Conditions: Papulopustular Rosacea
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 504
Healthy volunteers: no

Brief summary:
The primary objective is to show that open-label extended treatment with FMX103 1.5%, for up to an additional 40 weeks, is safe and well tolerated.

Detailed description:
This is an open-label, multicenter, 40-week extension study to evaluate the long-term safety, tolerability, and efficacy of FMX103 1.5% topical foam in the treatment of moderate-to-severe facial papulopustular rosacea. Subjects entering this study will have recently participated in 1 of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy studies (FX2016-11 and FX2016-12 - NCT03142451). Subjects must demonstrate that they are eligible to continue into Study FX2016-13 based on safety evaluations and IGA score performed at Final Visit of one of the previous double-blind studies.

At the completion of the Final Visit in Study FX2016-11 or Study FX2016-12, subjects may be invited to continue into this open-label study for an additional 40 weeks of open-label treatment. A minimum of 400 subjects will be enrolled into from Studies FX2016-11 and FX2016-12. Subjects who elect to continue into this open-label study will receive supplies of active FMX103 1.5% minocycline foam.

Arms:
arm 1: FMX-103

Interventions: intervention 1: FMX103 1.5%
Intervention descriptions: intervention 1: FMX103 1.5% minocycline foam

Protocol document:
Prot_000.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
 
ClinicalTrials.gov Identifier: NCT03276936 
 
 
 
Date of Protocol: 22 June 2017 


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CLINICAL PROTOCOL 
Title Page 
Study Title: 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-13 
Product: 
FMX103 1.5% minocycline foam 
Indication Studied: 
Papulopustular Rosacea 
Study Phase: 
3 
Sponsor’s Signatory: 
GCP Statement: 
This study will be conducted in accordance with Good 
Clinical Practice. Essential documents will be archived 
according to CPMP/ICH/135/95 
Date of Protocol: 
22 June 2017 
Version of Protocol 
Version 2 (Amendment 1) 
Supercedes: 
Version 1, issued 06 March 2017 
Prepared by: 
The Write Company, LLC 
Confidentiality Statement 
This document is the property of Foamix Pharmaceuticals, Inc., and is confidential and proprietary.  The information 
contained herein is believed to be accurate and complete as of the date of preparation.  The contents may not be used, 
divulged, published or otherwise disclosed without the expressed consent of Foamix Pharmaceuticals, Inc. 
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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: 
An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate 
to Severe Facial Papulopustular Rosacea (Study FX2016-13) 
Protocol No: 
FX2016-13 
Study Centers: 
Multicenter (approximately 80 sites in the USA) 
Publication (reference): 
None 
Primary Objective: 
The primary objective is to show that open-label extended treatment 
with FMX103 1.5%, for up to an additional 40 weeks, is safe and well 
tolerated. 
Study Design and 
Methods: 
This is an open-label, multicenter, 40-week extension study to evaluate 
the long-term safety, tolerability, and efficacy of FMX103 1.5% topical 
foam in the treatment of moderate-to-severe facial papulopustular 
rosacea. Subjects entering this study will have recently participated in 1 
of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy 
studies (FX2016-11 and FX2016-12). Subjects must demonstrate that 
they are eligible to continue into Study FX2016-13 based in part on 
safety evaluations performed at Visit 5/Week 12 (Final Visit) of one of 
the previous double-blind studies. In addition, the subject’s 
Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final 
Visit) should not have worsened relative to the subject’s IGA at Day 
0/Baseline of one of the previous double-blind studies. 
At the completion of Visit 5/Week 12 (Final Visit) in Study FX2016-11 
or Study FX2016-12, subjects may be invited to continue into this 
open-label study for an additional 40 weeks of open-label treatment. A 
minimum of 400 subjects will be enrolled into from Studies FX2016-11 
and FX2016-12. Subjects who elect to continue into this open-label 
study will receive supplies of active FMX103 1.5% minocycline foam. 
Treatment during the open-label study will be guided by each subject’s 
clinical response. The Investigator may elect to suspend treatment if 
there is clinical improvement or resolution of rosacea. Even if the 
treatment is suspended temporarily, the subject will continue in the 
study and will attend all scheduled clinic visits. If at any time the 
rosacea recurs or worsens, treatment may be resumed. 
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Subjects may be discontinued from the study at any time if their disease 
becomes refractory or they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as 
Visit 5/Week 12 (Final Visit) of either Study FX2016-11 or 
Study FX2016-12. Subsequent visits for this open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and 
efficacy evaluations will be performed. Week 40 is the Final Visit 
(Visit 7) of this study. A safety follow-up telephone call will occur 4 
weeks after Final Visit (Visit 7). 
Number of Subjects 
(planned): 
The planned minimum enrollment is a minimum of 400 male and 
female subjects who were previously enrolled in Study FX2016-11 or 
Study FX2016-12. The sample size is intended to ensure that at least 
300 subjects continue to self-administer the study drug as needed for at 
least 6 months and 100 subjects continue for at least 1 year (ie, 
combined duration of treatment between the double-blind and open-
label studies). The number of subjects at each site will be determined 
by the rate of recruitment in Studies FX2016-11 and FX2016-12. No 
statistical rationale for subject number is provided. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years, who had a 
clinical diagnosis of moderate to severe facial papulopustular rosacea at 
the start of the previous double-blind study who completed 12 weeks of 
double-blind treatment in Study FX2016-11 or Study FX2016-12;  are 
willing to continue on open-label treatment with FMX103 in the current 
study and do not have a worsening of disease, determined by IGA, at 
Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment 
of the previous study. 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, self-
administered dosing as needed, for up to 40 weeks. 
Reference Therapy: 
Not applicable. 
Study Duration: 
Subject participation in the study will be up to 44 weeks.  
Endpoints and Outcomes: 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner); clinical laboratory tests; vital signs; physical examinations; 
and local signs and symptom assessments of the skin at the application 
sites (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation scores). 
Efficacy Evaluations 
The efficacy parameters will include inflammatory lesion counts and 
IGA at Baseline and at Weeks 4, 10, 16, 22, 28, 34, and 40 (Final 
Visit). 
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Statistical Methods: 
The All-Treated population, defined as all subjects who use the study 
drug at least once, will be used for all analyses. Missing data will not be 
imputed. All analyses will be based on observed data. The primary 
endpoints are the absolute change in the inflammatory lesion count 
compared to Baseline and the dichotomized IGA score, where success 
is defined as a 2-step improvement resulting in a 0 (clear) or 1 (almost 
clear) score at Week 40 compared to Baseline. The secondary endpoints 
of change from Baseline of Study FX2016-11 and Study FX2016-12 to 
each visit in inflammatory lesion count, IGA treatment success and a 
Subject Satisfaction Questionnaire administered at Visit 7 
(Week 40/Final Visit) will also be summarized.  
No statistical tests will be performed for any of the endpoints. 
The safety and tolerability safety of topical minocycline foam applied 
as needed for an additional 40 weeks will be evaluated using summary 
statistics and individual subject data listings. No statistical tests will be 
performed for any of the safety assessments. 
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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 ............................................................................................................................11 
4.1 
PRIMARY OBJECTIVE .......................................................................................................................11 
5 
INVESTIGATIONAL PLAN ..................................................................................................................11 
5.1 
OVERALL STUDY DESIGN ................................................................................................................11 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................12 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................13 
7.1 
BASELINE (ALSO VISIT 5/WEEK 12 [FINAL VISIT] OF PREVIOUS DOUBLE-BLIND STUDY) .................16 
7.2 
VISITS 1 THROUGH 6, WEEKS 4, 10, 16, 22, 28, AND 34 (±5 DAYS) ..................................................16 
7.3 
VISIT 7, WEEK 40/FINAL VISIT (±5 DAYS) OR EARLY TERMINATION ...............................................17 
7.4 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................17 
8 
STUDY TREATMENTS ..........................................................................................................................18 
8.1 
TREATMENT ADMINISTERED ............................................................................................................18 
8.1.1 
Dosing Instructions ........................................................................................................18 
8.1.2 
Manufacturer ..................................................................................................................18 
8.1.3 
Labeling of Study Drug ..................................................................................................19 
8.1.4 
Storage of Study Drug ....................................................................................................19 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................19 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................20 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................20 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................20 
8.6 
BLINDING  ........................................................................................................................................20 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................20 
8.8 
USE OF CONTRACEPTION .................................................................................................................21 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................21 
9 
EFFICACY ASSESSMENTS ..................................................................................................................22 
9.1 
PRIMARY EFFICACY ASSESSMENTS..................................................................................................22 
9.1.1 
Lesion Counts.................................................................................................................22 
9.1.2 
Investigator Global Assessment .....................................................................................22 
9.2 
SECONDARY EFFICACY ASSESSMENTS .............................................................................................22 
9.2.1 
Subject Satisfaction Questionnaire .................................................................................22 
10 
SAFETY ASSESSMENTS .......................................................................................................................23 
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10.1 
CONCOMITANT MEDICATIONS .........................................................................................................23 
10.2 
VITAL SIGNS ....................................................................................................................................23 
10.3 
PHYSICAL EXAMINATION .................................................................................................................23 
10.4 
CLINICAL LABORATORY TESTS........................................................................................................23 
10.4.1 
Urine Pregnancy Test .....................................................................................................24 
10.4.2 
Sample Collection, Storage, and Shipping .....................................................................24 
10.5 
OTHER SAFETY MEASUREMENTS .....................................................................................................24 
10.5.1 
Local Signs and Symptom Assessments ........................................................................24 
10.5.1.1 Erythema (Clinical Erythema Assessment Scale) .........................................25 
10.5.1.2 Telangiectasia ................................................................................................25 
10.5.1.3 Burning/Stinging ...........................................................................................25 
10.5.1.4 Flushing/Blushing .........................................................................................26 
10.5.1.5 Dryness/Xerosis ............................................................................................26 
10.5.1.6 Itching ...........................................................................................................26 
10.5.1.7 Peeling/Desquamation ...................................................................................26 
10.5.1.8 Hyperpigmentation ........................................................................................26 
10.6 
ADVERSE EVENTS ............................................................................................................................27 
10.6.1 
Method of Determining Adverse Events ........................................................................27 
10.6.2 
Adverse Event Definitions .............................................................................................27 
10.6.2.1 Adverse Events ..............................................................................................27 
10.6.2.2 Serious Adverse Events .................................................................................28 
10.6.2.3 Severity of Adverse Events ...........................................................................28 
10.6.2.4 Relationship of Adverse Events to Study Treatments ...................................29 
10.6.2.5 Adverse Events Expectedness .......................................................................29 
10.6.3 
Reporting Adverse Events ..............................................................................................29 
10.6.4 
Adverse Event Follow-up ...............................................................................................29 
10.6.4.1 Pregnancy Reporting .....................................................................................30 
10.6.5 
Clinically Significantly Abnormal Laboratory Results ..................................................30 
10.7 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................30 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................30 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................30 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................31 
11.3 
ANALYSIS POPULATIONS .................................................................................................................31 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND BASELINE CHARACTERISTICS .................................31 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................31 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................31 
11.5.2 
Secondary Efficacy Endpoint .........................................................................................31 
11.6 
SAFETY ENDPOINTS .........................................................................................................................32 
11.6.1 
Adverse Events ...............................................................................................................32 
11.6.2 
Local Signs and Symptoms Assessments .......................................................................32 
11.6.3 
Clinical Laboratory Results ............................................................................................33 
11.7 
INTERIM ANALYSIS ..........................................................................................................................33 
12 
STUDY MANAGEMENT .......................................................................................................................33 
12.1 
MONITORING ...................................................................................................................................33 
12.2 
PROTOCOL AMENDMENTS................................................................................................................33 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................34 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................34 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................35 
12.6 
PUBLICATION POLICY ......................................................................................................................35 
13 
ETHICS .....................................................................................................................................................35 
13.1 
CONDUCT OF THE STUDY .................................................................................................................35 
13.2 
INSTITUTIONAL REVIEW BOARDS ....................................................................................................35 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................35 
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13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................36 
13.5 
RECORDS RETENTION ......................................................................................................................36 
13.6 
FINANCING .......................................................................................................................................36 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................37 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................37 
16 
REFERENCE LIST .................................................................................................................................37 
17 
STUDY AMENDMENTS ........................................................................................................................37 
17.1 
AMENDMENT 1, EFFECTIVE JUNE 22ND, 2017 ..................................................................................38 
APPENDIX 1:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................43 
APPENDIX 2: ACKNOWLEDGMENT OF RECEIPT AND REVIEW OF PROTOCOL .........................44 
 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 ........................... 15 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 ..................................................... 18 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 ................................................................... 22 
Table 4 
Clinical Laboratory Tests – Study FX2016-13 .............................................................. 24 
 
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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 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
FV 
Final Visit 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed cases 
OTC 
Over-the-counter 
PT 
Preferred term 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
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3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and eyes. It is a syndrome of 
undetermined etiology characterized by both vascular and papulopustular components involving 
the face and occasionally the neck and upper trunk. Clinical findings are usually limited to the 
sun exposed areas of the face and chest and include mid-facial erythema, telangiectasia, papules 
and pustules, and sebaceous gland hypertrophy. Rosacea is characterized by episodic flushing of 
affected areas, which may be associated with consumption of alcohol, hot drinks, or spicy foods. 
During inflammatory episodes, affected areas of the skin, primarily the convexities of the face, 
develop swelling, papules, and pustules. 
Rosacea occurs most commonly in adult life, between the ages of 30 and 60 years. It is very 
common in the United States (US) and Europe. Ocular involvement occurs in more than 50% of 
patients. 
Mainstays of treatment for papulopustular rosacea are the oral tetracyclines: doxycycline and 
minocycline. Systemic doxycycline (Oracea®, doxycycline 40 mg capsules) is approved. Topical 
treatments for rosacea include metronidazole, azelaic acid, and brimonidine tartrate. 
Minocycline hydrochloride is an established broad-spectrum antibiotic that is used orally “off-
label” in the treatment of papulopustular rosacea. Foamix has developed a topical minocycline 
foam product that is being evaluated for the treatment of papulopustular rosacea. The study 
medication FMX103 (minocycline HCl 1.5% foam) facilitates easy application and even 
distribution of the agent, thereby improving treatment convenience. 
The efficacy and safety of FMX103 have been established in a Phase 2 study in 232 adult 
subjects with moderate to severe papulopustular rosacea (Study FX2015-10). 
The purpose of this Phase 3 open-label extension study is to evaluate the long-term safety, 
tolerability, and efficacy of topical FMX103 1.5% (minocycline foam) during a 40-week period 
of self-administered dosing as needed in subjects with moderate to severe facial papulopustular 
rosacea who have previously participated in 1 of 2 Phase 3, 12-week, double-blind, 
vehicle-controlled safety and efficacy studies: Studies FX2016-11 and FX2016-12. 
4 
STUDY OBJECTIVES 
4.1 
Primary Objective 
The primary objective is to show that open-label extended treatment with FMX103 1.5%, for up 
to an additional 40 weeks, is safe and well tolerated.  
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is an open-label, multicenter, 40-week extension study to evaluate the long-term safety, 
tolerability, and efficacy of FMX103 1.5% topical foam in the treatment of moderate to severe 
facial papulopustular rosacea. Subjects will be eligible to enter this study upon successful 
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completion of 1 of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy Phase 3 studies 
(FX2016-11 and FX2016-12) and if they meet all of the entry criteria.  
At the completion of Visit 5/Week 12 (Final Visit, or FV) in Study FX2016-11 or Study FX2016-
12, subjects who meet entry criteria will be invited to continue into this open-label study for an 
additional 40 weeks of treatment. A minimum of 400 subjects from Studies FX2016-11 and 
FX2016-12 will be enrolled into open-label Study FX2016-13. Subsequent enrollment of 
additional subjects will be considered as necessary to meet regulatory requirements. Subjects 
who elect to continue into this open-label study will receive supplies of active FMX103 1.5% 
minocycline foam. 
Treatment during the open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all facial areas if there is clinical 
improvement or resolution of the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the study and will attend all 
scheduled clinic visits. If at any time their rosacea recurs or worsens, treatment of the affected 
areas may be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as Visit 5/Week 12 (Final Visit) of 
either Study FX2016-11 or Study FX2016-12. Subsequent visits for the open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and efficacy evaluations will be 
performed. Week 40 is the Final Visit (Visit 7) of this study. 
Safety and efficacy evaluations will be performed as shown in Table 1. 
5.2
Rationale for Study Design and Dose Selection 
Chronic exposure in an open-label design is appropriate to evaluate the safety of long-term use. 
The omission of a control group is appropriate. Subjects will be selected according to pre-
defined entry criteria from 2 pivotal, Phase 3, randomized, multicenter, double-blind, vehicle-
controlled, 12-week studies. The open-label study treatment duration of 40 weeks will thus result 
in a total treatment duration of 52 weeks, adequate for chronic exposure. 
This open-label extension study is necessary to obtain safety information about the long-term use 
of FMX103 1.5% to treat facial papulopustular rosacea because of its chronic nature. The study 
design is expected to provide sufficient safety information to fulfill the International Conference 
on Harmonization (ICH) E1 guideline. 
The concentration of minocycline (1.5%) was selected according to formulation integrity and 
stability considerations and based on the results of the Phase 2 Study FX2015-10. 
6
STUDY POPULATION 
The study population will be comprised of subjects who have completed Study FX2016-11 or 
Study FX2016-12 and have agreed and are eligible to continue into this 40-week open-label 
extension study. A minimum of 400 subjects will be enrolled at approximately 80 sites in the US. 
All subjects will receive active treatment with FMX103 1.5% minocycline foam. 
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6.1
Inclusion Criteria 
Subjects will be included in the study if they meet all of the following inclusion criteria at the 
time of enrollment: 
1. Healthy male or non-pregnant females, aged ≥18 years, who had a clinical diagnosis of
moderate to severe facial papulopustular rosacea at the start of the previous double-blind
study (Study FX2016-11 or Study FX2016-12).
2. Have completed and signed an appropriately administered informed consent form (ICF)
prior to any study-related procedures.
3. Have completed 12 weeks of treatment in either Study FX2016-11 or Study FX2016-12.
4. Have not had a worsening of disease, determined by the Investigator’s Global Assessment
(IGA), at Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment in Study
FX2016-11 or Study FX2016-12.
5. Are willing to continue on open-label treatment with FMX103 as described in this
protocol.
6. If a woman of child-bearing potential, have a negative urine pregnancy test and agree to
use an effective method of contraception (Section 8.8). A sterile sexual partner is NOT
considered an adequate form of birth control.
7. If a woman of child-bearing potential is using an oral contraceptive product, she should
have been on the same product for at least 3 months and she should continue using the
same or equivalent product for the duration of the of the study.
6.2 
Exclusion Criteria 
Subjects will be excluded from enrollment in the study for any of the following reasons: 
1. Women who are pregnant, lactating, or planning to become pregnant during the study.
2. Have a new systemic disease or condition, including an ongoing AE that might interfere
with the conduct of the study or the interpretation of results.
3. Have developed a condition that would have been exclusionary for Study FX2016-11 or
Study FX2016-12, including pseudomembranous colitis, antibiotic-associated colitis,
hepatitis, liver damage, renal impairment, drug addiction, or alcohol abuse.
4. Have abnormal laboratory values at the Final Visit (Week 12) of Study FX2016-11 or
Study FX2016-12 that are considered clinically significant. Subjects are permitted to
enroll in the study whilst laboratory results for Final Visit (Week 12) for Study FX2016-11
or Study FX2016-12 are pending receipt.
5. Are unable to fully comply with the study requirements.
7
STUDY PROCEDURES 
The schedule of study assessments and procedures is presented in Table 1. If a subject withdraws 
from the study prematurely, he or she should return to the study site for an early termination 
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visit, during which all evaluations described under Visit 7/Week 40 (Final Visit) should be 
performed. 
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Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 
Assessment or Procedure 
Baselinea 
Visits 
Final 
Visitb 
Safety 
Follow-upc 
Study Visit 
(FV of 
previous 
DB Study) 
1 
2 
3 
4 
5 
6 
7 
N/A 
Study Week 
(Week since beginning of 
previous DB study) 
1 
(12) 
4 
(16) 
10 
(22) 
16 
(28) 
22 
(34) 
28 
(40) 
34 
(46) 
40 
(52) 
44 
(56) 
Informed consent 
X 
Record subject identificationd 
X 
Inclusion/exclusion criteria 
X 
Physical examination (including 
weight) 
X 
X 
Blood pressure/heart ratee 
X 
X 
X 
X 
X 
X 
X 
X 
Blood/urine samples for clinical 
laboratory tests 
X 
X 
X 
Urine pregnancy testf 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global 
Assessment 
Xg 
X 
X 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
Questionnaire 
X 
Local signs and symptom 
assessmentsh 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
X 
X 
X 
X 
Review application instructions 
X 
X 
X 
X 
X 
X 
X 
Schedule/confirm next visit or 
call (for safety follow-up only) 
X 
X 
X 
X 
X 
X 
X 
X 
DB = double-blind; FV = final visit; N/A = not applicable, no visit 
a.
Baseline for the study will be conducted at the same time as Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12. All 
assessments performed at Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12 should not be repeated but should be 
recorded as the same assessments at Baseline for this study.
b.
If a subject withdraws from the study prematurely, all evaluations described under Visit 7/Week 40 (Final Visit) should be performed.
c.
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit). 
d.
Previously assigned subject identification from Study FX2016-11 or Study FX2016-12 will be used in this study.
e.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest. 
f.
A urine pregnancy test will be done at the study site at every visit for all subjects of childbearing potential; home pregnancy tests will be 
dispensed at each visit, if needed, and will be performed at least monthly or whenever there is a suspicion of pregnancy (eg, a missed 
menstrual period). 
g.
The subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final Visit) should not have worsened relative to the subject’s
IGA at Day 0/Baseline of one of the previous double-blind studies. 
h.
The severity of each of the following local rosacea signs/symptoms will be measured:  erythema, telangiectasia, burning/stinging,
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. 
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7.1
Baseline (also Visit 5/Week 12 [Final Visit] of previous double-blind study) 
•
Obtain a signed and dated ICF.
•
Record subject identification from Study FX2016-11 or Study FX2016-12.
•
Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria
(Section 6.2).
•
Record physical examination results, including weight, from Final Visit (Section 10.3).
•
Record blood pressure and heart rate results from Final Visit (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform IGA (Section 9.1.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Review application instructions to confirm that the subject continues to use the study drug
properly.
•
Dispense 1 study drug kits (ie, 2 canisters) of FMX103 1.5%.
•
Dispense facial cleanser and moisturizer.
•
Schedule/confirm the next study visit.
7.2
Visits 1 through 6, Weeks 4, 10, 16, 22, 28, and 34 (±5 days) 
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit as needed (Section 10.4.1).
•
At Visit 3 (Week 16) only – Collect blood and urine samples for clinical laboratory tests
and send to the central laboratory (Section 10.4.2).
•
Perform IGA (Section 9.1.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
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•
Review application instructions to confirm that the subject continues to use study drug
properly.
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Dispense 2 study drug kits (ie, 4 canisters) of FMX103 1.5% if required.
•
Confirm that subject continues to use only the provided facial cleanser and moisturizer
and dispense additional quantities as required.
•
Schedule/confirm the next study visit.
7.3
Visit 7, Week 40/Final Visit (±5 days) or Early Termination 
•
Perform physical examination, including weight (Section 10.3).
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform IGA (Section 9.1.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.2).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 7/Week 40 if
required (Section 7.4).
7.4
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit). 
Follow up on adverse events and any new concomitant medications will be recorded. 
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8 
STUDY TREATMENTS 
This is an open-label study; all subjects will receive FMX103 1.5% minocycline foam. 
8.1 
Treatment Administered 
The description of study drug kits and treatment is shown in Table 2. 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 
Dosage form description: 
Foam containing minocycline HCl 1.5% 
Package description: 
2 canisters of FMX103 1.5%, each canister containing 35 g of the clinical 
trial supply foam 
Daily dose: 
As needed application of a sufficient amount of foam to cover the whole face. 
Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% active) 
of minocycline. 
Cumulative maximal dose over 
40 weeks: 
Up to approximately 2100 mg of minocycline assuming application of 0.5 g 
of FMX103 1.5% foam once daily to the face for 280 days. 
Dispensing: 
Up to 2 kits consisting of 2 canisters/kit (ie, 4 canisters total) dispensed at 
Baseline and Visits 1-6 (Weeks 4-34). Up to a total of 14 kits (28 canisters) 
dispensed to the subject for the study.   
8.1.1
Dosing Instructions 
At enrollment, subjects will receive supplies of active FMX103 1.5% minocycline foam. 
Up to 2 study drug kits consisting of 2 canisters/kit (ie, 4 canisters total of investigational drug) 
will be dispensed at Baseline and Visits 1 through 6 (Weeks 4 through 34). Subjects will be 
instructed to express a small amount of study drug from the canister onto the finger tips and then 
apply as a thin layer over the whole face. Additional drug may be used as needed to assure the 
entire face is treated. Sufficient product will be dispensed at each visit to allow continuation of 
treatment as required. 
Study drug should be applied at approximately the same time each day, about 1 hour before 
bedtime. 
Treatment during this open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment if there is clinical improvement or resolution of 
rosacea. Even if treatment is suspended temporarily, the subject will continue in the study and 
will attend all scheduled clinic visits. If at any time the rosacea recurs or worsens, treatment may 
be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
8.1.2
Manufacturer 
The manufacturer of the investigational product is
 
