 
Clinical Laboratory Tests – Study FX2016-11 
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 
 
10.6.1 
Urine Pregnancy Test 
A urine pregnancy test will be performed on all females of childbearing potential at the 
Screening Visit, Visit 1 (Day 0/Baseline), Visit 3 (Week 4), Visit 5 (Week 8), and Visit 7 (Week 
12/Final Visit) or when a subject prematurely withdraws from the study. 
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10.6.2 
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. 
10.7 
Other Safety Measurements 
10.7.1 
Electrocardiograms 
A standard 12-lead ECG will be performed at Screening only. Subjects will be supine and at rest 
for at least 10 minutes before measurement. Subjects will have their participation discontinued if 
an ECG reveals a QTcF >500 msec (see Exclusion Criterion 23). 
10.7.2 
Local Signs and Symptoms Assessments 
The severity of each of the following local signs and symptoms will be measured at Screening, 
Visit 1 (Day 0/Baseline), and at each study visit:  erythema, telangiectasia, 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 medication or is the reason for discontinuation from the study. 
10.7.2.1 
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 
10.7.2.2 
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 
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10.7.2.3 
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 
10.7.2.4 
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 
10.7.2.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
 0 = None 
 1 = Mild 
 2 = Moderate 
 3 = Severe 
10.7.2.6 
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 
10.7.2.7 
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 
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 3 = Severe:  pronounced flaking/shedding scales covering entire application area 
10.7.2.8 
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 
10.8 
Adverse Events 
10.8.1 
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator. AEs will be recorded at each visit on the appropriate 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 10.8.4) 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 10.8.2 and Section 10.8.3, 
respectively. 
10.8.2 
Adverse Event Definitions 
10.8.2.1 
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. 
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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 
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. 
10.8.2.2 
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. 
10.8.2.3 
Severity of Adverse Events 
Severity of an AE refers to the extent to which an AE affects the subject’s daily activities and 
differs from “serious”, which is a regulatory classification. Severity will be categorized 
according to the following criteria: 
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
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.
10.8.2.4
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to 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.
10.8.2.5
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. 
10.8.3
Reporting Adverse Events 
Adverse events that occur from the time of informed consent/assent through 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 or 
designee 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 or designee. Any pertinent follow-up information should be provided in a similar 
manner. Contact information is provided below: 
10.8.4
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until resolution or stabilization (in the opinion of the Investigator), or for 30 days, 
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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, stabilized, or no longer serious enough to warrant follow-up. 
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 resolved or stabilized. 
10.8.4.1 
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 Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of laboratory pregnancy testing 
are available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
A urine pregnancy test will be performed on all females of childbearing potential as described in 
Section 10.6.1. 
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, missed or late menstrual 
period). 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 laboratory 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. 
10.8.5 
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be so flagged 
when reported to the site. The Investigator will determine which out-of-range laboratory test 
results should be characterized as clinically significant and will so 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. 
10.9 
Appropriateness of Safety Measurement 
The safety assessments to be utilized 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 (SAP) will be finalized prior to breaking of the study blind. 
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Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated, but the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. All hypothesis testing will be conducted 
using two-sided tests with a 0.05 level of significance. 
11.2 
Determination of Sample Size 
In the Phase 2 Study FX2015-10, the proportion of subjects with an IGA score of 0 or 1 after 
 of treatment was 
 in the FMX103 1.5% dose group compared to 
 for the 
vehicle dose group. Table 5 provides alternate assumptions on this primary response criterion 
with corresponding implications on sample size. Power was set to 90% and a type-1 error was set 
to a two-sided test with a 0.05 level of significance. Sample size was calculated based on 
Fisher’s Exact test. 
Table 5 
Sample Size Calculations Based on IGA Scores after 
 of 
Treatment in Phase 2 Study FX2015-10 
Vehicle IGA (Score 0,1) 
