Clinical trial NCT02815280
Conditions: Acne Vulgaris
Keywords: acne
Sponsor: Vyne Therapeutics Inc.
Start date: 2016-05-01; Completion date: 2017-10-13
Enrollment: 495 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 3 study to evaluate the efficacy, safety and long-term safety of the topical administration of FMX-101, 4% minocycline foam for the treatment of moderate-to-severe acne vulgaris.

Detailed description:
This is a Phase 3 study to evaluate the efficacy, safety and long-term safety of the topical administration of FMX-101, 4% minocycline foam for the treatment of moderate-to-severe acne vulgaris. The first 12 weeks of the study involves randomized, double-blind treatment with active FMX-101, 4% or matching vehicle. Subjects who successfully complete the 12-week double blind portion of the study will be offered the opportunity to continue in the trial for up to an additional 40 weeks (for a total of 1 year) and receive open-label treatment with FMX-101, 4%.

Arms: arm 1: FMX-101, 4% minocycline foam applied topically once daily for 12 weeks arm 2: Vehicle foam applied topically once daily for 12 weeks
Interventions: intervention 1: FMX-101, 4% minocycline foam intervention 2: Vehicle Foam
Intervention descriptions: intervention 1: FMX-101, 4% minocycline foam applied topically once daily for 12 weeks intervention 2: Vehicle foam applied topically once daily for 12 weeks

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
A Randomized, Double-Blind Study to Compare the Efficacy, 
Safety and Long-Term Safety of Topical Administration of 
FMX-101 for 1 Year in the Treatment of Moderate-to-Severe Acne 
Vulgaris, Study FX2014-05 
 
ClinicalTrials.gov Identifier: NCT02815280 
 
 
 
Date of Protocol: 14 October 2016 


 
 
Privileged and Confidential 
 
Clinical Study Report FX2014-05 
 
 
 
 
 
16.1.1 
Protocol and Amendments 
 
Protocol version 4, 14 October 2016 
Protocol version 3, 06 April 2016 
 
 


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CONFIDENTIAL 
 
  
 
CLINICAL STUDY PROTOCOL  
Title: 
A Randomized, Double-Blind Study to Compare the Efficacy, 
Safety and Long-Term Safety of Topical Administration of 
FMX-101 for 1 Year in the Treatment of Moderate-to-Severe Acne 
Vulgaris, Study FX2014-05 
Development Phase: 
3 
Project Number: 
FMX-101 
Study drug(s): 
FMX-101, minocycline foam 4%; matching vehicle foam 
Indication: 
Acne vulgaris 
Authors: 
 
Protocol Number: 
FX2014-05 
Version  
4 
Date of Protocol: 
October 14, 2016 
Supersedes 
Version 3 of April 6, 2016 
 
 
This Protocol is the property of Foamix Pharmaceuticals, Inc.  This Protocol must be kept in a 
confidential manner, and may only be used in connection with the clinical study.  It must be 
returned on request.  No part of this Protocol may be reproduced or transmitted in any form 
without written permission of Foamix Pharmaceuticals, Inc.  If you are not authorized to receive 
this document, please return it immediately to: 
Foamix Pharmaceuticals, Inc.  520 U.S. Hwy 22, Suite 305  Bridgewater, NJ 08807 
 
 
PPD




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1. 
SYNOPSIS 
This is a Phase 3 study to evaluate the efficacy, safety and long-term safety of the topical 
administration of FMX-101, 4% minocycline foam for the treatment of moderate-to-severe acne 
vulgaris.  The first 12 weeks of the study involves randomized, double-blind treatment with 
active FMX-101, 4% or matching vehicle.  Subjects who successfully complete the 12-week 
double blind portion of the study may be offered the opportunity to continue in the trial for up to 
an additional 40 weeks (for a total of 1 year) and receive open-label treatment with 
FMX-101, 4%. 
1.1. 
Investigational Product, Dosage, and Mode of Administration 
The investigational product is FMX-101, minocycline foam 4%.  FMX-101 4% will be applied 
topically daily for the 12-week treatment duration of the study. 
1.2. 
Active Ingredient 
The active ingredient is minocycline HCl. 
1.3. 
Reference Product, Dosage, and Mode of Administration 
The reference product is vehicle foam.  Vehicle foam will be applied topically daily for the  
12-week treatment duration of the study. 
1.4. 
Study Centers 
Approximately 30 study centers will participate in this study. 
1.5. 
Study Period 
Estimated date first subject enrolled: April 2016 
Estimated date last subject completed: August 2017 
1.6. 
Study Objectives 
The objectives of this study are: 
• To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX-
101, 4% administered daily for 12 weeks 
• To evaluate the safety compared to vehicle of topical FMX-101, 4% administered 
daily for 12 weeks 
• To evaluate the long-term safety of topical FMX-101, 4% administered daily for up to 
40 additional weeks 


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1.7. 
Methodology 
The study will have 2 parts.  The first will involve 12 weeks of double-blind treatment with 
FMX-101, 4% or vehicle foam.  The second will involve up to 40 additional weeks of open-label 
treatment with FMX-101, 4% of subjects who complete the first part of the study. 
1.7.1. 
Part 1 – Double-blind Period 
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy over 12 weeks of FMX-101 minocycline foam, 4%, compared to vehicle, in 
the treatment of subjects with moderate to severe facial acne vulgaris. 
Qualified subjects will be randomized to receive 1 of the following 2 treatments: 
• FMX-101, 4%  minocycline foam 
• Vehicle foam 
Subjects with qualifying lesion counts (Section 8.1.2) and Investigator’s Global Assessments 
(IGA, Section 8.1.1) of acne severity scores and will be assigned to 1 of 2 treatments according 
to the randomization schedule.  Subjects will apply the assigned study drug topically once daily 
for 12 weeks as directed.  Subjects will be advised to apply the study drug at approximately the 
same time each day, preferably in the evening at bedtime.  Both the Investigator and subject will 
be blinded to the study drug identity. 
Subjects will return for visits at Weeks 1, 3, 6, 9, and 12. At the discretion of the clinic staff, for 
the convenience of subjects or clinic staff, visits can be scheduled to occur 3 days before or after 
the nominal schedule date for the Weeks 1, 3 and 6 visits and 7 days before or after for the 
Weeks 9 and 12 visits.  Efficacy evaluations (acne lesion counts and IGAs will be performed at 
Weeks 3, 6, 9, and 12 during the study.  Other assessments will be performed as described in 
Section 9.  
1.7.2. 
Part 2 – Open-label  
At the Week 12 Visit, subjects whose IGA score has not worsened may be invited to continue 
into the open-label part of this study for an additional 9 months of treatment.  Subjects will be 
enrolled in this phase of the study until a total of approximately 400 subjects from Studies 
FX2014-04 and FX2014-05 have elected to continue in the open-label portion of their respective 
study.  Subjects who elect to continue into the open-label part of this study will receive supplies 
of active FMX-101, 4% minocycline foam.   
Treatment during this part of the study will be guided by each subject’s clinical response.  The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas.  Even if the treatment is partially or completely 
temporarily suspended, the subject will be continued in the study and will make all scheduled 
clinic visits.  If at any time the acne recurs or worsens, treatment of the affected areas may be 
resumed.  
Subjects may be discontinued from the study after 12 weeks if their disease becomes refractory 
or they become intolerant of the product.   


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1.8. 
Number of Subjects 
The planned enrollment is 450 subjects.  Subjects will be randomized to active or vehicle in a 2:1 
ratio.  Approximately 300 and 150 subjects will be assigned to the FMX-101, 4% or vehicle 
treatment groups, respectively. 
1.9. 
Diagnosis and Main Criteria for Inclusion 
Subjects are to be at least 9 years of age. 
Eligible subjects are to have a diagnosis of facial acne vulgaris characterized by (subjects are 
permitted to also have acne on other parts of the body): 
• 20 to 50 inflammatory lesions (papules, pustules, and nodules) 
• 25 to 100 noninflammatory lesions (open and closed comedones) 
• No more than 2 nodules on the face  
• Investigator’s Global Assessment (IGA) score of moderate (3) to severe (4) 
1.10. 
Criteria for Evaluation 
1.10.1. Efficacy 
The efficacy assessments will include the IGA and lesion counts at Baseline and Weeks 3, 6, 9 
and 12.  
1.10.2. Safety 
The safety assessments in this study are physical examinations, vital signs, assessment of the 
skin at application site(s), adverse events (volunteered, observed, and elicited by general 
questioning in a non-suggestive manner), and clinical laboratory test results. 
1.11. 
Statistical Methods 
Efficacy analyses will be conducted on the Intent-to-Treat (ITT) population, using the last-
observation-carried-forward (LOCF) approach to impute missing values.  Supportive efficacy 
analyses will also be conducted on the Per Protocol (PP) population, with no imputation for 
missing values.  The co-primary efficacy endpoints are the absolute change from Baseline in the 
inflammatory lesion count at Week 12 IGA Treatment Success (dichotomized as Yes/No) at 
Week 12, where success is defined as an IGA score of 0 or 1, and at least a 2-grade decrease 
from Baseline.  FMX-101 4% will be tested against vehicle at the two-sided 0.05 level of 
significance without adjustment for multiplicity.  The absolute change from Baseline in 
inflammatory lesions at Week 12 will be analyzed using an Analysis of Covariance (ANCOVA) 
model with main effect treatment and investigational site as a covariate.  The IGA Treatment 
Success rates will be compared between the treatment groups using a Cochran–Mantel–Haenszel 
(CMH) test stratified for investigational site. 
No statistical tests will be performed for any of the safety assessments. 
 


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TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES 
 
1. 
SYNOPSIS ...................................................................................................................3 
1.1. 
Investigational Product, Dosage, and Mode of Administration ...................................3 
1.2. 
Active Ingredient ..........................................................................................................3 
1.3. 
Reference Product, Dosage, and Mode of Administration ...........................................3 
1.4. 
Study Centers ................................................................................................................3 
1.5. 
Study Period..................................................................................................................3 
1.6. 
Study Objectives ...........................................................................................................3 
1.7. 
Methodology .................................................................................................................4 
1.7.1. 
Part 1 – Double-blind Period ........................................................................................4 
1.7.2. 
Part 2 – Open-label .......................................................................................................4 
1.8. 
Number of Subjects ......................................................................................................5 
1.9. 
Diagnosis and Main Criteria for Inclusion ...................................................................5 
1.10. 
Criteria for Evaluation ..................................................................................................5 
1.10.1. 
Efficacy .........................................................................................................................5 
1.10.2. 
Safety ............................................................................................................................5 
1.11. 
Statistical Methods ........................................................................................................5 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ....................................6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................12 
STUDY ADMINISTRATIVE STRUCTURE ...............................................................................13 
2. 
INTRODUCTION ......................................................................................................14 
3. 
STUDY OBJECTIVES ..............................................................................................14 
4. 
INVESTIGATIONAL PLAN .....................................................................................14 
4.1. 
Overall Study Design ..................................................................................................14 
4.1.1. 
Part 1 – Double-blind ..................................................................................................15 
4.1.2. 
Part 2 – Open-label .....................................................................................................15 
4.2. 
Rationale for Study Design and Dose Selection .........................................................15 
5. 
STUDY POPULATION .............................................................................................16 
5.1. 
Inclusion Criteria ........................................................................................................16 
5.2. 
Exclusion Criteria .......................................................................................................16 


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6. 
STUDY PROCEDURES ............................................................................................18 
6.1. 
Part 1 – Double-Blind .................................................................................................20 
6.1.1. 
Screening Visit ............................................................................................................20 
6.1.2. 
Baseline Visit, Visit 1 .................................................................................................20 
6.1.3. 
Visit 2, Week 1 ...........................................................................................................21 
6.1.4. 
Visit 3, Week 3 ...........................................................................................................21 
6.1.5. 
Visit 4, Week 6 ...........................................................................................................22 
6.1.6. 
Visit 5, Week 9 ...........................................................................................................22 
6.1.7. 
Visit 6, Week 12 End of Double-Blind or Continuation in Open Label / 
Early Termination .......................................................................................................23 
6.2. 
Part 2 – Open-label .....................................................................................................24 
6.2.1. 
Visit 7 - Week 16 ........................................................................................................25 
6.2.2. 
Visits 8, 9, 10, 11 and 12 – Weeks 22, 28, 34, 40 and 46...........................................25 
6.2.3. 
Visit 13, Final Visit – Week 52 ..................................................................................26 
7. 
STUDY TREATMENTS............................................................................................26 
7.1. 
Treatments Administered ............................................................................................26 
7.1.1. 
Part 1 (double-blind) – Weeks 1 to 12 ........................................................................26 
7.1.2. 
Part 2 (open-label) – Weeks 13 to 52 .........................................................................27 
7.1.3. 
Dosing Instructions .....................................................................................................27 
7.1.3.1. 
Part 1 – Double-blind ..................................................................................................27 
7.1.3.2. 
Part 2 – Open-label .....................................................................................................27 
7.1.4. 
Manufacturer ...............................................................................................................28 
7.1.5. 
Labeling of Study Drug ..............................................................................................28 
7.1.6. 
Storage of Study Drug ................................................................................................28 
7.2. 
Study Drug Accountability .........................................................................................29 
7.3. 
Handling and Disposal of Study Drug ........................................................................29 
7.4. 
Method of Assignment of Study Drug ........................................................................29 
7.4.1. 
Part 1 – Double- blind .................................................................................................29 
7.4.2. 
Part 2 – Open-label .....................................................................................................29 
7.5. 
Selection and Timing of Doses in the Study ..............................................................29 
7.6. 
Blinding ......................................................................................................................30 
7.7. 
Prior and Concomitant Therapy ..................................................................................30 
7.8. 
Use of Contraception ..................................................................................................31 


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7.9. 
Treatment Compliance ................................................................................................31 
8. 
EFFICACY ASSESSMENTS ....................................................................................32 
8.1. 
Primary Efficacy Assessments ...................................................................................32 
8.1.1. 
Investigator Global Assessment Score (IGA) .............................................................32 
8.1.2. 
Lesion Counts .............................................................................................................32 
8.2. 
Photography ................................................................................................................33 
8.3. 
Subject Satisfaction Questionnaire .............................................................................33 
9. 
SAFETY ASSESSMENTS ........................................................................................33 
9.1. 
Medical/Surgical History ............................................................................................33 
9.2. 
Medication History .....................................................................................................34 
9.3. 
Concomitant Medications ...........................................................................................34 
9.4. 
Vital Signs ..................................................................................................................34 
9.5. 
Physical Examination .................................................................................................34 
9.6. 
Clinical Laboratory Tests ...........................................................................................34 
9.6.1. 
Urine Pregnancy Test .................................................................................................35 
9.6.2. 
Sample Collection, Storage, and Shipping .................................................................35 
9.7. 
Other Safety Measurements ........................................................................................35 
9.7.1. 
Tolerability .................................................................................................................35 
9.8. 
Adverse Events ...........................................................................................................36 
9.8.1. 
Method of Determining Adverse Events ....................................................................36 
9.8.2. 
Adverse Event Definitions ..........................................................................................36 
9.8.2.1. 
Adverse Events ...........................................................................................................36 
9.8.2.2. 
Serious Adverse Events ..............................................................................................37 
9.8.2.3. 
Severity of Adverse Events ........................................................................................37 
9.8.2.4. 
Relationship of Adverse Events to Study Treatments ................................................38 
9.8.2.5. 
Adverse Events Expectedness ....................................................................................38 
9.8.3. 
Reporting Adverse Events ..........................................................................................38 
9.8.4. 
Adverse Event Follow-up ...........................................................................................38 
9.8.4.1. 
Pregnancy reporting ....................................................................................................39 
9.8.5. 
Clinically Significantly Abnormal Laboratory Results ..............................................39 
9.9. 
Appropriateness of Safety Measurement ....................................................................39 
10. 
STATISTICAL DESIGN AND ANALYSIS .............................................................40 
10.1. 
Statistical Analysis Plan .............................................................................................40 