 
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8.1.3
Labeling of Study Drug 
The Sponsor or designee will label study drug supplies according to the requirements of the 
Code of Federal Regulations (21CFR§ 210, Subpart G-Packaging & Labeling Control). 
The labels of the investigational (test) product will contain appropriate information as required 
by regional regulatory authorities and include, as needed, the following information: 
•
Name and address of the Sponsor
•
Protocol number
•
Product name/dosage form/mode of administration
•
Kit Number/Canister Number
•
Site number/Subject number
•
Name and address of manufacturer
•
Date of manufacture
•
Lot/batch number
•
Canister contents
•
Storage conditions
•
Caution statements, as follow:
o
“New Drug – Limited by Federal Law to Investigational Use”
o
“Flammable”
o
“Shake well before use”
o
“Keep out of the reach of children”
The composition, pharmaceutical quality, batch number, and expiration date of the 
investigational (test) product will be traceable via the kit number. 
8.1.4
Storage of Study Drug 
FMX103 1.5% canisters must be stored at 2°C – 8°C until being dispensed to the subject. 
Subsequently, the canisters must be stored at 20°C – 25°C (refer to USP Controlled Room 
Temperature). The Investigator will be responsible for the suitable storage of the investigational 
product in compliance with the storage instructions and must restrict access to the study 
personnel only. 
8.2
Study Drug Accountability 
The Investigator will have overall responsibility for the study drug. The Investigator or designee 
will verify the contents of the drug shipment and confirm receipt of the study drug in the 
Interactive Response Technology (IRT) system. In addition, an accurate study drug dispensing 
record that specifies the date and amount dispensed to each subject must be kept. This inventory 
record must be available for inspection by representatives of the Sponsor and is subject to 
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If a subject is taking anticoagulant therapy, he or she should be advised that a downward 
adjustment of their anticoagulant dose may be required. 
See the FMX103 investigator’s brochure (IB) for information about tetracyclines and possible 
drug-drug interactions. 
8.8
Use of Contraception 
Tetracycline-class antibiotics can cause fetal harm when administered to a pregnant woman. 
Tetracycline-class antibiotics used during tooth development (last half of pregnancy, infancy, and 
childhood to the age of 8 years) may cause permanent discoloration of teeth (yellow-gray-
brown). 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. Females of childbearing potential include any female who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation/occlusion, or bilateral oophorectomy) or who is not postmenopausal (defined as 
amenorrhea >12 consecutive months). Females of childbearing potential must have a negative 
urine pregnancy test and, if they are sexually active or become sexually active during the study, 
must use an effective method of birth control such as those in the follow list during the course of 
the study. The following is not an all-inclusive list; the subject must discuss with the Investigator 
the most appropriate form of birth control: 
•
Hormonal methods
o
Oral contraceptives – (Oral antibiotics may lessen the effectiveness of oral
contraceptives. Therefore, a second form of birth control must be utilized in
subjects using oral contraceptives.)
o
Implant
o
Injection
o
Transdermal patch
o
Intravaginal ring
•
Intrauterine device (hormonal or non-hormonal)
•
Barrier methods
o
Condom (male or female) with spermicide
o
Diaphragm with spermicide
•
Complete abstinence
8.9
Treatment Compliance 
Each subject is to be instructed on the importance of following the dosing schedule and returning 
all study drug kits (empty/used/unused) at the appropriate visits. The study site personnel will 
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question each subject on study drug use since the last visit. A subject who deviates significantly 
from the prescribed dosage will be counseled. 
9
EFFICACY ASSESSMENTS 
Every attempt must be made to ensure the same evaluator performs the efficacy evaluations for a 
particular subject throughout the study; when this is not possible, another approved evaluator 
may perform the evaluations. Following are the methods and scales that will be used to measure 
each of the efficacy parameters to be performed. 
9.1
Primary Efficacy Assessments 
The efficacy assessments will include the inflammatory lesion counts and the IGA of severity of 
disease and will be performed by the Investigator/evaluator. 
9.1.1
Lesion Counts 
The number of papules, pustules, and nodules will be counted and the numbers recorded. Facial 
area lesion counts will be made for the forehead, left and right cheeks, nose, and chin. The lesion 
counts performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will 
constitute the Baseline value for this study. Lesion counts will be repeated at Visit 1 (Week 4), 
Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), 
and Visit 7 (Week 40/Final Visit). 
9.1.2
Investigator Global Assessment 
The Investigator will also assess the global severity of rosacea using the IGA scale as described 
in Table 3. The IGA performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) will constitute the Baseline value for this study. Assessment will be repeated 
at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), 
Visit 6 (Week 34), and Visit 7 (Week 40/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 
Score 
Grade 
Description 
0 
Clear 
No inflammatory papules or pustules 
1 
Almost clear 
Few inflammatory papules or pustules 
2 
Mild 
Several inflammatory papules or pustules 
3 
Moderate 
Moderate number of inflammatory papules or pustules and no nodules 
4 
Severe 
Many inflammatory papules or pustules, and up to 2 nodules 
9.2
Secondary Efficacy Assessments 
9.2.1
Subject Satisfaction Questionnaire 
A Subject Satisfaction Questionnaire (Appendix 1) will be administered at Visit 7 
(Week 40/Final Visit). 
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10
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
the monitoring of AEs (volunteered, observed, and elicited by general questioning in a non-
suggestive manner), clinical laboratory tests, vital signs, physical examinations, and local signs 
and symptom assessments (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) 
scores. 
10.1
Concomitant Medications 
All medications that the subject is currently taking or any change in medication or dosage since 
the last visit will be documented throughout the study. The reason for use or change of dose of a 
concomitant therapy may need to be reported as an AE. 
10.2
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all visits. All BP measurements will be 
made using a sphygmomanometer with an appropriate cuff size for the individual subject. 
Measurements will be taken while the subject is seated after at least 5 minutes at rest. 
10.3
Physical Examination 
A complete physical examination (excluding the genitourinary examination), including body 
weight, will be performed at Baseline (ie, Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) and at Visit 7 (Week 40/Final Visit). 
10.4
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at Baseline (ie, Visit 5/Week 12 
[Final Visit] in Study FX2016-11 or Study FX2016-12) and at Visit 3 (Week 16) and Visit 7 
(Week 40/Final Visit). All clinical laboratory tests will be analyzed by a central laboratory. 
Table 4 presents the specific clinical laboratory tests to be evaluated. 
Please refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples. 
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Table 4 
Clinical Laboratory Tests – Study FX2016-13 
Hematology 
Urinalysis 
Serum chemistry 
Hematocrit 
Hemoglobin 
Platelet count 
Red blood cell (RBC) 
count 
White blood cell (WBC) 
count with differential 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes esterase 
pH 
Protein 
Specific gravity 
Urine pregnancy test performed at the site 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase 
Aspartic acid transaminase (AST) 
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Creatinine kinase 
Gamma glutamyl transferase (GGT) 
Globulin 
Glucose 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (if elevated obtain 
direct bilirubin) 
Total protein 
Uric acid 
10.4.1
Urine Pregnancy Test 
A urine pregnancy test will be performed at the study site on all females of childbearing potential 
at all study visits and when a subject withdraws from the study prematurely. In addition, home 
pregnancy tests will be dispensed at each study visit to all female subjects of a childbearing 
potential and will be performed at least monthly and whenever there is a suspicion of pregnancy 
(eg, a missed or late menstrual period). 
10.4.2
Sample Collection, Storage, and Shipping 
Sample collection kits, requisition slips, and shipping boxes will be supplied by the central 
laboratory. Sample collection procedures and shipping instructions will be detailed in the 
laboratory manual. Study sites must be equipped to store the samples according to the laboratory 
manual procedures before shipping to the central laboratory. 
10.5
Other Safety Measurements 
10.5.1
Local Signs and Symptom Assessments 
Local signs and symptom assessments of the skin at the application sites measured at 
Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will constitute Baseline 
values for this study.  Assessments will be repeated at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 
(Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), and Visit 7 (Week 40/Final 
Visit). The following local signs and symptoms will be measured:  erythema, telangiectasia, 
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burning/stinging, flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation. The score for signs will be determined by the Investigator and must represent 
the subject’s condition at the time of the evaluation; the score for symptoms (ie, burning/stinging, 
flushing/blushing) should be scored based on the subject’s symptoms reported for the previous 
3 days. 
These signs/symptoms should not be included as AEs, unless a sign/symptom is believed to have 
been related to the study drug or is the reason for discontinuation from the study. 
10.5.1.1
Erythema (Clinical Erythema Assessment Scale) 
Erythema of the face will be graded according to the following scale: 
•
0 = clear skin/no signs of erythema
•
1 = almost clear of erythema, slight redness
•
2 = mild erythema, definite redness
•
3 = moderate erythema, marked redness
•
4 = severe erythema, fiery redness
10.5.1.2 
Telangiectasia 
The severity of facial telangiectasia will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  scattered telangiectasia
•
2 = Moderate:  numerous telangiectasia
•
3 = Severe:  dense telangiectasia forming sprays of vessels
10.5.1.3 
Burning/Stinging 
The severity of facial burning/stinging will be graded according to the following scale: 
•
0 = None:  no warm or burning sensation
•
1 = Mild:  slight warm tingling/stinging sensation; not really bothersome
•
2 = Moderate:  constant or intermittent warm tingling/stinging sensation that is somewhat
bothersome
•
3 = Severe:  bothersome warm to hot tingling/stinging sensation
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10.5.1.4 
Flushing/Blushing 
The severity of facial flushing/blushing will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic episodes lasting for a few moments to several minutes
•
2 = Moderate:  intermittent episodes lasting for greater than 30 minutes
•
3 = Severe:  almost constant episodes lasting for several hours
10.5.1.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
•
0 = None
•
1 = Mild
•
2 = Moderate
•
3 = Severe
10.5.1.6 
Itching 
The severity of facial itching will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic itching lasting for a few moments to several minutes
•
2 = Moderate:  intermittent itching lasting for greater than 30 minutes
•
3 = Severe:  almost constant, intense itching lasting for several hours
10.5.1.7 
Peeling/Desquamation 
The severity of facial peeling/desquamation will be graded according to the following scale: 
•
0 = No peeling
•
1 = Mild:  small, scattered areas of scaling/flaking
•
2 = Moderate:  larger, contiguous areas of scaling/flaking
•
3 = Severe:  pronounced flaking/shedding scales covering entire application area
10.5.1.8 
Hyperpigmentation 
The severity of facial skin hyperpigmentation will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  few scattered, small areas of light hyperpigmentation
•
2 = Moderate:  larger or more intense areas of hyperpigmentation
•
3 = Severe:  intense, extensive hyperpigmentation
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10.6
Adverse Events 
10.6.1
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator. Adverse events will be recorded at each visit on the appropriate case report 
form (CRF). Every attempt should be made to describe the AE in terms of a diagnosis. If a clear 
diagnosis has been made, individual signs and symptoms will not be recorded unless they 
represent atypical or extreme manifestations of the diagnosis, in which case they should be 
reported as separate events. If a clear diagnosis cannot be established, each sign and symptom 
must be recorded separately. 
Subjects should be asked whether, since the time of the last observation or visit, they had any of 
the following: 
•
Experienced any changes in well-being
•
Used any new medications
•
Changed medication regimens (both prescription and OTC)
•
Were admitted to a hospital or had any accidents
•
Developed unusual headaches or changes in vision
With exception to the above, all questions should be of a general nature and should not suggest 
symptoms. 
When an AE is suspected, all relevant evaluations will be performed and appropriate treatment 
provided. Additional follow-up will be done as necessary (Section 10.6.4) and recorded in the 
subject’s source documents, and the results will be provided to the Sponsor. 
For AE definitions and reporting requirements, refer to Section 10.6.2 and Section 10.6.3, 
respectively. 
10.6.2
Adverse Event Definitions 
10.6.2.1
Adverse Events 
An AE is any unfavorable or unintended sign, symptom, or disease that appears or worsens in a 
subject after the subject signs the ICF for a clinical study. 
Examples of what may be considered an AE include any of the following: 
•
A new illness.
•
An exacerbation of a sign or symptom of an underlying condition or of a concomitant
illness unrelated to participation in the clinical study or an effect of the study drug or
comparator drug.
No causal relationship with the study drug is implied by the use of the term “adverse event.” An 
exacerbation of a pre-existing condition/illness is defined as a more frequent occurrence or as an 
increase in the severity of the pre-existing condition/illness during the study. Planned or elective 
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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. 
10.6.2.2
Serious Adverse Events 
A serious adverse event (SAE) is any AE that: 
•
Results in death.
•
Is life-threatening.
(Note:  The term “life-threatening” refers to any AE that, as it occurs, puts the subject at
immediate risk of death. It does not refer to an AE that hypothetically might have caused
death if it were more severe.)
•
Results in hospitalization or prolongation of current hospitalization (not including
hospitalization for a pre-existing condition that has not increased in severity or frequency
from the subject’s underlying medical condition prior to entry into the study).
•
Results in persistent or significant disability/incapacity.
•
Is a congenital anomaly/birth defect in the offspring of a subject.
•
Is another serious (important medical events) event.
(Note:  Important medical events may not be immediately life-threatening or result in
death or hospitalization but may be considered serious when, based upon appropriate
medical judgment, they may jeopardize the subject or require medical or surgical
intervention to prevent one of the outcomes listed above. Examples of such medical
events include allergic bronchospasm requiring intensive treatment in an emergency room
or at home; blood dyscrasias or convulsions that do not result in inpatient hospitalization;
or development of drug dependency or drug abuse.)
SAEs will be reported by the Sponsor to the regulatory authorities as required. 
10.6.2.3
Severity of Adverse Events 
The severity of an AE refers to the extent to which it affects the subject’s daily activities and 
differs from “serious”, which is a regulatory classification. Severity will be categorized 
according to the following criteria: 
•
Mild:  The symptom has a negligible effect or no impairing effect on the subject’s normal
function.
•
Moderate:  The symptom impairs the subject’s normal function to some extent.
•
Severe:  The symptom has an obvious, significantly impairing effect on the subject’s
normal function.
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10.6.2.4
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to the study drug and will be categorized according 
to the following criteria: 
•
Unlikely:  There is no medical evidence to suggest that the AE may be related to study
drug usage, or there is another more probable medical explanation.
•
Possible:  There is medical evidence to suggest that there is a reasonable possibility that
the AE may be related to study drug usage. However, other medical explanations cannot
be excluded as a possible cause.
•
Probable:  There is strong medical evidence to suggest that the AE is related to study
drug usage.
10.6.2.5
Adverse Events Expectedness 
Expected AEs are defined as those described in the FMX103 IB. If an event increases in intensity 
or severity from that described in the IB, it will be considered unexpected. 
10.6.3
Reporting Adverse Events 
Adverse events that occur from the time of informed consent completion of the last study visit 
should be reported. Any AE that the Investigator becomes aware of that occurs within 30 days of 
study completion or withdrawal should also be reported. 
Any SAEs occurring in a subject receiving study drug must be reported to the Sponsor within 
24 hours of the site being informed of the event, even if the event does not appear to be drug 
related. The report must be done by faxing the completed SAE Report Form to the Sponsor. Any 
pertinent follow-up information should be provided in a similar manner. Contact information is 
provided below: 
Foamix Pharmaceuticals Inc./Premier Research 
Pharmacovigilance 
Phone:  +1 215-282-5434 
Fax:  +1 215-972-8765 
Email:  globalPv-US@premier-research.com 
10.6.4
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until they resolve or the subject stabilizes (in the opinion of the Investigator), or for 30 
days, whichever is shorter. Investigators and the Sponsor will decide if longer follow-up is 
appropriate on a case-by-case basis. Subjects who experience any clinically significant AE will 
remain under medical supervision until the Investigator or the Sponsor’s medical monitor deems 
the AE to be resolved, the subject is stable, or the event is no longer serious enough to warrant 
follow-up. 
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Laboratory values that are abnormal and not assessed as AEs may be followed at the discretion 
of the Investigator or the Sponsor’s medical monitor until they resolve or the subject is stable. 
10.6.4.1
Pregnancy Reporting 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. The ICF that the subject signs must document this discussion. 
If a subject or an Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of site pregnancy testing are 
available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
Urine pregnancy tests will be performed on all females of childbearing potential as described in 
Section 10.4.1. 
During the study, all female subjects of childbearing potential should be instructed to contact the 
Investigator immediately if they suspect they might be pregnant (eg, positive home pregnancy 
test [Section 10.4.1], missed or late menstrual period, etc.). If a subject or Investigator suspects 
that the subject may be pregnant at any time before or during the study, the study drug must be 
withheld until the results of site pregnancy testing are available. The Sponsor and site monitor 
must be notified and relevant information collected on the appropriate form. If pregnancy is 
confirmed, the subject must be withdrawn from the study and the Sponsor and site monitor 
notified. Additional relevant information about the confirmed pregnancy will be recorded on the 
appropriate form(s); pregnancy will not be captured as an AE. 
The subject should be followed until the outcome of the pregnancy is known. 
10.6.5
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be flagged when 
reported to the site. The Investigator will determine which out-of-range laboratory test results 
should be characterized as clinically significant and annotate the laboratory report. If a clinically 
significant laboratory abnormality requires treatment or is the reason for a subject being 
discontinued from the study, the abnormal result must also be classified as an AE. 
10.7
Appropriateness of Safety Measurement 
The safety assessments to be used in this study are standard safety measures in clinical trials. 
11
STATISTICAL DESIGN AND ANALYSIS 
11.1
Statistical Analysis Plan 
A detailed statistical analysis plan will be finalized prior to database lock. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated; however, the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
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descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. 
11.2
Determination of Sample Size 
The planned minimum enrollment is 400 male and female subjects who were previously enrolled 
in Study FX2016-11 or Study FX2016-12. The sample size is intended to ensure that at least 300 
subjects continue to self-administer the study drug as needed for at least 6 months and 100 
subjects continue for at least 1 year (ie, combined duration of treatment between the double-blind 
and open-label studies). The number of subjects at each site will be determined by the rate of 
recruitment in Studies FX2016-11 and FX2016-12. No statistical rationale for subject number is 
provided. 
11.3
Analysis Populations 
The following populations are defined for analysis: 
•
The All-Treated population:  all subjects who use study drug at least once. This population
will be used for safety and efficacy analyses.
11.4
Subject Accounting, Demographics, and Baseline Characteristics 
Demographics, baseline characteristics, medical and surgical history (FX2016-11 and 
FX2016-12) and prior and concomitant medications will be summarized. Study completion 
status and reasons for discontinuation will also be displayed. 
11.5
Efficacy Endpoints 
11.5.1
Primary Efficacy Endpoints 
The primary efficacy endpoints are: 
•
The absolute change in the inflammatory lesion count at Week 40 compared to Baseline.
•
The dichotomized IGA score where success is defined as a 2-step improvement resulting
in a 0 (clear) or 1 (almost clear) score at Week 40 compared to Baseline.
For the efficacy analyses, Baseline will be defined as Day 0/Baseline of the initial double-blind 
study, ie either Study FX2016-11 or Study FX2016-12. The changes from Baseline of Studies 
FX2016-11 and FX2016-12 to Week 40 of this study for each of the primary endpoints will be 
calculated. Descriptive statistics (number of subjects, mean, median, standard error, coefficient 
of variation, minimum and maximum) for each variable will be presented for each visit and for 
the changes from Baseline. No hypothesis testing will be performed. 
11.5.2
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
•
The absolute change from Day 0/Baseline in the inflammatory lesion count at Weeks 4,
10, 16, 22, 28 and 34.
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•
The dichotomized IGA score where success is defined as a 2-step improvement resulting
in a 0 (clear) or 1 (almost clear) score at Weeks 4, 10, 16, 22, 28 and 34 compared to Day
0/Baseline.
•
The percent change in inflammatory lesion count at Weeks 4, 10, 16, 22, 28 and 34
compared to Day 0/Baseline.
•
The Subject Satisfaction Questionnaire administered at Visit 7 (Week 40/Final Visit).
11.6
Safety Endpoints 
Safety endpoints will be reported on the All Treated population. Safety assessments will be 
summarized in tables using descriptive statistics and in individual by-subject listings. No 
statistical tests will be performed for any of the safety assessments. For the safety analyses, 
Baseline will be defined as Day 0/Baseline of the initial double-blind study, ie either Study 
FX2016-11 or Study FX2016-12. 
Treatment-emergent AEs (TEAEs) will be defined as events that emerge having been absent 
prior to enrollment in this study or worsen relative to the pre-enrollment state. Summaries of AEs 
will be limited to TEAEs. The number and percentage of subjects reporting events under each 
System Organ Class (SOC) and preferred term (PT) will be summarized. At each level of 
summarization, a subject will be counted only once if he or she reported one or more events. The 
severity of TEAEs and relationship to the study drug will be summarized in a similar manner. 
For summaries of relationship to the study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE severity, a subject will be classified according to 
the highest severity. All TEAEs continuing, but not worsening, after enrollment in this study will 
also be tabulated. 
Treatment-emergent AEs, vital signs, physical examination assessments and clinical laboratory 
measurements will be summarized using descriptive statistics. For vital signs, change from 
Baseline values will also be summarized. For all safety variables, subject data listings will be 
provided. 
11.6.1
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to SOC and PT. 
Summaries of SAEs and subjects who withdraw from the study prematurely due to AEs will be 
presented. 
11.6.2
Local Signs and Symptoms Assessments 
Local signs and symptom assessments will include active assessments of erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, itching, 
peeling/desquamation, and hyperpigmentation using the scales described under Section 10.5.1. 
Local signs and symptom assessments will be summarized using descriptive statistics at Baseline 
and at each post-Baseline time point. Changes from Baseline will also be summarized. 
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11.6.3
Clinical Laboratory Results 
Shift tables for each clinical laboratory test will cross-tabulate the number of subjects with values 
below the laboratory reference range (low), values within the laboratory reference range 
(normal), or above the laboratory range (high) at Baseline with the number of subjects with low, 
normal, or high values at the Final Visit.  
A listing of subjects with treatment-emergent clinically significant abnormal laboratory values 
will be presented for each treatment group. Clinical significance is based on the Investigator’s 
judgment. 
11.7
Interim Analysis 
No interim analysis is planned. 
12
STUDY MANAGEMENT 
12.1
Monitoring 
The Investigator will be responsible for preparing and maintaining adequate and accurate source 
documents (medical records, raw data collection forms, etc.) designed to record all observations 
and other pertinent data for each subject treated with the study drug. The Investigator will allow 
representatives of the Sponsor, contract designees, authorized regulatory authority inspectors, 
and the institutional review board (IRB) to have direct access to all documents pertaining to the 
study. The Investigator is to notify the Sponsor immediately of any regulatory authority 
inspections. The Investigator will be informed about the outcome of any Sponsor audit. 
This study will be monitored regularly, by or under supervision of a monitor from the Sponsor. 
The frequency of monitoring visits will be agreed upon by the Sponsor’s representative and the 
study site. 
Monitoring visits will take place on a regular basis according to the enrollment rate and number 
of subjects enrolled at each investigational site. During these visits, the monitor will check the 
completion of the CRF entries, compliance with the study protocol and with Good Clinical 
Practice (GCP)-ICH, and their agreement with the source data. The monitor will also verify the 
correct use of the study drug. At the final visit, the monitor will check all remaining material, 
including the remaining quantities of the study drug, and will organize their return to the Sponsor 
or designee. At each visit, the Investigator and staff will be expected to cooperate with the 
Sponsor’s representative(s) for the purposes of review and verification of protocol compliance, 
AE reporting, CRFs, source documents, clinical supplies and inventory records, and any 
additional records as may have been previously arranged between the Investigator and the 
Sponsor’s representative(s). 
The Investigator and/or other designated study personnel are expected to contact the Sponsor’s 
clinical research associate, as needed, regarding study concerns and/or questions. Contact 
information is provided in the Study Reference Manual for the site. 
12.2
Protocol Amendments 
The Sponsor may propose to amend this protocol at any time. 
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No change to the protocol will be implemented until the Sponsor and the IRB have reviewed and 
approved the amendment. 
12.3
Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the IRB-approved protocol 
(intentional or unintentional). All deviations are to be documented at the site and reported to the 
IRB according to their guidelines. 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety. All such procedures must have written documentation and be 
promptly reported to the Sponsor and IRB. 
12.4
Withdrawal of Subjects 
Subjects or Investigators may choose to discontinue a subject’s participation in the study at any 
time. Subjects may be withdrawn from the study because of any of the following: 
•
Adverse Event:  An AE that in the opinion of the Investigator or Sponsor suggests that 
continued participation in the study is not in the subject’s best interest for safety reasons. 
All AEs that are present when the subject withdraws from the study will be followed as 
described in Section 10.6.4.
•
Abnormal Laboratory Result:  Any clinically significant laboratory abnormality that 
requires withdrawal of the subject from the study should be considered an AE leading to 
withdrawal. If possible, laboratory tests will be repeated for any results that were 
clinically significantly abnormal until the abnormality is resolved or the subject is stable 
to the satisfaction of the Investigator in consultation with the medical monitor.
•
Lost to Follow-up:  Confirmed at minimum by two phone calls and a traceable letter 
without answer.
•
Subject Request:  Subject requests, for any reason (eg, AE), to be withdrawn or 
withdraws his or her consent.
•
Protocol Deviation:  A subject may be withdrawn from the study at the discretion of the 
Investigator or Sponsor due to poor compliance with protocol requirements that may 
compromise the study results or subject safety.
•
Other:  Other reasons include but are not limited to Investigator decision that it is in the 
subject’s best interest to be withdrawn, administrative reasons, subject’s relocation, etc. If 
a subject becomes pregnant during the study, she will be withdrawn from the study and 
followed through conclusion of the pregnancy (Section 10.6.4.1). 
If a subject is withdrawn from the study following the start of study drug, all Visit 7 
(Week 40/Final Visit) assessments should be completed. Subjects withdrawn from the study will 
not be replaced. 
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12.5
Termination of the Study 
The study may be terminated at any time at the request of the Sponsor or a regulatory authority, 
with proper and timely notification of all parties concerned. The IRB will be informed promptly 
and the Sponsor or the Investigator will supply reason(s) for the termination or suspension, as 
specified by the applicable regulatory requirements. Otherwise, the study is considered 
terminated upon completion of all subject treatments and evaluations. 
12.6
Publication Policy 
The data obtained in this study are the property of the Sponsor, who will make reasonable efforts 
to assure that the results are published in a peer-reviewed journal. Since some of the information 
concerning the investigational product and development activities at the Sponsor may be strictly 
confidential in nature, any manuscript or other presentation of data must first be reviewed by the 
Sponsor before its submission. 
13
ETHICS 
13.1
Conduct of the Study 
This study will be conducted in accordance with the ICH Harmonized Tripartite Guideline for 
GCP, 1997; the US Title 21 CFR parts 50, 56, and 312; and the ethical principles that have their 
origin in the Declaration of Helsinki. The study will not begin until all of the requirements of the 
appropriate regulatory authorities have been fulfilled. 
13.2
Institutional Review Boards 
This protocol (and any changes), all consent forms, and subject consent procedures must be 
reviewed and approved by a properly constituted IRB. The information presented to the IRB at 
the time initial approval is sought must include any plans for subject recruitment that involve 
advertising or other direct contact with potential subjects outside of the physician-subject 
relationship. A letter of approval issued by the IRB must be sent to the Sponsor prior to initiation 
of the study. Any changes made to the protocol must be approved by the IRB prior to 
implementation, except where needed to eliminate a potential imminent safety hazard to the 