FMX103 1.5% IGA (Score 0,1) 
Sample Size (Vehicle, Active) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assuming a 
 dropout rate, 300 subjects receiving FMX103 and 150 subjects receiving 
vehicle will provide at least 90% power for a statistically significant difference on an IGA score 
of 0 or 1. 
For the co-primary endpoint of change from Day 0/Baseline to 
 in inflammatory lesion 
count, in the Phase 2 study the FMX103 1.5% dose group had a mean reduction of 
 lesions 
whereas the vehicle had a mean reduction of 
 lesions. The standard deviation was 
. For a 
90% power, 
 and 
 subjects in the FMX103 1.5% and vehicle groups, respectively, will be 
needed. Therefore, the sample size needed to provide 90% power for both co-primary endpoints 
is 
 and 
 subjects in the FMX103 1.5% and vehicle groups, respectively. 
11.3 
Analysis Populations 
The following populations will be defined for analysis: 
 Intent-to-Treat (ITT) population:  all randomized subjects. 
 Per-Protocol (PP) population:  defined as the subset of the ITT population without any 
protocol deviations that may have an impact on the efficacy assessments. Subjects to be 
included in the PP population will be determined by the Sponsor/CRO prior to the 
unblinding of the study. 
Subjects may be excluded from the PP population if any of the following are met: 
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o Failure to meet inclusion/exclusion criteria 
o Have administered any interfering concomitant medications 
o Have not, in the opinion of the Investigator, been compliant with the treatment 
regimen (eg, reported frequent missed doses) 
o Randomization error 
Prior to breaking the blind, additional criteria for exclusion from the PP population may 
be included to accommodate for unforeseen events that occurred during the conduct of 
the study. 
 Safety Population:  all randomized subjects who use any study product. Subjects who 
have no post-Day 0/Baseline assessments will be included in the Safety population unless 
all dispensed study drug is returned unused. 
The ITT population will be the primary population for efficacy analysis. The PP population will 
be secondary for the co-primary endpoints only. The Safety population will be used for the 
analyses of safety endpoints. 
All efficacy analyses will be conducted according to the randomized treatment assignment; all 
safety analyses will be conducted according to the treatment actually received. 
11.4 
Subject Accounting, Demographics, and Day 0/Baseline Characteristics 
Demographics, Day 0/Baseline characteristics, and prior and concomitant medications will be 
summarized by treatment. Study completion status and reasons for discontinuation will also be 
displayed by treatment. 
Medical and surgical history will only be presented in the listings. 
11.5 
Efficacy Endpoints 
The primary population for all efficacy analyses will be the ITT population. For the analyses of 
the co-primary and secondary efficacy endpoints based on the ITT population, a variety of 
methods will be used to impute missing data, including multiple imputation (MI), last-
observation-carried forward (LOCF), and Day 0/Baseline observation carried forward (BOCF). 
MI will be the primary imputation method. Sensitivity analyses using LOCF and BOCF will be 
performed only on the co-primary efficacy endpoints to assess the robustness of alternate 
imputation assumptions. For the continuous efficacy measure, a mixed effects model for repeated 
measures (MMRM) analysis will also be conducted as a sensitivity analysis. All supportive 
analyses using the PP population will use the Observed-Cases (OC) approach, that is there will 
be no imputation for missing data at any time point. No other imputations will be made unless 
otherwise specified. 
For all efficacy analyses, subjects will be analyzed according to the treatment group to which 
they were randomized. 
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11.5.1 
Primary Efficacy Endpoints 
The co-primary efficacy endpoints are: 
 The absolute change in the inflammatory lesion count at Week 12 compared to Day 
0/Baseline. 
 The dichotomized IGA score where treatment success is defined as a 2-step improvement 
resulting in a 0 (clear) or 1 (almost clear) score at Week 12 compared to Day 0/Baseline. 
The null hypothesis of the equality of the FMX103 1.5% and vehicle means for absolute change 
from Day 0/Baseline to Week 12 in the inflammatory lesion count and the equality of IGA 
success rates at Week 12 will each be tested at a two-sided 0.05 level of significance. Change 
from Day 0/Baseline in inflammatory lesion count will be analyzed using an analysis of 
covariance (ANCOVA), with treatment as a main effect, Day 0/Baseline inflammatory lesion 
count as a covariate, and investigational site as a blocking factor. Investigational site-by-
treatment interaction will be tested at a two-sided 0.1 level, and if significant, will be further 
explored. The dichotomized IGA will be analyzed using the Cochran-Mantel-Haenszel (CMH) 
test, stratified by investigational site. 
11.5.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
 The dichotomized IGA score where success is defined as a 2-step improvement in score at 
Week 12 compared to Day 0/Baseline. 
 The percent change in inflammatory lesion count at Week 12 compared to Day 0/Baseline. 
 The absolute change from Day 0/Baseline in the inflammatory lesion count and IGA 
treatment success at the interim visit at Week 8. 
 The absolute change from Day 0/Baseline in the inflammatory lesion count and IGA 
treatment success at the interim visit at Week 4. 
Secondary efficacy endpoints will be treated sequentially in the order listed above, at a 0.05 level 
of significance, only if the co-primary efficacy endpoints are significant. 
11.5.3 
 