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10.2. 
Determination of Sample Size ....................................................................................40 
10.3. 
Analysis Populations ..................................................................................................41 
10.4. 
Efficacy Endpoints ......................................................................................................42 
10.4.1. 
Primary Efficacy Endpoints ........................................................................................42 
10.4.2. 
Secondary Efficacy Endpoints ....................................................................................43 
10.4.3. 
Tertiary efficacy endpoints .........................................................................................43 
10.5. 
Safety endpoints ..........................................................................................................43 
10.5.1. 
Adverse Events ...........................................................................................................43 
10.5.2. 
Vital Signs ..................................................................................................................44 
10.5.3. 
Physical Examinations ................................................................................................44 
10.5.4. 
Clinical Laboratory Results ........................................................................................44 
10.6. 
Statistical Analysis ......................................................................................................44 
10.6.1. 
Interim Analysis ..........................................................................................................44 
10.6.2. 
Subject Accounting, Demographic, and Baseline Characteristics ..............................44 
10.6.3. 
Efficacy Analysis ........................................................................................................44 
10.6.4. 
Safety Analysis ...........................................................................................................45 
11. 
STUDY MANAGEMENT .........................................................................................46 
11.1. 
Monitoring ..................................................................................................................46 
11.2. 
Protocol Amendments ................................................................................................46 
11.3. 
Protocol Deviations ....................................................................................................47 
11.4. 
Withdrawal of Subjects ...............................................................................................47 
11.5. 
Termination of the Study ............................................................................................48 
11.6. 
Publication Policy .......................................................................................................48 
12. 
ETHICS ......................................................................................................................48 
12.1. 
Conduct of the Study ..................................................................................................48 
12.2. 
Institutional Review Boards (IRB) .............................................................................48 
12.3. 
Written Informed Consent ..........................................................................................48 
12.4. 
Subject Confidentiality ...............................................................................................49 
12.5. 
Records Retention .......................................................................................................49 
12.6. 
Financing ....................................................................................................................50 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................50 
14. 
DATA HANDLING AND RECORD KEEPING ......................................................50 
15. 
REFERENCE LIST ....................................................................................................51 


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16. 
APPENDICES ............................................................................................................52 
16.1. 
Appendix 1 – Subjects Satisfaction Questionnaire .....................................................52 
16.2. 
Appendix 2 – Protocol Amendments ..........................................................................53 
16.2.1. 
Amendment 1, effective February 26, 2016 ...............................................................53 
16.2.2. 
Amendment 2, effective April 6, 2016 .......................................................................61 
16.2.3. 
Amendment 3, effective September 12, 2016 ............................................................66 


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List of Tables 
Table 1: Schedule of Procedures - Study FX2014-05 – Part 1 ......................................................19 
Table 2: Schedule of Procedures - Study FX2014-05 – Part 2 ......................................................24 
Table 3: IGA Scale for Acne Vulgaris ...........................................................................................32 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition 
AE 
Adverse event 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
eCRF 
Electronic case report form 
EKG 
Electrocardiogram 
FDA 
Food & Drug Administration 
GCP 
Good Clinical Practice 
HEENT 
Head, eyes, ears, nose, and throat 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System (IWRS) 
LOCF 
Last-observation-carried-forward 
ITT 
Intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed-Cases 
P. acnes 
Propionibacterium acnes 
PP 
Per protocol 
TEAE 
Treatment-emergent adverse event 
SAE 
Serious adverse event 
SOC 
System organ class 
 
 
 
 
 
 
 
 
 


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STUDY ADMINISTRATIVE STRUCTURE 
Name 
Affiliation / Address /  
Telephone Number 
Responsibility 
Foamix Pharmaceuticals, Inc 
520 U.S. Highway 22, Suite 305 
Bridgewater, NJ 08807 
Sponsor 
TKL Research, Inc. 
 
365 West Passaic Street, Suite 550 
Rochelle Park, NJ 07662 
CRO 
 
TKL Research, Inc. 
 
 
TKL Research, Inc. 
 
 
PPD
PPD
PPD
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2. 
INTRODUCTION 
Acne vulgaris is a common disease of both males and females, usually manifesting initially 
during adolescence.  The primary pathologic events are initiated in the pilo-sebaceous units, 
especially of sebaceous-gland-bearing areas of the face, chest, and back as a result of increased 
androgen stimulation initiated at adrenarche or puberty.  As a result of both abnormal 
keratinization of the infra-infundibular portion of the pilo-sebaceous follicle and increased 
sebum produced in the gland, a blockage of the duct results in the inapparent clinical lesion of 
the microcomedone.  Continued blockage, colonization of the follicle by Propionibacterium 
acnes (P. acnes), and generation of multiple chemoattractant and proinflammatory moieties may 
result in non-inflammatory clinical lesions, comedones, and inflammatory lesions: papules, 
pustules, nodules, and cysts.1 
FMX-101, 4% is a minocycline containing topical foam being developed as a treatment for acne 
vulgaris.  Antibiotics, especially erythromycin, minocycline, and doxycycline, have been 
prescribed as acne treatments for many years.  These antibiotics effectively control the signs of 
inflammatory acne while patients continue to use them.  Nonclinical studies have demonstrated 
that FMX-101, 4% exhibits favorable characteristics.  
Foamix has conducted 2 Phase 1 and 1 Phase 2 study of FMX-101, 4% to assess its safety and 
tolerability.  FMX-101, 4% has been shown to be effective and well tolerated at the 4% dose that 
is being utilized in this study.  The Investigator’s Brochure should be consulted for summaries of 
the results of these studies.  
This Phase 3 study (Study FX2014-05) will assess the efficacy, safety and long-term safety of 
FMX-101, 4% for the treatment of moderate to severe facial acne vulgaris. 
3. 
 STUDY OBJECTIVES  
The objectives of this study are: 
• To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX-
101, 4% administered daily for 12 weeks 
• To evaluate the safety compared to vehicle of topical FMX-101, 4% administered 
daily for 12 weeks 
• To evaluate the long-term safety of topical FMX-101, 4% administered daily for up to 
an additional 40 weeks 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
The one-year study will have 2 parts.  The first 12 weeks will be double-blind treatment with 
FMX-101, 4% or vehicle foam.  The remaining 40 weeks will involve open-label treatment with 
FMX-101, 4% by any subjects who complete the first part of the study. 


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4.1.1. 
Part 1 – Double-blind  
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy over 12 weeks of FMX-101 minocycline foam, 4%, compared to vehicle, in 
the treatment of subjects with moderate to severe facial acne vulgaris. 
Qualified subjects will be randomized to receive 1 of the following 2 treatments: 
• FMX-101, 4%  minocycline foam 
• Vehicle foam 
Subjects with qualifying lesion counts (Section 8.1.2) and Investigator’s Global Assessments 
(IGA, Section 8.1.1) of acne severity scores and will be assigned to 1 of 2 treatments according 
to the randomization schedule.  Subjects will apply the assigned study drug topically once daily 
for 12 weeks as directed.  Subjects will be advised to apply the study drug at approximately the 
same time each day, preferably in the evening before bedtime.  Both the Investigator and subject 
will be blinded to the study drug identity. 
Subjects will return for visits at Weeks 1, 3, 6, 9, and 12.  Efficacy evaluations (acne lesion 
counts and IGAs will be performed at Weeks 3, 6, 9, and 12 during the study.  Other assessments 
will be performed as described in Sections 8.2 and 9. 
4.1.2. 
Part 2 – Open-label  
At the Week 12 Visit, subjects whose IGA score has not worsened may be invited to continue 
into the open-label part of this study for an additional 9 months of treatment.  Subjects will be 
enrolled in this phase of the study until a total of approximately 400 subjects from Studies 
FX2014-04 and FX2014-05 have elected to continue in the open-label portion of their respective 
study.  Subjects who elect to continue into the open-label part of this study will receive supplies 
of active FMX-101, 4% minocycline foam.   
Treatment during this part of the study will be guided by each subject’s clinical response.  The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas.  Even if the treatment is partially or completely 
temporarily suspended, the subject will continue in the study and make all scheduled clinic visits.  
If at any time the acne recurs or worsens, treatment of the affected areas may be resumed.  
Subjects may be discontinued from the study after 12 weeks if their disease becomes refractory 
or they become intolerant of the product.   
4.2. 
Rationale for Study Design and Dose Selection 
A randomized, multicenter, double-blind, vehicle-controlled study design has been selected in 
order to assess the efficacy of the study drug in accordance with the FDA Guidance.2  The 
subjects will be selected according to predefined entry criteria.  The study will have a 12-week 
treatment duration.    
FMX-101 foam, 4% is a novel minocycline formulation that has been shown to have efficacy in 
once daily use in a Phase 2 study.  The once daily dosing regimen is appropriate given the 
pharmacokinetic characteristics of FMX-101, 4%. 


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Because of the mode of action of tetracycline drugs, the primary efficacy endpoints will be the 
effect on inflammatory lesion count and IGA (Section 8.1.1).  The effect on noninflammatory 
lesions will be the most important secondary endpoint.  
The extension of the study for an additional 40 weeks is necessary to obtain safety information 
about the long-term use of FMX-101, 4% to treat acne, which is a chronic condition.  The design 
of the study is expected to provide sufficient safety information to fulfill the ICH E1 guideline. 
5. 
STUDY POPULATION 
The planned enrollment is 450 subjects.  Subjects will be randomized to active or vehicle in a 2:1 
ratio.  Approximately 300 and 150 subjects will be assigned to the FMX-101, 4% or vehicle 
treatment groups, respectively. 
5.1. 
Inclusion Criteria 
A male or female subject will be considered eligible for participation in the study if all of the 
following inclusion criteria are satisfied prior to randomization: 
1. Has completed and signed an appropriately administered Informed Consent Form (ICF) 
prior to any study-related procedures.  Subjects less than 18 years of age (or as required 
by state law) must sign an Assent Form for the study and a parent or legal guardian must 
sign the ICF.  
2. Is 9 years of age or greater,  
3. Has facial acne vulgaris with: 
• 20 to 50 inflammatory lesions (papules, pustules, and nodules) 
• 25 to 100 noninflammatory lesions (open and closed comedones) 
• No more than 2 nodules on the face 
• IGA score of moderate (3) to severe (4) 
4. If women of child-bearing potential, have a negative urine pregnancy test 
5. For women of child-bearing potential at risk of becoming pregnant, agree to an effective 
method of contraception (Sections 7.7 and 7.8) 
6. Willing to use only the supplied non-medicated cleanser 
 
and to refrain from use of any other acne medication, medicated cleanser, excessive sun 
exposure, and tanning booths for the duration of the study 
5.2. 
Exclusion Criteria 
Subjects who have any of the following will be excluded from the study: 
1. Female who is pregnant or lactating, or is planning a pregnancy during the study 
2. Acne conglobata, acne fulminans, secondary acne (chloracne, drug induced acne) or any 
dermatological condition of the face or facial hair (eg, beard, sideburns, mustache) that 
could interfere with the clinical evaluations 
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3. Sunburn on the face  
4. Severe systemic disease, which might interfere with the conduct of the study or the 
interpretation of the results. 
5. Abnormal baseline laboratory values that are considered clinically significant. 
6. Currently participating, or has participated within 30 days prior to this study, in an 
investigational drug or device study 
7. Inability to fully comply with the study requirements 
Subjects who have a history of any of the following will be excluded: 
8. Allergy to tetracycline-class antibiotics or to any ingredient in the study drug 
9. Pseudomembranous colitis or antibiotic-associated colitis 
10. Hepatitis or liver damage or renal impairment 
11. Known or suspected premalignant or malignant disease (excluding successfully treated 
skin cancers)  
12. Subjects who have used the following medications (topical refers only to the facial area) 
will not be eligible: 
Within 1 week prior to randomization:  
• Medicated facial cleansers 
• Topical acne treatments (other than those listed below) 
Within 4 weeks prior to randomization: 
• Topical retinoids 
• Topical anti-inflammatories and corticosteroids 
• Systemic antibiotics 
• Systemic acne treatments 
Within 12 weeks prior to randomization:  
• Systemic retinoids 
• Systemic corticosteroids 
13. Drug addiction or alcohol abuse (within the last 2 years). 
14. Current or significant past history of depression. 
 


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6. 
STUDY PROCEDURES 
Potential subjects will be assessed for eligibility at Screening.  During this visit, the purpose, 
timing, procedures, and risks of the study will be explained to the subject, including 
requirements for enrollment and participation in the study, medication restrictions during the 
study, and requirements for washout of certain medications that the subject may already be 
taking.  
The eligible subject who is willing to participate in the study will then sign an appropriately 
administered Informed Consent Form (ICF) prior to any study-related procedures.  Subjects less 
than 18 years of age (or per state law) must sign an Assent Form for the study and a parent or 
legal guardian must sign the ICF. 
Procedures at the Screening Visit will include obtaining blood and urine samples for clinical 
laboratory tests.  These results must be no more than 30 days old at the time of Baseline Visit  
randomization.   
If a subject, who has agreed to participate in the study and signed the ICF or Assent Form, is 
currently undergoing acne therapy identified in Exclusion Criterion 12, they must first enter a 
washout period, before beginning the Screening procedures.   
A summary of study assessments and the time point at which they will be performed during the 
study is presented in Table 1.  If a subject prematurely withdraws from the study before the 
Week 12 Visit, the subject should return to the study site for a withdrawal visit, during which all 
evaluations described under Visit 6/Week 12 must be performed. 
See  
Table 2 and Section 6.2 for descriptions of the procedures required during the open-label part of 
the study. 