subjects. In this case, immediate implementation may take place followed by IRB approval. 
Review and approval by the IRB for continuation of the study must take place at least once a 
year. 
13.3
Written Informed Consent 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential benefits and risks of participation to each 
subject prior to his or her entry into the study (ie, before examinations and procedures associated 
with selection for the study are initiated). Each subject will have ample opportunity to ask 
questions and will be informed about the right to withdraw from the study at any time without 
any disadvantage and without having to provide reasons for this decision. 
Following this informative discussion, the subject will be asked if he or she is willing to sign a 
statement of informed consent. Only subjects who voluntarily sign the ICF may enter the study. 
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The ICF must be reviewed and approved by the Sponsor and the IRB prior to use. 
The original signed ICF will remain in the Investigator’s files. The Investigator or designee will 
indicate in each subject’s source documents that he or she has informed the subject about the 
study and its procedures, the subject has signed and dated the ICF, and the subject has been given 
a copy of the documents. The Investigator or designee will inform subjects of any new 
information that may be relevant to the subject’s willingness to continue in the study. 
13.4
Subject Confidentiality 
The Sponsor will ensure that the following have permission to review all study-related 
documents:  monitor, auditor, IRB, and regulatory authorities. The subject’s identity and 
study-related records will remain confidential throughout the duration of the study data 
collection and reporting process. 
The investigative site assigns a unique subject identification code to each potential study subject. 
The identification code protects the subject’s identity and is used in lieu of the subject’s name 
when reporting subject data. The data will always maintain the confidentiality of the subject. 
The Investigator or designee will review the subject data, which will be referenced using the 
subject identifier. At the conclusion of the study, the data obtained may be presented to regional 
regulatory authorities but the subject’s identity will not be revealed. In addition, if any clinical 
data obtained from the study is published in scientific journals or presented at scientific meetings 
the subject’s identity will not be revealed. 
13.5
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, source 
documentation corresponding to all information contained in the CRFs, signed ICF forms, 
relevant correspondence, and all other supporting documentation) until at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years after the formal 
discontinuation of clinical development of the investigational product. These documents should 
be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted. Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same time period. Custody of the records may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies. Written notice of 
transfer must be submitted to the Sponsor. The Investigator must contact the Sponsor prior to 
disposing of any study records. 
13.6
Financing 
Funding for this study will be agreed upon between the Investigator and the Sponsor and will be 
confirmed in writing before the study starts. 
Completion of Financial Disclosure Forms will be required before the study starts. Any additions 
to the primary site personnel will necessitate the completion of new Financial Disclosure Forms. 
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This information will also be collected at site closure and 1 year after the completion of the 
study. 
14
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and the Investigator will take all steps possible to ensure the accuracy, consistency, 
completeness, and reliability of the data, including participating in an Investigator meeting 
and/or site initiation visit, routine site monitoring, review of CRFs against source documents, and 
quality control checks. 
In addition, a representative from the Sponsor’s Clinical Quality Assurance Department may 
conduct periodic audits of the study processes, including, but not limited to, auditing the clinical 
site, laboratories, vendors and contract research organizations CROs, the clinical database, and 
the final study report. 
15
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, eCRFs developed through a validated, Electronic 
Records/Electronic Signatures-compliant platform (US Title 21 CFR Part 11). Foamix Clinical 
Data Management department or designee will create the eCRFs and corresponding clinical 
database based on the final protocol. 
All site personnel who will be using this system will receive formal training on the system, after 
which each person will be issued a unique username and password. Only the person who owns 
the username and password will enter the system using that username and password. For data 
security reasons and to be in compliance with regulatory guidelines, usernames and passwords 
are not transferable. 
The Investigator is responsible for all data entered via the remote data capture (RDC) system 
eCRFs and must confirm the accuracy of the data by electronically approving (signing) the 
eCRFs. This responsibility includes the timely completion and accuracy of the data entered into 
the eCRFs by their site personnel as well as the review and approval of some data entered 
directly into the database (eg, clinical laboratory results) by an external vendor. The Sponsor will 
review the database to identify data errors or inconsistencies, which will be posted in the RDC 
system as queries for resolution. In addition, the Sponsor may make obvious corrections to the 
data in the database (eg, obvious errors in dates) and so inform the Investigator without issuing a 
query to the site. 
16
REFERENCE LIST 
Not applicable. 
17
STUDY AMENDMENTS 
This section describes the amendment(s) that have been made to the protocol for Study 
FX2016-13. 
Section 17.1 describes the changes made to Protocol FX2016-13 Version 1 issued March 6th, 
2017, via Amendment 1 effective June 22nd, 2017. 
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17.1 
Amendment 1, effective June 22nd, 2017 
The following is the summary of the changes that were made to Protocol FX2016-11 Version 1 
issued March 6th, 2017. 
Content changes:  
New or changed text is bolded. 
Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Section 2 Study 
Administrative 
Structure 
Premier Research 
Removal of 
study team 
member due to 
retirement.  
Synopsis 
(Statistical 
Methods) 
Change from baseline of 
Study FX2016-11 and 
Study FX2016-12 to each 
visit from inflammatory 
lesion count and IGA 
will also be summarized. 
The secondary endpoint 
is the Subject 
Satisfaction 
Questionnaire 
administered at Visit 7 
(Week 40/Final Visit). 
The secondary endpoints of 
change from Baseline of 
Study FX2016-11 and 
Study FX2016-12 to each 
visit  in inflammatory 
lesion count, IGA 
treatment success and a 
Subject Satisfaction 
Questionnaire administered 
at Visit 7 
(Week 40/Final Visit) will 
also be summarized. 
Clarification of 
study secondary 
efficacy 
endpoints and 
their statistical 
treatment. 
Section 6.3 
Exclusion 
Criteria 4 
None. 
Subjects are permitted to 
enroll in the study whilst 
laboratory results for 
Final Visit (Week 12) for 
Study FX2016-11 or 
Study FX2016-12 are 
pending receipt. 
Clarification of 
subject study 
qualification 
status while 
laboratory 
results are 
pending receipt. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Table 1 Schedule 
of Study 
Assessments and 
Procedures – 
Study FX2016-
13, Footnote f 
A urine pregnancy test 
will be done at the study 
site at every visit for all 
subjects of childbearing 
potential; home 
pregnancy tests will be 
dispensed at each visit 
and will be performed at 
least monthly or 
whenever there is a 
suspicion of pregnancy 
(eg, a missed period). 
A urine pregnancy test will 
be done at the study site at 
every visit for all subjects 
of childbearing potential; 
home pregnancy tests will 
be dispensed at each visit, 
if needed, and will be 
performed at least monthly 
or whenever there is a 
suspicion of pregnancy (eg, 
a missed menstrual 
period). 
Home pregnancy 
tests will be 
dispensed as 
needed and not 
necessarily at 
every visit. 
Section 7.1 
Baseline (also 
Visit 5/Week 12 
[Final Visit] of 
previous double-
blind study) 
Have the subject 
complete the Subject 
Global Assessment 
(Section 9.2.1). 
Have the subject 
complete the Subject 
Satisfaction 
Questionnaire (Section 
9.2.2). 
Text removed. 
Typographical 
error. 
Section 7.2 
Visits 1 through 
6, Weeks 4, 10, 
16, 22, 28, and 
34 (±5 days) 
…and dispense a home 
pregnancy test kit 
(Section 10.4.1). 
…and dispense a home 
pregnancy test kit as 
needed (Section 10.4.1). 
Home pregnancy 
tests will be 
dispensed as 
needed and not 
necessarily at 
every visit. 
Section 7.2 
Visits 1 through 
6, Weeks 4, 10, 
16, 22, 28, and 
34 (±5 days) 
Dispense a home 
pregnancy test kit 
(Section 10.4.1). 
Text removed. 
Repetition from 
previous bullet-
point. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Synopsis (Study 
Design and 
Methods), Table 
1 footnote c., 
Section 7.4 
Safety Follow-up 
(±5 days).  
A safety follow-up 
telephone call will be 
made 4 weeks after Visit 
7/Week 40 (Final Visit) 
for only those subjects 
who presented with 
either new or on-going 
adverse events at Visit 
7/Week 40 (Final Visit). 
Follow up on these 
adverse events… 
A safety follow-up 
telephone call will be made 
4 weeks after Visit 7/Week 
40. Follow up on adverse
events…
Removal of 
qualifiers for 
safety follow-up. 
Synopsis (Study 
Design and 
Methods), Table 
2, Section 8.1.1 
Dosing 
Instructions 
…involved areas (of the 
face)… 
…whole (entire) face… 
Alignment with 
treatment area 
text within 
FX2016-11 and 
FX2016-12. 
Table 2, Section 
8.1.1 Dosing 
Instructions 
…canister containing 
25 g of the clinical… 
canister containing 35 g of 
the clinical… 
Correction of 
unit pack size. 
Section 8.1.1 
Dosing 
Instructions 
None. 
Study drug should be 
applied at approximately 
the same time each day, 
about 1 hour before 
bedtime. 
Alignment with 
treatment 
application text 
within FX2016-
11 and FX2016-
12. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Section 11.5.2 
Secondary 
Efficacy 
Endpoints 
New text. 
The secondary efficacy 
endpoints are: 
The absolute change from 
Day 0/Baseline in the 
inflammatory lesion 
count at Weeks 4, 10, 16, 
22, 28 and 34. 
The dichotomized IGA 
score where success is 
defined as a 2-step 
improvement resulting in 
a 0 (clear) or 1 (almost 
clear) score at Weeks 4, 
10, 16, 22, 28 and 34 
compared to Day 
0/Baseline. 
The percent change in 
inflammatory lesion 
count at Weeks 4, 10, 16, 
22, 28 and 34 compared 
to Day 0/Baseline. 
Addition of 
secondary 
efficacy 
endpoints. 
Section 11.6 
Safety Endpoints New text. 
For the safety analyses, 
Baseline will be defined 
as Day 0/Baseline of the 
initial double-blind study, 
ie either Study FX2016-11 
or Study FX2016-12. 
Clarification of 
Baseline 
timepoint for 
safety analyses. 
Section 11.6 
Safety Endpoints 
Treatment-emergent AEs, 
vital signs, and clinical 
laboratory 
measurements… 
Treatment-emergent AEs, 
vital signs, physical 
examination assessments 
and clinical laboratory 
measurements… 
Section 
incorrectly 
placed. 
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Section(s) 
Revision 
Rationale 
Old Text 
New Text 
Section 11.6 
Safety Endpoints 
Local signs and symptom 
assessments will include 
active assessments of 
erythema, telangiectasia, 
burning/stinging, 
flushing/blushing, 
dryness/xerosis, itching, 
peeling/desquamation, 
and hyperpigmentation 
using the scales 
described under Section 
10.5.1. 
Text removed to Section 
11.6.2. 
As above. 
Section 11.6.2 
Local Signs and 
Symptoms 
Assessments 
Vital sign and physical 
examination parameters 
will be summarized using 
descriptive statistics at 
Baseline and at each 
post-Baseline timepoint. 
Changes from Baseline 
will also be summarized. 
Local signs and symptom 
assessments will include 
active assessments of 
erythema, telangiectasia, 
burning/stinging, 
flushing/blushing, 
dryness/xerosis, itching, 
peeling/desquamation, and 
hyperpigmentation using 
the scales described under 
Section 10.5.1. 
As above. 
Section 11.6.3 
Baseline is defined as the 
last non-missing value 
prior to enrollment in this 
study. 
Text removed. 
Baseline has 
been defined 
within Section 
11.6. 
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APPENDIX 1:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 7 (Week 40/Final Visit): 
1.
How satisfied are you with how easy this product is to use?
2. How satisfied are you with how this product feels on your skin after treatment?
3. How satisfied are you with the odor of this product after treatment?
4. How satisfied are you with the color of this product after treatment?
5. How satisfied are you with the ease of application of the product to your skin?
6. How satisfied are you with the ease in which this product fits into your daily routine?
7. How satisfied are you with this product compared to other products you have previously
used for rosacea, such as gels and creams?
8. Overall, how likely are you to use this product with other rosacea treatments?
9. Overall, how likely are you to recommend this product to a friend?
10. Overall, how satisfied are you with this product?
Answers to Questions 1 through 9 will be selected from the following: 
•
1 = Very Satisfied
•
2 = Satisfied
•
3 = Somewhat Satisfied
•
4 = Dissatisfied
•
5 = Very Dissatisfied
The answer to Questions 10 and 11 will be selected from the following: 
•
1 = Very Likely
•
2 = Likely
•
3 = Somewhat Likely
•
4 = Unlikely
•
5 = Very Unlikely
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APPENDIX 2: Acknowledgment Of Receipt And Review Of 
Protocol 
Protocol Number: FX2016-13, Version 2 
Protocol Title: An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate to Severe Facial 
Papulopustular Rosacea (Study FX2016-13) 
I hereby acknowledge receipt and review of the following Protocol: 
1. Version 2, dated June 22nd, 2017
Principal Investigator Name (Print) 
Principal Investigator Signature 
Date of Signature  
(DD MMM YYYY) 
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CLINICAL PROTOCOL 
Title Page 
Study Title: 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
Sponsor: 
Foamix Pharmaceuticals, Inc. 
520 US Highway 22, Suite 305 
Bridgewater, NJ  08807 
Protocol Identification: 
FX2016-13 
Product: 
FMX103 1.5% minocycline foam 
Indication Studied: 
Papulopustular Rosacea 
Study Phase: 
3 
Sponsor’s Signatory: 
GCP Statement: 
This study will be conducted in accordance with Good 
Clinical Practice. Essential documents will be archived 
according to CPMP/ICH/135/95 
Date of Protocol: 
06 Mar 2017 
Version of Protocol 
1 
Supercedes: 
None 
Prepared by: 
The Write Company, LLC 
Confidentiality Statement 
This document is the property of Foamix Pharmaceuticals, Inc., and is confidential and proprietary.  The information 
contained herein is believed to be accurate and complete as of the date of preparation.  The contents may not be used, 
divulged, published or otherwise disclosed without the expressed consent of Foamix Pharmaceuticals, Inc. 
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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: 
An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate 
to Severe Facial Papulopustular Rosacea (Study FX2016-13) 
Protocol No: 
FX2016-13 
Study Centers: 
Multicenter (approximately 80 sites in the USA) 
Publication (reference): 
None 
Primary Objective: 
The primary objective is to show that open-label extended treatment 
with FMX103 1.5%, for up to an additional 40 weeks, is safe and well 
tolerated. 
Study Design and 
Methods: 
This is an open-label, multicenter, 40-week extension study to evaluate 
the long-term safety, tolerability, and efficacy of FMX103 1.5% topical 
foam in the treatment of moderate-to-severe facial papulopustular 
rosacea. Subjects entering this study will have recently participated in 1 
of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy 
studies (FX2016-11 and FX2016-12). At Baseline, subjects must 
demonstrate that they are eligible to continue into Study FX2016-13 
based in part on safety evaluations performed at Visit 5/Week 12 (Final 
Visit) of one of the previous double-blind studies. In addition, the 
subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 
(Final Visit) should not have worsened relative to the subject’s IGA at 
Day 0/Baseline of one of the previous double-blind studies. 
At the completion of Visit 5/Week 12 (Final Visit) in Study FX2016-11 
or Study FX2016-12, subjects may be invited to continue into this 
open-label study for an additional 40 weeks of open-label treatment. A 
minimum of 400 subjects will be enrolled into from Studies FX2016-11 
and FX2016-12. Subjects who elect to continue into this open-label 
study will receive supplies of active FMX103 1.5% minocycline foam. 
Treatment during the open-label study will be guided by each subject’s 
clinical response. The Investigator may elect to suspend treatment of 
some or all facial areas if there is clinical improvement or resolution of 
the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the 
study and will attend all scheduled clinic visits. If at any time the 
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rosacea recurs or worsens, treatment of the affected areas may be 
resumed. 
Subjects may be discontinued from the study at any time if their disease 
becomes refractory or they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as 
Visit 5/Week 12 (Final Visit) of either Study FX2016-11 or 
Study FX2016-12. Subsequent visits for this open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and 
efficacy evaluations will be performed. Week 40 is the Final Visit 
(Visit 7) of this study. A safety follow-up telephone call will occur 4 
weeks after Final Visit (Visit 7) for only those subjects that present 
with new or on-going adverse events at Week 40 (Final Visit). 
Number of Subjects 
(planned): 
The planned minimum enrollment is a minimum of 400 male and 
female subjects who were previously enrolled in Study FX2016-11 or 
Study FX2016-12. The sample size is intended to ensure that at least 
300 subjects continue to self-administer the study drug as needed for at 
least 6 months and 100 subjects continue for at least 1 year (ie, 
combined duration of treatment between the double-blind and open-
label studies). The number of subjects at each site will be determined 
by the rate of recruitment in Studies FX2016-11 and FX2016-12. No 
statistical rationale for subject number is provided. 
Diagnosis and Main 
Criteria for Inclusion: 
Healthy male or non-pregnant females, aged ≥18 years, who had a 
clinical diagnosis of moderate to severe facial papulopustular rosacea at 
the start of the previous double-blind study who completed 12 weeks of 
double-blind treatment in Study FX2016-11 or Study FX2016-12;  are 
willing to continue on open-label treatment with FMX103 in the current 
study and do not have a worsening of disease, determined by IGA, at 
Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment 
of the previous study. 
Test Product, Dose and 
Mode of Administration: 
FMX103 minocycline foam 1.5%. Topical application, self-
administered dosing as needed, for up to 40 weeks. 
Reference Therapy: 
Not applicable. 
Study Duration: 
Subject participation in the study will be up to 44 weeks. 
Endpoints and Outcomes: 
Safety Evaluations 
The safety assessments will include adverse events (volunteered, 
observed, and elicited by general questioning in a non-suggestive 
manner); clinical laboratory tests; vital signs; physical examinations; 
and local signs and symptom assessments of the skin at the application 
sites (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation scores). 
Efficacy Evaluations 
The efficacy parameters will include inflammatory lesion counts and 
IGA at Baseline and at Weeks 4, 10, 16, 22, 28, 34, and 40 (Final 
Visit). 
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Statistical Methods: 
The All-Treated population, defined as all subjects who use the study 
drug at least once, will be used for all analyses. Missing data will not be 
imputed. All analyses will be based on observed data. The primary 
endpoints are the absolute change in the inflammatory lesion count 
compared to Baseline and the dichotomized IGA score, where success 
is defined as a 2-step improvement resulting in a 0 (clear) or 1 (almost 
clear) score at Week 40 compared to Baseline. Change from baseline of 
Study FX2016-11 and Study FX2016-12 to each visit from 
inflammatory lesion count and IGA will also be summarized. The 
secondary endpoint is the Subject Satisfaction Questionnaire 
administered at Visit 7 (Week 40/Final Visit). 
No statistical tests will be performed for any of the endpoints. 
The safety and tolerability safety of topical minocycline foam applied 
as needed for an additional 40 weeks will be evaluated using summary 
statistics and individual subject data listings. No statistical tests will be 
performed for any of the safety assessments. 
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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 ............................................................................................................................11 
4.1 
PRIMARY OBJECTIVE .......................................................................................................................11 
5 
INVESTIGATIONAL PLAN ..................................................................................................................11 
5.1 
OVERALL STUDY DESIGN ................................................................................................................11 
5.2 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ..................................................................12 
6 
STUDY POPULATION ...........................................................................................................................12 
6.1 
INCLUSION CRITERIA .......................................................................................................................13 
6.2 
EXCLUSION CRITERIA ......................................................................................................................13 
7 
STUDY PROCEDURES ..........................................................................................................................13 
7.1 
BASELINE (ALSO VISIT 5/WEEK 12 [FINAL VISIT] OF PREVIOUS DOUBLE-BLIND STUDY) .................15 
7.2 
VISITS 1 THROUGH 6, WEEKS 4, 10, 16, 22, 28, AND 34 (±5 DAYS) ..................................................15 
7.3 
VISIT 7, WEEK 40/FINAL VISIT (±5 DAYS) OR EARLY TERMINATION ...............................................16 
7.4 
SAFETY FOLLOW-UP (±5 DAYS) .......................................................................................................16 
8 
STUDY TREATMENTS ..........................................................................................................................17 
8.1 
TREATMENT ADMINISTERED ............................................................................................................17 
8.1.1 
Dosing Instructions ........................................................................................................17 
8.1.2 
Manufacturer ..................................................................................................................17 
8.1.3 
Labeling of Study Drug ..................................................................................................18 
8.1.4 
Storage of Study Drug ....................................................................................................18 
8.2 
STUDY DRUG ACCOUNTABILITY ......................................................................................................18 
8.3 
HANDLING AND DISPOSAL OF STUDY DRUG ....................................................................................19 
8.4 
METHOD OF ASSIGNMENT OF STUDY DRUG ....................................................................................19 
8.5 
SELECTION AND TIMING OF DOSES IN THE STUDY ...........................................................................19 
8.6 
BLINDING  ........................................................................................................................................19 
8.7 
PRIOR/CONCOMITANT THERAPY ......................................................................................................19 
8.8 
USE OF CONTRACEPTION .................................................................................................................20 
8.9 
TREATMENT COMPLIANCE ...............................................................................................................20 
9 
EFFICACY ASSESSMENTS ..................................................................................................................21 
9.1 
PRIMARY EFFICACY ASSESSMENTS..................................................................................................21 
9.1.1 
Lesion Counts.................................................................................................................21 
9.1.2 
Investigator Global Assessment .....................................................................................21 
9.2 
SECONDARY EFFICACY ASSESSMENTS .............................................................................................21 
9.2.1 
Subject Satisfaction Questionnaire .................................................................................21 
10 
SAFETY ASSESSMENTS .......................................................................................................................22 
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10.1 
CONCOMITANT MEDICATIONS .........................................................................................................22 
10.2 
VITAL SIGNS ....................................................................................................................................22 
10.3 
PHYSICAL EXAMINATION .................................................................................................................22 
10.4 
CLINICAL LABORATORY TESTS........................................................................................................22 
10.4.1 
Urine Pregnancy Test .....................................................................................................23 
10.4.2 
Sample Collection, Storage, and Shipping .....................................................................23 
10.5 
OTHER SAFETY MEASUREMENTS .....................................................................................................23 
10.5.1 
Local Signs and Symptom Assessments ........................................................................23 
10.5.1.1 Erythema (Clinical Erythema Assessment Scale) .........................................24 
10.5.1.2 Telangiectasia ................................................................................................24 
10.5.1.3 Burning/Stinging ...........................................................................................24 
10.5.1.4 Flushing/Blushing .........................................................................................25 
10.5.1.5 Dryness/Xerosis ............................................................................................25 
10.5.1.6 Itching ...........................................................................................................25 
10.5.1.7 Peeling/Desquamation ...................................................................................25 
10.5.1.8 Hyperpigmentation ........................................................................................25 
10.6 
ADVERSE EVENTS ............................................................................................................................26 
10.6.1 
Method of Determining Adverse Events ........................................................................26 
10.6.2 
Adverse Event Definitions .............................................................................................26 
10.6.2.1 Adverse Events ..............................................................................................26 
10.6.2.2 Serious Adverse Events .................................................................................27 
10.6.2.3 Severity of Adverse Events ...........................................................................27 
10.6.2.4 Relationship of Adverse Events to Study Treatments ...................................28 
10.6.2.5 Adverse Events Expectedness .......................................................................28 
10.6.3 
Reporting Adverse Events ..............................................................................................28 
10.6.4 
Adverse Event Follow-up ...............................................................................................28 
10.6.4.1 Pregnancy Reporting .....................................................................................29 
10.6.5 
Clinically Significantly Abnormal Laboratory Results ..................................................29 
10.7 
APPROPRIATENESS OF SAFETY MEASUREMENT ...............................................................................29 
11 
STATISTICAL DESIGN AND ANALYSIS ..........................................................................................29 
11.1 
STATISTICAL ANALYSIS PLAN .........................................................................................................29 
11.2 
DETERMINATION OF SAMPLE SIZE ...................................................................................................30 
11.3 
ANALYSIS POPULATIONS .................................................................................................................30 
11.4 
SUBJECT ACCOUNTING, DEMOGRAPHICS, AND BASELINE CHARACTERISTICS .................................30 
11.5 
EFFICACY ENDPOINTS ......................................................................................................................30 
11.5.1 
Primary Efficacy Endpoints ...........................................................................................30 
11.5.2 
Secondary Efficacy Endpoint .........................................................................................30 
11.6 
SAFETY ENDPOINTS .........................................................................................................................31 
11.6.1 
Adverse Events ...............................................................................................................31 
11.6.2 
Vital Signs and Physical Examinations ..........................................................................31 
11.6.3 
Clinical Laboratory Results ............................................................................................31 
11.7 
INTERIM ANALYSIS ..........................................................................................................................32 
12 
STUDY MANAGEMENT .......................................................................................................................32 
12.1 
MONITORING ...................................................................................................................................32 
12.2 
PROTOCOL AMENDMENTS................................................................................................................32 
12.3 
PROTOCOL DEVIATIONS ...................................................................................................................32 
12.4 
WITHDRAWAL OF SUBJECTS ............................................................................................................33 
12.5 
TERMINATION OF THE STUDY ..........................................................................................................33 
12.6 
PUBLICATION POLICY ......................................................................................................................34 
13 
ETHICS .....................................................................................................................................................34 
13.1 
CONDUCT OF THE STUDY .................................................................................................................34 
13.2 
INSTITUTIONAL REVIEW BOARDS ....................................................................................................34 
13.3 
WRITTEN INFORMED CONSENT ........................................................................................................34 
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13.4 
SUBJECT CONFIDENTIALITY .............................................................................................................35 
13.5 
RECORDS RETENTION ......................................................................................................................35 
13.6 
FINANCING .......................................................................................................................................35 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................35 
15 
DATA HANDLING AND RECORD KEEPING ...................................................................................36 
16 
REFERENCE LIST .................................................................................................................................36 
APPENDIX 1:  SUBJECT SATISFACTION QUESTIONNAIRE .................................................................37 
APPENDIX 2: ACKNOWLEDGMENT OF RECEIPT AND REVIEW OF PROTOCOL .........................38 
 