 
 
 
 
 
 
 
11.6 
Safety Endpoints 
Safety endpoints will be reported on the Safety population. Subjects will be reported according 
to the treatment they actually received. Safety assessment will be based on descriptive statistics 
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and individual 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 
pre-treatment, or worsen relative to the pre-treatment 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 for each treatment group. At each level of 
summarization, a subject will be counted only once if he/she reported one or more events. The 
severity of TEAEs and relationship to study drug will be summarized in a similar manner. For 
summaries of relationship to 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. 
TEAEs, vital signs, and clinical laboratory measurements will be summarized by treatment group 
using descriptive statistics. For vital signs, change from Day 0/Baseline values will also be 
summarized. For all safety variables, subject data listings will be provided. 
Local signs and symptoms 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 10.7.2. 
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 prematurely withdraw from the study 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 
Day 0/Baseline and at each post-Day 0/Baseline time point. Changes from Day 0/Baseline will 
also be summarized. Day 0/Baseline is defined as the last non-missing value prior to the first 
dose of study drug. 
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 Day 0/Baseline with the number of subjects 
with low, normal, or high values at the Final Visit. Day 0/Baseline is defined as the last non-
missing value prior to the first dose of study drug. 
A listing of subjects with pre-treatment and 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. 
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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 immediately notify the Sponsor 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 GCP-ICH, and their 
agreement with the source data. The monitor will also verify the correct use of the study drug. At 
a 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. 
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. 
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 the IRB’s guidelines. 
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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 
Withdrawn subjects are those who do not complete all evaluations and procedures outlined in the 
protocol. Subjects who discontinue taking study drug for any reason must also be withdrawn 
from the study. 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 10.8.4. 
 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 stabilized 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/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, relocation of subject, etc. If 
a subject becomes pregnant during the study, the subject will be withdrawn from the study 
and followed through conclusion of the pregnancy. 
If a subject is withdrawn from the study following the start of study drug, all Visit 7 
(Week 12/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. 
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12.6 
Publication Policy 
The data obtained in this study are the property of the Sponsor, which will make reasonable 
efforts to assure that the results are published in a peer-reviewed journal. As some of the 
information concerning the investigational product and development activities at the Sponsor 
may be of a strictly confidential 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 (IRB) 
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/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/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 their 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/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. 
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13.4 
Subject Confidentiality 
The Sponsor ensures 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 and assent 
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 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 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. 
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In addition, a representative from the Sponsor’s Clinical Quality Assurance (CQA) Department 
may conduct periodic audits of the study processes, including, but not limited to, auditing the 
clinical site, laboratories, vendors and CROs, the clinical database, and the final study report. 
15 
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, electronic case report forms (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. 
 
 
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APPENDIX 1:  Subject Global Assessment Questionnaire 
Question:  “Considering your rosacea just before starting treatment and considering your 
condition today, indicate the change you have experienced according to the scale below”: 
 5 = Much better than prior to treatment 
 4 = Slightly better than prior to treatment 
 3 = Same as prior to treatment 
 2 = Slightly worse than prior to treatment 
 1 = Much worse than prior to treatment 
 
 
 
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APPENDIX 2:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 7 (Week 12 / Final Visit): 
 
1. How satisfied are you with this product in treating your rosacea? 
2. How satisfied are you with how easy this product is to use? 
3. How satisfied are you with this product compared to other products you have previously 
used for rosacea, such as gels and creams? 
4. How satisfied are you with how this product feels on your skin after treatment? 
5. How satisfied are you with the odor of this product after treatment? 
6. How satisfied are you with the color of this product after treatment? 
7. Overall, how satisfied are you with this product? 
8. Overall, how likely are you to recommend this product to a friend? 
 
Answers to Questions 1 through 7 will be selected from the following: 
 1 = Very Satisfied 
 2 = Satisfied 
 3 = Somewhat Satisfied 
 4 = Dissatisfied 
 5 = Very Dissatisfied 
 
The answer to Question 8 will be selected from the following: 
 1 = Very Likely 
 2 = Likely 
 3 = Somewhat Likely 
 4 = Unlikely 
 5 = Very Unlikely 
 
 
 
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