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Table 1: Schedule of Procedures - Study FX2014-05 – Part 1 
 
Assessment 
 
Screening 1 
 
Baseline 1 
 
Visits 
“Final” 
Visit 2 
Visit 
 
1 
2 
3 
4 
5 
6 
Week 
 
 
1 
3 
6 
9 
12 
Informed Consent/Assent 
X 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
Assign identification number 
X 
 
 
 
 
 
 
Medical/Surgical/Medication 
(prior/concomitant) History 
X 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
X 
 
 
 
 
 
Physical Exam, height, weight 3,4 
 
X  
 
 
 
 
X 
Blood Pressure/heart rate 5 
 
X 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
X 
 
 
X 
 
 
X 
Urine pregnancy test (females of 
childbearing potential only)6 
 
X 
 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
 
X 
X 
X 
X 
Lesion Count 
X 
X 
 
X 
X 
X 
X 
Photography 
 
X 
 
 
X 
 
X 
Subject Satisfaction Questionnaire 
 
 
 
 
 
 
X 
Randomization  
 
X 
 
 
 
 
 
Concomitant Medication  
 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
Tolerability Assessments 
 
 
X 
X 
X 
X 
X 
Perform drug accountability 
 
 
X 
X 
X 
X 
X 
Collect empty canisters 
 
 
X 
X 
X 
X 
X 
Dispense Study Drug 
 
X 
X 
X 
X 
X 
X7 
Schedule/Confirm Next Visit 
X 
X 
X 
X 
X 
X 
X 
                                                 
1 The duration of Screening is variable but if there are medications to be discontinued it can not be less than the time indicated in 
Exclusion Criterion 12. The procedures required at these visits can be combined.  However, drug should not be dispensed until 
all inclusion and exclusion criteria are met. 
2 Subject may continue into open-label phase of study. If a subject is not continuing into open-label phase for any reason 
(see Section 4.1.2, all evaluations described under Visit 6/Week 12 must be performed.   
3 Height to be measured only at Baseline 
4 Including 12-lead EKG at Screening in subjects over 39 years of age 
5 Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest 
6 Perform urine pregnancy test at indicated visits.  Also dispense home urine pregnancy test at Week 12 if subject is 
continuing into open-label treatment 
7 If subject is continuing into open-label treatment phase, dispense appropriate Study Drug Kit 


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6.1. 
Part 1 – Double-Blind 
6.1.1. 
Screening Visit  
• Obtain a signed and dated, written Informed Consent Form (ICF) prior to any study-
related procedures; subjects less than 18 years of age (or as required by state law) 
must sign an Assent Form for the study and a parent or legal guardian must sign the 
ICF.  (Subjects must be at least 9 years of age at the time of assent/consent) 
• Obtain demographic data 
• Assign the subject a unique subject identification number 
• Obtain medical history  
• Obtain surgical history 
• Obtain history of prior and concomitant medication usage (including previous use of 
acne medications); record start and stop dates of any medications used in the last 
3 months  
• Perform IGA (Section 8.1.1) 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
(Section 8.1.2)  
• Record regions beyond face affected by acne 
• Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory (Section 9.6)  
• If subject wears make-up, remind the subject not to wear any make-up at future visits. 
• Record AEs 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 
6.1.2. 
Baseline Visit, Visit 1 
The procedures required at this visit can be combined with Screening.  However, drug should not 
be dispensed until all inclusion and exclusion criteria are met.   
• Confirm/reconfirm eligibility according to the inclusion/exclusion criteria and 
o Perform IGA  
o Perform facial lesion count of inflammatory, noninflammatory, and nodular 
lesions  
• Perform photography (Section 8.2) 
• Measure blood pressure and heart rate (Section 9.4)  
• Perform physical examination including height and weight (Section 9.5) 


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• Perform 12-lead EKG if subject is over 39 years of age 
• Perform urine pregnancy test in females of childbearing potential 
• Randomize the subject using the IWRS system, when all criteria have been met  
• Record concomitant medications 
• Record AEs 
• Dispense 1 kit (2 canisters) of study drug  
• Dispense cleanser 
     
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 
6.1.3. 
Visit 2, Week 1 
• Measure blood pressure and heart rate 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
• Collect previously dispensed study drug canister(s) if applicable 
• Dispense 1 kit (2 canisters) of study drug  
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 
6.1.4. 
Visit 3, Week 3 
• Measure blood pressure and heart rate 
• Perform urine pregnancy test in females of childbearing potential 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory (Section 9.6)  
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
• Collect previously dispensed study drug canister(s) if applicable 
• Dispense 1 kit (2 canisters) of study drug  
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• Determine if additional drug or cleanser needs to be dispensed.   
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 
6.1.5. 
 Visit 4, Week 6 
• Measure blood pressure and heart rate 
• Perform urine pregnancy test in females of childbearing potential 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Perform photography 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
• Collect previously dispensed study drug canister(s) if applicable 
• Dispense 1 kit (2 canisters) of study drug  
• Determine if additional drug or cleanser needs to be dispensed.   
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 
6.1.6. 
Visit 5, Week 9  
• Measure blood pressure and heart rate 
• Perform urine pregnancy test in females of childbearing potential 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
• Collect previously dispensed study drug canister(s) if applicable 
• Dispense 1 kit (2 canisters) of study drug  
• Determine if additional drug or cleanser needs to be dispensed.   
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 


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6.1.7. 
Visit 6, Week 12 End of Double-Blind or Continuation in Open Label / Early 
Termination   
• Perform physical examination including weight 
• Measure blood pressure and heart rate 
• Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory 
• Perform urine pregnancy test in females of childbearing potential 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Perform photography 
• Administer Subject Satisfaction Questionnaire 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
• Collect previously dispensed study drug canister(s) 
• If subject is continuing into the open-label phase of the study (see Section 4.1.2), 
dispense 2 kit (4 canisters) of FMX-101, 4% minocycline foam 
o If subjects facial acne is “clear” or “almost clear,” consider withholding 
treatment with FMX-101, 4% at this time but continue subject in study and 
schedule next visit. 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 


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6.2. 
Part 2 – Open-label 
A summary of study assessments and the time point at which they will be performed during the 
Part 2 of this study is presented in 
Table 2.  If a subject prematurely withdraws from the study, the subject should return to the 
study site at which time all evaluations described under Final Visit 13/Week 52 must be 
performed. 
 
Table 2: Schedule of Procedures - Study FX2014-05 – Part 2 
 
Assessment 
 
 Visits 
Final 
Visit 1 
Visit 
7 
8 
9 
10 
11 
12 
13 
Week 
16 
22 
28 
34 
40 
46 
52 
Physical Exam, weight, 
 
 
 
 
 
 
X 
Blood Pressure/heart rate 2 
X 
X 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
 
 
X 
 
 
 
X 
Urine pregnancy test (females of 
childbearing potential only)3 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
X 
X 
X 
X 
X 
Lesion Count 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medication  
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
Tolerability Assessment 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction Questionnaire 
 
 
 
 
 
 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect empty canisters 
X 
X 
X 
X 
X 
X 
X 
Dispense Study Drug 
X 
X 
X 
X 
X 
X 
 
Schedule/Confirm Next Visit 
X 
X 
X 
X 
X 
X 
 
 
                                                 
1 If a subject prematurely withdraws from the study, all evaluations described under Final Visit 13/Week 52 must be performed.   
2 Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest 
3 Home pregnancy tests will be dispensed at each visit to all female subjects of a childbearing potential and will be performed at 
least monthly and whenever there is a suspicion of pregnancy (e.g., a missed period). Perform urine pregnancy test at Final visit. 


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6.2.1. 
Visit 7 - Week 16 
• Measure blood pressure and heart rate 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Assess product use to confirm that subject continues to use study drug properly 
• Collect empty study drug canister(s) 
• Dispense 2 kits (4 canisters) of FMX-101, 4% minocycline foam if required 
• Dispense Home pregnancy kit to all female subjects of childbearing potential 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 
o If subjects facial acne is “clear” or “almost clear,” consider withholding 
treatment with FMX-101, 4% at this time but continue subject in study and 
schedule next visit.  
o If treatment has been interrupted, consider restarting treatment if clinically 
indicated 
6.2.2. 
Visits 8, 9, 10, 11 and 12 – Weeks 22, 28, 34, 40 and 46 
• Measure blood pressure and heart rate 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• At Visit 9 (Week 28) only - Collect blood and urine samples for clinical laboratory 
tests and send to the central laboratory (Section 9.6)  
• Assess product use to confirm that subject continues to use study drug properly 
• Collect empty study drug canister(s) 
• Dispense 2 kits (4 canisters) of FMX-101, 4% minocycline foam if required 
• Dispense Home pregnancy kit to all female subjects of childbearing potential 
• Schedule/confirm the next study visit and remind subject to avoid overexposure to 
natural or artificial sunlight 


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o If subjects facial acne is “clear” or “almost clear,” consider withholding 
treatment with FMX-101, 4% at this time but continue subject in study and 
schedule next visit.  
o If treatment has been interrupted, consider restarting treatment if clinically 
indicated 
6.2.3. 
Visit 13, Final Visit – Week 52 
• Measure blood pressure and heart rate 
• Perform physical examination including weight 
• Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory 
• Perform urine pregnancy test in females of childbearing potential 
• Perform IGA 
• Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
• Record concomitant medications 
• Record AEs and Tolerability Assessment 
• Administer Subject Satisfaction Questionnaire 
• Collect previously dispensed study drug canister(s) 
7. 
STUDY TREATMENTS 
FMX-101, 4% and vehicle will be supplied as identical canisters.  All study drug will be stored, 
inventoried, reconciled, and destroyed according to US regulations. 
7.1. 
Treatments Administered 
The description of study drug kits and treatments is shown below.  
7.1.1. 
Part 1 (double-blind) – Weeks 1 to 12 
Dosage form description Active kit: FMX-101 minocycline foam, 4%;  
Vehicle kit: Matching vehicle foam 
Package description 
Active kit: 2 canisters of FMX-101, 4% dispensed as foam when actuator is depressed 
Vehicle kit: 2 canisters dispensing vehicle foam when actuator is depressed 
Daily dose 
Approximately 0.5 gm of FMX-101, 4% (containing 40 mg minocycline per gram of foam; 0 mg 
for vehicle subjects); applied to face topically each day.  Additional drug product may be applied 
to other acne-affected areas 
Cumulative maximal 
dose 
Approximately 1,680 mg of minocycline (0 mg for vehicle subjects) assuming application of 0.5 
gm of foam daily to the face for 84 days. Maximum total amount of drug dispensed contains 14 
gm of minocycline.  
Dispensing 
1 Kit (2 canisters) dispensed at Baseline and Weeks 1, 3, 6, and 9.  Total of 5 kits (10 canisters) 
dispensed to the subject for the study. 


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7.1.2. 
Part 2 (open-label) – Weeks 13 to 52 
Dosage form description FMX-101 minocycline foam, 4%;  
Package description 
Active kit: 2 canisters of FMX-101, 4% dispensed as foam when actuator is depressed 
Daily dose 
Approximately 0.5 gm of FMX-101, 4% (containing 40 mg minocycline per gram of foam) 
applied to face topically each day.  Additional drug product may be applied to other acne-affected 
areas 
Cumulative maximal 
dose 
Up to approximately 5,600 mg of minocycline assuming application of 0.5 gm of FMX-101 foam 
daily to the face for 280 days. Maximum total amount of drug dispensed contains 39.2 gm of 
minocycline. 
Dispensing 
Up to 2 Kits (4 canisters) dispensed at Weeks 12, 16, 22, 28, 34, 40 and 46 depending on rate of 
usage. Up to a total of 14 kits (28 canisters) dispensed to the subject for the study. 
7.1.3. 
Dosing Instructions 
7.1.3.1. 
Part 1 – Double-blind 
The dosing regimen will be the same for both treatment groups.  
After shaking the canister well, a small amount of foam (about 1/2 gram or a cherry-sized 
amount) should be expressed from the canister onto the fingertips of the hand and then rubbed 
into acne-affected parts of the face.  This should be repeated as needed until all acne-affected 
parts of the face are treated.  If acne is present on other parts of the subject’s body (neck, 
shoulders, arms, back or chest) additional amounts (up to a total of 4g) of foam should also be 
applied to these areas. The foam should be applied at approximately the same time each day 
preferably in the evening at bedtime. The subject should not bathe, shower or swim for at least 1 
hour after application of the product. 
Study kits of blinded drug supplies will be dispensed at Baseline and Weeks 1, 3, 6 and 9 to 
ensure continuous dosing in case the subject is late for subsequent visits.  
Dose adjustments are not permitted in this part of the study.  Subjects who require a dose 
adjustment or discontinuation of study drug must be withdrawn from the study (Section 11.4). 
7.1.3.2. 
Part 2 – Open-label 
At the Week 12 Visit, subjects who elect to continue into the open-label part of this study will 
receive supplies of active FMX-101, 4% minocycline foam.   
Treatment during this part of the study will be guided by each subject’s clinical response.  The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas.  Even if the treatment is partially or completely 
temporarily suspended, the subject will be continued in the study and make all scheduled clinic 
visits.  If at any time the acne recurs or worsens, retreatment of the affected areas may be 
resumed. At each visit, the changes in treatment will be documented.  
Sufficient product will be dispensed at each visit to allow continuation of treatment as required. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product.   


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7.1.4. 
Manufacturer 
The manufacturer of the investigational product is 
 
 
7.1.5. 
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:  
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. 
7.1.6. 
Storage of Study Drug 
FMX-101, 4% and vehicle canisters must be stored at 2°C – 8°C until being dispensed to the 
subjects.  Subsequently, they must be stored at 20°C – 25°C (refer to USP Controlled Room 
Temperature).  The investigator will be responsible for the suitable storage of the investigational 
product in compliance with the storage instructions and must restrict access to the study 
personnel only. 
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7.2. 
Study Drug Accountability 
The Investigator will have overall responsibility for the use of the study drug.  The Investigator 
or designee will verify the contents of the drug shipment and confirm receipt of the study drug in 
the Interactive Web Response System (IWRS) system.  In addition, an accurate study drug 
dispensing record that specifies the date and amount dispensed to each subject must be kept.  
This inventory record must be available for inspection by representatives of the Sponsor and is 
subject to regional regulatory authority inspection at any time.  At the conclusion of the study, 
the Investigator must provide a copy of this record to the Sponsor.  In addition, the weight of 
each canister will be determined prior to being dispensed to the subjects and each canister that 
has been retrieved from the subject will be returned to the vendor to be weighed. 
Under no circumstances will the Investigator allow the investigational drugs to be used other 
than as directed by this protocol.  Qualified study personnel must use the IWRS to assign and 
dispense kits to the subjects.  Reasons for digression from the expected dispensing regimen must 
also be recorded. 
7.3. 
Handling and Disposal of Study Drug 
The study drug must be protected from unauthorized access (eg, in a locked storage facility). 
Any unused, partially used, or empty bottles of study drug will be returned to the Sponsor or 
designee by the time of the site’s close-out visit.  Receipt, distribution, and return of the study 
drug must be properly documented on forms provided by the Sponsor or designee. 
7.4. 
Method of Assignment of Study Drug 
7.4.1. 
Part 1 – Double- blind 
After pretreatment clinical evaluations and all other screening procedures have been completed, 
authorized site personnel will acknowledge that the applicable subject met all the specified 
inclusion criteria and none of the exclusion criteria.  Assignment to a treatment group will then 
follow a predetermined list of randomization numbers, with each successive number receiving 
1 of the 2 treatments in random order.  Authorized site personnel will use the IWRS system to 
assign a kit number that corresponds to the randomization schedule.  The kit box with the 
assigned kit number will be dispensed to the subject.  
The randomization code will be provided by TKL.  
7.4.2. 
Part 2 – Open-label 
All subjects who elect to continue into the second part of the study will receive FMX-101, 4% 
minocycline foam as described in Section 7.1.3.2.        
7.5. 
Selection and Timing of Doses in the Study 
The 4% minocycline concentration of FMX-101 was shown to be more effective than 1% in a 
Phase 2 study.  The once-daily dosing regimen is appropriate given the pharmacokinetic 
characteristics of minocycline. 