List of Tables 
Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 ........................... 14 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 ..................................................... 17 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 ................................................................... 21 
Table 4 
Clinical Laboratory Tests – Study FX2016-13 .............................................................. 23 
 
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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 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
CRO 
Contract Research Organization 
eCRF 
Electronic case report form 
FV 
Final Visit 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed cases 
OTC 
Over-the-counter 
PT 
Preferred term 
RBC 
Red blood cell 
RDC 
Remote data capture 
SAE 
Serious adverse event 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell 
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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 
 
Premier Research 
Research Triangle Park 
One Park Drive, STE 150 
PO Box 13608 
Research Triangle Park, NC 27709 
Tel:  512-686-1256 
FMX103Medical@premier-
research.com 
Medical Monitor 
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3 
INTRODUCTION 
Papulopustular rosacea is a chronic disorder affecting both the skin and eyes. It is a syndrome of 
undetermined etiology characterized by both vascular and papulopustular components involving 
the face and occasionally the neck and upper trunk. Clinical findings are usually limited to the 
sun exposed areas of the face and chest and include mid-facial erythema, telangiectasia, papules 
and pustules, and sebaceous gland hypertrophy. Rosacea is characterized by episodic flushing of 
affected areas, which may be associated with consumption of alcohol, hot drinks, or spicy foods. 
During inflammatory episodes, affected areas of the skin, primarily the convexities of the face, 
develop swelling, papules, and pustules. 
Rosacea occurs most commonly in adult life, between the ages of 30 and 60 years. It is very 
common in the United States (US) and Europe. Ocular involvement occurs in more than 50% of 
patients. 
Mainstays of treatment for papulopustular rosacea are the oral tetracyclines: doxycycline and 
minocycline. Systemic doxycycline (Oracea®, doxycycline 40 mg capsules) is approved. Topical 
treatments for rosacea include metronidazole, azelaic acid, and brimonidine tartrate. 
Minocycline hydrochloride is an established broad-spectrum antibiotic that is used orally “off-
label” in the treatment of papulopustular rosacea. Foamix has developed a topical minocycline 
foam product that is being evaluated for the treatment of papulopustular rosacea. The study 
medication FMX103 (minocycline HCl 1.5% foam) facilitates easy application and even 
distribution of the agent, thereby improving treatment convenience. 
The efficacy and safety of FMX103 have been established in a Phase 2 study in 232 adult 
subjects with moderate to severe papulopustular rosacea (Study FX2015-10). 
The purpose of this Phase 3 open-label extension study is to evaluate the long-term safety, 
tolerability, and efficacy of topical FMX103 1.5% (minocycline foam) during a 40-week period 
of self-administered dosing as needed in subjects with moderate to severe facial papulopustular 
rosacea who have previously participated in 1 of 2 Phase 3, 12-week, double-blind, 
vehicle-controlled safety and efficacy studies: Studies FX2016-11 and FX2016-12. 
4 
STUDY OBJECTIVES 
4.1 
Primary Objective 
The primary objective is to show that open-label extended treatment with FMX103 1.5%, for up 
to an additional 40 weeks, is safe and well tolerated.  
5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is an open-label, multicenter, 40-week extension study to evaluate the long-term safety, 
tolerability, and efficacy of FMX103 1.5% topical foam in the treatment of moderate to severe 
facial papulopustular rosacea. Subjects will be eligible to enter this study upon successful 
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completion of 1 of 2 pivotal, double-blind, vehicle-controlled, safety and efficacy Phase 3 studies 
(FX2016-11 and FX2016-12) and if they meet all of the entry criteria.  
At the completion of Visit 5/Week 12 (Final Visit, or FV) in Study FX2016-11 or Study FX2016-
12, subjects who meet entry criteria will be invited to continue into this open-label study for an 
additional 40 weeks of treatment. A minimum of 400 subjects from Studies FX2016-11 and 
FX2016-12 will be enrolled into open-label Study FX2016-13. Subsequent enrollment of 
additional subjects will be considered as necessary to meet regulatory requirements. Subjects 
who elect to continue into this open-label study will receive supplies of active FMX103 1.5% 
minocycline foam. 
Treatment during the open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all facial areas if there is clinical 
improvement or resolution of the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the study and will attend all 
scheduled clinic visits. If at any time their rosacea recurs or worsens, treatment of the affected 
areas may be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
Baseline of Study FX2016-13 will occur on the same day as Visit 5/Week 12 (Final Visit) of 
either Study FX2016-11 or Study FX2016-12. Subsequent visits for the open-label study will 
occur at Weeks 4, 10, 16, 22, 28, 34, and 40, during which safety and efficacy evaluations will be 
performed. Week 40 is the Final Visit (Visit 7) of this study. 
Safety and efficacy evaluations will be performed as shown in Table 1. 
5.2
Rationale for Study Design and Dose Selection 
Chronic exposure in an open-label design is appropriate to evaluate the safety of long-term use. 
The omission of a control group is appropriate. Subjects will be selected according to pre-
defined entry criteria from 2 pivotal, Phase 3, randomized, multicenter, double-blind, vehicle-
controlled, 12-week studies. The open-label study treatment duration of 40 weeks will thus result 
in a total treatment duration of 52 weeks, adequate for chronic exposure. 
This open-label extension study is necessary to obtain safety information about the long-term use 
of FMX103 1.5% to treat facial papulopustular rosacea because of its chronic nature. The study 
design is expected to provide sufficient safety information to fulfill the International Conference 
on Harmonization (ICH) E1 guideline. 
The concentration of minocycline (1.5%) was selected according to formulation integrity and 
stability considerations and based on the results of the Phase 2 Study FX2015-10. 
6
STUDY POPULATION 
The study population will be comprised of subjects who have completed Study FX2016-11 or 
Study FX2016-12 and have agreed and are eligible to continue into this 40-week open-label 
extension study. A minimum of 400 subjects will be enrolled at approximately 80 sites in the US. 
All subjects will receive active treatment with FMX103 1.5% minocycline foam. 
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6.1
Inclusion Criteria 
Subjects will be included in the study if they meet all of the following inclusion criteria at the 
time of enrollment: 
1. Healthy male or non-pregnant females, aged ≥18 years, who had a clinical diagnosis of
moderate to severe facial papulopustular rosacea at the start of the previous double-blind
study (Study FX2016-11 or Study FX2016-12).
2. Have completed and signed an appropriately administered informed consent form (ICF)
prior to any study-related procedures.
3. Have completed 12 weeks of treatment in either Study FX2016-11 or Study FX2016-12.
4. Have not had a worsening of disease, determined by the Investigator’s Global Assessment
(IGA), at Visit 5/Week 12 (Final Visit) relative to the Day 0/Baseline assessment in Study
FX2016-11 or Study FX2016-12.
5. Are willing to continue on open-label treatment with FMX103 as described in this
protocol.
6. If a woman of child-bearing potential, have a negative urine pregnancy test and agree to
use an effective method of contraception (Section 8.8). A sterile sexual partner is NOT
considered an adequate form of birth control.
7. If a woman of child-bearing potential is using an oral contraceptive product, she should
have been on the same product for at least 3 months and she should continue using the
same or equivalent product for the duration of the of the study.
6.2 
Exclusion Criteria 
Subjects will be excluded from enrollment in the study for any of the following reasons: 
1. Women who are pregnant, lactating, or planning to become pregnant during the study.
2. Have a new systemic disease or condition, including an ongoing AE that might interfere
with the conduct of the study or the interpretation of results.
3. Have developed a condition that would have been exclusionary for Study FX2016-11 or
Study FX2016-12, including pseudomembranous colitis, antibiotic-associated colitis,
hepatitis, liver damage, renal impairment, drug addiction, or alcohol abuse.
4. Have abnormal laboratory values at the Final Visit (Week 12) of Study FX2016-11 or
Study FX2016-12 that are considered clinically significant.
5. Are unable to fully comply with the study requirements.
7
STUDY PROCEDURES 
The schedule of study assessments and procedures is presented in Table 1. If a subject withdraws 
from the study prematurely, he or she should return to the study site for an early termination 
visit, during which all evaluations described under Visit 7/Week 40 (Final Visit) should be 
performed. 
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Table 1 
Schedule of Study Assessments and Procedures – Study FX2016-13 
Assessment or Procedure 
Baselinea 
Visits 
Final 
Visitb 
Safety 
Follow-upc 
Study Visit 
(FV of 
previous 
DB Study) 
1 
2 
3 
4 
5 
6 
7 
N/A 
Study Week 
(Week since beginning of 
previous DB study) 
1 
(12) 
4 
(16) 
10 
(22) 
16 
(28) 
22 
(34) 
28 
(40) 
34 
(46) 
40 
(52) 
44 
(56) 
Informed consent 
X 
Record subject identificationd 
X 
Inclusion/exclusion criteria 
X 
Physical examination (including 
weight) 
X 
X 
Blood pressure/heart ratee 
X 
X 
X 
X 
X 
X 
X 
X 
Blood/urine samples for clinical 
laboratory tests 
X 
X 
X 
Urine pregnancy testf 
X 
X 
X 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global 
Assessment 
Xg 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
Questionnaire 
X 
Local signs and symptom 
assessmentsh 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
X 
X 
X 
X 
Review application instructions 
X 
X 
X 
X 
X 
X 
X 
Schedule/confirm next visit or 
call (for safety follow-up only) 
X 
X 
X 
X 
X 
X 
X 
X 
DB = double-blind; FV = final visit; N/A = not applicable, no visit 
a.
Baseline for the study will be conducted at the same time as Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12. All 
assessments performed at Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12 should not be repeated but should be 
recorded as the same assessments at Baseline for this study.
b.
If a subject withdraws from the study prematurely, all evaluations described under Visit 7/Week 40 (Final Visit) should be performed.
c.
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit) for those subjects who presented with either 
new or on-going adverse events at Visit 7/Week 40 (Final Visit). 
d.
Previously assigned subject identification from Study FX2016-11 or Study FX2016-12 will be used in this study.
e.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest. 
f.
A urine pregnancy test will be done at the study site at every visit for all subjects of childbearing potential; home pregnancy tests will be 
dispensed at each visit and will be performed at least monthly or whenever there is a suspicion of pregnancy (eg, a missed period). 
g.
The subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final Visit) should not have worsened relative to the subject’s 
IGA at Day 0/Baseline of one of the previous double-blind studies. 
h.
The severity of each of the following local rosacea signs/symptoms will be measured:  erythema, telangiectasia, burning/stinging,
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. 
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7.1
Baseline (also Visit 5/Week 12 [Final Visit] of previous double-blind study) 
•
Obtain a signed and dated ICF.
•
Record subject identification from Study FX2016-11 or Study FX2016-12.
•
Assess eligibility according to the inclusion (Section 6.1) and exclusion criteria
(Section 6.2).
•
Record physical examination results, including weight, from Final Visit (Section 10.3).
•
Record blood pressure and heart rate results from Final Visit (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform IGA (Section 9.1.2).
•
Have the subject complete the Subject Global Assessment (Section 9.2.1).
•
Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.2).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Review application instructions to confirm that the subject continues to use the study drug
properly.
•
Dispense 2 study drug kits (ie, 4 canisters) of FMX103 1.5%.
•
Dispense facial cleanser and moisturizer.
•
Schedule/confirm the next study visit.
7.2
Visits 1 through 6, Weeks 4, 10, 16, 22, 28, and 34 (±5 days) 
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test and dispense a home pregnancy test kit (Section 10.4.1).
•
Dispense a home pregnancy test kit (Section 10.4.1).
•
At Visit 3 (Week 16) only – Collect blood and urine samples for clinical laboratory tests
and send to the central laboratory (Section 10.4.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform IGA (Section 9.1.2).
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Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Review application instructions to confirm that the subject continues to use study drug
properly.
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Dispense 2 study drug kits (ie, 4 canisters) of FMX103 1.5% if required.
•
Confirm that subject continues to use only the provided facial cleanser and moisturizer
and dispense additional quantities as required.
•
Schedule/confirm the next study visit.
7.3
Visit 7, Week 40/Final Visit (±5 days) or Early Termination 
•
Perform physical examination, including weight (Section 10.3).
•
Measure blood pressure and heart rate (Section 10.2).
•
Collect a urine sample from female subjects of childbearing potential for a urine
pregnancy test (Section 10.4.1).
•
Collect blood and urine samples for clinical laboratory tests and send to the central
laboratory (Section 10.4.2).
•
Perform facial lesion count of inflammatory lesions (Section 9.1.1).
•
Perform IGA (Section 9.1.2).
•
Have the subject complete the Subject Satisfaction Questionnaire (Section 9.2.2).
•
Perform local signs and symptom assessments (Section 10.5.1).
•
Record concomitant medications (Section 8.7).
•
Record AEs (Section 10.6).
•
Collect used study drug canister(s).
•
Perform drug accountability.
•
Schedule/confirm a safety follow-up telephone call 4 weeks from Visit 7/Week 40 if
required (Section 7.4).
7.4
Safety Follow-Up (±5 days) 
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit) for 
only those subjects who presented with either new or on-going adverse events at Visit 7/Week 40 
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(Final Visit). Follow up on these adverse events and any new concomitant medications will be 
recorded. 
8 
STUDY TREATMENTS 
This is an open-label study; all subjects will receive FMX103 1.5% minocycline foam. 
8.1 
Treatment Administered 
The description of study drug kits and treatment is shown in Table 2. 
Table 2 
Study Drug Kits and Treatment – Study FX2016-13 
Dosage form description: 
Foam containing minocycline HCl 1.5% 
Package description: 
2 canisters of FMX103 1.5%, each canister containing 25 g of the clinical 
trial supply foam 
Daily dose: 
As needed application of a sufficient amount of foam to cover the involved 
area. Estimated maximum is 0.5 g of drug product containing 7.5 mg (1.5% 
active) of minocycline. 
Cumulative maximal dose over 
40 weeks: 
Up to approximately 2100 mg of minocycline assuming application of 0.5 g 
of FMX103 1.5% foam once daily to the face for 280 days. 
Dispensing: 
Up to 2 kits consisting of 2 canisters/kit (ie, 4 canisters total) dispensed at 
Baseline and Visits 1-6 (Weeks 4-34). Up to a total of 14 kits (28 canisters) 
dispensed to the subject for the study. 
8.1.1
Dosing Instructions 
At enrollment, subjects will receive supplies of active FMX103 1.5% minocycline foam. 
Up to 2 study drug kits consisting of 2 canisters/kit (ie, 4 canisters total of investigational drug) 
will be dispensed at Baseline and Visits 1 through 6 (Weeks 4 through 34). Subjects will be 
instructed to express a small amount of study drug from the canister onto the finger tips and then 
apply as a thin layer over all involved areas of the face as needed. Additional drug may be used 
as needed to assure the entire involved area is treated. Sufficient product will be dispensed at 
each visit to allow continuation of treatment as required. 
Treatment during this open-label study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all facial areas if there is clinical 
improvement or resolution of the rosacea in those areas. Even if the treatment is partially or 
completely suspended temporarily, the subject will continue in the study and will attend all 
scheduled clinic visits. If at any time the rosacea recurs or worsens, treatment of the affected 
areas may be resumed. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
8.1.2
Manufacturer 
The manufacturer of the investigational product is
 
 
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8.1.3
Labeling of Study Drug 
The Sponsor or designee will label study drug supplies according to the requirements of the 
Code of Federal Regulations (21CFR§ 210, Subpart G-Packaging & Labeling Control). 
The labels of the investigational (test) product will contain appropriate information as required 
by regional regulatory authorities and include, as needed, the following information: 
•
Name and address of the Sponsor
•
Protocol number
•
Product name/dosage form/mode of administration
•
Kit Number/Canister Number
•
Site number/Subject number
•
Name and address of manufacturer
•
Date of manufacture
•
Lot/batch number
•
Canister contents
•
Storage conditions
•
Caution statements, as follow:
o
“New Drug – Limited by Federal Law to Investigational Use”
o
“Flammable”
o
“Shake well before use”
o
“Keep out of the reach of children”
The composition, pharmaceutical quality, batch number, and expiration date of the 
investigational (test) product will be traceable via the kit number. 
8.1.4
Storage of Study Drug 
FMX103 1.5% canisters must be stored at 2°C – 8°C until being dispensed to the subject. 
Subsequently, the canisters must be stored at 20°C – 25°C (refer to USP Controlled Room 
Temperature). The Investigator will be responsible for the suitable storage of the investigational 
product in compliance with the storage instructions and must restrict access to the study 
personnel only. 
8.2
Study Drug Accountability 
The Investigator will have overall responsibility for the study drug. The Investigator or designee 
will verify the contents of the drug shipment and confirm receipt of the study drug in the 
Interactive Response Technology (IRT) system. In addition, an accurate study drug dispensing 
record that specifies the date and amount dispensed to each subject must be kept. This inventory 
record must be available for inspection by representatives of the Sponsor and is subject to 
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If a subject is taking anticoagulant therapy, he or she should be advised that a downward 
adjustment of their anticoagulant dose may be required. 
See the FMX103 investigator’s brochure (IB) for information about tetracyclines and possible 
drug-drug interactions. 
8.8
Use of Contraception 
Tetracycline-class antibiotics can cause fetal harm when administered to a pregnant woman. 
Tetracycline-class antibiotics used during tooth development (last half of pregnancy, infancy, and 
childhood to the age of 8 years) may cause permanent discoloration of teeth (yellow-gray-
brown). 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. Females of childbearing potential include any female who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation/occlusion, or bilateral oophorectomy) or who is not postmenopausal (defined as 
amenorrhea >12 consecutive months). Females of childbearing potential must have a negative 
urine pregnancy test and, if they are sexually active or become sexually active during the study, 
must use an effective method of birth control such as those in the follow list during the course of 
the study. The following is not an all-inclusive list; the subject must discuss with the Investigator 
the most appropriate form of birth control: 
•
Hormonal methods
o
Oral contraceptives – (Oral antibiotics may lessen the effectiveness of oral
contraceptives. Therefore, a second form of birth control must be utilized in
subjects using oral contraceptives.)
o
Implant
o
Injection
o
Transdermal patch
o
Intravaginal ring
•
Intrauterine device (hormonal or non-hormonal)
•
Barrier methods
o
Condom (male or female) with spermicide
o
Diaphragm with spermicide
•
Complete abstinence
8.9
Treatment Compliance 
Each subject is to be instructed on the importance of following the dosing schedule and returning 
all study drug kits (empty/used/unused) at the appropriate visits. The study site personnel will 
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question each subject on study drug use since the last visit. A subject who deviates significantly 
from the prescribed dosage will be counseled. 
9
EFFICACY ASSESSMENTS 
Every attempt must be made to ensure the same evaluator performs the efficacy evaluations for a 
particular subject throughout the study; when this is not possible, another approved evaluator 
may perform the evaluations. Following are the methods and scales that will be used to measure 
each of the efficacy parameters to be performed. 
9.1
Primary Efficacy Assessments 
The efficacy assessments will include the inflammatory lesion counts and the IGA of severity of 
disease and will be performed by the Investigator/evaluator. 
9.1.1
Lesion Counts 
The number of papules, pustules, and nodules will be counted and the numbers recorded. Facial 
area lesion counts will be made for the forehead, left and right cheeks, nose, and chin. The lesion 
counts performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will 
constitute the Baseline value for this study. Lesion counts will be repeated at Visit 1 (Week 4), 
Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), 
and Visit 7 (Week 40/Final Visit). 
9.1.2
Investigator Global Assessment 
The Investigator will also assess the global severity of rosacea using the IGA scale as described 
in Table 3. The IGA performed at Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) will constitute the Baseline value for this study. Assessment will be repeated 
at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 (Week 16), Visit 4 (Week 22), Visit 5 (Week 28), 
Visit 6 (Week 34), and Visit 7 (Week 40/Final Visit). 
Table 3 
IGA Scale for Rosacea – Study FX2016-13 
Score 
Grade 
Description 
0 
Clear 
No inflammatory papules or pustules 
1 
Almost clear 
Few inflammatory papules or pustules 
2 
Mild 
Several inflammatory papules or pustules 
3 
Moderate 
Moderate number of inflammatory papules or pustules and no nodules 
4 
Severe 
Many inflammatory papules or pustules, and up to 2 nodules 
9.2
Secondary Efficacy Assessments 
9.2.1
Subject Satisfaction Questionnaire 
A Subject Satisfaction Questionnaire (Appendix 1) will be administered at Visit 7 
(Week 40/Final Visit). 
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10
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
the monitoring of AEs (volunteered, observed, and elicited by general questioning in a non-
suggestive manner), clinical laboratory tests, vital signs, physical examinations, and local signs 
and symptom assessments (including erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation) 
scores. 
10.1
Concomitant Medications 
All medications that the subject is currently taking or any change in medication or dosage since 
the last visit will be documented throughout the study. The reason for use or change of dose of a 
concomitant therapy may need to be reported as an AE. 
10.2
Vital Signs 
Heart rate and blood pressure (BP) will be measured at all visits. All BP measurements will be 
made using a sphygmomanometer with an appropriate cuff size for the individual subject. 
Measurements will be taken while the subject is seated after at least 5 minutes at rest. 
10.3
Physical Examination 
A complete physical examination (excluding the genitourinary examination), including body 
weight, will be performed at Baseline (ie, Visit 5/Week 12 [Final Visit] in Study FX2016-11 or 
Study FX2016-12) and at Visit 7 (Week 40/Final Visit). 
10.4
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at Baseline (ie, Visit 5/Week 12 
[Final Visit] in Study FX2016-11 or Study FX2016-12) and at Visit 3 (Week 16) and Visit 7 
(Week 40/Final Visit). All clinical laboratory tests will be analyzed by a central laboratory. 
Table 4 presents the specific clinical laboratory tests to be evaluated. 
Please refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples. 
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Table 4 
Clinical Laboratory Tests – Study FX2016-13 
Hematology 
Urinalysis 
Serum chemistry 
Hematocrit 
Hemoglobin 
Platelet count 
Red blood cell (RBC) 
count 
White blood cell (WBC) 
count with differential 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes esterase 
pH 
Protein 
Specific gravity 
Urine pregnancy test performed at the site 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase 
Aspartic acid transaminase (AST) 
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Creatinine kinase 
Gamma glutamyl transferase (GGT) 
Globulin 
Glucose 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (if elevated obtain 
direct bilirubin) 
Total protein 
Uric acid 
10.4.1
Urine Pregnancy Test 
A urine pregnancy test will be performed at the study site on all females of childbearing potential 
at all study visits and when a subject withdraws from the study prematurely. In addition, home 
pregnancy tests will be dispensed at each study visit to all female subjects of a childbearing 
potential and will be performed at least monthly and whenever there is a suspicion of pregnancy 
(eg, a missed or late menstrual period). 
10.4.2
Sample Collection, Storage, and Shipping 
Sample collection kits, requisition slips, and shipping boxes will be supplied by the central 
laboratory. Sample collection procedures and shipping instructions will be detailed in the 
laboratory manual. Study sites must be equipped to store the samples according to the laboratory 
manual procedures before shipping to the central laboratory. 
10.5
Other Safety Measurements 
10.5.1
Local Signs and Symptom Assessments 
Local signs and symptom assessments of the skin at the application sites measured at 
Visit 5/Week 12 [Final Visit] in Study FX2016-11 or Study FX2016-12) will constitute Baseline 
values for this study.  Assessments will be repeated at Visit 1 (Week 4), Visit 2 (Week 10), Visit 3 
(Week 16), Visit 4 (Week 22), Visit 5 (Week 28), Visit 6 (Week 34), and Visit 7 (Week 40/Final 
Visit). The following local signs and symptoms will be measured:  erythema, telangiectasia, 
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burning/stinging, flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation. The score for signs will be determined by the Investigator and must represent 
the subject’s condition at the time of the evaluation; the score for symptoms (ie, burning/stinging, 
flushing/blushing) should be scored based on the subject’s symptoms reported for the previous 
3 days. 
These signs/symptoms should not be included as AEs, unless a sign/symptom is believed to have 
been related to the study drug or is the reason for discontinuation from the study. 
10.5.1.1
Erythema (Clinical Erythema Assessment Scale) 
Erythema of the face will be graded according to the following scale: 
•
0 = clear skin/no signs of erythema
•
1 = almost clear of erythema, slight redness
•
2 = mild erythema, definite redness
•
3 = moderate erythema, marked redness
•
4 = severe erythema, fiery redness
10.5.1.2 
Telangiectasia 
The severity of facial telangiectasia will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  scattered telangiectasia
•
2 = Moderate:  numerous telangiectasia
•
3 = Severe:  dense telangiectasia forming sprays of vessels
10.5.1.3 
Burning/Stinging 
The severity of facial burning/stinging will be graded according to the following scale: 
•
0 = None:  no warm or burning sensation
•
1 = Mild:  slight warm tingling/stinging sensation; not really bothersome
•
2 = Moderate:  constant or intermittent warm tingling/stinging sensation that is somewhat
bothersome
•
3 = Severe:  bothersome warm to hot tingling/stinging sensation
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10.5.1.4 
Flushing/Blushing 
The severity of facial flushing/blushing will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic episodes lasting for a few moments to several minutes
•
2 = Moderate:  intermittent episodes lasting for greater than 30 minutes
•
3 = Severe:  almost constant episodes lasting for several hours
10.5.1.5 
Dryness/Xerosis 
The severity of facial dryness/xerosis will be graded according to the following scale: 
•
0 = None
•
1 = Mild
•
2 = Moderate
•
3 = Severe
10.5.1.6 
Itching 
The severity of facial itching will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  sporadic itching lasting for a few moments to several minutes
•
2 = Moderate:  intermittent itching lasting for greater than 30 minutes
•
3 = Severe:  almost constant, intense itching lasting for several hours
10.5.1.7 
Peeling/Desquamation 
The severity of facial peeling/desquamation will be graded according to the following scale: 
•
0 = No peeling
•
1 = Mild:  small, scattered areas of scaling/flaking
•
2 = Moderate:  larger, contiguous areas of scaling/flaking
•
3 = Severe:  pronounced flaking/shedding scales covering entire application area
10.5.1.8 
Hyperpigmentation 
The severity of facial skin hyperpigmentation will be graded according to the following scale: 
•
0 = None
•
1 = Mild:  few scattered, small areas of light hyperpigmentation
•
2 = Moderate:  larger or more intense areas of hyperpigmentation
•
3 = Severe:  intense, extensive hyperpigmentation
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10.6
Adverse Events 
10.6.1
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator. Adverse events will be recorded at each visit on the appropriate case report 
form (CRF). Every attempt should be made to describe the AE in terms of a diagnosis. If a clear 
diagnosis has been made, individual signs and symptoms will not be recorded unless they 
represent atypical or extreme manifestations of the diagnosis, in which case they should be 
reported as separate events. If a clear diagnosis cannot be established, each sign and symptom 
must be recorded separately. 
Subjects should be asked whether, since the time of the last observation or visit, they had any of 
the following: 
•
Experienced any changes in well-being
•
Used any new medications
•
Changed medication regimens (both prescription and OTC)
•
Were admitted to a hospital or had any accidents
•
Developed unusual headaches or changes in vision
With exception to the above, all questions should be of a general nature and should not suggest 
symptoms. 
When an AE is suspected, all relevant evaluations will be performed and appropriate treatment 
provided. Additional follow-up will be done as necessary (Section 10.6.4) and recorded in the 
subject’s source documents, and the results will be provided to the Sponsor. 
For AE definitions and reporting requirements, refer to Section 10.6.2 and Section 10.6.3, 
respectively. 
10.6.2
Adverse Event Definitions 
10.6.2.1
Adverse Events 
An AE is any unfavorable or unintended sign, symptom, or disease that appears or worsens in a 
subject after the subject signs the ICF for a clinical study. 
Examples of what may be considered an AE include any of the following: 
•
A new illness.
•
An exacerbation of a sign or symptom of an underlying condition or of a concomitant
illness unrelated to participation in the clinical study or an effect of the study drug or
comparator drug.
No causal relationship with the study drug is implied by the use of the term “adverse event.” An 
exacerbation of a pre-existing condition/illness is defined as a more frequent occurrence or as an 
increase in the severity of the pre-existing condition/illness during the study. Planned or elective 
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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. 
10.6.2.2
Serious Adverse Events 
A serious adverse event (SAE) is any AE that: 
•
Results in death.
•
Is life-threatening.
(Note:  The term “life-threatening” refers to any AE that, as it occurs, puts the subject at
immediate risk of death. It does not refer to an AE that hypothetically might have caused
death if it were more severe.)
•
Results in hospitalization or prolongation of current hospitalization (not including
hospitalization for a pre-existing condition that has not increased in severity or frequency
from the subject’s underlying medical condition prior to entry into the study).
•
Results in persistent or significant disability/incapacity.
•
Is a congenital anomaly/birth defect in the offspring of a subject.
•
Is another serious (important medical events) event.
(Note:  Important medical events may not be immediately life-threatening or result in
death or hospitalization but may be considered serious when, based upon appropriate
medical judgment, they may jeopardize the subject or require medical or surgical
intervention to prevent one of the outcomes listed above. Examples of such medical
events include allergic bronchospasm requiring intensive treatment in an emergency room
or at home; blood dyscrasias or convulsions that do not result in inpatient hospitalization;
or development of drug dependency or drug abuse.)
SAEs will be reported by the Sponsor to the regulatory authorities as required. 
10.6.2.3
Severity of Adverse Events 
The severity of an AE refers to the extent to which it affects the subject’s daily activities and 
differs from “serious”, which is a regulatory classification. Severity will be categorized 
according to the following criteria: 
•
Mild:  The symptom has a negligible effect or no impairing effect on the subject’s normal
function.
•
Moderate:  The symptom impairs the subject’s normal function to some extent.
•
Severe:  The symptom has an obvious, significantly impairing effect on the subject’s
normal function.
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10.6.2.4
Relationship of Adverse Events to Study Treatments 
Causality refers to the relationship of the AE to the study drug and will be categorized according 
to the following criteria: 
•
Unlikely:  There is no medical evidence to suggest that the AE may be related to study
drug usage, or there is another more probable medical explanation.
•
Possible:  There is medical evidence to suggest that there is a reasonable possibility that
the AE may be related to study drug usage. However, other medical explanations cannot
be excluded as a possible cause.
•
Probable:  There is strong medical evidence to suggest that the AE is related to study
drug usage.
10.6.2.5
Adverse Events Expectedness 
Expected AEs are defined as those described in the FMX103 IB. If an event increases in intensity 
or severity from that described in the IB, it will be considered unexpected. 
10.6.3
Reporting Adverse Events 
Adverse events that occur from the time of informed consent completion of the last study visit 
should be reported. Any AE that the Investigator becomes aware of that occurs within 30 days of 
study completion or withdrawal should also be reported. 
Any SAEs occurring in a subject receiving study drug must be reported to the Sponsor within 
24 hours of the site being informed of the event, even if the event does not appear to be drug 
related. The report must be done by faxing the completed SAE Report Form to the Sponsor. Any 
pertinent follow-up information should be provided in a similar manner. Contact information is 
provided below: 
Foamix Pharmaceuticals Inc./Premier Research 
Pharmacovigilance 
Phone:  +1 215-282-5434 
Fax:  +1 215-972-8765 
Email:  globalPv-US@premier-research.com 
10.6.4
Adverse Event Follow-up 
Adverse events that are ongoing when a subject withdraws from or completes the study will be 
followed until they resolve or the subject stabilizes (in the opinion of the Investigator), or for 30 
days, whichever is shorter. Investigators and the Sponsor will decide if longer follow-up is 
appropriate on a case-by-case basis. Subjects who experience any clinically significant AE will 
remain under medical supervision until the Investigator or the Sponsor’s medical monitor deems 
the AE to be resolved, the subject is stable, or the event is no longer serious enough to warrant 
follow-up. 
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Laboratory values that are abnormal and not assessed as AEs may be followed at the discretion 
of the Investigator or the Sponsor’s medical monitor until they resolve or the subject is stable. 
10.6.4.1
Pregnancy Reporting 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. The ICF that the subject signs must document this discussion. 
If a subject or an Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of site pregnancy testing are 
available. If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
Urine pregnancy tests will be performed on all females of childbearing potential as described in 
Section 10.4.1. 
During the study, all female subjects of childbearing potential should be instructed to contact the 
Investigator immediately if they suspect they might be pregnant (eg, positive home pregnancy 
test [Section 10.4.1], missed or late menstrual period, etc.). If a subject or Investigator suspects 
that the subject may be pregnant at any time before or during the study, the study drug must be 
withheld until the results of site pregnancy testing are available. The Sponsor and site monitor 
must be notified and relevant information collected on the appropriate form. If pregnancy is 
confirmed, the subject must be withdrawn from the study and the Sponsor and site monitor 
notified. Additional relevant information about the confirmed pregnancy will be recorded on the 
appropriate form(s); pregnancy will not be captured as an AE. 
The subject should be followed until the outcome of the pregnancy is known. 
10.6.5
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be flagged when 
reported to the site. The Investigator will determine which out-of-range laboratory test results 
should be characterized as clinically significant and annotate the laboratory report. If a clinically 
significant laboratory abnormality requires treatment or is the reason for a subject being 
discontinued from the study, the abnormal result must also be classified as an AE. 
10.7
Appropriateness of Safety Measurement 
The safety assessments to be used in this study are standard safety measures in clinical trials. 
11
STATISTICAL DESIGN AND ANALYSIS 
11.1
Statistical Analysis Plan 
A detailed statistical analysis plan will be finalized prior to database lock. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response. Missing responses will be enumerated; however, the 
calculation of percentages will exclude missing responses. For quantitative variables (eg, age), 
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descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, and minimum and maximum values. 
11.2
Determination of Sample Size 
The planned minimum enrollment is 400 male and female subjects who were previously enrolled 
in Study FX2016-11 or Study FX2016-12. The sample size is intended to ensure that at least 300 
subjects continue to self-administer the study drug as needed for at least 6 months and 100 
subjects continue for at least 1 year (ie, combined duration of treatment between the double-blind 
and open-label studies). The number of subjects at each site will be determined by the rate of 
recruitment in Studies FX2016-11 and FX2016-12. No statistical rationale for subject number is 
provided. 
11.3
Analysis Populations 
The following populations are defined for analysis: 
•
The All-Treated population:  all subjects who use study drug at least once. This population
will be used for safety and efficacy analyses.
11.4
Subject Accounting, Demographics, and Baseline Characteristics 
Demographics, baseline characteristics, medical and surgical history (FX2016-11 and 
FX2016-12) and prior and concomitant medications will be summarized. Study completion 
status and reasons for discontinuation will also be displayed. 
11.5
Efficacy Endpoints 
11.5.1
Primary Efficacy Endpoints 
The primary efficacy endpoints are: 
•
The absolute change in the inflammatory lesion count at Week 40 compared to Baseline.
•
The dichotomized IGA score where success is defined as a 2-step improvement resulting
in a 0 (clear) or 1 (almost clear) score at Week 40 compared to Baseline.
For the efficacy analyses, Baseline will be defined as Day 0/Baseline of the initial double-blind 
study, ie either Study FX2016-11 or Study FX2016-12. The changes from Baseline of Studies 
FX2016-11 and FX2016-12 to Week 40 of this study for each of the primary endpoints will be 
calculated. Descriptive statistics (number of subjects, mean, median, standard error, coefficient 
of variation, minimum and maximum) for each variable will be presented for each visit and for 
the changes from Baseline. No hypothesis testing will be performed. 
11.5.2
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is: 
•
The Subject Satisfaction Questionnaire administered at Visit 7 (Week 40/Final Visit).
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11.6
Safety Endpoints 
Safety endpoints will be reported on the All Treated population. Safety assessments will be 
summarized in tables using descriptive statistics and in individual by-subject listings. No 
statistical tests will be performed for any of the safety assessments. 
Treatment-emergent AEs (TEAEs) will be defined as events that emerge having been absent 
prior to enrollment in this study or worsen relative to the pre-enrollment state. Summaries of AEs 
will be limited to TEAEs. The number and percentage of subjects reporting events under each 
System Organ Class (SOC) and preferred term (PT) will be summarized. At each level of 
summarization, a subject will be counted only once if he or she reported one or more events. The 
severity of TEAEs and relationship to the study drug will be summarized in a similar manner. 
For summaries of relationship to the study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE severity, a subject will be classified according to 
the highest severity. All TEAEs continuing, but not worsening, after enrollment in this study will 
also be tabulated. 
Treatment-emergent AEs, vital signs, and clinical laboratory measurements will be summarized 
using descriptive statistics. For vital signs, change from Baseline values will also be summarized. 
For all safety variables, subject data listings will be provided. 
Local signs and symptom assessments will include active assessments of erythema, 
telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, itching, 
peeling/desquamation, and hyperpigmentation using the scales described under Section 10.5.1. 
11.6.1
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to SOC and PT. 
Summaries of SAEs and subjects who withdraw from the study prematurely due to AEs will be 
presented. 
11.6.2
Vital Signs and Physical Examinations 
Vital sign and physical examination parameters will be summarized using descriptive statistics at 
Baseline and at each post-Baseline time point. Changes from Baseline will also be summarized. 
11.6.3
Clinical Laboratory Results 
Shift tables for each clinical laboratory test will cross-tabulate the number of subjects with values 
below the laboratory reference range (low), values within the laboratory reference range 
(normal), or above the laboratory range (high) at Baseline with the number of subjects with low, 
normal, or high values at the Final Visit. Baseline is defined as the last non-missing value prior to 
enrollment in this study. 
A listing of subjects with treatment-emergent clinically significant abnormal laboratory values 
will be presented for each treatment group. Clinical significance is based on the Investigator’s 
judgment. 
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11.7
Interim Analysis 
No interim analysis is planned. 
12
STUDY MANAGEMENT 
12.1
Monitoring 
The Investigator will be responsible for preparing and maintaining adequate and accurate source 
documents (medical records, raw data collection forms, etc.) designed to record all observations 
and other pertinent data for each subject treated with the study drug. The Investigator will allow 
representatives of the Sponsor, contract designees, authorized regulatory authority inspectors, 
and the institutional review board (IRB) to have direct access to all documents pertaining to the 
study. The Investigator is to notify the Sponsor immediately of any regulatory authority 
inspections. The Investigator will be informed about the outcome of any Sponsor audit. 
This study will be monitored regularly, by or under supervision of a monitor from the Sponsor. 
The frequency of monitoring visits will be agreed upon by the Sponsor’s representative and the 
study site. 
Monitoring visits will take place on a regular basis according to the enrollment rate and number 
of subjects enrolled at each investigational site. During these visits, the monitor will check the 
completion of the CRF entries, compliance with the study protocol and with Good Clinical 
Practice (GCP)-ICH, and their agreement with the source data. The monitor will also verify the 
correct use of the study drug. At the final visit, the monitor will check all remaining material, 
including the remaining quantities of the study drug, and will organize their return to the Sponsor 
or designee. At each visit, the Investigator and staff will be expected to cooperate with the 
Sponsor’s representative(s) for the purposes of review and verification of protocol compliance, 
AE reporting, CRFs, source documents, clinical supplies and inventory records, and any 
additional records as may have been previously arranged between the Investigator and the 
Sponsor’s representative(s). 
The Investigator and/or other designated study personnel are expected to contact the Sponsor’s 
clinical research associate, as needed, regarding study concerns and/or questions. Contact 
information is provided in the Study Reference Manual for the site. 
12.2
Protocol Amendments 
The Sponsor may propose to amend this protocol at any time. 
No change to the protocol will be implemented until the Sponsor and the IRB have reviewed and 
approved the amendment. 
12.3
Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the IRB-approved protocol 
(intentional or unintentional). All deviations are to be documented at the site and reported to the 
IRB according to their guidelines. 
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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 
Subjects or Investigators may choose to discontinue a subject’s participation in the study at any 
time. Subjects may be withdrawn from the study because of any of the following: 
•
Adverse Event:  An AE that in the opinion of the Investigator or Sponsor suggests that 
continued participation in the study is not in the subject’s best interest for safety reasons. 
All AEs that are present when the subject withdraws from the study will be followed as 
described in Section 10.6.4.
•
Abnormal Laboratory Result:  Any clinically significant laboratory abnormality that 
requires withdrawal of the subject from the study should be considered an AE leading to 
withdrawal. If possible, laboratory tests will be repeated for any results that were 
clinically significantly abnormal until the abnormality is resolved or the subject is stable 
to the satisfaction of the Investigator in consultation with the medical monitor.
•
Lost to Follow-up:  Confirmed at minimum by two phone calls and a traceable letter 
without answer.
•
Subject Request:  Subject requests, for any reason (eg, AE), to be withdrawn or 
withdraws his or her consent.
•
Protocol Deviation:  A subject may be withdrawn from the study at the discretion of the 
Investigator or Sponsor due to poor compliance with protocol requirements that may 
compromise the study results or subject safety.
•
Other:  Other reasons include but are not limited to Investigator decision that it is in the 
subject’s best interest to be withdrawn, administrative reasons, subject’s relocation, etc. If 
a subject becomes pregnant during the study, she will be withdrawn from the study and 
followed through conclusion of the pregnancy (Section 10.6.4.1). 
If a subject is withdrawn from the study following the start of study drug, all Visit 7 
(Week 40/Final Visit) assessments should be completed. Subjects withdrawn from the study will 
not be replaced. 
12.5
Termination of the Study 
The study may be terminated at any time at the request of the Sponsor or a regulatory authority, 
with proper and timely notification of all parties concerned. The IRB will be informed promptly 
and the Sponsor or the Investigator will supply reason(s) for the termination or suspension, as 
specified by the applicable regulatory requirements. Otherwise, the study is considered 
terminated upon completion of all subject treatments and evaluations. 
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12.6
Publication Policy 
The data obtained in this study are the property of the Sponsor, who will make reasonable efforts 
to assure that the results are published in a peer-reviewed journal. Since some of the information 
concerning the investigational product and development activities at the Sponsor may be strictly 
confidential in nature, any manuscript or other presentation of data must first be reviewed by the 
Sponsor before its submission. 
13
ETHICS 
13.1
Conduct of the Study 
This study will be conducted in accordance with the ICH Harmonized Tripartite Guideline for 
GCP, 1997; the US Title 21 CFR parts 50, 56, and 312; and the ethical principles that have their 
origin in the Declaration of Helsinki. The study will not begin until all of the requirements of the 
appropriate regulatory authorities have been fulfilled. 
13.2
Institutional Review Boards 
This protocol (and any changes), all consent forms, and subject consent procedures must be 
reviewed and approved by a properly constituted IRB. The information presented to the IRB at 
the time initial approval is sought must include any plans for subject recruitment that involve 
advertising or other direct contact with potential subjects outside of the physician-subject 
relationship. A letter of approval issued by the IRB must be sent to the Sponsor prior to initiation 
of the study. Any changes made to the protocol must be approved by the IRB prior to 
implementation, except where needed to eliminate a potential imminent safety hazard to the 
subjects. In this case, immediate implementation may take place followed by IRB approval. 
Review and approval by the IRB for continuation of the study must take place at least once a 
year. 
13.3
Written Informed Consent 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential benefits and risks of participation to each 
subject prior to his or her entry into the study (ie, before examinations and procedures associated 
with selection for the study are initiated). Each subject will have ample opportunity to ask 
questions and will be informed about the right to withdraw from the study at any time without 
any disadvantage and without having to provide reasons for this decision. 
Following this informative discussion, the subject will be asked if he or she is willing to sign a 
statement of informed consent. Only subjects who voluntarily sign the ICF may enter the study. 
The ICF must be reviewed and approved by the Sponsor and the IRB prior to use. 
The original signed ICF will remain in the Investigator’s files. The Investigator or designee will 
indicate in each subject’s source documents that he or she has informed the subject about the 
study and its procedures, the subject has signed and dated the ICF, and the subject has been given 
a copy of the documents. The Investigator or designee will inform subjects of any new 
information that may be relevant to the subject’s willingness to continue in the study. 
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13.4
Subject Confidentiality 
The Sponsor will ensure that the following have permission to review all study-related 
documents:  monitor, auditor, IRB, and regulatory authorities. The subject’s identity and 
study-related records will remain confidential throughout the duration of the study data 
collection and reporting process. 
The investigative site assigns a unique subject identification code to each potential study subject. 
The identification code protects the subject’s identity and is used in lieu of the subject’s name 
when reporting subject data. The data will always maintain the confidentiality of the subject. 
The Investigator or designee will review the subject data, which will be referenced using the 
subject identifier. At the conclusion of the study, the data obtained may be presented to regional 
regulatory authorities but the subject’s identity will not be revealed. In addition, if any clinical 
data obtained from the study is published in scientific journals or presented at scientific meetings 
the subject’s identity will not be revealed. 
13.5
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, source 
documentation corresponding to all information contained in the CRFs, signed ICF forms, 
relevant correspondence, and all other supporting documentation) until at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years after the formal 
discontinuation of clinical development of the investigational product. These documents should 
be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted. Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same time period. Custody of the records may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies. Written notice of 
transfer must be submitted to the Sponsor. The Investigator must contact the Sponsor prior to 
disposing of any study records. 
13.6
Financing 
Funding for this study will be agreed upon between the Investigator and the Sponsor and will be 
confirmed in writing before the study starts. 
Completion of Financial Disclosure Forms will be required before the study starts. Any additions 
to the primary site personnel will necessitate the completion of new Financial Disclosure Forms. 
This information will also be collected at site closure and 1 year after the completion of the 
study. 
14
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and the Investigator will take all steps possible to ensure the accuracy, consistency, 
completeness, and reliability of the data, including participating in an Investigator meeting 
and/or site initiation visit, routine site monitoring, review of CRFs against source documents, and 
quality control checks. 
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In addition, a representative from the Sponsor’s Clinical Quality Assurance Department may 
conduct periodic audits of the study processes, including, but not limited to, auditing the clinical 
site, laboratories, vendors and contract research organizations CROs, the clinical database, and 
the final study report. 
15
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, eCRFs developed through a validated, Electronic 
Records/Electronic Signatures-compliant platform (US Title 21 CFR Part 11). Foamix Clinical 
Data Management department or designee will create the eCRFs and corresponding clinical 
database based on the final protocol. 
All site personnel who will be using this system will receive formal training on the system, after 
which each person will be issued a unique username and password. Only the person who owns 
the username and password will enter the system using that username and password. For data 
security reasons and to be in compliance with regulatory guidelines, usernames and passwords 
are not transferable. 
The Investigator is responsible for all data entered via the remote data capture (RDC) system 
eCRFs and must confirm the accuracy of the data by electronically approving (signing) the 
eCRFs. This responsibility includes the timely completion and accuracy of the data entered into 
the eCRFs by their site personnel as well as the review and approval of some data entered 
directly into the database (eg, clinical laboratory results) by an external vendor. The Sponsor will 
review the database to identify data errors or inconsistencies, which will be posted in the RDC 
system as queries for resolution. In addition, the Sponsor may make obvious corrections to the 
data in the database (eg, obvious errors in dates) and so inform the Investigator without issuing a 
query to the site. 
16
REFERENCE LIST 
Not applicable. 
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APPENDIX 1:  Subject Satisfaction Questionnaire 
The following 8 questions will be asked of the subject at Visit 7 (Week 40/Final Visit): 
1.
How satisfied are you with how easy this product is to use?
2. How satisfied are you with how this product feels on your skin after treatment?
3. How satisfied are you with the odor of this product after treatment?
4. How satisfied are you with the color of this product after treatment?
5. How satisfied are you with the ease of application of the product to your skin?
6. How satisfied are you with the ease in which this product fits into your daily routine?
7. How satisfied are you with this product compared to other products you have previously
used for rosacea, such as gels and creams?
8. Overall, how likely are you to use this product with other rosacea treatments?
9. Overall, how likely are you to recommend this product to a friend?
10. Overall, how satisfied are you with this product?
Answers to Questions 1 through 9 will be selected from the following: 
•
1 = Very Satisfied
•
2 = Satisfied
•
3 = Somewhat Satisfied
•
4 = Dissatisfied
•
5 = Very Dissatisfied
The answer to Questions 10 and 11 will be selected from the following: 
•
1 = Very Likely
•
2 = Likely
•
3 = Somewhat Likely
•
4 = Unlikely
•
5 = Very Unlikely
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APPENDIX 2: Acknowledgment Of Receipt And Review Of 
Protocol 
Protocol Number: FX2016-13, Version 1 
Protocol Title: An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of Moderate to Severe Facial 
Papulopustular Rosacea (Study FX2016-13) 
I hereby acknowledge receipt and review of the following Protocol: 
1. Version 1, dated March 6th, 2017
Principal Investigator Name (Print) 
Principal Investigator Signature 
Date of Signature  
(DD MMM YYYY) 
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SAP_001.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
 