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7.6. 
Blinding 
The first part of this study is double-blind with limited access to the randomization code.  The 
randomization code will be held in confidence until after the study database is locked and a 
memo documenting the database lock has been issued.  Every effort will be made to retain the 
integrity of the blind.  When issued to the sites, the study drug will be identical in appearance for 
all subjects, regardless of treatment assignment. 
The treatment each subject receives will not be disclosed to the Investigator, study site personnel, 
subjects, monitors, or the Sponsor staff except as required for the purposes of conducting this 
study. 
In the event that emergency identification of study drug is required (eg, if the Investigator 
believes that the information is necessary to properly treat a subject with an AE), the study drug 
identity can be obtained by the Investigator through the IRT system. 
Before breaking the blind for a subject, the Investigator should determine that the information is 
necessary (ie, that it will alter the subject’s immediate course of treatment and will contribute to 
the management of the AE).  In many cases, particularly when the emergency is clearly not 
related to study drug, the problem may be effectively managed by assuming that the subject is 
receiving active study drug without the need for unblinding.  Every effort should be made to alert 
the Medical Monitor before requesting that the blind be broken.  If this is not possible, the 
Medical Monitor should be immediately notified of the breaking of the blind.  The Investigator 
will record the unblinding procedures in the subject’s source documents. 
If unblinding is necessary, the subject will be withdrawn from the study and Week 12 Visit 
assessments will be completed. 
7.7. 
Prior and Concomitant Therapy   
Subjects should use the cleanser, 
 (provided by the Sponsor).  An 
alternative, non-medicated, cleanser may be used if agreed to by the Sponsor. 
The use of or change in the dose of any and all concomitant medication, either prescription or 
over-the-counter, during the study will be recorded. The reason for use or change of dose of a 
concomitant therapy may need to be reported as an AE.  Therapies (medication and non-
medication therapies) not restricted by the protocol may be used.  Non-prohibited chronic 
therapies being used at Baseline may be continued. If a subject is using an oral contraceptive 
product, she should have been on the same product for at least 3 months and she should continue 
using the same or equivalent product for the duration of the double-blind portion of the study. 
If a subject is taking anticoagulant therapy, the subject should be advised that they may require a 
downward adjustment of their anticoagulant dosage. 
All topical or systemic medications listed in the exclusion criteria are prohibited during the 
double-blind part of this study (through Week 12).  Similarly, no other topical medications are 
permitted to be used on the face during this period.  Subjects requiring systemic antibiotics not 
known to affect acne will be considered on a case-by-case basis.   
During the open-label part of the study, concomitant acne medications are permitted; their use 
should be properly recorded. Benzoyl peroxide (e.g., Pro-Activ, Clearasil) can inactivate 
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minocycline and may thus decrease the effectiveness of FMX-101 if the two products are applied 
at the same time. Treated areas should be washed between applications of FMX-101 and 
products containing benzoyl peroxide.  Preferably, the products should be applied no less than 8 
hours apart. 
See the Investigators’ Brochure for information about tetracyclines and possible drug-drug 
interactions 
7.8. 
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 or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea > 12 
consecutive months).  Females of childbearing potential must have a negative urine pregnancy 
test and, if they are sexually active or become sexually active during the study, must use an 
effective method of birth control such as those listed below during the course of the study.  The 
following is not an all-inclusive list; the subject must discuss with the Investigator the most 
appropriate form of birth control: 
• Hormonal methods 
o Oral contraceptives – (Topical 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 
• Abstinence 
7.9. 
Treatment Compliance 
Each subject is to be instructed on the importance of following the dosing schedule and returning 
all kits (empty/used/unused) at the appropriate visits.  The study personnel will question the 


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subject on the history of study drug use since the last visit. A subject who deviates significantly 
from the prescribed dosage will be counseled.  
8. 
EFFICACY ASSESSMENTS 
8.1. 
Primary Efficacy Assessments 
The primary efficacy assessments will be the IGA and lesion counts. 
8.1.1. 
Investigator Global Assessment Score (IGA) 
Table 3 displays the IGA scale for acne vulgaris, which will be used by the investigators to 
assess the severity of a subject’s acne vulgaris.  The Case Report Forms (CRFs) will allow for 
Investigators to report lesions worsening beyond Grade 4 with treatment.    The IGA must be 
performed prior to the lesion count. 
The same evaluator should perform all evaluations for a subject; when this is not possible, 
another approved evaluator may perform the evaluations. 
Table 3: IGA Scale for Acne Vulgaris 
Score 
Grade 
  Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
 
1 
Almost clear 
Rare noninflammatory lesions may be present, with rare non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink- red) 
2 
Mild 
Some noninflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Many noninflammatory lesions.  Multiple inflammatory lesions evident with several 
to many papules/pustules, and there may be one small nodulocystic lesion 
4 
Severe 
Inflammatory lesions are more apparent, many comedones and papules/pustules, there 
may be a few nodulocystic lesions 
5 
Very Severe 
Highly inflammatory lesions predominate, variable number of comedones, many 
papules/pustules and many nodulocystic lesions 
8.1.2. 
Lesion Counts 
Subjects are eligible for enrollment if they have: 
• 20 to 50 inflammatory lesions (papules, pustules, and nodules) 
• 25 to 100 noninflammatory lesions (open and closed comedones) 
• No more than 2 nodules can be present on the face at Screening 
Lesions will be characterized as inflammatory or non-inflammatory using the following criteria: 
• Inflammatory lesions: 
Papule – a solid, elevated lesion less than 0.5 cm in diameter 
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Nodule – palpable solid lesion greater than 0.5 cm in diameter; has depth, not 
necessarily elevated 
 
 
• Noninflammatory lesions: 
Open comedones (blackhead) – non-infected plugged hair follicle with 
dilated/open orifice; black in color 
Closed comedones (whitehead) – non-infected plugged hair follicle: small 
(microscopic) opening at skin surface 
Facial lesion counts will be made for the forehead, left and right cheeks, nose and chin at each 
visit.  Total inflammatory lesions (pustules, papules, and nodular lesions) and noninflammatory 
lesions (open and closed comedones) will be counted and recorded separately.  Lesion counts 
will be repeated at Weeks 3, 6, 9 and 12. 
8.2. 
Photography 
Photography of the face will be performed at Baseline and at Weeks 6 and 12 using recognized 
methods.  The equipment and techniques for this photography and for archiving the images are 
described in the Study Manual.  Photographs will be reviewed at the site and by the sponsor for 
quality.  Photographs will not be used to assess the lesion counts or the Investigator’s assessment 
of global severity but will be archived to be available for subsequent review, if required, by the 
sponsor, auditors or the FDA. 
8.3. 
Subject Satisfaction Questionnaire 
A satisfaction questionnaire will be administered at Visit 6, Week 12 and Visit 13, Week 52 (see 
Section 16.1, Appendix 1). 
9. 
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
physical examinations, the monitoring of vital signs, AEs (volunteered, observed, and elicited by 
general questioning in a non-suggestive manner), and clinical laboratory test results.  In addition, 
skin assessments at the drug application site(s) will be performed. 
9.1. 
Medical/Surgical History 
A complete medical and surgical history will be obtained at Screening, which will include 
diseases of the head, ears, eyes, nose and throat; respiratory diseases; cardiovascular diseases; 
gastrointestinal diseases, hepatic diseases, genitourinary diseases, musculoskeletal diseases, 
endocrine diseases, neurological diseases, psychiatric diseases, skin diseases, allergies, 
hematological diseases, and other abnormalities. 


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9.2. 
Medication History 
A history of medication usage (including previous use of acne medications and non-medication 
therapies) will be recorded at Screening.  The start and stop dates of previous use of medications 
in the last 3 months will be recorded. 
9.3. 
Concomitant Medications 
All medication that the subject is currently taking or any change in medication or dosage since 
the last visit will be documented throughout the study. 
9.4. 
Vital Signs 
Heart rate and blood pressure will be measured at all post-Baseline visits.  All blood pressure 
measurements will be made using a sphygmomanometer with an appropriate cuff size for the 
individual subject.  Measurements will be administered while the subject is seated after at least 
5 minutes at rest. 
9.5. 
Physical Examination 
A complete physical examination will include an evaluation of general appearance, skin, 
HEENT, neck, lymph nodes, lungs, heart, abdomen, musculoskeletal system, and neurologic 
system. A standard 12-lead EKG (after at least 5 minutes rest) will be performed at Baseline in 
subjects over 39 years of age. 
Weight will be recorded at the Baseline Visit, Visit 6 (Week 12) and Final Visit (Week 52).  
Height will be measured at Baseline, only. 
9.6. 
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at Baseline, Week 12/ Final Visit 
of the double-blind phase of the Study, and at Week 28 and Week 52/Final Visit of the open-
label phase of the Study. Serum chemistry, hematology, and urinalysis tests will be performed at 
a central laboratory. 
Refer to the manual from the central laboratory for detailed instructions on collecting, 
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Hematology 
Urinalysis 
Serum chemistry 
Hematocrit 
Hemoglobin 
MCH 
MCHC 
MCV 
MPV 
Platelet count 
RBC 
RDW 
WBC 
Reticulocyte count  
WBC differential  (% & 
absolute) : 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes esterase 
pH 
Protein 
Specific gravity 
 
Urine pregnancy 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 
Triglycerides 
Uric acid 
9.6.1. 
Urine Pregnancy Test 
A urine pregnancy test will be performed on all females of childbearing potential at Baseline, 
Week 3, Week 6, Week 9 and Week 12 of the double-blind phase of the Study and Final Visit or 
when a subject prematurely withdraws from the study. 
Home pregnancy kits will be provided at each visit to all female subjects of childbearing 
potential in the open-label phase of the Study and are to be used at least monthly and if a 
pregnancy is suspected between visits (e.g., if a subject misses a period). A urine pregnancy test 
will be performed at Week 52/ Final Visit. 
9.6.2. 
Sample Collection, Storage, and Shipping 
Sample collection kits, requisition slips, and shipping boxes will be supplied by the central 
laboratory. Sample collection procedures and shipping instructions will be detailed in the 
laboratory manual. Study centers must be equipped to store the samples according to the 
laboratory manual procedures before shipping samples to the central laboratory. 
9.7. 
Other Safety Measurements 
9.7.1. 
Tolerability 
Erythema, dryness, hyperpigmentation and skin peeling at the sites of study drug application will 
be assessed by the investigator at each study visit on a scale of 0 to 3 (0=none; 1=mild; 
2=moderate; 3=severe). Itching will be assessed using the same scale based on the subjects’ 
subjective assessment.  The intensity and location of each finding will be recorded.  These signs 
and symptoms should not be recorded as AEs unless they require concomitant treatment or lead 
to the subject’s discontinuation from the study. 


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9.8. 
Adverse Events 
9.8.1. 
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator.  AEs will be recorded at each visit throughout the study on the appropriate 
CRF. Every attempt should be made to describe the AE in terms of a diagnosis.  If a clear 
diagnosis has been made, individual signs and symptoms will not be recorded unless they 
represent atypical or extreme manifestations of the diagnosis, in which case they should be 
reported as separate events.  If a clear diagnosis cannot be established, each sign and symptom 
must be recorded individually. 
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 over-the-counter) 
• Were admitted to a hospital or had any accidents 
• Developed unusual headaches or changes in vision 
With the exception of the last item above, all questions should be of a general nature and should 
not suggest symptoms. 
When an AE is suspected, all relevant evaluations will be carried out and appropriate treatment 
provided.  Additional follow-up will be done as necessary (Section 9.8.4) and recorded in the 
subject’s source documents, and the results will be provided to the Sponsor. 
For AE definitions and reporting requirements, refer to Section 9.8.2 and Section 9.8.3, 
respectively. 
9.8.2. 
Adverse Event Definitions 
9.8.2.1. 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended sign, symptom, or disease that appears 
or worsens in a subject after the subject signs the ICF (and/or Assent Form) for a clinical study. 
Examples of what may be considered an AE include any of the following: 
• A new illness 
• An exacerbation of a sign or symptom of an underlying condition or of a concomitant 
illness unrelated to participation in the clinical study or an effect of the study drug or 
comparator drug 
No causal relationship with the study drug is implied by the use of the term “adverse event.”  An 
exacerbation of a pre-existing condition/illness is defined as a more frequent occurrence or as an 
increase in the severity of the pre-existing condition/illness during the study.  Planned or elective 
surgical procedures for pre-existing conditions that have not worsened are not AEs.  However, 


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any complication that occurs during a planned or elective surgery is an AE.  (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. 
9.8.2.2. 
Serious Adverse Events 
A “serious adverse event” (SAE) is any AE that: 
• Results in death 
• Is life-threatening 
(Note: The term “life-threatening” refers to any AE that, as it occurs, puts the subject 
at immediate risk of death.  It does not refer to an AE that hypothetically might have 
caused death if it were more severe.) 
• Results in hospitalization or prolongation of current hospitalization (not including 
hospitalization for a pre-existing condition that has not increased in severity or 
frequency from the subject’s underlying medical condition prior to entry into the 
study) 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect in the offspring of a subject 
• Is another serious (important medical events) events 
 
(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. 
9.8.2.3. 
Severity of Adverse Events 
“Severity” of the AE refers to the extent to which an AE affects the subject’s daily activities and 
differs from “Serious,” which is a regulatory classification.  Severity will be categorized 
according to the following criteria: 
• Mild:  The symptom has a negligible effect or no impairing effect on the subject’s 
normal function. 
• Moderate:  The symptom impairs the subject’s normal function to some extent. 
• Severe:  The symptom has an obvious, significantly impairing effect on the subject’s 
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9.8.2.4. 
Relationship of Adverse Events to Study Treatments 
“Causality” refers to the relationship of the AE to study drug and will be categorized according 
to the following criteria: 
• Unlikely:  There is no medical evidence to suggest that the AE may be related to 
study drug usage, or there is another more probable medical explanation. 
• Possible:  There is medical evidence to suggest that there is a reasonable possibility 
that the AE may be related to study drug usage. However, other medical explanations 
cannot be excluded as a possible cause. 
• Probable:  There is strong medical evidence to suggest that the AE is related to study 
drug usage. 
9.8.2.5. 
Adverse Events Expectedness 
Expected AEs are defined as those described in the Investigator’s Brochure.  If an event 
increases in intensity or severity from that described in the IB, it will be considered unexpected. 
9.8.3. 
Reporting Adverse Events 
AEs that occur from the time of informed consent/assent through completion of the last study 
visit should be reported.  Any AE that the Investigator becomes aware of that occurs within 30 
days of study completion or withdrawal should also be reported. 
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 individually. 
Any serious AEs occurring in a subject receiving study drug must be reported to the Sponsor or 
designee within 24 hours of the site being informed of the event, even if the event does not 
appear to be drug-related.  The report must be made by sending a completed Serious Adverse 
Event (SAE) Report form to the Sponsor or designee.  Any pertinent follow-up information 
should be provided in a similar manner.  Contact information is provided below:  
TKL Clinical Pharmacovigilance 
 
9.8.4. 
Adverse Event Follow-up 
Adverse events, and tolerability signs and symptoms greater than zero (0), that are ongoing when 
a subject withdraws from or completes the study will be followed until resolution or stabilization 
(in the opinion of the Investigator), or for 30 days, whichever is shorter.  Investigators and the 
Sponsor will decide if longer follow-up is appropriate on a case-by-case basis.  Subjects who 
experience any clinically significant AE will remain under medical supervision until the 
Investigator or the Sponsor’s Medical Monitor deems the AE to be resolved, stabilized, or no 
longer serious enough to warrant follow-up. 
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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 resolved or stabilized. 
9.8.4.1. 
Pregnancy reporting 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy.  The Informed Consent or Assent Form that the subject signs must document this 
discussion.  
If a subject or Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of laboratory pregnancy testing 
are available.  If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
A urine pregnancy test will be performed on all females of childbearing potential at Baseline, 
Week 3, Week 6, Week 9 and Week 12 of the double-blind phase of the Study and Final Visit or 
when a subject prematurely withdraws from the study. 
Home pregnancy kits will be provided at each visit to all female subjects of childbearing 
potential in the open-label phase of the Study and are to be used at least monthly and if a 
pregnancy is suspected between visits (e.g., if a subject misses a period). A urine pregnancy test 
will be performed at Week 52/Final Visit. 
During the study, all females of childbearing potential should be instructed to contact the 
Investigator immediately if they suspect they might be pregnant (eg, missed or late menstrual 
period).  If a subject or Investigator suspects that the subject may be pregnant at any time before 
or during the study, the study drug must be withheld until the results of laboratory pregnancy 
testing are available.  The Sponsor and Site Monitor must be notified and available information 
captured on a “Suspected Pregnancy” 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) but the 
pregnancy will not be captured as an AE. 
The subject should be followed until the outcome of the pregnancy is known. 
9.8.5. 
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be so flagged 
when reported to the site.  The Investigator will determine which out-of-range laboratory test 
results should be characterized as clinically significant and will so annotate the laboratory report.  
If a clinically significant laboratory abnormality requires treatment or is the reason for a subject 
being discontinued from the study, the abnormal result must also be classified as an AE. 
9.9. 
Appropriateness of Safety Measurement 
The safety assessments in this study are standard safety measures in clinical trials. 


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10. 
STATISTICAL DESIGN AND ANALYSIS 
10.1. 
Statistical Analysis Plan 
A detailed statistical analysis plan will be finalized prior to breaking of the study blind. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response.  Missing responses will be enumerated, but the 
calculation of percentages will exclude missing responses.  For quantitative variables (eg, age), 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, minimum value and maximum value.  All hypothesis testing will be 
conducted using two-sided tests with α=0.05 level of significance unless otherwise specified. 
All study data will be presented in listings. 
10.2. 
Determination of Sample Size 
In a phase 2 study, the proportion of subjects with an IGA score of 0 or 1 after 12 weeks of 
treatment was 
 in the minocycline 4% foam group compared to 2% in the vehicle group. The 
following table provides a few alternate assumptions and corresponding sample sizes. Power was 
set to 
 and type-1 error to two-sided 0.05. Sample size was calculated based on Fisher’s 
Exact test. 
Vehicle IGA (0,1) Minocycline 4% 
foam IGA (0,1) 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
Assuming 12% dropout rate, 300 subjects on active, and 150 subjects on vehicle will provide at 
least 
 power for a statistically significant difference on IGA 0 or 1. In the same phase 2 
study, the change from baseline in inflammatory lesions was 
 in the minocycline 4% foam 
versus 
 in the vehicle group. The standard deviation in change from baseline was 
approximately 
 The following table shows alternate assumptions and corresponding sample 
sizes, for 90% power and a two-sided type 1 error of 0.05. The sample sizes were calculated 
using a t-test. 
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Vehicle mean 
inflammatory 
lesion reduction 
Minocycline 4% foam 
mean inflammatory 
lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
To summarize, using some conservative estimates of the effect on minocycline 4% foam versus 
the vehicle for both IGA and change in inflammatory lesions at week 
 subjects on active, 
and 150 on vehicle will provide > 90% power for s statistically significant difference. 
Another consideration for the sample size must be given to the secondary endpoint of 
noninflammatory lesions which will be compared to the vehicle for non-inferiority. The margin 
for non-inferiority will be 
f the change from baseline to week 12. In a phase 2 study, 
change from baseline in noninflammatory lesions at week 9 was 
 for the vehicle group with 
a standard deviation of 18. Assuming approximately the same reduction at week 12, a 
 non-
inferiority margin is about 
 lesions. The following table provides approximate sample sizes 
for alternate assumptions for 90% power to show non-inferiority. 
Vehicle mean 
noninflammatory 
lesion reduction 
Minocycline 4% foam 
mean noninflammatory 
lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
 
If Minocycline 4% foam has the same effect on noninflammatory lesions as vehicle, 
 subjects 
on vehicle and 
 on 4% foam will be needed for 90% power to show non-inferiority. If 
Minocycline 4% foam has a slightly less effect on noninflammatory lesions (
 lesion 
reduction versus 
 in vehicle), there will be about 90% power to show non-inferiority. 
10.3. 
 Analysis Populations 
The Intent-to-Treat (ITT) population will include all randomized subjects. The ITT population 
will be the primary population for all efficacy analyses. 
The Safety population will include all randomized subjects who took at least one dose of study 
drug.  Subjects who have no post-Baseline assessments will be included in the Safety population 
unless all dispensed study drug is returned unused. 
The Per Protocol (PP) population is defined as the subset of the ITT population without any 
protocol deviations that may have an impact on the efficacy assessments.  The subjects to be 
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included in the PP population will be determined by the Sponsor/CRO prior to the unblinding of 
the study.  The PP population will be secondary for the co-primary endpoints only. 
Subjects may be excluded from the PP population if any of the following are met:  
• Did not meet inclusion/exclusion criteria 
• Have administered any interfering concomitant medications 
• Have not, in the opinion of the investigator, been compliant with the treatment 
regimen (e.g. reported frequent missed doses) 
Prior to breaking the blind, additional criteria for exclusion from the PP population may be 
included to accommodate for unforeseen events that occurred during the conduct of the study.  
10.4. 
Efficacy Endpoints 
The primary population for all efficacy analyses will be the ITT population.  Subjects will be 
analyzed according to their randomized treatment.  The primary method of handling missing data 
will be the last observation carried forward (LOCF) approach.   Sensitivity analyses using 
multiple imputations and baseline observation carried forward (BOCF) will be performed on the 
co-primary endpoints only. 
Supportive efficacy analyses will also be performed on the PP population.  All analyses using the 
PP population will use the Observed-Cases (OC) approach.  i.e., there will be no imputation for 
missing data at any time point. 
Changes from Baseline lesion count will be calculated as the Baseline value minus the post-
Baseline value.  Thus, a positive change will reflect a reduction in lesion count.  The percent 
change from Baseline lesion count will be calculated as the Baseline value minus the post-
Baseline value divided by the Baseline value, expressed as a percentage.  Thus, a positive 
percent change will reflect a reduction in lesion count. 
10.4.1. Primary Efficacy Endpoints 
The co-primary efficacy endpoints are: 
• The absolute change from Baseline in the inflammatory lesion count at Week 12 
• Treatment Success (dichotomized as Yes/No) at Week 12, where success is defined 
as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from 
Baseline 
The null hypotheses of the equality of the FMX-101 4% and vehicle means for absolute change 
from Baseline to Week 12 in the inflammatory lesion count and the equality of IGA success rates 
at Week 12 will each be tested at a two-sided 0.05 level of significance. Change from baseline in 
inflammatory lesion count will be analyzed using an Analysis of Covariance (ANCOVA), with 
Treatment as a main effect, baseline inflammatory lesion count as a covariate, and 
investigational site a blocking factor. Investigational site by Treatment interaction will be tested 
at 0.1 level, and if significant, it will further be explored. The dichotomized IGA will be 
analyzed using a Cochran-Mantel-Haenszel (CMH) test, stratified by investigational site.  


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10.4.2. Secondary Efficacy Endpoints 
• The absolute change from Baseline in the noninflammatory lesion count at Week 12 
• The absolute change from Baseline in the inflammatory lesion count and IGA 
Treatment Success at the interim visit at Week 9 
• The absolute change from Baseline in the inflammatory lesion count and IGA 
Treatment Success at the interim visit at Week 6 
10.4.3. Tertiary efficacy endpoints 
• The percent change from Baseline in the inflammatory lesion count at Weeks 3, 6, 9 
and 12 
• The absolute change from Baseline in the inflammatory and noninflammatory lesions, 
and the IGA Treatment Success at Week 3 
• The absolute change from Baseline in the noninflammatory lesion count at Weeks 3, 
6, 9 and 12 
• The percent change from Baseline in the noninflammatory lesion count at Weeks 3, 6, 
9 and 12 
Secondary efficacy endpoint will be tested sequentially in the order listed above, at 0.05 level of 
significance, only if the co-primary efficacy endpoints are significant. 
10.5. 
Safety endpoints   
Treatment-emergent adverse events (TEAEs), vital signs, physical examinations, and clinical 
laboratory measurements will be reported on the Safety population.  Subjects will be reported 
according to the treatment they actually received.  No statistical tests will be performed for any 
of the safety assessments. 
Baseline for vital signs, physical examinations, and clinical laboratory measurements is defined 
as the last non-missing value prior to the first dose of study drug. 
10.5.1. Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to system organ class (SOC) and preferred term. 
TEAEs will be defined as events that emerge during treatment having been absent pre-treatment, 
or worsen relative to the pre-treatment state.  Summaries of AEs will be limited to TEAEs.  The 
number and percentage of subjects reporting each SOC and preferred term will be summarized 
for each treatment group and by the Study Period.  At each level of summarization, a subject will 
be counted once if he/she reported one or more events.  The severity of TEAEs and relationship 
to study drug will be summarized in a similar manner.  For summaries of relationship to study 
drug, a subject will be classified according to the closest relationship.  For summaries of TEAE 
severity, a subject will be classified according to the highest severity. 
Summaries of SAEs and subjects who prematurely withdraw from the study due to AEs will be 
presented. 


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10.5.2. Vital Signs  
Vital sign parameters will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point.  Changes from Baseline will also be summarized.  Baseline is defined 
as the last non-missing value prior to the first dose of study drug. 
10.5.3. Physical Examinations 
Physical examinations will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point.  Shifts from Baseline will also be summarized.  Baseline is defined as 
the last non-missing value prior to the first dose of study drug. 
10.5.4. Clinical Laboratory Results 
 
Baseline is defined as the last non-missing value prior to the first dose of study drug. 
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 each post-baseline time point.  
A listing of subjects with pre-treatment and treatment-emergent clinically significant abnormal 
laboratory values will be presented for each treatment group. Clinical significance is based on 
the Investigator’s judgment.  
10.6. 
Statistical Analysis 
10.6.1. Interim Analysis 
 
No interim analysis is planned. 
10.6.2. Subject Accounting, Demographic, and Baseline Characteristics 
Demographic, baseline characteristics, and prior and concomitant medications will be 
summarized by treatment.  Study completion status and reasons for discontinuation will also be 
displayed by treatment.   
Medical and surgical history will only be presented in the listings. 
10.6.3. Efficacy Analysis 
The co-primary endpoint of absolute change from Baseline in inflammatory lesions at Week 12 
will be analyzed using an Analysis of Covariance (ANCOVA) model with main effect treatment 
and investigational site as a covariate.  The treatment by investigational site interaction will be 
tested separately at 0.1 level of significance, and if significant, will be further be explored.  A 
95% confidence interval will be calculated on the difference in mean changes from baseline 
between FMX-101 4% and vehicle. 
The co-primary endpoint of IGA Treatment Success rate at Week 12 will be analyzed using a 
Cochran–Mantel–Haenszel (CMH) test with investigational site as the stratification factor.  If the 
overall IGA Treatment Success rate is less than 10%, a Fisher’s Exact test will be used to 


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corroborate the CMH test.  A 95% confidence interval will be constructed on the difference in 
IGA Treatment Success rates between FMX-101 4% and vehicle. 
If FMX-101, 4% is found superior to vehicle (one-sided p<=0.025) for both co-primary 
endpoints, the secondary endpoints will be tested sequentially. The first secondary endpoint of 
noninflammatory lesions at Week 12 will be tested initially as a non-inferiority comparison of 
FMX-101, 4% to vehicle. Non-inferiority margin is defined as 30% of the noninflammatory 
lesion reduction in the vehicle group at Week 12. A lower 97.5% confidence limit will be 
calculated for µa-0.6×µv, where µa and µv are the mean reduction of noninflamatory lesions of 
FMX-101, 4% and vehicle respectively. If the confidence limit is above 0, non-inferiority will be 
concluded. If non-inferiority is concluded, the superiority of FMX-101, 4% to vehicle for 
noninflammatory lesions at Week 12 will be tested. The sequential testing will proceed 
according to the order in Section 10.4.2.1.  Testing of secondary efficacy endpoints at an earlier 
timepoint for each type of lesion and IGA Treatment Success will be performed only if 
superiority (one-sided p<=0.025) is seen at the later timepoint.  
Secondary efficacy parameters will be analyzed similar to the appropriate co-primary efficacy 
parameter. 
Absolute change from baseline in inflammatory lesion count and the IGA assessments in the 
open-label phase of the study will be summarized. No statistical testing will be performed for the 
open label efficacy data. 
10.6.4. Safety Analysis 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to system organ class (SOC) and preferred term. 
TEAEs will be defined as events that emerge during treatment having been absent pre-treatment, 
or worsen relative to the pre-treatment state.  Summaries of AEs will be limited to TEAEs.  The 
number and percentage of subjects reporting each SOC and preferred term will be summarized 
for each treatment group.  At each level of summarization, a subject will be counted once if 
he/she reported one or more events.  The severity of TEAEs and relationship to study drug will 
be summarized in a similar manner.  For summaries of relationship to study drug, a subject will 
be classified according to the closest relationship.  For summaries of TEAE severity, a subject 
will be classified according to the highest severity. 
Summaries of SAEs and subjects who prematurely withdraw from the study due to AEs will be 
presented. 
Vital sign parameters will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point.  Changes from Baseline will also be summarized. 
Physical examinations will be summarized using descriptive statistics at Baseline and for the 
final visit.  Shifts from Baseline will also be summarized. 
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. 