ClinicalTrials.gov Identifier: NCT03276936 
 
 
 
Date of Statistical Analysis Plan: 08 January 2019 
 


 
Statistical Analysis Plan,  
 
Sponsor Foamix Pharmaceuticals  
 
Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 1 of 28 
 
Sponsor 
Foamix Pharmaceuticals 
Protocol Title: 
An Open-Label Study to Evaluate the Long-Term Safety of Topical 
Administration of FMX103 for 40 weeks in the Treatment of 
Moderate to Severe Facial Papulopustular Rosacea (Study 
FX2016-13) 
Protocol Number: 
FX2016-13 
Premier Research PCN: 
FOAM166108 
Document Version: 
Version 1.0 
Document Date:  
08-Jan-2019 
Approvals 
Role 
Signatures 
Date (dd-Mmm-yyyy) 
Biostatistician 
Print Name: 
 
 
Sign Name: 
 
 
 
 
 
Foamix 
Pharmaceuticals 
Representative 
Print Name: 
 
 
Sign Name: 
 
 
 
 
 
 
 
14-Jan-2019 | 14:25:19 EST
14-Jan-2019 | 15:42:26 PST
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PPD
PPD
PPD
PPD
PPD
PPD


Statistical Analysis Plan,  
Sponsor Foamix Pharmaceuticals  
Protocol Number FX2016-13  
PCN Number FOAM166108
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Table of Contents 
Approvals ........................................................................................................................................ 1 
Table of Contents ............................................................................................................................ 2 
List of Tables .................................................................................................................................. 3 
1.
Overview ............................................................................................................................. 4 
2.
Study Objectives and Endpoints ......................................................................................... 4 
2.1. 
Study Objectives ........................................................................................................... 4 
2.1.1. Primary Objective ......................................................................................................... 4 
2.2. 
Study Endpoints ............................................................................................................ 4 
2.2.1. Safety Endpoints ........................................................................................................... 4 
2.2.2. Efficacy Endpoints ........................................................................................................ 5 
3.
Overall Study Design .......................................................................................................... 5 
3.1. 
Overall Design .............................................................................................................. 6 
3.2. 
Sample Size and Power ................................................................................................. 6 
3.3. 
Study Population ........................................................................................................... 6 
3.4. 
Treatments Administered .............................................................................................. 6 
3.5. 
Method of Assigning Subjects to Treatment Groups .................................................... 6 
3.6. 
Blinding and Unblinding............................................................................................... 6 
3.7. 
Schedule of Events ........................................................................................................ 6 
4.
Statistical Analysis and Reporting ...................................................................................... 8 
4.1. 
Introduction ................................................................................................................... 8 
4.2. 
Interim Analysis and Data Monitoring ......................................................................... 8 
5.
Analysis Populations ........................................................................................................... 8 
6.
General Issues for Statistical Analysis ................................................................................ 8 
6.1. 
Statistical Definitions and Algorithms .......................................................................... 8 
6.1.1. Baseline ......................................................................................................................... 8 
6.1.2. Adjustments for Covariates........................................................................................... 9 
6.1.3. Multiple Comparisons ................................................................................................... 9 
6.1.4. Handling of Dropouts or Missing Data ......................................................................... 9 
6.1.5. Analysis Visit Windows ............................................................................................... 9 
6.1.6. Derived Variables ....................................................................................................... 10 
6.1.7. Data Adjustments/Handling/Conventions .................................................................. 12 
7.
Study Subjects and Demographics.................................................................................... 13 
7.1. 
Disposition of Patients/Subjects and Withdrawals ..................................................... 13 
7.2. 
Protocol Violations and Deviations ............................................................................ 14 
7.3. 
Demographics and Other Baseline Characteristics ..................................................... 14 
7.4. 
Exposure and Compliance .......................................................................................... 14 
8.
Efficacy Analysis .............................................................................................................. 15 
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Statistical Analysis Plan,  
 
Sponsor Foamix Pharmaceuticals  
 
Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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8.1. 
Primary Efficacy Analysis .......................................................................................... 15 
8.2. 
Secondary Efficacy Analysis ...................................................................................... 15 
8.3. 
Subject Satisfaction Questionnaire ............................................................................. 16 
9. 
Safety and Tolerability Analysis ....................................................................................... 16 
9.1. 
Adverse Events ........................................................................................................... 16 
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 17 
9.1.2. Deaths and Serious Adverse Events ........................................................................... 17 
9.2. 
Clinical Laboratory Evaluations ................................................................................. 17 
9.3. 
Vital Signs ................................................................................................................... 18 
9.4. 
Physical Examinations ................................................................................................ 18 
9.5. 
Local Signs and Symptoms Assessments ................................................................... 18 
9.6. 
Concomitant Medication ............................................................................................. 18 
10. 
Changes from Planned Analysis ....................................................................................... 19 
11. 
Other Planned Analysis..................................................................................................... 19 
11.1. Pharmacokinetic Analysis ........................................................................................... 19 
12. 
References ......................................................................................................................... 19 
13. 
Tables, Listings, and Figures ............................................................................................ 19 
13.1. Planned Table Descriptions ........................................................................................ 19 
13.2. Planned Figure Descriptions ....................................................................................... 26 
14. 
Tables, Listings, and Listing Shells .................................................................................. 27 
14.1. Standard Layout for all Tables, Listings, and Figures ................................................ 27 
Appendix 1: Premier Research Library of Abbreviations ............................................................ 28 
 
List of Tables 
Table 1: Schedule of Study Assessments and Procedures .............................................................. 7 
Table 2:  Analysis Visit Windows ................................................................................................ 10 
Table 3:  Disposition, Demographic, Prior Medications, and Study Drug Exposure Data 
Summary Tables ................................................................................................................... 20 
Table 4:  Efficacy Data ................................................................................................................. 20 
Table 5:  Safety Data..................................................................................................................... 21 
Table 6:  Planned Listings............................................................................................................. 23 
 
 
 
 
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Statistical Analysis Plan,  
Sponsor Foamix Pharmaceuticals  
Protocol Number FX2016-13  
PCN Number FOAM166108
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 4 of 28 
1. 
Overview
This statistical analysis plan (SAP) describes the planned analysis and reporting for Foamix 
Pharmaceuticals protocol number FX2016-13 (An Open-Label Study to Evaluate the Long-Term 
Safety of Topical Administration of FMX103 for 40 weeks in the Treatment of Moderate to 
Severe Facial Papulopustular Rosacea), Version 2 (Amendment 1) dated 22-Jun-2017. Reference 
materials for this statistical plan include the protocol and the accompanying sample data 
collection documents. Operational aspects related to collection and timing of planned clinical 
assessments are not repeated in this SAP unless relevant to the planned analysis. 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials1. All work planned and reported for this SAP will follow internationally accepted 
guidelines, published by the American Statistical Association2 and the Royal Statistical 
Society3, for statistical practice. 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc 
or unplanned, exploratory analysis performed will be clearly identified as such in the final CSR. 
The statistical plan described hereafter is an a priori plan. It will be submitted to file prior to any 
descriptive analysis of data pertaining to Foamix Pharmaceuticals Study FX2016-13. 
Subjects for this open-label extension study were selected according to pre-defined entry criteria 
from 2 Phase 3, randomized, multicenter, 12-week, double-blind, vehicle-controlled studies. 
Analyses for those 2 studies, FX2016-11 and FX2016-12, are reported separately.   
2. 
Study Objectives and Endpoints
2.1. 
Study Objectives 
2.1.1. Primary Objective 
The primary objective is to show that open-label extended treatment with FMX103 1.5%, for up 
to an additional 40 weeks, is safe and well tolerated.  
2.2. 
Study Endpoints 
2.2.1. Safety Endpoints 
The safety endpoints of this study include the following: 
•
Incidence, severity, and causality of any treatment-emergent adverse events (TEAEs),
any serious TEAE, any treatment-related TEAE, and any TEAE leading to study
discontinuation.
•
Change from baseline in vital signs (at Weeks 4, 10, 16, 22, 28, 34, and 40), laboratory
parameters (at Weeks 16 and 40), and physical examinations (at Week 40).
5 of 84


 
Statistical Analysis Plan,  
 
Sponsor Foamix Pharmaceuticals  
 
Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 5 of 28 
 
• Assessment of local signs and symptoms, erythema, telangiectasia, burning/stinging, 
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and 
hyperpigmentation. 
2.2.2. Efficacy Endpoints 
2.2.2.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoints are: 
• The absolute change in the inflammatory lesion count at Week 40 compared to Baseline. 
• The dichotomized IGA score where success is defined as a 2-step improvement resulting 
in a 0 (clear) or 1 (almost clear) score at Week 40 compared to Baseline. 
2.2.2.2. 
Secondary Efficacy Endpoint(s) 
The secondary efficacy endpoints are: 
• The absolute change from Day 0/Baseline in the inflammatory lesion count at Weeks 4, 
10, 16, 22, 28 and 34. 
• The dichotomized IGA score where success is defined as a 2-step improvement resulting 
in a 0 (clear) or 1 (almost clear) score at Weeks 4, 10, 16, 22, 28, and 34 compared to Day 
0/Baseline. 
• The percent change in inflammatory lesion count at Weeks 4, 10, 16, 22, 28, and 34 
compared to Day 0/Baseline. 
• The Subject Satisfaction Questionnaire administered at Visit 7 (Week 40/Final Visit). 
3. 
Overall Study Design 
This is an open-label, multicenter, 40-week extension study to evaluate the long-term safety, 
tolerability, and efficacy of FMX103 1.5% topical foam in the treatment of subjects with 
moderate to severe facial papulopustular rosacea. Subjects who complete 1 of 2 double-blind, 
vehicle-controlled, 12 week, Phase 3 studies (FX2016-11 or FX2016-12) and meet all of the 
entry criteria will be invited to enroll in the extension study until enrollment goal is met.   
Subjects will apply (or have applied) the assigned study drug topically as directed. Treatment 
will be guided by each subject’s clinical response. The Investigator may elect to suspend 
treatment of some or all facial areas if there is clinical improvement or resolution of the rosacea 
in those areas. Even if treatment is partially or completely suspended temporarily, the subject 
will continue in the study and will attend all scheduled clinic visits. If at any time, their rosacea 
worsens, treatment of the affected areas may be resumed.  Subjects will be advised to apply the 
study drug at approximately the same time each day, preferably about 1 hour before bedtime.  
The baseline visit will occur on the same day as the Week 12 visit of either Study FX2016-11 or 
Study FX2016-12. Subjects will return for in-person visits at Weeks 4, 10, 16, 22, 28, 34, and 40. 
At the discretion of the clinic staff and for the convenience of subjects or clinic staff, visits can 
be scheduled to occur 5 days before or after the nominal scheduled date for all visits. A safety 
telephone call will be made 4 weeks after the Week 40 clinic visit to follow-up on AEs and 
record any new concomitant medications.  
6 of 84


Statistical Analysis Plan,  
Sponsor Foamix Pharmaceuticals  
Protocol Number FX2016-13  
PCN Number FOAM166108
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 6 of 28 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product. 
3.1. 
Overall Design 
3.2. 
Sample Size and Power 
The planned minimum enrollment is 400 male and female subjects who were previously enrolled 
in Study FX2016-11 or Study FX2016-12. The sample size is intended to ensure that at least 300 
subjects continue to self-administer the study drug as needed for at least 6 months and 100 
subjects continue for at least 1 year (ie, combined duration of treatment between the double-blind 
and open-label studies). The number of subjects at each site will be determined by the rate of 
recruitment in Studies FX2016-11 and FX2016-12. No statistical rationale for subject number is 
provided. 
3.3. 
Study Population 
The study population will be comprised of healthy male and non-pregnant females, aged ≥18 
years who had a clinical diagnosis of moderate-to-severe facial papulopustular rosacea at the 
start of the previous double-blind study (Study FX2016-11 or Study FX2016-12) and who have 
completed the previous study to Week 12, did not have a worsening of disease during the study, 
and are willing and eligible to continue into this 40-week open-label extension study. 
3.4. 
Treatments Administered 
All subjects will receive FMX103 1.5% minocycline foam. Treatment will be administered daily 
for 40 weeks. The description of the study drug kits and treatment is shown in Table 2 of the 
protocol.  
3.5. 
Method of Assigning Subjects to Treatment Groups 
This is an open-label extension study with all subjects assigned to the active treatment. 
For analysis purposes, subjects will be categorized depending on the treatment they received in 
the initial double-blind study. Subjects who received active treatment during the double-blind 
phase will be in the DB - FMX103 1.5% subgroup and subjects who received Vehicle Foam 
during the double-blind phase will be in the DB – Vehicle subgroup.  
3.6. 
Blinding and Unblinding 
Subjects will not be blinded as part of this study. 
3.7. 
Schedule of Events 
A detailed schedule of events for the study is provided in Table 1. 
AD-ST-33.05  Effective date: 22-Jan-2018 
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Statistical Analysis Plan,  
Sponsor Foamix Pharmaceuticals  
Protocol Number FX2016-13  
PCN Number FOAM166108
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Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 7 of 28 
Table 1: Schedule of Study Assessments and Procedures 
Assessment or Procedure 
Baselinea 
Visits 
Final 
Visitb 
Safety 
Follow-upc 
Study Visit 
(FV of 
previous 
DB Study) 
1 
2 
3 
4 
5 
6 
7 
N/A 
Study Week 
(Week since beginning of 
previous DB study) 
1 
(12) 
4 
(16) 
10 
(22) 
16 
(28) 
22 
(34) 
28 
(40) 
34 
(46) 
40 
(52) 
44 
(56) 
Informed consent 
X 
Record subject identificationd 
X 
Inclusion/exclusion criteria 
X 
Physical examination 
(including weight) 
X 
X 
Blood pressure/heart ratee 
X 
X 
X 
X 
X 
X 
X 
X 
Blood/urine samples for 
clinical laboratory tests 
X 
X 
X 
Urine pregnancy testf 
X 
X 
X 
X 
X 
X 
X 
X 
Lesion counts 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global 
Assessment 
Xg 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
Questionnaire 
X 
Local signs and symptom 
assessmentsh 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect used drug canister(s) 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
X 
X 
X 
X 
X 
X 
Review application instructions 
X 
X 
X 
X 
X 
X 
X 
Schedule/confirm next visit or 
call (for safety follow-up only) 
X 
X 
X 
X 
X 
X 
X 
X 
DB = double-blind; FV = final visit; N/A = not applicable, no visit 
a.
Baseline for the study will be conducted at the same time as Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12. All 
assessments performed at Visit 5/Week 12 (Final Visit) of Study FX2016-11 or Study FX2016-12 should not be repeated but should be 
recorded as the same assessments at Baseline for this study.
b.
If a subject withdraws from the study prematurely, all evaluations described under Visit 7/Week 40 (Final Visit) should be performed.
c.
A safety follow-up telephone call will be made 4 weeks after Visit 7/Week 40 (Final Visit). 
d.
Previously assigned subject identification from Study FX2016-11 or Study FX2016-12 will be used in this study.
e.
Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest. 
f.
A urine pregnancy test will be done at the study site at every visit for all subjects of childbearing potential; home pregnancy tests will be 
dispensed at each visit, if needed, and will be performed at least monthly or whenever there is a suspicion of pregnancy (eg, a missed menstrual 
period).
g.
The subject’s Investigator’s Global Assessment (IGA) at Visit 5/Week 12 (Final Visit) should not have worsened relative to the subject’s IGA 
at Day 0/Baseline of one of the previous double-blind studies. 
h.
The severity of each of the following local rosacea signs/symptoms will be measured:  erythema, telangiectasia, burning/stinging,
flushing/blushing, dryness/xerosis, itching, peeling/desquamation, and hyperpigmentation. 
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Statistical Analysis Plan,  
Sponsor Foamix Pharmaceuticals  
Protocol Number FX2016-13  
PCN Number FOAM166108
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 8 of 28 
4.
Statistical Analysis and Reporting
Statistical analysis will be performed following Premier Research’s standard operating procedures. 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will be performed primarily using SAS (release 9.4 or higher). If the 
use of other software is warranted, the final statistical methodology report will detail what 
software was used for what purposes. 
Continuous (quantitative) variable summaries will include the number of subjects (n) with 
non-missing values, mean, standard deviation (SD), median, minimum, and maximum. 
Coefficient of variation will also be presented for primary efficacy endpoints.  
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular category or each possible value. Missing responses will be 
enumerated, unless otherwise specified.  
The minimum and maximum will be reported with the same degree of precision (ie, the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
reported to 1 degree of precision more than the observed data and measures of spread (eg, SD) 
will be reported to 2 degrees of precision more than the observed data. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
There will be no hypothesis testing performed. 
4.2.
Interim Analysis and Data Monitoring 
No interim analyses are planned. 
5.
Analysis Populations
The following analysis population is planned for this study: 
•
All Treated Population: The All Treated Population includes all subjects who use the
study drug at least once. This population will be used for safety and efficacy analyses.
6.
General Issues for Statistical Analysis
6.1.
Statistical Definitions and Algorithms 
6.1.1. Baseline 
For all safety and efficacy analyses, Baseline will be defined as Day 0/Baseline of the initial 
double-blind study, ie, either Study FX2016-11 or Study FX2016-12. The last observation 
recorded prior to the first dose of FMX103 1.5% or vehicle foam will be used as the baseline 
observation for all calculations of the primary and secondary endpoints. 
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Statistical Analysis Plan,  
Sponsor Foamix Pharmaceuticals  
Protocol Number FX2016-13  
PCN Number FOAM166108
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 9 of 28 
The baseline visit of the extension study which is equal to the Final Visit/Week 12 of the initial 
double-blind study will also be presented as Baseline (Week 12) in the listings for inflammatory 
lesion count and IGA.  
6.1.2. Adjustments for Covariates 
No adjustments will be made for covariates. 
6.1.3. Multiple Comparisons 
No adjustments will be made for multiple comparisons.   
6.1.4. Handling of Dropouts or Missing Data 
Any subject who withdraws from the study before the Week 40 visit should undergo all 
assessments specified for the Week 40/Final visit. For subjects who prematurely discontinue the 
study, their early termination (ET) visit data will be assigned to the closest visit by study day 
as described in Section 6.1.5. Missing data will not be imputed. All analyses will be based 
on observed data.  
6.1.5. Analysis Visit Windows 
All visit-based variables for this study will be analyzed according to their windowed visits 
defined by actual study day (see Table 2 below). Scheduled visits will be selected over 
unscheduled visits.  
For those subjects who discontinue early from the study, Table 2 will be used to assign the 
appropriate analysis visit.  
The study day, relative to first dose of study drug during the open-label phase, will be calculated 
for each scheduled or ET visit and compared to the lower and upper bounds presented in Table 2 
to define the visit window used for analyses. The analysis visit windows only apply to those 
visits that are applicable to the specific assessment. For example, if the scheduled or ET visit falls 
at Week 4 but a specific assessment was not scheduled at that visit (see Table 1, Schedule of 
Events) then that assessment will not be used. 
The following analysis visit windows will apply: 
AD-ST-33.05  Effective date: 22-Jan-2018 
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Statistical Analysis Plan,  
 