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A listing of subjects with pre-treatment and treatment-emergent clinically significant abnormal 
laboratory values will be presented for each treatment group. Clinical significance is based on 
the Investigator’s judgment. 
11. 
STUDY MANAGEMENT 
11.1. 
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 IRB to have direct access to all documents pertaining to the study.  The Investigator is to 
immediately notify the Sponsor or the Sponsor’s representative of any regulatory authority 
inspections.  The Investigator will be informed about the outcome of any Sponsor audit. 
This study will be monitored regularly, by or under supervision of a monitor from the Sponsor.  
The frequency of monitoring visits will be agreed upon by the Sponsor’s representative and the 
study site.  
Monitoring visits will take place on a regular basis according to the enrollment rate and number 
of subjects enrolled at each investigational site.  During these visits, the monitor will check the 
completion of the CRF entries, compliance with the study protocol and with GCP-ICH, and the 
agreement of key entries with the source data.  The monitor will also verify the correct use of the 
study drug.  At the Final Visit or at an agreed to time prior to 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 
or the Sponsor’s representative’s clinical research associate, as needed, regarding study concerns 
and/or questions.  Contact information is provided in the Study Binder for the site. 
11.2. 
Protocol Amendments 
The Sponsor may propose to amend this protocol at any time. 
No change to the protocol will be implemented until the Sponsor and the IRB have reviewed and 
approved the amendment. 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety.  All such procedures must have written documentation and be 
promptly reported to the Sponsor. 
Amendments to the protocol, if any, are included in Section 16.2, page 53.  This protocol version 
includes Amendment 1, effective February 26, 2016 and Amendment 2, effective April 6, 2016.   


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11.3. 
Protocol Deviations 
A protocol deviation is any change, divergence or departure from the IRB-approved protocol by 
the study staff (intentional or unintentional).  All deviations are to be documented at the site and 
reported to the IRB according to the IRB’s guidelines. 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety.  All such procedures must have written documentation and be 
promptly reported to the Sponsor. 
11.4. 
Withdrawal of Subjects 
Withdrawn subjects are those who do not complete all evaluations and procedures outlined in the 
protocol.  Subjects who discontinue taking study drug for any reason must also be withdrawn 
from the study.  Subjects may be withdrawn from the study because of one 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 9.8.4. 
• Abnormal Laboratory Result:  Any clinically significant laboratory abnormality 
that requires withdrawal of the subject from the study should be considered an AE 
leading to withdrawal.  If possible, laboratory tests will be repeated for any results 
that were clinically significantly abnormal until the abnormality is resolved or 
stabilized to the satisfaction of the Investigator in consultation with the Medical 
Monitor. 
• Lost to Follow-up:  Confirmed at minimum by 2 phone calls and a traceable letter 
without response. 
• Subject Request:  Subject requests, for any reason (eg, AE), to be withdrawn or 
withdraws his/her consent. 
• Poor protocol adherence:  A subject may be withdrawn from the study at the 
discretion of the Investigator or Sponsor due to poor compliance with protocol 
requirements that may compromise the study results or subject safety. 
• Other:  Other reasons include but are not limited to: Investigator decision that it is in 
the subject’s best interest to be withdrawn, administrative reasons, relocation of 
subject, etc.  If a subject becomes pregnant during the study, the subject will be 
withdrawn from the study and followed through conclusion of the pregnancy. 
If a subject is withdrawn from the study following the start of study drug during Period 1 of the 
study, all Week 12 assessments should be completed.  If a subject is withdrawn from the study 
following the start of study drug during Period 2 of the study, all Final Visit assessments should 
be completed.  Subjects withdrawn from the study will not be replaced. 


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11.5. 
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. 
11.6. 
Publication Policy 
The data obtained in this study are the property of the Sponsor, which will make reasonable 
efforts to assure that the results are published in a peer-reviewed journal.  As some of the 
information concerning the investigational product and development activities at the Sponsor 
may be of strictly confidential nature, any manuscript or other presentation of data must first be 
reviewed by the Sponsor before its submission. 
12. 
ETHICS 
12.1. 
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. 
12.2. 
Institutional Review Boards (IRB) 
This protocol (and any changes), all consent/assent 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 doctor-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 apply place followed by IRB approval. 
Review and approval by the IRB for continuation of the study must apply place at least once a 
year. 
12.3. 
Written Informed Consent 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration and the potential benefits and risks of participation to each 
subject prior to his/her entry into the study (ie, before examinations and procedures associated 
with selection for the study are initiated).  Each subject will have ample opportunity to ask 
questions and will be informed about the right to withdraw from the study at any time without 
any disadvantage and without having to provide reasons for this decision. 


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Following this informative discussion, the subject will be asked if he/she is willing to sign a 
statement of informed consent.  Only subjects who voluntarily sign the Informed Consent Forms 
(ICF) may enter the study. Subjects less than 18 years of age (or as required by state law) must 
sign an Assent Form for the study and a parent or legal guardian must sign the ICF. 
The ICF and Assent Form must be reviewed and approved by the Sponsor and the IRB prior to 
their use. 
The original signed ICF and Assent Form will remain in the Investigator’s files.  The 
Investigator or designee will indicate in each subject’s source documents that he / she has 
informed the subject about the study and its procedures, the subject has signed and dated the 
ICF/Assent Form, 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 subjects’ 
willingness to continue in the study. 
12.4. 
Subject Confidentiality 
The Sponsor ensures that the following have permission to review all study-related documents: 
monitor, auditor, IRB and regulatory authorities.  The subject’s identity and study-related records 
will remain confidential throughout the duration of the study data collection and reporting 
process. 
A unique subject identification code is assigned 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. 
12.5. 
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, source 
documentation corresponding to all information contained in the CRFs, signed informed consent 
and assent forms, relevant correspondence, and all other supporting documentation) until at least 
2 years after the last approval of a marketing application in an ICH region and until there are no 
pending or contemplated marketing applications in an ICH region, or at least 2 years after the 
formal discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted.  Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same time period. Custody of the records may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies.  Written notice of 
transfer must be submitted to the Sponsor.  The Investigator must contact the Sponsor prior to 
disposing of any study records. 


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12.6. 
Financing 
Funding for this study will be agreed between the Investigator and the Sponsor and will be 
confirmed in writing before the study starts. 
Completion of Financial Disclosure Forms will be required before the study starts.  Any 
additions to the primary site personnel will necessitate the completion of new Financial 
Disclosure Forms.  This information will also be collected at site closure and one year after the 
completion of the study. 
Disclosure Forms.  Investigators will be informed that they must report any new information to 
the sponsor or designate at site closure and one year after the completion of the study. 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and Investigator will apply all steps possible to ensure the accuracy, consistency, 
completeness, and reliability of the data, including participating in an Investigator meeting 
and/or site initiation visit, routine site monitoring, review of CRFs against source documents, and 
quality control checks.  
In addition, a representative from the Sponsor’s Clinical Quality Assurance (CQA) Department 
or designee may conduct periodic audits of the study processes, including, but not limited to, 
auditing the clinical site, laboratories, vendors and CROs, the clinical database, and the final 
study report. 
14. 
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, electronic case report forms (eCRFs) developed through a 
validated, Electronic Records / Electronic Signatures-compliant platform (US Title 21 CFR Part 
11).  Foamix Clinical Data Management department or designee will create the electronic CRFs 
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 user name and password.  Only the person who owns 
the user name and password will enter the system using that user name 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 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 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. 


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15. 
REFERENCE LIST 
1. Brown SK, Shalita A R; Acne Vulgaris, Follicutitis, and Acne Rosacea. Lancet 
351:1871-76, 1998 
2. Guidance for Industry: “Acne Vulgaris: developing Drugs for Treatment ” September 
2005 FDA Draft Guidance 
 


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16. 
APPENDICES 
16.1. 
Appendix 1 – Subjects Satisfaction Questionnaire 
 
The following 8 questions will be asked of the subject at Visit 6, Week12 and Visit 13, Week 52: 
1. How satisfied are you with this product in treating your acne? 
2. How satisfied are you with how easy this product is to use? 
3. How satisfied are you with this product compared to other products you have previously 
used for acne, such as gels and creams? 
4. How satisfied are you with how this product feels on your skin after treatment? 
5. How satisfied are you with the odor of this product after treatment? 
6. How satisfied are you with the color of this product after treatment? 
7. Overall, how satisfied are you with this product? 
8. Overall, how likely are you to recommend this product to a friend? 
 
Answers to Questions 1-7 will be selected from the following: 
1=Very Satisfied 
2=Satisfied 
3=Somewhat Satisfied 
4=Dissatisfied 
5=Very Dissatisfied 
 
Answer to Question 8 will be selected from the following: 
1=Very Likely 
2=Likely 
3=Somewhat Likely 
4=Unlikely 
5=Very Unlikely 
 




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Section 
Revision 
Rationale 
Old Text 
New Text 
 
6.  Study 
Procedures 
Inserted 
Procedures at the 
Screening Visit will include 
obtaining blood and urine 
samples for clinical 
laboratory tests.  These 
results must be no more 
than 30 days old at the 
time of Baseline Visit  
randomization. 
Clarification of timing of 
laboratory tests during 
Screening 
6.  Study 
Procedures – 
Table 1 
Inserted 
“X” for Tolerability 
Assessment at all post-
Baseline visits  
Added at request of FDA 
“X” for Blood and urine 
samples at Baseline 
“X” for Blood and urine 
samples at Screening 
Sampling moved to earlier 
timepoint 
Inserted 
“X” for Blood and urine 
samples at Week 3  
Added at request of FDA 
Inserted  
“X” for Dispense study drug 
at Week 1 
Correction  
Inserted 
“X” to Confirm next visit 
Correction 
Footnote inserted  
Footnote 6  -  Home 
pregnancy tests will be 
dispensed to all female 
subjects at risk of 
becoming pregnant and 
will be performed 
whenever there is a 
suspicion of pregnancy 
(e.g., a missed period) 
Added at request of FDA 
6.  Study 
Procedures – 
Table 1 
Footnote 2 
If a subject prematurely 
withdraws from the study, 
all evaluations described 
under Visit 6/Week 12 must 
be performed.   
Subject may continue into 
open-label phase of study. 
If a subject is not 
continuing into open-label 
phase for any reason (see 
Section 4.1.2), all 
evaluations described under 
Visit 6/Week 12 must be 
performed.   
Clarification of process at 
Visit 6 
6.1 – 6.2   Study 
Procedures 
at Visits 3 – 14 
Record AEs  
Record AEs and 
Tolerability Assessments  
Changed at all post-Baseline 
Visits at request of FDA  
6.1.1  Screening 
Visit 
Using the Interactive Web 
Response system (IWRS), 
assign the subject a . . . 
Assign the subject a  . . . 
Screening number will not 
be assigned by IWRS 


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Section 
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Rationale 
Old Text 
New Text 
 
Inserted  
•   Collect blood and urine 
samples for clinical 
laboratory tests . . . 
Lab tests moved from 
Baseline to Screening Visit 
6.1.2  Baseline 
Visit, Visit 1 
• Confirm eligibility 
none 
Deleted repetition 
• Collect blood and urine 
samples for clinical 
laboratory tests . . . 
deleted 
Lab tests moved from 
Baseline to Screening Visit 
6.1.3    Visit 2, 
Week 1  
Inserted  
• 
Dispense 1 kit (2 
canisters) of study drug 
Correction 
6.1.4. Visit 3, 
Week 3 
inserted 
• Collect blood and urine 
samples for clinical . . . 
Added per FDA request 
• 
Confirm that subject 
continues to use the drug 
product and only provided 
cleanser correctly 
Deleted 
Redundant 
6.1.7. Visit 6, 
Week 12  
End of Double-Blind or 
Early Termination   
End of Double-Blind or 
Continuation in Open 
Label / Early Termination   
Title changed for clarity 
6.2   Part 2 – 
Open-label  Table 
2 
Footnote inserted  
Footnote 3  -  Home 
pregnancy tests will be 
dispensed to all female 
subjects at risk of 
becoming pregnant and 
will be performed 
whenever there is a 
suspicion of pregnancy 
(e.g., a missed period) 
Added at request of FDA 
Inserted 
“X” for Tolerability 
Assessment at all post-
Baseline visits  
Added at request of FDA 
Inserted 
“X” for Blood and urine 
samples at Week 28 
Added at request of FDA 
6.2.1   Visit 7 – 
Week 16 
Dispense 1 kits (2 canisters) 
of FMX-101, 4% 
minocycline foam if required 
Dispense 2 kits (4 canisters) 
of FMX-101, 4% 
minocycline foam if required 
Correction 
6.2.2  Visit 9, 
Week 28 
inserted 
• At Visit 9 (Week 28) only 
– Collect blood and urine . 
. . 
Added per FDA request 
7.1.3.1  Part 1 – 
Double-blind 
none 
After shaking the canister 
well . . . 
Added text to include 
instruction to shake 
 . . .supplies will be 
dispensed at Baseline and 
Weeks 3, 6 and 9 . . . 
. . . supplies will be 
dispensed at Baseline and 
Weeks 1, 3, 6 and 9 . . . 
Correction 


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7.1.5  Labeling of 
Study Drug 
none 
“Shake well before using” 
Added text to label about 
shaking  
7.1.6  Storage of 
Drug 
FMX-101, 4% and vehicle 
canisters must be stored at 
20°C – 25°C  . . . 
FMX-101, 4% and vehicle 
canisters must be stored at 
2°C – 8°C until being 
dispensed to the subjects.  
Subsequently, they must be 
stored at 20°C – 25°C . . . 
Inclusion of instruction that 
site must keep drug 
refrigerated until it is 
dispensed 
7.2   Study Drug 
Accountability 
Inserted 
 
In addition, the weight of 
each canister will be 
determined prior to being 
dispensed to the subjects 
and each canister that has 
been retrieved from the 
subject will be returned to 
the vendor to be weighed 
Added per FDA request 
7.7  Prior and 
Concomitant 
Therapy  
Inserted 
 
If a subject is taking 
anticoagulant therapy, the 
subject should be advised 
that they may require a 
downward adjustment of 
their anticoagulant dosage. 
Tetracyclines may decrease 
plasma prothrombin activity 
7.8  Use of 
Contraception 
• 
Hormonal methods 
o 
Oral contraceptives  
. . . birth control must be 
utilized in subjects using 
topical contraceptives) 
• 
Hormonal methods 
o 
Oral contraceptives  
. . . birth control must be 
utilized in subjects using 
oral contraceptives) 
Correction 
8.1.1  IGA 
Table 3 
See a) below 
See b) below 
Removal of quantitative 
description of non-
inflammatory lesions 


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8.1.2  Lesion 
counts 
Facial lesion counts . . . 
Inflammatory lesions 
(pustules, papules, and 
nodular lesions) and 
noninflammatory lesions 
(open and closed 
comedones) will be counted 
for each area and recorded 
separately.  The totals of 
inflammatory and non-
inflammatory lesions will 
be calculated from these 
regional lesion counts.   
Lesion counts will be 
repeated at Weeks 3, 6, 9 
and 12. Totals do not need 
to be calculated at these 
visits. 
Facial lesion counts  . . .  
Total inflammatory lesions 
(pustules, papules, and 
nodular lesions) and 
noninflammatory lesions 
(open and closed 
comedones) will be counted 
and recorded separately.   
Lesion counts will be 
repeated at Weeks 3, 6, 9 
and 12.  
Counting method modified 
and addressed in Data 
Management Plan 
9.2  Medication 
History 
A history of medication 
usage . . . medications in the 
last 3 months (6 months for 
acne medications) will be 
recorded. 
A history of medication 
usage . . . medications in the 
last 3 months will be 
recorded. 
Consistency with Section 
6.1.1. 
9.4  Vital Signs 
Heart rate and blood 
pressure will be measured at 
all visits.   
Heart rate and blood 
pressure will be measured at 
all post-Baseline visits.   
Correction 
9.8.1   Method of 
Determining 
Adverse Events 
inserted 
•  Developed unusual 
headaches or changes in 
vision 
Queried at each visit as per 
FDA request 
9.8.3.  Reporting 
Adverse Events 
Any serious AEs . . . must be 
reported to the Sponsor 
within . . . 
Any serious AEs . . . must be 
reported to the Sponsor or 
designee within . . . 
Correction of omission 
10.2  
Determination of 
Sample Size  
None 
See text at c) below  
Modified as per FDA 
suggestion 
10.4.1  Primary 
Efficacy 
Endpoints  
IGA score at Week 12 
(where success is defined as 
at least a 2-grade decrease 
from Baseline). 
Treatment Success 
(dichotomized as Yes/No) 
at Week 12, where success 
is defined as an IGA score 
of 0 or 1, and at least a 2-
grade improvement 
(decrease) from Baseline.   
Modified as per FDA 
suggestion 


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10.4.2. Secondary 
Efficacy 
Endpoints 
 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 12 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA at the interim visit 
at Week 9 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 9 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA Treatment Success 
at the interim visit at Week 6 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 6 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 12 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA Treatment 
Success at the interim visit 
at Week 9 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA Treatment 
Success at the interim visit 
at Week 6 
Modified as per FDA 
suggestion 
10.4.3. Tertiary 
Efficacy 
Endpoints 
 
• 
The percent change from 
Baseline in the inflammatory 
lesion count at Weeks 3, 6, 9 
and 12 
• 
The percent change 
from Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, 9 and 
12 
• 
The absolute change 
from Baseline in the 
inflammatory and 
noninflammatory lesions, 
and the dichotomized IGA 
score, (where success is 
defined as at least a 2-
grade decrease from 
Baseline), at Week 3 
• 
The percent change from 
Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, 9 and 
12 
• 
The percent change from 
Baseline in the inflammatory 
lesion count at Weeks 3, 6, 9 
and 12 
• 
The absolute change 
from Baseline in the 
inflammatory and 
noninflammatory lesions, 
and the IGA Treatment 
Success at Week 3 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, and 9 
• 
The percent change from 
Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, 9 and 
12 
Modified as per FDA 
suggestion 


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10.6.3 Efficacy 
Analysis 
The co-primary endpoint of 
at least a 2-grade 
improvement (decrease) 
from Baseline in the IGA 
score at Week 12 will be 
analyzed . . . overall IGA 
response rates are less than 
10% . . . on the difference in 
IGA success rates between 
FMX-101 4% and vehicle. 
The co-primary endpoint of 
IGA Treatment Success 
rate at Week 12 will be 
analyzed . . . overall IGA 
Treatment Success rate is 
less than 10% . . . on the 
difference in IGA 
Treatment Success rates 
between FMX-101 4% and 
vehicle. 
Modified as per FDA 
suggestion 
. . .Testing of secondary 
efficacy endpoints at an 
earlier timepoint for each 
type of lesion and IGA will 
be performed only if 
superiority (one-sided 
p<=0.025) is seen at the later 
timepoint. 
.  Testing of secondary 
efficacy endpoints at an 
earlier timepoint for each 
type of lesion and IGA 
Treatment Success will be 
performed only if superiority 
(one-sided p<=0.025) is seen 
at the later timepoint. 
Modified as per FDA 
suggestion 
11.1  Monitoring 
Monitoring visits will apply 
place . . . 
Monitoring visits will take 
place 
Correction  
 . . . Sponsor . . . 
. . . Sponsor or Sponsor’s 
representative . . . 
Multiple corrections 
 
 
 


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a) Old Table 3 – IGA Scale 
 
Table 3: IGA Scale for Acne Vulgaris 
Score 
Grade 
Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
1 
Almost clear 
Rare noninflammatory lesions present; rare (eg, <5) non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink-
red) 
2 
Mild 
Some noninflammatory lesions are present; few (eg, <10) inflammatory 
lesions (papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Many noninflammatory lesions; multiple (eg, between 25 and 40) 
inflammatory lesions present; many papules/pustules; there may or may not 
be a few nodulocystic lesions 
4 
Severe 
Inflammatory lesions predominate, many papules/pustules (eg, between 40 and 75); 
there may be a few nodulocystic lesions 
5 
Very Severe 
Highly inflammatory lesions predominate, variable number of comedones, many 
papules/pustules and many nodulocystic lesions 
 
b) New Table 3 – IGA Scale 
 
Table 3: IGA Scale for Acne Vulgaris 
Score 
Grade 
  Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
 
1 
Almost clear 
Rare noninflammatory lesions may be present, with rare non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink- red) 
2 
Mild 
Some noninflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Many noninflammatory lesions.  Multiple inflammatory lesions evident with 
several to many papules/pustules, and there may be one small nodulocystic lesion 
4 
Severe 
Inflammatory lesions are more apparent, many comedones and papules/pustules, 
there may be a few nodulocystic lesions 
5 
Very Severe 
Highly inflammatory lesions predominate, variable number of comedones, many 
papules/pustules and many nodulocystic lesions 
 
 
c) 
Inserted in Section 10.2 
Another consideration for the sample size must be given to the secondary endpoint of 
noninflammatory lesions which will be compared to the vehicle for non-inferiority. The margin 
for non-inferiority will be 30% of the change from baseline to week 12. In a phase 2 study, 
change from baseline in noninflammatory lesions at week 9 was 22.8 for the vehicle group with 
a standard deviation of 18. Assuming approximately the same reduction at week 12, a 30% non-
inferiority margin is about 6.8 lesions. The following table provides approximate sample sizes 
for alternate assumptions for 90% power to show non-inferiority. 


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Vehicle mean 
noninflammatory 
lesion reduction 
Minocycline 4% foam 
mean noninflammatory 
lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
 
If Minocycline 4% foam has the same effect on noninflammatory lesions as vehicle, 
 subjects 
on vehicle and 
 on 4% foam will be needed for 90% power to show non-inferiority. If 
Minocycline 4% foam has a slightly less effect on noninflammatory lesions (
 lesion 
reduction versus 
 in vehicle), there will be about 90% power to show non-inferiority. 
16.2.2. Amendment 2, effective April 6, 2016 
The following is the summary of the changes that were made to Protocol FX2014-05 Version 2 
issued February 26, 2016. 
 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
5.2 Exclusion Criteria 
2. Dermatological condition 
of the face or facial hair 
(eg, beard, sideburns, 
mustache) that could 
interfere with the clinical 
evaluations 
 2. Acne conglobata, acne 
fulminans, secondary 
acne (chloracne, drug 
induced acne) or any 
dermatological condition.  
Specific exclusions added 
for clarity 
6. Study Procedures 
Table 1: Schedule of 
Procedures 
 
 
 
 
 
 
 
 
Footnote 3 
 
 
Urine pregnancy test 
(females, only) 
Urine pregnancy test 
(females of childbearing 
potential only) 
Clarification  
Inserted 
“X” for pregnancy tests to 
be performed at Week 3, 6 
and 9 
Modified per FDA 
Inserted 
New line and “X” for 
Subject Satisfaction 
Questionnaire for Week 12 
Procedure added 
. . . This visit and the 
procedures required at this 
visit can be combined with 
Screening. . . 
. . . The procedures required 
at these visits can be 
combined . . . 
Clarification  
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Footnote 6 
Home pregnancy tests will 
be dispensed to all female 
subjects at risk of becoming 
pregnant and will be 
performed whenever there 
is a suspicion of pregnancy 
(e.g., a missed period) 
Perform urine pregnancy 
test at indicated visits.  
Also dispense home urine 
pregnancy test at Week 12 
if subject is continuing 
into open-label treatment 
Modified per FDA 
6.1.2. Baseline Visit, 
Visit 1 
 
. . . This visit and the 
procedures required at this 
visit can be combined with 
Screening. . . 
. . . The procedures required 
at this visit can be 
combined with Screening . . 
. 
Clarification 
Perform urine pregnancy 
test 
Perform urine pregnancy 
test in females of 
childbearing potential 
Clarification 
6.1.4. Visit 3, Week 3; 
6.1.5. Visit 4, Week 6; 
6.1.6. Visit 5, Week 9 
Inserted 
 
Perform urine pregnancy 
test in females of 
childbearing potential 
Modified per FDA 
6.1.7. Visit 6, Week 12 Collect a urine sample from 
female subjects for a urine 
pregnancy test  
Perform urine pregnancy 
test in females of 
childbearing potential 
Clarification 
Inserted 
• 
Administer Subject 
Satisfaction 
Questionnaire 
Procedure added 
• 
If subject is continuing 
. . . dispense 1 kit (2 
canisters) of FMX-101 . . . 
• 
If subject is continuing 
. . . dispense 2 kits (4 
canisters) of FMX-101 . 
Correction 
6.2 Part 2 – Open-label 
Table 4: Schedule of 
Procedures 
 
 
 
 
Footnote 3  
 
 
 
Inserted 
“X” for pregnancy tests to 
be dispensed at Weeks 16, 
22, 28, 34, 40 and 46. 
Modified per FDA 
Inserted 
New line and “X” for 
Subject Satisfaction 
Questionnaire for Week 52 
Procedure added 
Home pregnancy tests will 
be dispensed to all female 
subjects at risk of becoming 
pregnant whenever . . . 
Home pregnancy tests will 
be dispensed at each visit 
to all female subjects of 
childbearing potential and 
will be performed at least 
monthly and whenever . . . 
Perform urine pregnancy 
test at Final Visit. 
Modified per FDA 
 


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6.2.1. Visit 7, Week 16 Inserted 
 
Dispense Home 
pregnancy kit to all 
female subjects of 
childbearing potential 
Modified per FDA 
 
6.2.2. Visits 8 – 12, 
Weeks 22 – 46 
Inserted 
 
Dispense Home 
pregnancy kit to all 
female subjects of 
childbearing potential 
Modified per FDA 
 
6.2.3. Visit 13, Final 
Visit – Week 52 
Collect a urine sample from 
female subjects for a urine 
pregnancy test 
Perform urine pregnancy 
test in females of 
childbearing potential 
Clarification 
Inserted 
• 
Administer Subject 
Satisfaction 
Questionnaire 
Procedure added 
7.1.3.1. Part 1 – 
Double-blind 
 
After shaking . . . , a small 
amount of foam should be 
expressed . . . . additional 
amounts of foam should 
also be applied . . 
.approximately the same 
time each day preferably in 
the evening. 
After shaking . . .a small 
amount of foam (about 1/2 
gram or a cherry-sized 
amount) should be 
expressed . . .  additional 
amounts (up to a total of 
4g) of foam should also be 
applied . . .the same time 
each day preferably in the 
evening at bedtime. 
Clarification of amounts 
and timing 
8.3. Subject 
Satisfaction 
Questionnaire 
 
Inserted 
A satisfaction 
questionnaire will be 
administered at Visit 6, 
Week 12 and Visit 13, 
Week 52 (see Section 16.1, 
Appendix 1). 
Procedure added 
9.6. Clinical 
Laboratory Tests 
Serum chemistry, 
hematology and 
urinalysis will be 
evaluated at Baseline, 
Week 12 and Final Visit. 
Serum chemistry, 
hematology and 
urinalysis will be 
evaluated at Baseline, 
Week 12/ Final Visit of 
the double-blind phase 
of the Study, and at 
Week 28 and Week 
52/Final Visit of the 
open-label phase of the 
Study. 
Modified per FDA 
 


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9.6.1. Urine Pregnancy 
Test 
A urine sample will be 
collected from all female 
subjects for a urine 
pregnancy test at Baseline, 
Week 12 and Final Visit or 
when a subject prematurely 
withdraws from the study. 
A urine pregnancy test 
will be performed on all 
females of childbearing 
potential at Baseline, 
Week 3, Week 6, Week 9 
and Week 12 of the 
double-blind phase of the 
Study and Final Visit or 
when a subject prematurely 
withdraws from the study. 
Home pregnancy kits will 
be provided at each visit 
to all female subjects of 
childbearing potential in 
the open-label phase of 
the Study and are to be 
used at least monthly and 
if a pregnancy is 
suspected between visits 
(e.g., if a subject misses a 
period). A urine 
pregnancy test will be 
performed at Week 52/ 
Final Visit. 
Modified per FDA 
 
9.7.1. Tolerability 
 . . pigmentation . . . 
. . .hyperpigmentation . . . 
Correction 
9.8.4. Adverse Event 
Follow-up 
Adverse events that are 
ongoing when a subject 
withdraws from or 
completes the study will be 
followed until resolution or 
stabilization (in the opinion 
of the Investigator), or for 
30 days, whichever is 
shorter.   
Adverse events, and 
tolerability signs and 
symptoms greater than 
zero (0), that are ongoing 
when a subject withdraws 
from or completes the study 
will be followed until 
resolution or stabilization 
(in the opinion of the 
Investigator), or for 30 
days, whichever is shorter.   
Modified as per FDA 
suggestion 
9.8.4.1. Pregnancy 
reporting 
A urine pregnancy test will 
be performed . . . at 
Baseline and 
Week 12/Final Visit of the 
double-blind phase of the 
Study or when a subject 
prematurely withdraws . . . 
A urine pregnancy test will 
be performed . . .at 
Baseline, Week 3, Week 6,  
Week 9 and Week 12/Final 
Visit of the double-blind 
phase of the Study or when 
a subject prematurely 
withdraws . . . 
Modified as per FDA 
suggestion 


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Home pregnancy kits will 
be provided to all female 
subjects at risk of becoming 
pregnant and are to be used 
if a pregnancy is suspected 
between visits (e.g., if a 
subject misses a period). 
 