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Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 10 of 28 
 
Table 2:  Analysis Visit Windows 
Analysis 
Visit 
Analysis Visit 
Name 
Target 
Day of 
Planned 
Visit 
Assessment Window 
(Days) 
1 
Baseline/Week 12 
0 
NA – this is the 
baseline visit of the 
open-label study 
2 
Week 4 
28 
Post-dose ─ 49 
3 
Week 10 
70 
50 ─ 91 
4 
Week 16 
112 
92 ─ 133 
5 
Week 22 
154 
134 ─ 175 
6 
Week 28 
196 
176 ─ 217 
7 
Week 34 
238 
218 ─ 259 
8 
Week 40 
280 
260 ─ 301 
If more than 1 visit occurs within a single visit window, then the analysis will use the visit 
closest to the target day. If 2 visits within the same visit window are equidistant from the target 
day, then the analysis will use the later visit. 
6.1.6. Derived Variables 
• Total number of inflammatory lesion count = number of papules + number of pustules + 
number of nodules in all facial areas (forehead, left and right cheeks, nose, and chin) 
• Change from baseline in inflammatory lesion count  = (value at baseline) – (post-baseline 
value) 
Thus, a positive change will reflect a reduction in inflammatory lesion count. 
Change from baseline will be calculated at the following time points:  4, 10, 16, 
22, 28, 34, and 40 weeks.  
• Percentage change from baseline inflammatory lesion count =  
100 × 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏−𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣
𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏
 
Thus, a positive percentage change will reflect a reduction in inflammatory lesion 
count. The percentage change from baseline will be calculated at the following 
time points: 4, 10, 16, 22, 28, 34, and 40 weeks.  
11 of 84


 
Statistical Analysis Plan,  
 
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Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 11 of 28 
 
• Coefficient of Variation  =  
100 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝑜𝑜𝑜𝑜 𝑐𝑐ℎ𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏
𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 𝑐𝑐ℎ𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏
 
for absolute and percent change in inflammatory lesion count.  
• TEAE = any AE with an onset date after the first dose date of the open-label extension 
study and before the last application of study drug plus 3 days having been absent 
pre-treatment or worsening relative to the pre-treatment state.  Adverse events reported at 
the baseline visit (Week 12 visit of the double-blind phase) will be assigned to the 
respective double-blind study. For subjects with >3 days of study drug interruption 
during the 40-week treatment period, the definition of a TEAE will also consider the date 
of the last dose before study drug interruption. For these subjects, AEs that start >3 days 
after the last dose before study drug interruption and before the drug is re-administered 
will not be considered as treatment-emergent.  
• Body mass index (kg/m2) = 
𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤ℎ𝑡𝑡 𝑖𝑖𝑖𝑖 𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘𝑘
(ℎ𝑒𝑒𝑒𝑒𝑒𝑒ℎ𝑡𝑡 𝑖𝑖𝑖𝑖 𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚)2  
• Age groups 
Age group=1 if 18≤ age (full years) ≤40 
Age group=2 if 41≤ age (full years) ≤64 
Age group=3 if 65≤ age (full years) 
• Treatment duration (days) =  
Date of last dose of study drug – Date of first dose of study drug + 1 day 
• Study drug exposure (days) =  
Treatment duration (days) – Number of days that a subject reported 
missing a dose – Number of days of drug interruption (as instructed by the 
investigator, between the date of first and last dose) 
• Compliance (%) = 100 x Study drug exposure (days) / Treatment duration (days) 
Study drug compliance will not be calculated for subjects whose date of last study drug 
application is unknown. 
For subjects who are instructed to discontinue and then restart study drug application 
during the study, number of days off treatment will be added back into the numerator in 
the calculation of compliance since they will be considered compliant during that time. 
For subjects who are missing the date of last study drug application, the last known 
contact date will be used in the calculation of treatment duration and study drug 
exposure.  
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Statistical Analysis Plan,  
 
Sponsor Foamix Pharmaceuticals  
 
Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 12 of 28 
 
• Treatment duration (days) of FMX103 1.5% =  
Date of last dose of FMX103 1.5% – Date of first dose of FMX103 1.5% + 1 day 
For subjects who received vehicle during study FX2016-11 and FX2016-12, the date for first 
dose of FMX103 1.5% will occur during the FX2016-13 study 
• IGA treatment success = yes if the following conditions are both satisfied: 
o IGA score of 0 or 1 
o at least a 2-grade improvement (decrease) from baseline 
Otherwise, IGA treatment success = no 
6.1.7. Data Adjustments/Handling/Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA), Version 20.0. In general, a TEAE is defined as an AE with an onset date after the 
first dose of the open-label extension study and before the last application of study drug plus 3 
days having been absent pre-treatment or worsening relative to the pre-treatment state.  AEs 
reported at the baseline visit (Week 12 visit of the double-blind phase) will be assigned to the 
initial double-blind study. For subjects with >3 days of study drug interruption during the 40-
week treatment period, the definition of a TEAE will also consider the date of the last dose 
before study drug interruption. For these subjects, AEs that start >3 days after the last dose 
before study drug interruption and before the drug is re-administered will not be considered as 
treatment-emergent. 
Any AE that started before the first dose of study drug and worsens in severity or changes from 
non-serious to serious on or after the first dose date of the open-label phase will also be 
designated as a TEAE. If an event worsens in severity during the study, the outcome of the lower 
grade event would be RECOVERED/RESOLVED or RECOVERED/RESOLVED WITH 
SEQUELAE with an end date (of that grade). A new event is recorded on the AE case report 
form (CRF) with a start date that matches the end date, and the term recorded includes 
“Worsened” (eg, “Worsened Headaches”). If an event becomes serious, the date that the event 
became serious is recorded on the AE CRF as the End Date of that AE and the Start Date of the 
corresponding SAE. 
Any AE or concomitant medication that was ongoing at the end of the double-blind study will be 
copied into the extension study database with start dates entered as the original start date. 
Adverse events and concomitant medications that are ongoing at the end of the open-label study 
will be closed out with a stop date of “ongoing.” 
A treatment-related AE is any AE with a relationship to the study drug of possible or probable. 
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Statistical Analysis Plan,  
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Protocol Number FX2016-13  
PCN Number FOAM166108
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Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 13 of 28 
Adverse events or medications with missing complete start dates will be classified as treatment 
emergent or concomitant, as appropriate. 
For analysis purposes, an AE that does not have a recorded relationship to the study drug value 
will be considered as “Probably Related” to the study drug, unless the start date of the AE is 
before the date of first study drug administration, in which case the event would be considered as 
“Unlikely Related.” If the severity of an AE is missing, the severity will be considered as 
“Missing.”  
If partial AE or concomitant medication onset dates occur, the convention for replacing missing 
dates for the purpose of statistical analysis is as follows: if just day is missing then the day 
assigned is the first day of the month or the date of first dose (if in the same month), whichever is 
later; if just month is missing then the month assigned is the month of the first dose, unless that 
results in a date prior to the first dose in which case the month after the first dose is used; and if 
both month and day are missing then the month assigned is the month of the first dose and the 
day assigned is either the first day of the month or the first dose date, whichever is later. 
These conventions will be applied only to onset dates with the following precaution related to 
AE onset dates: if the missing date reflects the date of onset of an AE, the modified date will be 
constructed to match the first documented date post-drug administration while preserving the 
order in which the AE was reported in the CRF. 
For partial end dates, the convention for replacing missing dates for the purpose of statistical 
analysis is as follows: if only the day is missing, then the day is assigned the last day of the 
month; if both day and month are missing, they are assigned the last day of the year (31 Dec). 
For subjects who are missing the date of last study drug application, for any reason, the last 
known contact date will be used in the calculation of treatment duration and study drug exposure. 
Study drug compliance will not be calculated for those subjects whose date of last study drug 
application is unknown. 
For analysis purposes, repeat laboratory test results will not be used unless the original 
laboratory value is missing or indicated as invalid, in which case the first non-missing repeat 
laboratory value will be used for data analysis. 
7.
Study Subjects and Demographics
All analyses outlined in this section will be performed on the All Treated population. 
7.1. 
Disposition of Patients/Subjects and Withdrawals 
The number and percentage of subjects that are included in the All Treated population, 
completed the study, participated in each double-blind study (FX2016-11 and FX2016-12), and 
withdrew from the study (overall and by reason for withdrawal), summarized overall and by 
treatment group (9 month active and 12 month active).  
The number and percentage of subjects who were in the safety populations of each double-blind 
study (FX2016-11 and FX2016-12) and the number and percentage of subjects who continued on 
to study FX2016-13 will be summarized overall and treatment group. Percentages will be 
calculated out of the total number of subjects in studies FX2016-11 and FX2016-12 combined.   
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A by-subject enrollment and disposition listing will be presented for all treated subjects. Subjects 
who are screen failures will be presented in a separate listing. 
7.2. 
Protocol Violations and Deviations 
Protocol deviations will be listed for all treated subjects.  
7.3. 
Demographics and Other Baseline Characteristics 
Summary statistics of demographics and baseline characteristics will be summarized overall and 
by treatment group. The following demographic and baseline variables will be included: 
• 
Age (years) 
• 
Age group in full years (18 to 40 years, 41 to 64 years, ≥ 65 years) 
• 
Sex 
• 
Race  
• 
Ethnicity  
• 
Baseline body weight (kg), height (cm), and body mass index (BMI) (kg/m2) 
• 
Baseline inflammatory lesion count (from Day 0 of the initial double-blind study) 
• 
Baseline IGA score (moderate=3, severe=4) 
For continuous variables, the number of non-missing values and the mean, SD, minimum, 
median, and maximum will be tabulated.  
For categorical variables, the counts and proportions of each value will be tabulated. Subjects 
reporting more than 1 race will be included in a “More than one race” category for purposes of 
tabulating summary statistics. Past medical histories for all treated subjects will be provided in a 
by-subject listing. 
7.4. 
Exposure and Compliance 
The following parameters of study drug exposure and compliance will be summarized overall 
and by treatment groups for the FX2016-13 study: 
• 
Treatment duration (days) 
• 
Study drug exposure (days) 
• 
Study drug compliance (%) 
For a given day, a subject is considered compliant with treatment if any amount of study drug is 
applied to the facial area. For subjects who are missing the date of last study drug application, for 
any reason, the last known contact date will be used in the calculation of treatment duration and 
study drug exposure. Study drug compliance will not be calculated for those subjects whose date 
of last study drug application is unknown. For subjects who are instructed to discontinue 
treatment and then restart study drug during the study, days that the subject was not taking study 
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Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 15 of 28 
drug will be included in treatment duration and exposure and will be considered compliant 
during that time. 
Overall treatment duration (days) of FMX103 1,5% will also be summarized by treatment 
received during the initial double-blind study as the date of the last dose of FMX103 1.5% minus 
the date of the first dose of FMX103 1.5% plus one day. For subjects who initially received 
vehicle, treatment with FMX103 1.5% began during study FX2016-13. The number and 
percentage of subjects who were exposed to FMX103 1.5% for six months(>168 days) or more 
and one year or more (>350 days) will be summarized.  
8.
Efficacy Analysis
All efficacy analyses outlined in this section will be performed on the All Treated population. 
8.1.
Primary Efficacy Analysis 
The primary efficacy analyses are based on the AT population and are as follows:  
•
Absolute change from baseline in inflammatory lesion count at Week 40
•
Dichotomized IGA Success Rate at Week 40
Descriptive summaries will be presented for each of the co-primary endpoints. For change from 
baseline, the number of non-missing values, mean, SD, coefficient of variation (CV), median, 
minimum and maximum will be presented. For IGA Success Rate, the number of non-missing 
values and the frequency and proportion of subjects who achieve treatment success will be 
summarized. No hypothesis testing will be performed.  
In order to evaluate any differences in the co-primary endpoints due to the treatment received in 
the initial double-blind study, the primary endpoints will be summarized overall and by treatment 
sequence. 
8.2.
Secondary Efficacy Analysis 
The following secondary efficacy endpoints will be analyzed similarly to the appropriate 
co-primary efficacy parameters: 
•
The absolute change from baseline in inflammatory lesion count at Weeks 4, 10, 16, 22,
28, and 34
•
The dichotomized IGA Success Rate at Weeks 4, 10, 16, 22, 28 and 34
•
The percent change from baseline in inflammatory lesion count at Weeks 4, 10, 16, 22,
28, 34, and 40.
•
The Subject Satisfaction Questionnaire (SSQ) at Week 40.
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 Page 16 of 28 
 
8.3. 
Subject Satisfaction Questionnaire 
Answers to the SSQ will be summarized for Week 40 (or the ET visit) using frequency counts 
and percentages for the All Treated population. The SSQ will be summarized overall and by 
treatment group.  
9. 
Safety and Tolerability Analysis 
Safety will be evaluated from reported AEs, changes in clinical laboratory values, changes in vital 
signs, and physical examination results. All safety analyses will be performed on the All Treated 
Population. 
Safety assessments will be summarized using descriptive statistics overall and by treatment 
group and in individual subject listings.  
No statistical tests will be performed for any of the safety assessments. 
9.1. 
Adverse Events 
All AE terms will be coded using MedDRA, Version 20.0. 
All AEs that occur after enrollment in the extension study but before administration of the study 
drug will be reported as an AE in the respective double-blind study and recorded as medical 
history in this study. TEAEs will be defined as any adverse event with an onset date after the 
first dose date of the open-label extension study and before the last application of study drug plus 
3 days having been absent pre-treatment or worsening relative to the pre-treatment state.  AEs 
reported at the baseline visit (Week 12 visit of the double-blind phase) will be assigned to the 
respective double-blind study. For subjects with >3 days of study drug interruption during the 
40-week treatment period, the definition of a TEAE will also consider the date of the last dose 
before study drug interruption. For these subjects, AEs that start >3 days after the last dose 
before study drug interruption and before the drug is re-administered will not be considered as 
treatment-emergent. If relationship to treatment is missing, the event will be summarized 
conservatively as probably related to study drug unless the start date of the AE is before the first 
study drug administration, in which case the event would be considered as not related. If severity 
is missing, the event will be summarized as “missing”. Through the data cleaning process, all 
attempts will be made to avoid missing values for relationship and severity. 
All AEs summarized by system organ class (SOC) and preferred term (PT) will be sorted in 
order of descending frequency of the SOC and then by descending frequency order (total across 
treatment groups) of the PT within each SOC.  
An overall summary of AEs will be presented for the All Treated population. This summary will 
include the total number of events, frequency counts, and percentages for: 
• Any AEs 
• Any TEAEs 
• Any SAEs 
• Any treatment-related TEAEs  
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• Any TEAE leading to study discontinuation 
• TEAEs resulting in death 
Summaries of the incidence of TEAEs and SAEs will be displayed by: 
• SOC and PT 
• SOC, PT, and maximum severity (mild, moderate, severe) 
• SOC, PT, and maximum causality (not related, related) to the study drug 
If there are multiple occurrences of the same TEAE within the same subject, each subject will 
only be counted once for each PT. In the summaries showing severity and relationship to the 
study drug, the event with the maximum severity or strongest relationship will be reported.  
All AEs will be presented in a by-subject listing, detailing the verbatim term given by the 
Investigator, the PT, SOC, onset date and time, end date and time, severity, outcome, 
relationship to study drug, action taken with study drug, other action taken, seriousness, and 
criteria for seriousness. All SAEs will be presented in a separate listing.  
9.1.1. Adverse Events Leading to Withdrawal 
A summary of incidence rates (frequencies and percentages) of TEAEs leading to withdrawal of 
study drug (and subsequent permanent discontinuation from the study), by SOC, and preferred 
term will be presented.  
A data listing of AEs leading to withdrawal of study drug will also be provided, displaying 
details of the event(s) captured on the CRF. 
9.1.2. Deaths and Serious Adverse Events 
Any deaths that occur during the study will be listed. 
Serious adverse events will be listed and also tabulated by system organ class and preferred term. 
All SAEs will also be presented by maximum severity and maximum causality.  
9.2. 
Clinical Laboratory Evaluations 
Absolute and changes from baseline values will be summarized by treatment group and time 
point for clinical laboratory (chemistry and hematology) results using descriptive statistics. The 
number of subjects with clinical laboratory values below, within, or above the normal range will 
be tabulated for each clinical laboratory test at the Week 40 visit. Shift tables for each clinical 
laboratory test will cross-tabulate the number of subjects with values below the laboratory 
reference range (low), values within the laboratory reference range (normal), or above the 
laboratory range (high) at baseline with the number of subjects with low, normal or high values 
at the Week 40 visit. Normal ranges and values outside the normal ranges will be identified by 
the central laboratory. A separate listing of out of normal range laboratory results will be 
provided for all chemistry, hematology, and urinalysis tests. 
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A listing of all subjects with treatment-emergent clinically significant abnormal chemistry, 
hematology, or urinalysis values will be presented for each treatment group. Clinical significance 
will be based on the Investigator’s judgment. 
Urinalysis and urine pregnancy test results will be presented in by-subject listings. 
9.3. 
Vital Signs 
Descriptive summaries of actual values and changes from baseline will be calculated for supine 
systolic blood pressure, supine diastolic blood pressure, heart rate, respiratory rate, and oral body 
temperature.   
9.4. 
Physical Examinations 
Shifts from baseline for physical examinations will be presented for the Week 40 visit overall 
and by treatment group.  
Abnormal physical examination findings will be displayed in a by-subject listing. 
9.5. 
Local Signs and Symptoms Assessments 
Erythema, telangiectasia, burning/stinging, flushing/blushing, dryness/xerosis, itching, 
peeling/desquamation, and hyperpigmentation at the sites of study drug application will be 
assessed at each study visit. All local signs/symptoms with the exception of erythema will be 
graded on a 0 to 3 scale (0=none; 1=mild; 2=moderate; 3=severe). Erythema will be graded on a 
0 to 4 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). Itching will be assessed on the same 0 to 3 scale based on the subjects’ subjective 
assessment. 
The severity of each assessed local sign/symptom will be summarized using frequency counts 
and percentages at each visit by treatment group and overall.  
9.6. 
Concomitant Medication 
A concomitant medication is any non-protocol specified drug or substance administered during 
participation in the study, including medications that are ongoing at the time of informed 
consent. This period of participation is from the time of enrollment in the extension study 
through the last contact at 4 weeks after the Week 40 clinic visit. Medications that were 
considered concomitant during the initial double-blind study but were stopped before enrollment 
in the extension study will be considered prior medications.  
Prior and concomitant medications will be summarized descriptively by treatment group and 
overall using counts and percentages in each Anatomical Therapeutic Chemical (ATC) level 2 
group and PT (ie, generic name). 
Prior medications will be presented separately from concomitant medications. Medications that 
started prior to Day 1 of the extension study will be considered prior medications whether or not 
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 Page 19 of 28 
 
they were stopped prior to Day 1. Any medications continuing or starting after Day 1 will be 
considered to be concomitant. If a medication starts prior to Day 1 and continues after Day 1 it 
will be considered both prior and concomitant.  
• Medications will be coded using the World Health Organization Drug Dictionary Version 
March 2017. 
10. 
Changes from Planned Analysis 
There are no changes from the analyses planned in the protocol. 
11. 
Other Planned Analysis 
11.1. Pharmacokinetic Analysis 
No pharmacokinetic analysis is planned for this study.  
12. 
References 
1. ASA. (2016) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2016. http://www.amstat.org/about/ethicalguidelines.cfm 
2. RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014. 
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf. 
3. US Federal Register. (1998) International Conference on Harmonization; Guidance on 
Statistical Principles for Clinical Trials. Department of Health and Human Services: Food 
and Drug Administration [Docket No. 97D-0174]. Federal Register Volume 63, Number 179, 
pages 49583-49598. September 16, 1998. 
13. 
Tables, Listings, and Figures 
All listings, tables, and graphs will have a header showing the sponsor company name and 
protocol and a footer showing the version of SAS, the file name and path, and the source of the 
data (ie, listing number where applicable). 
13.1. Planned Table Descriptions 
The following are planned summary tables for protocol number FX2016-13. The table numbers 
and page numbers are place holders only and will be determined when the tables are produced. 
During the 40-week open-label treatment extension study, subjects who were applying FMX103 
1.5% at the end of the respective double-blind study will continue this treatment, while subjects 
who were administering vehicle will crossover to FMX103 1.5%. 
For the table summaries, the 2 treatment groups representing FMX103 1.5% and Vehicle to 
FMX103 1.5% will be presented as:  DB – FMX103 1.5% and DB – Vehicle, respectively.
20 of 84


 
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Table 3:  Disposition, Demographic, Prior Medications, and Study Drug Exposure Data 
Summary Tables 
Table Number 
Population(s) 
Table Title / Summary 
Supporting 
listing 
14.1  Disposition, Demographic, Prior Medications, and Study Drug Exposure Data 
Table 14.1.1 
All Subjects 
Summary of Subject Enrollment and Disposition 
16.2.1.1            
16.2.1.2            
16.2.4.1 
Table 14.1.2 
All Subjects in 
Safety populations 
of FX2016-11 and 
FX2016-12 
Summary of Study Enrollment 
16.2.1.1            
 
Table 14.1.3 
All-Treated 
Population 
Summary of Demographics and Baseline Characteristics 
16.2.4.1 
16.2.6.1 
16.2.6.2 
Table 14.1.4 
All-Treated 
Population 
Summary of Prior Medications by ATC Level 2 and Preferred 
Term 
16.2.4.3 
Table 14.1.5 
All-Treated 
Population 
Summary of Study Drug Exposure 
16.2.5.1 
16.2.5.2 
Table 14.1.6 
All-Treated 
Population 
Summary of Overall FMX103 1.5% Treatment Duration (Days) 
by Treatment 
16.2.5.1 
16.2.5.2 
Table 14.1.7 
All-Treated 
Population 
Study Drug Compliance 
16.2.5.3 
 
Table 4:  Efficacy Data 
Table Number 
Population(s) 
Table Title / Summary 
Supporting 
listing 
14.2  Efficacy Data 
Table 14.2.1.1 
All-Treated Population Change from Baseline in Inflammatory Lesion Count 
16.2.6.2 
Table 14.2.1.2 
All-Treated Population Change from Baseline (Week 12) in Inflammatory Lesion 
Count 
16.2.6.2 
Table 14.2.2.1 
All-Treated Population Descriptive Summary of IGA Treatment Success 
16.2.6.1 
Table 14.2.2.2 
All-Treated Population Descriptive Summary of IGA Treatment Success from 
Baseline (Week 12) 
16.2.6.1 
Table 14.2.3 
All-Treated Population Descriptive Summary of Subject Satisfaction Questionnaire 
16.2.6.3 
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 Page 21 of 28 
 
Table 5:  Safety Data 
Table Number 
Population(s) Table Title / Summary 
Supporting 
listing 
14.3  Safety Data 
14.3.1  Displays of Adverse Events 
Table 14.3.1.1 
All-Treated 
Population 
Summary of All Adverse Events  
16.2.7.1 
Table 14.3.1.2 
All-Treated 
Population 
Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term 
16.2.7.1 
Table 14.3.1.3 
All-Treated 
Population 
Treatment-Emergent Adverse Events by Severity, System Organ 
Class, and Preferred Term 
16.2.7.1 
Table 14.3.1.4 
All-Treated 
Population 
Treatment-Emergent Adverse Events by Relationship to Study 
Drug, System Organ Class, and Preferred Term 
16.2.7.1 
14.3.2  Other Serious and Significant Adverse Events 
Table 14.3.2.1 
All-Treated 
Population 
Serious Adverse Events by System Organ Class and Preferred Term 16.2.7.2 
Table 14.3.2.2 
All-Treated 
Population 
Serious Adverse Events by Severity, System Organ Class, and 
Preferred Term 
16.2.7.2 
Table 14.3.2.3 
All-Treated 
Population 
Serious Adverse Events by Relationship to Study Drug, System 
Organ Class, and Preferred Term 
16.2.7.2 
Table 14.3.2.4 
All-Treated 
Population 
Adverse Events Leading to Withdrawal from the Study by System 
Organ Class and Preferred Term 
16.2.7.3 
Table 14.3.2.5 
All-Treated 
Population 
Adverse Events Leading to Withdrawal from the Study by Severity, 
System Organ Class, and Preferred Term 
16.2.7.3 
Table 14.3.2.6 
All-Treated 
Population 
Adverse Events Leading to Withdrawal from the Study by 
Relationship to Study Drug, Systemic Organ Class, and Preferred 
Term 
16.2.7.3 
 
 
 
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Table Number 
Population(s) 
Table Title / Summary 
Supporting 
listing 
14.3.5  Laboratory Data Summary Tables 
Table 14.3.5.1 
All-Treated 
Population 
Clinical Chemistry Results 
16.2.8.1 
Table 14.3.5.2 
All-Treated 
Population 
Shift Table of Clinical Chemistry Results 
16.2.8.1 
Table 14.3.5.3 
All-Treated 
Population 
Hematology Results 
16.2.8.2 
Table 14.3.5.4 
All-Treated 
Population 
Shift Tables of Hematology Results 
16.2.8.2 
14.3.6  Other Safety and Tolerability Summary Tables 
Table 14.3.6.1 
All-Treated 
Population 
Shift Table of Physical Examination Results 
16.2.9.2 
Table 14.3.6.2 
All-Treated 
Population 
Vital Sign Results 
16.2.9.1 
Table 14.3.6.3 
All-Treated 
Population 
Concomitant Medications by ATC Level 2 and Preferred Term 
16.2.9.3 
Table 14.3.6.4 
All-Treated 
Population 
Summary of Local Signs and Symptoms Assessments 
16.2.9.4 
 
 
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Protocol Number FX2016-13  
 
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 Planned Listing Descriptions 
The following are planned data and subject data listings for protocol FX2016-13.  
In general, one listing will be produced per CRF domain. All listings will be sorted by treatment, 
site, and subject number. Calculated variables will be included in the listings, as applicable. 
In all listings, a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (eg, repetition of subject number), then only the first occurrence will be 
displayed. 
In data listings, the information for one subject will be kept on one page if at all possible, rather 
than splitting a subject’s information across pages. 
Table 6:  Planned Listings 
Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
16.2.1 Subject Discontinuations/Completions 
Data listing 16.2.1.1  
All Treated 
Subjects 
Study Completion Status 
Data listing 16.2.1.2  
All Treated 
Subjects 
Inclusion and Exclusion Criteria Not Met 
16.2.2 Protocol Deviations 
Data listing 16.2.2.1 
All Treated 
Subjects 
Protocol Deviations 
16.2.3 Subjects Excluded from the Efficacy Analyses 
NA 
 
 
16.2.4 Demographic Data and Other Baseline Characteristics 
Data listing 16.2.4.1 
All Treated 
Subjects 
Demographic Data 
Data listing 16.2.4.2 
All Treated 
Subjects 
Medical History 
Data listing 16.2.4.3 
All Treated 
Subjects 
Prior Medications 
16.2.5 Compliance Data 
Data listing 16.2.5.1 
All Treated 
Subjects 
Study Drug Accountability 
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Data Listing Number 
Population 
Data Listing Title / Summary 
Data listing 16.2.5.2 
All Treated 
Subjects 
Study Drug Stoppage and Restart 
Data listing 16.2.5.3 
All Treated 
Subjects 
Study Drug Compliance 
16.2.6 Individual Efficacy Response Data 
Data listing 16.2.6.1 
All Treated 
Subjects 
IGA Score 
Data listing 16.2.6.2 
All Treated 
Subjects 
Inflammatory Lesion Count by Facial Area 
Data listing 16.2.6.3 
All Treated 
Subjects 
Subject Satisfaction Questionnaire (SSQ) 
16.2.7 Adverse Event Listings 
Data listing 16.2.7.1 
All Treated 
Subjects 
Adverse Events 
Data listing 16.2.7.2 
All Treated 
Subjects 
Serious Adverse Events 
Data listing 16.2.7.3 
All Treated 
Subjects 
Adverse Events Leading to Withdrawal 
Data listing 16.2.7.4 
All Treated 
Subjects 
Deaths 
16.2.8 Laboratory Data Listings 
Data listing 16.2.8.1 
All Treated 
Subjects 
Clinical Chemistry Results 
Data listing 16.2.8.2 
All Treated 
Subjects 
Hematology Results 
Data listing 16.2.8.3 
All Treated 
Subjects 
Urinalysis Results 
Data listing 16.2.8.4 
All Treated 
Subjects 
Clinically Significant Laboratory Tests for Hematology, 
Chemistry, and Urinalysis 
Data listing 16.2.8.5 
All Treated 
Subjects 
Out of Range (Abnormal) Laboratory Tests for Hematology, 
Chemistry, and Urinalysis  
Data listing 16.2.8.6 
All Treated 
Subjects 
Pregnancy Test Results 
16.2.9 Other Clinical Observations and Measurements 
Data listing 16.2.9.1 
All Treated 
Subjects 
Vital Signs 
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Data Listing Number 
Population 
Data Listing Title / Summary 
Data listing 16.2.9.2 
All Treated 
Subjects 
Abnormal Physical Examination Results 
Data listing 16.2.9.3 
All Treated 
Subjects 
Concomitant Medications 
Data listing 16.2.9.4 
All Treated 
Subjects 
Local Signs and Symptoms Assessments 
Data listing 16.2.9.5 
All Treated 
Subjects 
Telephone Contact 
 
 
 
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13.2. Planned Figure Descriptions 
There are no planned figures. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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14. 
Tables, Listings, and Listing Shells 
14.1. 
Standard Layout for all Tables, Listings, and Figures 
Table and listing shells are provided in a separate document. 
Note that programming notes may be added after each table, listing or figure (TLF) shell if appropriate.  
 
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Statistical Analysis Plan,  
 
Sponsor Foamix Pharmaceuticals  
 
Protocol Number FX2016-13  
 
PCN Number FOAM166108 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    08-Jan-2019    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 28 of 28 
 
Appendix 1: Premier Research Library of Abbreviations 
 
Abbreviation 
Definition 
AE 
adverse event 
AT 
All Treated population 
ATC 
Anatomical Therapeutic Chemical 
CRF 
case report form 
CSR 
clinical study report 
CV 
Coefficient of variation 
DB 
Double-blind 
ET 
early termination 
IGA 
Investigator’s Global Assessment 
MedDRA 
medical dictionary for regulatory activities 
PT 
preferred term 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS®  
a software system used for data analysis 
SD 
standard deviation 
SOC 
system organ class 
SSQ 
subject satisfaction questionnaire 
TEAE 
treatment-emergent adverse event 
 
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Sponsor: Foamix Pharmaceuticals 
Final 1.0 
Protocol Number FX2016-13 
08-Jan-2019 
 
CONFIDENTIAL  
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Statistical Analysis 
Table and Listing Shells 
 
Sponsor 
Foamix Pharmaceuticals 
Protocol Title: 
An Open-Label Study to Evaluate the Long-Term Safety of 
Topical Administration of FMX103 for 40 weeks in the 
Treatment of Moderate to Severe Facial Papulopustular 
Rosacea (Study FX2016-13) 
Protocol Number: 
FX2016-13 
Premier Research PCN: 
FOAM166108 
Document Version: 
Final Version 1.0 
Document Date:  
08-Jan-2019 
 
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Table and Listing Shells for Foamix FX2016-13 
14.1 
Disposition, Demographic, Prior Medications and Study Drug Exposure Data Summary Tables...................................................................... 6 
Table 14.1.1 Summary of Subject Enrollment and Disposition ............................................................................................................................. 6 
Table 14.1.2 Summary of Study Enrollment .......................................................................................................................................................... 7 
Table 14.1.3 Summary of Demographics and Baseline Characteristics ................................................................................................................. 8 
Table 14.1.4 Summary of Prior Medications by ATC Level 2 and Preferred Term .............................................................................................. 10 
Table 14.1.5 Summary of Study Drug Exposure................................................................................................................................................... 11 
Table 14.1.6 Summary of Overall FMX103 1.5% Treatment Duration (Days)[1] by Treatment[2]...................................................................... 12 
Table 14.1.7 Study Drug Compliance ................................................................................................................................................................... 13 
14.2 
Efficacy Data ..................................................................................................................................................................................................... 14 
Table 14.2.1.1 Change from Baseline in Inflammatory Lesion Count .................................................................................................................. 14 
Table 14.2.1.2 Change from Baseline (Week 12)[1] in Inflammatory Lesion Count ............................................................................................ 16 
Table 14.2.2.1 Descriptive Summary of IGA Treatment Success ......................................................................................................................... 17 
Table 14.2.2.2 Descriptive Summary of IGA Treatment Success from Baseline (Week 12)[1] ............................................................................ 18 
Table 14.2.3 Descriptive Summary of Subject Satisfaction Questionnaire .......................................................................................................... 19 
14.3 
Safety Data ....................................................................................................................................................................................................... 20 
14.3.1 
Displays of Adverse Events .......................................................................................................................................................................... 21 
Table 14.3.1.1 Summary of All Adverse Events ................................................................................................................................................... 21 
Table 14.3.1.2 Treatment-Emergent Adverse Events by System Organ Class and Preferred Term .................................................................... 22 
Table 14.3.1.3 Treatment-Emergent Adverse Events by Severity, System Organ Class, and Preferred Term .................................................... 23 
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Table 14.3.1.4 Treatment-Emergent Adverse Events by Relationship to Study Drug, System Organ Class, and Preferred Term ...................... 24 
14.3.2 
Other Serious and Significant Adverse Events ......................................................................................................................................... 25 
Table 14.3.2.1 Serious Adverse Events by System Organ Class and Preferred Term .......................................................................................... 25 
Table 14.3.2.2 Serious Adverse Events by Severity, System Organ Class, and Preferred Term .......................................................................... 25 
Table 14.3.2.3 Serious Adverse Events by Relationship to Study Drug, System Organ Class, and Preferred Term ............................................ 26 
Table 14.3.2.4 Adverse Events Leading to Withdrawal from the Study by System Organ Class and Preferred Term ........................................ 26 
Table 14.3.2.5 Adverse Events Leading to Withdrawal from the Study by Severity, System Organ Class, and Preferred Term ........................ 27 
Table 14.3.2.6 Adverse Events Leading to Withdrawal from the Study by Relationship to Study Drug, System Organ Class, and Preferred 
Term ..................................................................................................................................................................................................................... 27 
14.3.5 
Laboratory Data Summary Tables ............................................................................................................................................................ 28 
Table 14.3.5.1 Clinical Chemistry Results ............................................................................................................................................................ 28 
Table 14.3.5.2 Shift Table of Clinical Chemistry Results ...................................................................................................................................... 29 
Table 14.3.5.3 Hematology Results...................................................................................................................................................................... 30 
Table 14.3.5.4 Shift Table of Hematology Results ............................................................................................................................................... 30 
14.3.6 
Other Safety and Tolerability Summary Tables ....................................................................................................................................... 31 
Table 14.3.6.1 Shift Table of Physical Examination Results ................................................................................................................................. 31 
Table 14.3.6.2 Vital Sign Results .......................................................................................................................................................................... 32 
Table 14.3.6.3 Concomitant Medications by ATC Level 2 and Preferred Term ................................................................................................... 33 
Table 14.3.6.4 Summary of Local Signs and Symptoms Assessments ................................................................................................................. 34 
16.2 
Subject Data Listings ........................................................................................................................................................................................ 35 
16.2.1 
Subject Discontinuations/Completions .................................................................................................................................................... 36 
Listing 16.2.1.1 Study Completion Status ............................................................................................................................................................ 36 
Listing 16.2.1.2 Inclusion and Exclusion Criteria Not Met ................................................................................................................................... 37 
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16.2.2 
Protocol Deviations .................................................................................................................................................................................. 38 
Listing 16.2.2.1 Protocol Deviations ..................................................................................................................................................................... 38 
16.2.4 
Demographic Data and Other Baseline Characteristics ........................................................................................................................... 39 
Listing 16.2.4.1 Demographic Data ...................................................................................................................................................................... 39 
Listing 16.2.4.2 Medical History ........................................................................................................................................................................... 39 
Listing 16.2.4.3 Prior Medications ....................................................................................................................................................................... 40 
16.2.5 
Compliance Data ...................................................................................................................................................................................... 41 
Listing 16.2.5.1 Study Drug Accountability .......................................................................................................................................................... 41 
Listing 16.2.5.2 Study Drug Stoppage and Restart ............................................................................................................................................... 42 
Listing 16.2.5.3 Study Drug Compliance .............................................................................................................................................................. 43 
16.2.6 
Individual Efficacy Response Data ........................................................................................................................................................... 44 
Listing 16.2.6.1 IGA Score .................................................................................................................................................................................... 44 
Listing 16.2.6.2 Inflammatory Lesion Count by Facial Area ................................................................................................................................. 45 
Listing 16.2.6.3 Subject Satisfaction Questionnaire (SSQ) ................................................................................................................................... 46 
16.2.7 
Adverse Event Listings.............................................................................................................................................................................. 47 
Listing 16.2.7.1 Adverse Events ........................................................................................................................................................................... 47 
Listing 16.2.7.2 Serious Adverse Events ............................................................................................................................................................... 48 
Listing 16.2.7.3 Adverse Events Leading to Withdrawal ...................................................................................................................................... 48 
Listing 16.2.7.4 Deaths ......................................................................................................................................................................................... 48 
16.2.8 
Laboratory Values .................................................................................................................................................................................... 49 
Listing 16.2.8.1 Clinical Chemistry Results ........................................................................................................................................................... 49 
Listing 16.2.8.2 Hematology Results .................................................................................................................................................................... 49 
Listing 16.2.8.3 Urinalysis Results ........................................................................................................................................................................ 50 
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Listing 16.2.8.4 Clinically Significant Laboratory Tests for Hematology, Chemistry, and Urinalysis ................................................................... 50 
Listing 16.2.8.5 Out of Range (Abnormal) Laboratory Tests for Hematology, Chemistry, and Urinalysis ........................................................... 51 
Listing 16.2.8.6 Pregnancy Test Results ............................................................................................................................................................... 51 
16.2.9 
Other Clinical Observations and Measurements ..................................................................................................................................... 52 
Listing 16.2.9.1 Vital Signs .................................................................................................................................................................................... 52 
Listing 16.2.9.2 Abnormal Physical Examination Results ..................................................................................................................................... 52 
Listing 16.2.9.3 Concomitant Medications .......................................................................................................................................................... 53 
Listing 16.2.9.4 Local Signs and Symptoms Assessments .................................................................................................................................... 54 
Listing 16.2.9.5 Telephone Contact...................................................................................................................................................................... 55 
  
 
 
 
 
 
 
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14.1 Disposition, Demographic, Prior Medications and Study Drug Exposure Data Summary Tables 
 
Table 14.1.1 
Summary of Subject Enrollment and Disposition 
All Subjects  
 
Status 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
 
 
 
 
All Treated population 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Enrolled from the FX2016-11 study 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Enrolled from the FX2016-12 study 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
 
 
Completed the study 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
 
 
Discontinued early 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Reason for discontinuation 
 
 
 
    Adverse event 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
    Abnormal laboratory result 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
    Lost to follow-up 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
    Subject request 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
    Protocol deviation 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
    Other 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentages are based on the number of subjects in the All Treated population. DB = Treatment received during double-blind study  
The All Treated population is defined all subjects who use the study drug at least once. 
Source: Listing 16.2.1.1, 16.2.1.2, 16.2.4.1 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.1.2 
Summary of Study Enrollment 
All Subjects in Safety populations of FX2016-11 and FX2016-12 
 
Number of Subjects 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
 
 
 
 
FX2016-11 Safety Population[1] 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
FX2016-12 Safety Population[1] 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Subjects who continued to FX2016-13[2] 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
 
 
Note: Percentages are based on the total number of subjects in studies FX2016-11 and FX2016-12.   
[1]Includes all subjects that were randomized and received at least one application of study medication. 
[2]Includes all subjects who enrolled in study FX2016-13.  
 
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Table 14.1.3 
Summary of Demographics and Baseline Characteristics  
All Treated Population 
 
 
 
 
Sample 
DB - FMX103 
1.5% 
DB - Vehicle 
Overall 
Variable 
Characteristic/Category 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
Age [years] [1] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Weight [kg] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Height [cm] [2] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Body Mass Index (BMI) [kg/m2] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Age group [full years] [1] 
18 to 40 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
41 to 64 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
≥ 65 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing 
xx 
xx 
xx 
 
 
 
 
 
Sex 
Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing 
xx 
xx 
xx 
 
 
 
 
 
 
 
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Table 14.1.3 (cont’d) 
 
Sample 
DB - FMX103 
1.5% 
DB - Vehicle 
Overall 
Variable 
Characteristic/Category 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
Ethnicity 
Hispanic/Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Non-Hispanic/Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing 
xx  
xx  
xx  
 
 
 
 
 
Race 
American Indian or Alaska native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Native Hawaiian or other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
More than one race 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing 
xx 
xx 
xx 
 
 
 
 
 
IGA Score 
3 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
4 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Missing 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
Inflammatory Lesion Count 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Note: Percentages exclude missing data. SD = standard deviation. DB = Treatment received during double-blind study. Baseline is 
defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).    
[1] Age (years) at the baseline visit. 
[2] For subjects who were missing height, weight and/or BMI at baseline, these variables were imputed from the closest other study 
visit for which it was taken. 
Source: Listing 16.2.4.1, 16.2.6.1, 16.2.6.2 
 
 
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Table 14.1.4 
Summary of Prior Medications by ATC Level 2 and Preferred Term 
All Treated Population 
 
ATC Level 2 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
     Preferred Term [1] 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
Any prior medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
ATC level 2 entry 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     PT 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     PT 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     PT 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     ... 
 
 
 
ATC level 2 entry 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     PT 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     PT 5 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     PT 6 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
ATC level 2 entry 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
... 
... 
... 
... 
.. 
.. 
.. 
.. 
. 
. 
. 
. 
Note: Percentages are 100*n/N. Subjects were counted only once for each Anatomical Therapeutic Chemical 
(ATC) or preferred term. Medications that started prior to Day 1 are considered prior whether or not 
they were stopped prior to Day 1. Medications that were considered concomitant during the initial 
double-blind study but were stopped before enrollment in the extension study will be considered prior 
medications. DB = Treatment received during double-blind study 
[1] Medications were coded using WHO-DD (Enhanced version March 2017) ATC level 2. Preferred Term is 
ATC level 5. 
Source: Listing 16.2.4.3 
 
 
Programming Note: Whenever possible, keep all PT within an ATC level on one page. Sort by ATC level and then PT.  
 
 
 
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Table 14.1.5 
Summary of Study Drug Exposure  
All Treated Population 
 
 
 
 
 
DB - FMX103 
1.5% 
DB - Vehicle 
Overall 
Variable 
Sample 
Characteristics 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
Treatment Duration (days) [1] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
 Total Days of Exposure [2] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Note: For subjects who are missing the date of last dose, the last known contact date will be used in the calculation 
of treatment duration and exposure. DB = Treatment received during double-blind study 
[1] Treatment duration (days) is defined as the date of last dose of study drug minus the date of first dose of study 
drug plus 1 day.  
[2] Total days of exposure is defined as the difference in treatment duration (days) and the number of days that a 
subject reported missing a dose (between the date of first and last dose). For subjects who are instructed discontinue 
and then restart study drug application during the study, the number of days off treatment will also be subtracted 
exposure. 
Source: Listing 16.2.5.1, 16.2.5.2 
 
 
 
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Table 14.1.6 
Summary of Overall FMX103 1.5% Treatment Duration (Days)[1] by Treatment[2] 
All Treated Population 
 
 
 
 
 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
Variable 
Sample 
Characteristics 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
Treatment Duration (days) [1] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
Subjects exposed to ≥ 6 months (>168 days) 
n (%) 
xxx (xx.xx%) 
xxx (xx.xx%) 
xxx (xx.xx%) 
Subjects exposed to ≥ 1 year (>350 days) 
n (%) 
xxx (xx.xx%) 
xxx (xx.xx%) 
xxx (xx.xx%) 
 
 
 
 
 
[1] Treatment duration (days) is defined as the date of last dose of study drug FMX103 1.5% minus the date of first dose of 
study drug FMX103 1.5% plus 1 day. For subjects who are missing the date of last dose, the last known contact date will be used 
[2] Subjects are presented by the treatment received during studies FX2016-11 and FX2016-12. For the vehicle group, treatment of 
FMX103 1.5% started in study FX2016-13.  
 
 
 
 
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Table 14.1.7 
Study Drug Compliance 
All Treated Population  
 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
Statistic 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
n (# missing) 
xx (xx) 
xx (xx) 
xx (xx) 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
 
 
 
 
Note: Compliance (%) = 100 x Study drug exposure (days) / Treatment duration days). DB 
= Treatment received during double-blind study. For subjects who are instructed to 
discontinue then restart study drug application, the number of days of stoppage will 
not be removed from the numerator as they will be considered to be compliant during 
that time. Subjects who are missing last dose dates are not included.  
Source: Listing 16.2.5.3 
 
 
 
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14.2 Efficacy Data  
Table 14.2.1.1 
Change from Baseline in Inflammatory Lesion Count  
All Treated Population 
 
 
 
Visit 
Variable 
Sample 
Characteristics 
DB - FMX103 1.5% 
(N=xxx) 
DB - Vehicle 
(N=xxx) 
Overall 
(N=xxx) 
 
 
 
 
 
 
Baseline [1] 
Observed value 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
 
Baseline (Week 12) 
[2] 
Observed value 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
 
Week 4 
Observed value 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
 
 
Change from Baseline [3] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
 
 
Percent Change from Baseline [3] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
CV 
xx.x 
xx.x 
xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx to xx 
xx to xx 
xx to xx 
 
 
 
 
 
 
Programming Note:  Continue for Weeks 10, 16, 22, 28, 34, and 40. 
Note: The coefficient of variation (CV) is defined as the standard deviation (SD) divided by the mean times 100. DB = Treatment 
received during double-blind study. 
[1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).   
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[2] Baseline (Week 12) is defined as the baseline visit of the open-label extension study.  
[3] Change from baseline is calculated as the value at baseline minus the post-baseline value. Thus, a positive change will 
reflect a reduction in lesion count. The same definition is used in the numerator for percent change.  
Source: Listing 16.2.6.2 
 
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Table 14.2.1.2 
Change from Baseline (Week 12)[1] in Inflammatory Lesion Count  
All Treated Population 
 
 
 
 
 
 
 
 
 
See Table 14.2.1.1 
 
 
 
 
 
 
Programming Note:  Continue for Weeks 10, 16, 22, 28, 34, and 40. Use Baseline(Week 12) of the open-label extension study as the 
baseline visit for this table. 
Note: The coefficient of variation (CV) is defined as the standard deviation (SD) divided by the mean times 100. DB = Treatment 
received during double-blind study. 
[1] Baseline is defined as the Baseline visit in the open-label extension study (Week 12 of DB study).   
[2] Change from baseline is calculated as the value at baseline minus the post-baseline value. Thus, a positive change will 
reflect a reduction in lesion count. The same definition is used in the numerator for percent change.  
Source: Listing 16.2.6.2 
 
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Table 14.2.2.1 
Descriptive Summary of IGA Treatment Success 
All Treated Population 
 
 
 
 
 
 
Score/ 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
Visit  
Success? 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
Baseline [1] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Baseline [2] 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Week 4 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
Week 10 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Week 16 
n (# missing) 
xxx (xx) 
xxx (xx) 
xxx (xx) 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Programming Note: Continue for Weeks 22, 28, 34, and 40.  
 
 
 
 
 
Note: Percentages are based on the number of subjects with a non-missing value (yes or no) at each visit. IGA treatment 
success is Yes if the IGA score is either 0 or 1 and there is at least a 2-grade improvement (decrease) from baseline.  
Otherwise IGA treatment success is No. DB = Treatment received during double-blind study. 
 
    [1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).   
 
    [2] Baseline (Week 12) is defined as the baseline visit of the open-label extension study.  
Source: Listing 16.2.6.1 
 
 
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Table 14.2.2.2 
Descriptive Summary of IGA Treatment Success from Baseline (Week 12)[1] 
All Treated Population 
 
 
 
 
 
 
 
 
 
 
See Table 14.2.2.1 
 
 
 
 
 
 
 
 
 
Programming Note: Continue for Weeks 22, 28, 34, and 40. Use Baseline (Week 12) of the open-label extension 
study as the baseline visit for this table. 
 
 
 
 
 
Note: Percentages are based on the number of subjects with a non-missing value (yes or no) at each visit. IGA treatment 
success is Yes if the IGA score is either 0 or 1 and there is at least a 2-grade improvement (decrease) from baseline.  
Otherwise IGA treatment success is No. DB = Treatment received during double-blind study. 
 
    [1] Baseline is defined as the Baseline visit in the open-label extension study (Week 12 of DB study).   
    Source: Listing 16.2.6.1 
 
 
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Table 14.2.3 
Descriptive Summary of Subject Satisfaction Questionnaire  
All Treated Population 
 
 
 
 
 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
Variable 
Category 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
Easy to Use 
Non-missing response 
xx 
xx 
xx 
 
1-Very satisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
2-Satisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
3-Somewhat satisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4-Dissatisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
5-Very dissatisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing response 
xx 
xx 
xx 
 
 
 
 
 
Feels on skin 
Non-missing response 
xx 
xx 
xx 
 
1-Very satisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
2-Satisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
3-Somewhat satisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4-Dissatisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
5-Very dissatisfied 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing response 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
Programming Note:  Continue for ‘Odor’, ‘Color’, ‘Ease of application’, ‘Ease fitting into daily routine’, ‘Compared to Other 
Products’, ‘Use with other Rosacea treatments’, ‘Recommend to Friend’, and ‘Overall satisfaction’ 
 
 
 
 
 
 
 
 
 
 
Recommend to Friend 
Non-missing response 
xx 
xx 
xx 
 
1-Very likely 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
2-Likely 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
3-Somewhat likely 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4-Unlikely 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
5-Very unlikely 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Missing response 
xx 
xx 
xx 
 
 
 
 
 
Note: Percentages exclude missing responses. Subject Satisfaction Questionnaire is completed at the Week 40 visit or at the 
final visit for those subjects that prematurely withdraw from the study. DB = double-blind study. 
Source: Listing 16.2.6.3 
 
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14.3 Safety Data 
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14.3.1 
Displays of Adverse Events 
 
Table 14.3.1.1 
Summary of All Adverse Events  
All Treated Population 
 
 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
All Adverse Events (AEs) 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
Treatment-emergent adverse events (TEAEs) [1] 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
Serious TEAEs 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
Treatment-related TEAEs [2] 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
Adverse events leading to study discontinuation 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
TEAEs resulting in death 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
 
 
 
 
Note: Percentages are 100*n/N. Number (%) of subjects with at least 1 AE in the category are presented. Adverse events 
were coded using MedDRA, Version 20.0.  
[1] For subjects who are missing the date of last dose, any AE occurring after the first dose is considered treatment 
emergent. 
[2] Any TEAE reported as possibly related or probably related, or is missing, is considered as related to study drug. 
Source: Listing 16.2.7.1 
 
 
 
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Table 14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term  
All Treated Population 
 
 
System Organ Class 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
   Preferred Term 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
Number of Any event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   PT 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   PT 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   PT 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   PT 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
Programming Note: Order SOCs by descending number of subjects (total within both treatment groups) and 
preferred terms within SOC also by descending number of subjects (and for all other tables where AEs are 
arranged by SOC and PT) 
 
 
 
 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term.  
Adverse events were coded using MedDRA, Version 20.0. For subjects who are missing the date of last dose, any 
AE occuring after the first dose is considered treatment emergent. AEs are sorted in descending frequency of 
SOC and PT.  
Source: Listing 16.2.7.1 
 
 
 
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Table 14.3.1.3 
Treatment-Emergent Adverse Events by Severity, System Organ Class, and Preferred Term 
All Treated Population 
 
System Organ Class 
 
 
 
   Preferred Term 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
      Severity 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
Any System Organ Class 
 
 
 
  Any Event (Total) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 1 
 
 
 
  Any Event (Total) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  PT 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  PT 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 2 
 
 
 
  Any Event (Total) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
... 
Programming Note: Only include Missing category when SOC or PT has missing values, otherwise 
just include Severe, Moderate, and Mild 
 
 
 
 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and 
Preferred Term. Adverse events were coded using MedDRA version 20.0. For subjects who are missing 
the date of last dose, any AE occurring after the first dose is considered treatment emergent.  
Source: Listing 16.2.7.1  
 
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Table 14.3.1.4 
Treatment-Emergent Adverse Events by Relationship to Study Drug, System Organ Class, and Preferred Term 
All Treated Population 
System Organ Class 
 
 
 
   Preferred Term 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
      Relationship to Study Drug [1] 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
 
 
 
Any System Organ Class 
 
 
 
  Any Event (Total) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 1 
 
 
 
  Any Event (Total) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  PT 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  PT 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 2 
 
 
 
  Any Event (Total) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
... 
 
 
 
 
 
 
 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. 
Adverse events were coded using MedDRA version 20.0. For subjects who are missing the date of last dose, any 
AE occurring after the first dose is considered treatment emergent. Treatment groups are based on treatment 
received. DB = Treatment received during double-blind study 
[1] Any TEAE reported as possibly related or probably related, or is missing, is considered as related to 
study drug unless the start date is prior to the first date of study drug administration.  
Source: Listing 16.2.7.1  
 
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14.3.2 
Other Serious and Significant Adverse Events 
Table 14.3.2.1 
Serious Adverse Events by System Organ Class and Preferred Term 
All Treated Population 
See Table 14.3.1.2 
______________________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. Adverse events were 
coded using MedDRA, Version 20.0. Treatment groups are based on treatment received. 
Source: Listing 16.2.7.2  
Table 14.3.2.2 
Serious Adverse Events by Severity, System Organ Class, and Preferred Term 
All Treated Population 
See Table 14.3.1.3 
______________________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. Adverse events were 
coded using MedDRA version 20.0. Treatment groups are based on treatment received. 
Source: Listing 16.2.7.2 
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Table 14.3.2.3 
Serious Adverse Events by Relationship to Study Drug, System Organ Class, and Preferred Term 
All Treated Population 
 
 
See Table 14.3.1.4 
____________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. Adverse events were 
coded using MedDRA, Version 20.0. Treatment groups are based on treatment received. 
[1] Any AE reported as possibly related or probably related, or is missing, is considered as related to study drug unless the start 
date is prior to the first date of study drug administration. 
Source: Listing 16.2.7.2 
 
 
 
 
 
 
Table 14.3.2.4 
Adverse Events Leading to Withdrawal from the Study by System Organ Class and Preferred Term  
All Treated Population 
 
 
See Table 14.3.1.2 
____________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. Adverse events were 
coded using MedDRA, Version 20.0. Treatment groups are based on treatment received. 
Source: Listing 16.2.7.3 
 
 
 
 
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Table 14.3.2.5 
Adverse Events Leading to Withdrawal from the Study by Severity, System Organ Class, and Preferred Term 
All Treated Population 
 
 
See Table 14.3.1.3 
____________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. Adverse events were 
coded using MedDRA, Version 20.0. Treatment groups are based on treatment received. 
Source: Listing 16.2.7.3 
 
 
 
 
 
Table 14.3.2.6 
Adverse Events Leading to Withdrawal from the Study by Relationship to Study Drug, System Organ Class, and Preferred Term 
All Treated Population 
 
 
See Table 14.3.1.4 
____________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each System Organ Class and Preferred Term. Adverse events were 
coded using MedDRA, Version 20.0. Treatment groups are based on treatment received. 
[1] Any AE reported as possibly related or probably related, or is missing, is considered as related to study drug unless the start 
date is prior to the first date of study drug administration. 
Source: Listing 16.2.7.3 
 
 
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14.3.5 
Laboratory Data Summary Tables 
 
 
Table 14.3.5.1 
 
Clinical Chemistry Results 
 
All Treated Population 
 
 
 
 
 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
Analyte 
Visit 
Statistic 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
 
Analyte 1 (unit) - Absolute 
value  
Baseline 
[1] 
n (# missing) 
xx (xx) 
xx (xx) 
xx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
 
 
 
 
 
 
 
Week x 
n (# missing) 
xx (xx) 
xx (xx) 
xx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
... 
 
 
 
 
 
 
Analyte 1 (unit) - Change from 
baseline 
Week x 
n (# missing) 
xx (xx) 
xx (xx) 
xx (xx) 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
... 
 
 
 
 
 
 
 
 
Programming Note: Repeat for all applicable visits and all clinical chemistry analytes. 
 
 
 
 
Note: Change from baseline is calculated as the value at the specified visit minus the value recorded at baseline; negative values 
represent a decrease in laboratory values since baseline. DB = Treatment received during double-blind study  
[1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).   
Source: Listing 16.2.8.1 
 
 
 
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Table 14.3.5.2 
Shift Table of Clinical Chemistry Results 
All Treated Population 
 
 
 
 
 
 
 
 
Assessment at Baseline [1] 
 
Analyte 
Treatment 
Assessment at 
Final Visit 
[2] 
Missing 
N (%) 
Low  
N (%) 
Normal 
N (%) 
High 
N (%) 
Total 
N (%) 
 
 
 
 
 
 
 
 
Analyte 1 [unit] 
DB - FMX103 1.5% 
Missing 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Low 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Normal 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
High 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Total 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
 
 
 
 
 
 
 
DB - Vehicle 
Missing 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Low 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Normal 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
High 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Total 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
 
 
 
 
 
 
 
Overall 
Missing 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Low 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Normal 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
High 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
 
 
Total 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
xx (xxx.x%) 
... 
 
 
 
 
 
 
 
 
 
 
 
DB = Treatment received during double-blind study 
[1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).   
[2] Final Visit is the Week 40 visit for subjects that completed the study or the last post-dose lab assessment for 
subjects that withdrew from the study early.  
Source: Listing 16.2.8.1 
 
 
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Table 14.3.5.3 
Hematology Results 
All Treated Population 
 
 
     See Table 14.3.5.1 
     ____________________________________________________________________________________________________________________________ 
Note: Change from baseline is calculated as the value at the specified visit minus the value recorded at baseline; negative 
values represent a decrease in laboratory values since baseline. 
Source: Listing 16.2.8.2 
 
 
 
 
 
 
Table 14.3.5.4 
Shift Table of Hematology Results 
All Treated Population 
 
 
 See Table 14.3.5.2 
 ____________________________________________________________________________________________________________________________________ 
Source: Listing 16.2.8.2 
 
 
 
 
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14.3.6 
Other Safety and Tolerability Summary Tables 
 
Table 14.3.6.1 
Shift Table of Physical Examination Results 
All Treated Population 
 
 
 
 
Assessment at Baseline 
 
 
Assessment at 
Normal 
Abnormal, NCS 
Abnormal, CS 
Not Done 
Total 
Assessment 
Treatment 
Week 40 Visit 
N (%) 
N (%) 
N (%) 
N (%) 
N (%) 
 
 
 
 
 
 
 
 
General appearence 
DB - FMX103 
1.5% 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Abnormal, NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Abnormal, CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Not done 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
DB - Vehicle 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Abnormal, NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Abnormal, CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Not done 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
Overall 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Abnormal, NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Abnormal, CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Not done 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
Note: Percentages exclude missing data. NCS = not clinically significant; CS = clinically significant; DB = Treatment received during 
double-blind study 
Source: Listing 16.2.9.2 
 
 
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Table 14.3.6.2 
Vital Sign Results 
All Treated Population 
 
 
 
 
 
DB - FMX103 1.5% 
DB - Vehicle 
Overall 
Variable 
Visit 
Sample Characteristics 
(N=xxx) 
(N=xxx) 
(N=xxx) 
 
 
 
 
 
 
Variable1- Absolute value 
Baseline[1] 
n (# missing) 
xx 
xx 
xx 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
 
 
 
 
 
 
 
Week x 
n (# missing) 
xx 
xx 
xx 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
... 
 
 
 
 
 
 
Variable1- Change from baseline 
Week x 
n (# missing) 
xx 
xx 
xx 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Min to Max 
xx.x to xx.x 
xx.x to xx.x 
xx.x to xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Note: Repeat for all vital signs variables and all scheduled visits 
 
 
 
 
 
 
 
 
Note: Change from baseline is calculated as the value at the specified visit minus the value recorded at baseline; 
negative values represent a decrease from baseline. DB = Treatment received during double-blind study 
 [1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).   
Source: Listing 16.2.9.1 
 
 
 
 
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Table 14.3.6.3 
Concomitant Medications by ATC Level 2 and Preferred Term 
All Treated Population 
 
 
See Table 14.1.3  
______________________________________________________________________________________________________________________________________ 
Note: Percentages are 100*n/N. Subjects were counted only once for each Anatomical Therapeutic Chemical (ATC) or preferred term. Any 
medications continuing or starting after Day 1 were considered to be concomitant.  
[1] Medications were coded using WHO-DD (Enhanced version March 2017) ATC level 2. Preferred term is ATC level 5. 
Source: Listing 16.2.9.3 
 
 
 
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Table 14.3.6.4 
Summary of Local Signs and Symptoms Assessments 
All Treated Population  
DB - FMX103 
1.5% 
DB - Vehicle 
Overall 
Visit 
Sign/Symptom 
Category 
(N=xxx) 
(N=xxx) 
(N=xxx) 
Baseline[1] 
Erythema 
Non-missing response 
xx 
xx 
xx 
0-clear skin/no signs of erythema
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
1-almost clear of erythema, slight redness
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2-mild erythema, definite redness
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3-moderate erythema, marked redness
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
4-severe erythema, fiery redness
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Missing response
xx 
xx 
xx 
Telangiectasia 
Non-missing response 
xx 
xx 
xx 
0-None
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
1-Mild: scattered telangiectasia
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2-Moderate: numerous telangiectasia
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3-Severe: dense telangiectasia forming sprays
of vessels
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Missing response
xx 
xx 
xx 
Programming Note: Continue for ‘Burning/Stinging’, ‘Flushing/Blushing’, ‘Dryness/Xerosis’, ‘Itching’, ‘Peeling/Desquamation’, 
‘Hyperpigmentation’. Continue for Baseline (Week 12), Weeks 4, 10, 16, 22, 28, 34 and 40.  See protocol Section 10.7.1.1 for 
categories.  
Note: Percentages exclude missing responses. DB = Treatment received during double-blind study. 
[1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).
[2] Baseline (Week 12) is defined as the baseline visit of the open-label extension study.
Source: Listing 16.2.9.4
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16.2 Subject Data Listings 
 
 
 
 
 
 
 
 
 
 
 
 
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16.2.1 
Subject Discontinuations/Completions 
 
 
Listing 16.2.1.1 
 
Study Completion Status 
All Treated Subjects 
 
 
Treatment group during DB study: 
Subject 
ID 
Completed 
Study? 
Date of 
Completion or 
Discontinuation 
Reason for 
Discontinuation 
Treatment 
Start 
Date 
Treatment 
End Date 
AEs at 
Final 
Visit? 
[1] 
Date of 
Last 
Contact 
Xxxxxx 
xxxxx 
ddmmmyyyy 
xxxxx 
ddmmmyyyy ddmmmyyyy 
xxxxx 
ddmmmyyyy 
Xxxxxx 
xxxxx 
ddmmmyyyy 
xxxxx 
ddmmmyyyy ddmmmyyyy 
xxxxx 
ddmmmyyyy 
 
 
 
 
 
 
 
 
 
           [1] Indicates if subject presented with any new or ongoing AEs at the final visit. DB = double-blind. 
 
 
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Listing 16.2.1.2 
Inclusion and Exclusion Criteria Not Met 
All Subjects 
 
Treatment group during DB study: XXXXXXX 
Subject ID 
Met All 
Inclusion/Exclusion 
Criteria? 
Inclusion/Exclusion 
Criteria Number(s) Not 
Met [1] 
 
 
 
XXXXXX 
Yes 
 
XXXXXX 
Yes 
 
XXXXXX 
Yes 
 
XXXXXX 
No 
XX 
XXXXXX 
Yes 
 
XXXXXX 
No 
XX;XX 
 
 
 
DB = double-blind. 
[1] XX = XXXXXXXXXXXXXXXXXXXXXXXX. 
[2] XX = XXXXXXXXXXXXXXXXXX; XX = XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. 
 
Programming note: If more than 1 inclusion or exclusion criterion number exists, concatenate with a comma as shown above. Decode any 
relevant criteria in the footnotes as shown in the example. If no criteria are present for a column, remove the [1] and/or [2] from the column 
header.  
 
 
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16.2.2 
Protocol Deviations 
 
 
Listing 16.2.2.1 
Protocol Deviations 
All Treated Subjects 
 
Treatment group during DB study: 
Subject 
ID 
Date of 
Deviation 
Severity 
Classification Type 
Description 
Action Taken 
Submitted to 
IRB? 
xxxxxx 
ddmmmyyyy xxxxx 
xxxxx 
Xxxxx 
xxxxx 
xxxxx 
xxxxxx 
ddmmmyyyy xxxxx 
xxxxx 
Xxxxx 
xxxxx 
xxxxx 
 
 
 
 
 
 
 
Note: Missed doses <5 are not listed. DB = double-blind. 
 
 
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16.2.4 
Demographic Data and Other Baseline Characteristics 
 
Listing 16.2.4.1 
Demographic Data 
All Treated Subjects 
 
 
 
Treatment group during DB study: 
Subject ID 
Date of IC 
Date of Birth 
Age  
(full years) 
Sex 
Race 
Ethnicity 
Child-Bearing 
Potential? 
DB Protocol 
Subject was 
Enrolled 
Previously 
xxxxxx 
ddmmmyyyy 
ddmmmyyyy 
xx 
x 
xxx 
xxx 
xxx 
xxxxx 
xxxxxx 
ddmmmyyyy 
ddmmmyyyy 
xx 
x 
xxx 
xxx 
xxx 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IC = Informed Consent. DB = double-blind. 
 
 
Listing 16.2.4.2 
Medical History 
All Treated Subjects 
 
Treatment group during DB study: 
 
 
Subject 
ID 
Any 
Medical 
History? 
System Organ Class/ 
  Preferred Term/ 
    Verbatim Term 
Start Date 
End Date 
 
xxxxxx 
 
xxxxx 
 
xxxxxxxxxxx/ 
  xxxxxxxx/ 
    xxxxxxxxx 
 
ddmmmyyyy 
 
ddmmmyyyy 
 
xxxxxx 
 
xxxxx 
 
xxxxxxxxxxx/ 
  xxxxxxxx/ 
    xxxxxxxxx 
 
ddmmmyyyy 
 
Ongoing 
 
 
 
 
 
DB = double-blind. Programming Note:  If Medical Condition is Ongoing, then End Date will be “Ongoing”. 
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Listing 16.2.4.3 
Prior Medications 
All Treated Subjects 
 
Treatment group during DB study: 
Subject 
ID 
Any 
Medication? 
Anatomic Therapeutic Class/ 
  Preferred Term/ 
    Verbatim Term 
Start Date 
End Date 
Indication 
Dose (unit) 
  Route/ 
    Frequency 
 
 
 
 
 
 
 
xxxxxx 
xxxxx 
xxxxxxxxxxx/ 
  xxxxxxxx/ 
    xxxxxxxxx 
ddmmmyyyy 
ddmmmyyyy 
xxxxx 
xxx/ 
  xxxxx/ 
    xxxxxxx 
 
 
 
 
 
 
 
xxxxxx 
xxxxx 
xxxxxxxxx/ 
  xxxxxxxx/ 
    xxxxxxxxxxxx 
ddmmmyyyy 
Ongoing 
xxxxx 
xxx/ 
  xxxxxxxxx/ 
    xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Medications were coded using WHO-DD (Enhanced version March 2017) ATC level 2. Preferred Term is ATC level 5. DB = double-
blind. 
 
 
Programming Note:  If Medication is Ongoing, then End Date will be “Ongoing”. 
 
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16.2.5 
Compliance Data 
 
Listing 16.2.5.1 
Study Drug Accountability 
All Treated Subjects 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment group during DB study: 
 
 
 
 
Dispensed 
 
 
 
Returned 
 
Subject 
ID 
Visit 
Study Drug 
Dispensed? 
Reason 
Not 
Dispensed 
 
Date 
Kit 
ID  
Canister 
ID  
Study 
Drug 
Returned? 
Reason 
Not 
Returned 
Date 
Kit 
ID  
Canister 
ID  
Any Doses 
Missed?/Number 
xxxxxx 
xxxxx 
xxx 
xxxx 
ddmmmyyyy 
xxx 
xxxx 
xxx 
xxxx 
ddmmmyyyy 
xxx 
xxxx 
Yes/xx 
xxxxxx 
xxxxx 
xxx 
xxxx 
ddmmmyyyy 
xxx 
xxxx 
xxx 
xxxx 
ddmmmyyyy 
xxx 
xxxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DB = double-blind 
 
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Listing 16.2.5.2 
Study Drug Stoppage and Restart 
All Treated Subjects 
 
 
 
 
 
 
 
Treatment group during DB study: 
Subject 
ID 
Visit 
Did 
Investigator 
Suspend 
Treatment? 
Date 
Treatment 
Stopped 
Did Subject 
Restart 
Treatment at 
this Visit? 
Date 
Treatment 
Restarted 
xxxxxx 
xxxxx 
Xxx 
xxxx 
xxx 
xxxx 
xxxxxx 
xxxxx 
Xxx 
xxxx 
xxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.5.3 
 
Study Drug Compliance 
All Treated Subjects 
 
 
 
 
Treatment group during DB study: 
Subject ID 
First Dose Date 
Last Dose Date 
Duration Drug 
Suspended 
Treatment Duration 
(Days) [1] 
Number of 
Missed Doses 
Compliance (%) 
[2] 
xxxxxx 
ddmmmyyyy 
ddmmmyyyy 
Xxx 
xxx 
xx 
xxxx 
xxxxxx 
ddmmmyyyy 
ddmmmyyyy 
Xxx 
xxx 
xx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects who are missing last dose dates are not included. DB = double-blind 
[1] Treatment duration (days) = Date of last dose of study drug - Date of first dose of study drug + 1 day  
[2] Compliance (%) = 100 x Study drug exposure (days) / Treatment duration (days). For subjects who were instructed to stop and 
restart treatment over the course of the study, they will be considered compliant on those days.  
 
Programming Note:  Round compliance to one decimal.  
 
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08-Jan-2019 
 
16.2.6 
Individual Efficacy Response Data 
 
 
Listing 16.2.6.1 
 
IGA Score  
All Treated Subjects 
 
 
Treatment group during DB study: 
Site ID 
Subject ID 
Visit 
Was 
Assessment 
Performed? 
Reason Not 
Performed 
Assessor 
Initials 
Date  
Time 
Study Day 
IGA Score 
IGA 
Treatment 
Success [1] 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxxxxx 
Baseline [2] 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
- 
 
 
Baseline 
(Week 12) 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
- 
 
 
Week 4 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
Week 10 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
Week 16 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
Week 22 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
Week 28 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
Week 34 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
Week 40 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxxxxx 
Baseline 
xxx 
Xxxx 
xx 
ddmmmyyyy 
hh:mm 
xx 
x 
xxx 
 
 
 
 
 
 
 
 
 
 
 
[1] IGA treatment success is Yes if the IGA score is either 0 or 1 and there is at least a 2-grade improvement (decrease) from 
baseline.  Otherwise IGA treatment success is No. DB = double-blind. 
[2] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12).   
 
 
 
 
 
 
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Listing 16.2.6.2 
Inflammatory Lesion Count by Facial Area 
All Treated Subjects 
 
Treatment group during DB study: 
 
Site 
ID 
Subject 
ID 
Visit 
Assessor 
Initials 
Date 
Time 
Study 
Day 
Facial Area 
Facial 
Area Not 
Assessed? 
Reason 
Not 
Assessed 
Papules 
Pustules 
Nodules 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xxx 
xxxxxx 
Baseline 
[1] 
xx 
ddmmmyyyy 
hh:mm 
Xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Right cheek xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Left cheek 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Nose 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Chin 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Total 
 
 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
(Week 12) 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 4 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 10 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 16 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 22 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 28 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 34 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
Week 40 
xx 
ddmmmyyyy 
hh:mm 
xx 
Forehead 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xxx 
xxxxxx 
Baseline 
xx 
ddmmmyyyy 
hh:mm 
xx 
Left cheek 
xxx 
xxxxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the Baseline visit in the initial double-blind study (FX2016-11 or FX2016-12). DB = double-blind 
 
 
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Listing 16.2.6.3 
Subject Satisfaction Questionnaire (SSQ) 
All Treated Subjects 
 
 
Treatment group during DB study: 
 
Subject 
ID 
Date 
Study 
Day 
SSQ 
Performed? Question/Reason Not Performed 
Response 
 
 
 
 
 
 
xxxxxx 
ddmmmyyyy xx 
xx 
How satisfied are you with how easy this product is to use? 
xxxxx 
 
 
 
 
How satisfied are you with how this product feels on you skin after treatment? 
xxxxx 
 
 
 
 
How satisfied are you with the odor of this product after treatment? 
xxxxx 
 
 
 
 
How satisfied are you with the color of this product after treatment? 
xxxxx 
 
 
 
 
How satisfied are you with the ease of application of the product to your skin? 
xxxxx 
 
 
 
 
How satisfied are you with the ease in which this product fits into your daily 
routine? 
xxxxx 
 
 
 
 
How satisfied are you with this product compared to other products you  
have previously used for rosacea, such as gels and creams? 
xxxxx 
 
 
 
 
Overall, how likely are you to use this product with other rosacea treatments? 
xxxxx 
 
 
 
 
Overall, how likely are you to recommend this product to a friend? 
xxxxx 
 
 
 
 
Overall, how satisfied are you with this product? 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
ddmmmyyyy xx 
xx 
How satisfied are you with how easy this product is to use? 
xxxxx 
 
 
 
 
 
 
Note: SSQ was completed only at the Week 40/Final Visit. DB = double-blind. 
 
 
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16.2.7 
Adverse Event Listings  
 
 
Listing 16.2.7.1 
 
Adverse Events 
 
All Treated Subjects 
Treatment group during DB study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
ID 
Any 
AEs? TEAE? 
System Organ Class/ 
  Preferred Term/ 
    Verbatim Term 
Start 
Date 
End Date 
Was AE 
Reported 
as Ongoing 
in the 
Core 
Study? 
 
Severity/  
Rel to 
Study 
Drug 
Outcome/  
Study 
Drug  
Action 
Taken 
Serious?/ 
Life-
Threat? 
Hosp 
Disab 
Birth 
Defect? 
Med 
Sig? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx 
xx 
xxxxx/ 
  xxxxxxx/ 
    xxxxxxxxx 
ddmmmyyyy 
ddmmmyyyy 
xx 
xxxx/ 
  xxxxxx 
xxxx/ 
  
xxxxxxxx 
xx/ 
  xx 
 
xx 
xxx 
xxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xxxxxx 
xxx 
xxx 
xxxxx/ 
  xxxxxxx/ 
    xxxxxxxxx 
ddmmmyyyy 
Ongoing 
xx 
xxxx/ 
  xxxxxx 
xxxx/ 
  xxxxxxx 
xx/ 
  xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Adverse events were coded using MedDRA, Version 20.0. Rel = Relationship; Threat = Threatening; Hosp = Requires Inpatient/Prolonged 
Hospitalization; Disab = Results in Persistent or Significant Disability or Incapacity; Birth Defect = Congenital Anomaly or Birth 
Defect; Med Sig = Medically Significant. DB = double-blind. 
 
Programming Note:  If AE is Ongoing then report ‘Ongoing’ for ‘End Date’ 
 
 
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Listing 16.2.7.2 
Serious Adverse Events 
All Treated Subjects 
 
Treatment Group: 
 
 
 
 
 
 
 
 
 
 
See Listing 16.2.7.1; Remove ‘Any AEs?’ column 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 16.2.7.3 
Adverse Events Leading to Withdrawal 
All Treated Subjects 
 
Treatment Group: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Listing 16.2.7.1; Remove ‘Any AEs?’ column 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 16.2.7.4 
Deaths 
All Treated Subjects 
 
Treatment Group: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Listing 16.2.7.1; Remove ‘Any AEs?’ column 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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16.2.8 
Laboratory Values  
 
Listing 16.2.8.1 
Clinical Chemistry Results 
All Treated Subjects 
 
Treatment group during DB study: 
 
Subject 
ID 
Lab 
Test 
(unit) 
Visit 
Samples 
Collected? 
Reason 
Not 
Collected 
Collection 
Date 
Result 
Reference 
Range Low 
Reference 
Range 
High 
Abnormal? 
Clinically 
Significant? 
xxxxxx 
xxxxx 
xxxxx xxxx 
xxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
xxxxx xxxx 
xxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  DB = double-blind 
 
Listing 16.2.8.2 
Hematology Results 
All Treated Subjects 
 
Treatment group during DB study: 
 
Subject 
ID 
Lab 
Test 
(unit) 
Visit 
Samples 
Collected? 
Reason 
Not 
Collected 
Collection 
Date 
Result 
Reference 
Range Low 
Reference 
Range High 
Abnormal?  
Clinically 
Significant? 
xxxxxx 
xxxxx 
xxxxx xxxx 
xxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
xxxxx xxxx 
xxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.3 
Urinalysis Results 
All Treated Subjects 
 
Treatment group during DB study: 
 
Subject 
ID 
Lab 
Test 
(unit) 
Visit 
Samples 
collected? 
Reason 
Not 
Collected 
Collection 
Date 
Result 
Reference 
Range Low 
Reference 
Range 
High 
Abnormal? 
Clinically 
Significant? 
xxxxxx 
xxxxx 
Xxxxx xxxx 
xxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
Xxxxx xxxx 
xxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 16.2.8.4 
Clinically Significant Laboratory Tests for Hematology, Chemistry, and Urinalysis 
All Treated Subjects  
Treatment group during DB study: 
Subject 
ID 
Visit Category 
Lab Test 
(unit) 
Collection 
Date 
Result 
Reference 
Range Low 
Reference 
Range High 
Abnormal? 
xxxxxx 
xxxxx xxxx 
xxxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
 
xxxxx xxxx 
xxxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.5 
Out of Range (Abnormal) Laboratory Tests for Hematology, Chemistry, and Urinalysis 
All Treated Subjects  
Treatment group during DB study: 
Subject 
ID 
Visit Category 
Lab Test 
(unit) 
Collection 
Date 
Result 
Reference 
Range Low 
Reference 
Range High 
Abnormal? 
Clinically 
Significant? 
xxxxxx 
xxxxx Xxxx 
xxxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
xxxxx Xxxx 
xxxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 16.2.8.6 
Pregnancy Test Results 
All Treated Subjects 
 
Treatment group during DB study: 
Subject 
ID 
Visit 
Pregnancy Test 
Performed? 
Reason Not 
Performed 
Collection  
Date 
Result 
xxxxxx 
xxxxx 
xxxx 
xxxx 
ddmmmyyyy 
xxxxx 
 
xxxxx 
xxxx 
xxxx 
ddmmmyyyy 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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16.2.9 
Other Clinical Observations and Measurements 
 
 
 
Listing 16.2.9.1 
 
Vital Signs 
All Treated Subjects 
 
 
 
Treatment group during DB study: 
Subject 
ID 
Visit 
Vital 
Signs 
Collected? 
Collection 
Date 
Height (cm) 
Weight (kg) 
BMI (kg/m2) 
Heart Rate 
(beats/min) 
Systolic BP 
(mmHg) 
Diastolic 
BP (mmHg) 
Xxxxxx 
xxxxx 
Xxx 
ddmmmyyyy 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
xxxxx 
Xxx 
ddmmmyyyy 
 
xxx 
 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Note: Height and BMI will only be listed for Baseline (Pre-dose) visit. 
Listing 16.2.9.2 
Abnormal Physical Examination Results 
All Treated Subjects 
 
Treatment group during DB study: 
Subject 
ID 
Visit 
Examination 
Date 
Body 
System 
Result 
 
Abnormal Finding 
xxxxxx 
xxxxx 
ddmmmyyyy 
xxxx 
xxxx 
xxxx 
 
 
 
xxxx 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: FX2016-13 
Page 53 of 55 
Table and Listing Shells Final 1.0 
 
CONFIDENTIAL 
08-Jan-2019 
 
 
 
Listing 16.2.9.3 
Concomitant Medications 
All Treated Subjects 
 
Treatment group during DB study: 
 
 
 
 
 
 
 
 
See Listing 16.2.4.3 
 
 
 
 
 
 
 
 
Note: Medications were coded using WHO-DD (Enhanced version March 2017) ATC level 2. Preferred Term is ATC level 5. DB =    
double-blind. 
 
 
Programming Note:  If Medication is Ongoing, then End Date will be “Ongoing”. 
 
 
 
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Protocol: FX2016-13 
Page 54 of 55 
Table and Listing Shells Final 1.0 
 
CONFIDENTIAL 
08-Jan-2019 
 
 
Listing 16.2.9.4 
Local Signs and Symptoms Assessments 
All Treated Subjects 
 
Treatment group during DB study: 
Subject 
ID 
Visit 
Date 
Assessment 
Performed? 
Study 
Day 
Assessor 
Initials 
Sign/Symptom 
Severity 
[1] 
xxxxxx 
Xxxx 
ddmmmyyyy 
xxxxx 
xxxxx 
xxxxx 
Erythema 
xxxx 
 
 
 
 
 
 
Telangiectasia 
xxxx 
 
 
 
 
 
 
Burning/Stinging 
xxxx 
 
 
 
 
 
 
Flushing/Blushing 
xxxx 
 
 
 
 
 
 
Dryness/Xerosis 
xxxx 
 
 
 
 
 
 
Itching 
xxxx 
 
 
 
 
 
 
Peeling/Desquamation 
xxxx 
 
 
 
 
 
 
Hyperpigmentation 
xxxx 
xxxxxx 
Xxxx 
ddmmmyyyy 
xxxxx 
xxxxx 
xxxxx 
Erythema 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] All signs/symptoms, except erythema, are based on a 4-point scale with 0=none, 1=mild, 2=moderate, and 
3=severe. Erythema is based on a 5-point scale with 0=clear, 1=almost clear, 2=mild erythema, 3=moderate 
erythema, and 4=severe erythema.  
 
 
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Protocol: FX2016-13 
Page 55 of 55 
Table and Listing Shells Final 1.0 
 
CONFIDENTIAL 
08-Jan-2019 
 
 
 
Listing 16.2.9.5 
Telephone Contact 
All Treated Subjects 
 
Treatment group during DB study: 
 
Subject  
ID 
Was the 
subject 
contacted by 
phone? 
Reason not 
contacted 
Date of Call 
Were all 
adverse events 
assessed? 
Were all 
concomitant 
medications 
assessed? 
xxxxxx 
ddmmyyyy 
xxxxx 
ddmmmyyyy 
xxx 
xxx 
 
ddmmyyyy 
xxxxx 
ddmmmyyyy 
xxx 
xxx 
 
ddmmyyyy 
xxxxx 
ddmmmyyyy 
xxx 
xxx 
 
ddmmyyyy 
xxxxx 
ddmmmyyyy 
xxx 
xxx 
xxxxxx 
ddmmyyyy 
xxxxx 
ddmmmyyyy 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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