Home pregnancy kits will 
be provided to all female 
subjects of childbearing 
potential in the open-label 
phase of the Study and are 
to be used at least monthly 
and if a pregnancy is 
suspected between visits 
(e.g., if a subject misses a 
period). A urine pregnancy 
test will be performed at 
Final Visit. 
10.3 Analysis 
Populations 
• 
Have not been 
compliant with the dosing 
regimen (ie, subjects 
missed more than 5 
consecutive days of dosing 
and took less than 80% of 
expected doses) 
• 
Have not, in the 
opinion of the 
investigator, been 
compliant with the 
treatment regimen (e.g. 
reported frequent missed 
doses) 
Modify definition of Per 
Protocol Population 
10.6.3  Efficacy 
Analysis 
Non-inferiority margin is 
defined as 40% of the 
noninflammatory lesion 
reduction in the vehicle 
group at Week 12 
Non-inferiority margin is 
defined as 30% of the 
noninflammatory lesion 
reduction in the vehicle 
group at Week 12 
Correction 
16.1.  Appendix 1 – 
Subjects Satisfaction 
Questionnaire 
Inserted 
See Appendix 1 (p.52) 
Procedure added 


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16.2.3. Amendment 3, effective October 14, 2016 
The following is the summary of the changes that were made to Protocol FX2014-05 Version 3 
issued April 6, 2016. 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
1. Synopsis 
Subjects who successfully 
complete the 12-week 
double blind portion of the 
study will be offered . . . 
Subjects who successfully 
complete the 12-week 
double blind portion of the 
study may be offered . . . 
Not all subjects will be 
eligible to continue 
1.7.2. Part 2 – Open-
label  
At the Week 12 Visit, 
subjects may be invited to 
continue into the open-label 
part of this study . . .   
At the Week 12 Visit, 
subjects whose IGA score 
has not worsened may be 
invited to continue into the 
open-label part of this study 
. . . 
Minimize risk of 
prolonging ineffective 
treatment 
4.1.2. Part 2 – Open-
label 
1.7.2. Part 2 – Open-
label  
 
Subjects may be 
discontinued from the study 
at any time if their disease 
becomes refractory . . . 
Subjects may be 
discontinued from the study 
after 12 weeks if their 
disease becomes refractory 
. . . 
Avoid prolongation of 
ineffective therapy 
4.1.2. Part 2 – Open-
label 
6.1.2.Baseline Visit 1 
6.1.3 Visit 2, Week 1 
6.1.4 Visit 3, Week 3 
6.1.5 Visit 4, Week 6 
6.1.6 Visit 5, Week 9 
6.1.7 Visit 6, Week 12 
End of Double-Blind 
or Continuation in 
Open Label / Early 
Termination 
·  Schedule/confirm the 
next study visit and remind 
subject to avoid 
overexposure to sunlight 
·  Schedule/confirm the 
next study visit and remind 
subject to avoid 
overexposure to natural or 
artificial sunlight 
Remind subjects in 
double-blind phase of 
study to avoid exposure 
overexposure to natural 
and artificial sunlight 
6.2.1  Visit 7 
 
· Schedule/confirm the next 
study visit  
·  Schedule/confirm the 
next study visit and 
remind subject to avoid 
overexposure to natural 
or artificial sunlight 
Remind subjects in open-
label phase of study to 
continue to avoid 
overexposure to natural 
and artificial sunlight. 
6.2.2  Visits 8 - 12 


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7.7  Prior and 
Concomitant Therapy   
Inserted 
Benzoyl peroxide (e.g., 
Pro-Activ, Clearasil) can 
inactivate minocycline 
and may thus decrease the 
effectiveness of FMX-101 
if the two products are 
applied at the same time. 
Treated areas should be 
washed between 
applications of FMX-101 
and products containing 
benzoyl peroxide.  
Preferably, the products 
should be applied no less 
than 8 hours apart. 
Minimize potential for 
drug interaction 
9.8.1  Method of 
Determining Adverse 
Events 
All questions should be of a 
general nature and should 
not suggest symptoms. 
With the exception of the 
last item above, all 
questions should be of a 
general nature and should 
not suggest symptoms. 
Reminder that these AEs 
should be actively 
questioned. 
 


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CLINICAL STUDY PROTOCOL  
Title: 
A Randomized, Double-Blind Study to Compare the Efficacy, 
Safety and Long-Term Safety of Topical Administration of 
FMX-101 for 1 Year in the Treatment of Moderate-to-Severe Acne 
Vulgaris, Study FX2014-05  
Development Phase: 
3 
Project Number: 
FMX-101 
Study drug(s): 
FMX-101, minocycline foam 4%; matching vehicle foam 
Indication: 
Acne vulgaris 
Authors: 
 
Protocol Number: 
FX2014-05  
Version  
3 
Date of Protocol: 
April 6, 2016 
Supersedes 
Version 2 of February 26, 2016 
 
 
This Protocol is the property of Foamix Pharmaceuticals, Inc.  This Protocol must be kept in a 
confidential manner, and may only be used in connection with the clinical study.  It must be 
returned on request.  No part of this Protocol may be reproduced or transmitted in any form 
without written permission of Foamix Pharmaceuticals, Inc.  If you are not authorized to receive 
this document, please return it immediately to: 
Foamix Pharmaceuticals, Inc. 520 U.S. Hwy 22, Suite 305  Bridgewater, NJ 08807 
 
 
PPD




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1. 
SYNOPSIS 
This is a Phase 3 study to evaluate the efficacy, safety and long-term safety of the topical 
administration of FMX-101, 4% minocycline foam for the treatment of moderate-to-severe acne 
vulgaris.  The first 12 weeks of the study involves randomized, double-blind treatment with 
active FMX-101, 4% or matching vehicle.  Subjects who successfully complete the 12-week 
double blind portion of the study will be offered the opportunity to continue in the trial for up to 
an additional 40 weeks (for a total of 1 year) and receive open-label treatment with 
FMX-101, 4%. 
1.1. 
Investigational Product, Dosage, and Mode of Administration 
The investigational product is FMX-101, minocycline foam 4%.  FMX-101 4% will be applied 
topically daily for the 12-week treatment duration of the study. 
1.2. 
Active Ingredient 
The active ingredient is minocycline HCl. 
1.3. 
Reference Product, Dosage, and Mode of Administration 
The reference product is vehicle foam.  Vehicle foam will be applied topically daily for the  
12-week treatment duration of the study. 
1.4. 
Study Centers 
Approximately 30 study centers will participate in this study. 
1.5. 
Study Period 
Estimated date first subject enrolled: April 2016 
Estimated date last subject completed: August 2017 
1.6. 
Study Objectives 
The objectives of this study are: 
 To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX-
101, 4% administered daily for 12 weeks 
 To evaluate the safety compared to vehicle of topical FMX-101, 4% administered 
daily for 12 weeks 
 To evaluate the long-term safety of topical FMX-101, 4% administered daily for up to 
40 additional weeks 


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1.7. 
Methodology 
The study will have 2 parts.  The first will involve 12 weeks of double-blind treatment with 
FMX-101, 4% or vehicle foam.  The second will involve up to 40 additional weeks of open-label 
treatment with FMX-101, 4% of subjects who complete the first part of the study. 
1.7.1. 
Part 1 – Double-blind Period 
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy over 12 weeks of FMX-101 minocycline foam, 4%, compared to vehicle, in 
the treatment of subjects with moderate to severe facial acne vulgaris. 
Qualified subjects will be randomized to receive 1 of the following 2 treatments: 
 FMX-101, 4%  minocycline foam 
 Vehicle foam 
Subjects with qualifying lesion counts (Section 8.1.2) and Investigator’s Global Assessments 
(IGA, Section 8.1.1) of acne severity scores and will be assigned to 1 of 2 treatments according 
to the randomization schedule.  Subjects will apply the assigned study drug topically once daily 
for 12 weeks as directed.  Subjects will be advised to apply the study drug at approximately the 
same time each day, preferably in the evening at bedtime.  Both the Investigator and subject will 
be blinded to the study drug identity. 
Subjects will return for visits at Weeks 1, 3, 6, 9, and 12. At the discretion of the clinic staff, for 
the convenience of subjects or clinic staff, visits can be scheduled to occur 3 days before or after 
the nominal schedule date for the Weeks 1, 3 and 6 visits and 7 days before or after for the 
Weeks 9 and 12 visits.  Efficacy evaluations (acne lesion counts and IGAs will be performed at 
Weeks 3, 6, 9, and 12 during the study.  Other assessments will be performed as described in 
Section 9.  
1.7.2. 
Part 2 – Open-label  
At the Week 12 Visit, subjects may be invited to continue into the open-label part of this study 
for an additional 9 months of treatment.  Subjects will be enrolled in this phase of the study until 
a total of approximately 400 subjects from Studies FX2014-04 and FX2014-05 have elected to 
continue in the open-label portion of their respective study.  Subjects who elect to continue into 
the open-label part of this study will receive supplies of active FMX-101, 4% minocycline foam.   
Treatment during this part of the study will be guided by each subject’s clinical response.  The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas.  Even if the treatment is partially or completely 
temporarily suspended, the subject will be continued in the study and will make all scheduled 
clinic visits.  If at any time the acne 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.   


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1.8. 
Number of Subjects 
The planned enrollment is 450 subjects.  Subjects will be randomized to active or vehicle in a 2:1 
ratio.  Approximately 300 and 150 subjects will be assigned to the FMX-101, 4% or vehicle 
treatment groups, respectively. 
1.9. 
Diagnosis and Main Criteria for Inclusion 
Subjects are to be at least 9 years of age. 
Eligible subjects are to have a diagnosis of facial acne vulgaris characterized by (subjects are 
permitted to also have acne on other parts of the body): 
 20 to 50 inflammatory lesions (papules, pustules, and nodules) 
 25 to 100 noninflammatory lesions (open and closed comedones) 
 No more than 2 nodules on the face  
 Investigator’s Global Assessment (IGA) score of moderate (3) to severe (4) 
1.10. 
Criteria for Evaluation 
1.10.1. 
Efficacy 
The efficacy assessments will include the IGA and lesion counts at Baseline and Weeks 3, 6, 9 
and 12.  
1.10.2. 
Safety 
The safety assessments in this study are physical examinations, vital signs, assessment of the 
skin at application site(s), adverse events (volunteered, observed, and elicited by general 
questioning in a non-suggestive manner), and clinical laboratory test results. 
1.11. 
Statistical Methods 
Efficacy analyses will be conducted on the Intent-to-Treat (ITT) population, using the last-
observation-carried-forward (LOCF) approach to impute missing values.  Supportive efficacy 
analyses will also be conducted on the Per Protocol (PP) population, with no imputation for 
missing values.  The co-primary efficacy endpoints are the absolute change from Baseline in the 
inflammatory lesion count at Week 12 IGA Treatment Success (dichotomized as Yes/No) at 
Week 12, where success is defined as an IGA score of 0 or 1, and at least a 2-grade decrease 
from Baseline.  FMX-101 4% will be tested against vehicle at the two-sided 0.05 level of 
significance without adjustment for multiplicity.  The absolute change from Baseline in 
inflammatory lesions at Week 12 will be analyzed using an Analysis of Covariance (ANCOVA) 
model with main effect treatment and investigational site as a covariate.  The IGA Treatment 
Success rates will be compared between the treatment groups using a Cochran–Mantel–Haenszel 
(CMH) test stratified for investigational site. 
No statistical tests will be performed for any of the safety assessments. 
 


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TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES 
 
1. 
SYNOPSIS ...................................................................................................................3 
1.1. 
Investigational Product, Dosage, and Mode of Administration ...................................3 
1.2. 
Active Ingredient ..........................................................................................................3 
1.3. 
Reference Product, Dosage, and Mode of Administration ...........................................3 
1.4. 
Study Centers ................................................................................................................3 
1.5. 
Study Period..................................................................................................................3 
1.6. 
Study Objectives ...........................................................................................................3 
1.7. 
Methodology .................................................................................................................4 
1.7.1. 
Part 1 – Double-blind Period ........................................................................................4 
1.7.2. 
Part 2 – Open-label .......................................................................................................4 
1.8. 
Number of Subjects ......................................................................................................5 
1.9. 
Diagnosis and Main Criteria for Inclusion ...................................................................5 
1.10. 
Criteria for Evaluation ..................................................................................................5 
1.10.1. 
Efficacy .........................................................................................................................5 
1.10.2. 
Safety ............................................................................................................................5 
1.11. 
Statistical Methods ........................................................................................................5 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ....................................6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................12 
STUDY ADMINISTRATIVE STRUCTURE ...............................................................................13 
2. 
INTRODUCTION ......................................................................................................14 
3. 
STUDY OBJECTIVES ..............................................................................................14 
4. 
INVESTIGATIONAL PLAN .....................................................................................14 
4.1. 
Overall Study Design ..................................................................................................14 
4.1.1. 
Part 1 – Double-blind ..................................................................................................15 
4.1.2. 
Part 2 – Open-label .....................................................................................................15 
4.2. 
Rationale for Study Design and Dose Selection .........................................................15 
5. 
STUDY POPULATION .............................................................................................16 
5.1. 
Inclusion Criteria ........................................................................................................16 
5.2. 
Exclusion Criteria .......................................................................................................16 


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6. 
STUDY PROCEDURES ............................................................................................18 
6.1. 
Part 1 – Double-Blind .................................................................................................20 
6.1.1. 
Screening Visit ............................................................................................................20 
6.1.2. 
Baseline Visit, Visit 1 .................................................................................................20 
6.1.3. 
Visit 2, Week 1 ...........................................................................................................21 
6.1.4. 
Visit 3, Week 3 ...........................................................................................................21 
6.1.5. 
Visit 4, Week 6 ...........................................................................................................22 
6.1.6. 
Visit 5, Week 9 ...........................................................................................................22 
6.1.7. 
Visit 6, Week 12 End of Double-Blind or Continuation in Open Label / 
Early Termination .......................................................................................................23 
6.2. 
Part 2 – Open-label .....................................................................................................24 
6.2.1. 
Visit 7 - Week 16 ........................................................................................................25 
6.2.2. 
Visits 8, 9, 10, 11 and 12 – Weeks 22, 28, 34, 40 and 46...........................................25 
6.2.3. 
Visit 13, Final Visit – Week 52 ..................................................................................26 
7. 
STUDY TREATMENTS............................................................................................26 
7.1. 
Treatments Administered ............................................................................................26 
7.1.1. 
Part 1 (double-blind) – Weeks 1 to 12 ........................................................................26 
7.1.2. 
Part 2 (open-label) – Weeks 13 to 52 .........................................................................27 
7.1.3. 
Dosing Instructions .....................................................................................................27 
7.1.3.1. 
Part 1 – Double-blind ..................................................................................................27 
7.1.3.2. 
Part 2 – Open-label .....................................................................................................27 
7.1.4. 
Manufacturer ...............................................................................................................28 
7.1.5. 
Labeling of Study Drug ..............................................................................................28 
7.1.6. 
Storage of Study Drug ................................................................................................28 
7.2. 
Study Drug Accountability .........................................................................................29 
7.3. 
Handling and Disposal of Study Drug ........................................................................29 
7.4. 
Method of Assignment of Study Drug ........................................................................29 
7.4.1. 
Part 1 – Double- blind .................................................................................................29 
7.4.2. 
Part 2 – Open-label .....................................................................................................29 
7.5. 
Selection and Timing of Doses in the Study ..............................................................29 
7.6. 
Blinding ......................................................................................................................30 
7.7. 
Prior and Concomitant Therapy ..................................................................................30 
7.8. 
Use of Contraception ..................................................................................................31 


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7.9. 
Treatment Compliance ................................................................................................31 
8. 
EFFICACY ASSESSMENTS ....................................................................................32 
8.1. 
Primary Efficacy Assessments ...................................................................................32 
8.1.1. 
Investigator Global Assessment Score (IGA) .............................................................32 
8.1.2. 
Lesion Counts .............................................................................................................32 
8.2. 
Photography ................................................................................................................33 
8.3. 
Subject Satisfaction Questionnaire .............................................................................33 
9. 
SAFETY ASSESSMENTS ........................................................................................33 
9.1. 
Medical/Surgical History ............................................................................................33 
9.2. 
Medication History .....................................................................................................33 
9.3. 
Concomitant Medications ...........................................................................................34 
9.4. 
Vital Signs ..................................................................................................................34 
9.5. 
Physical Examination .................................................................................................34 
9.6. 
Clinical Laboratory Tests ...........................................................................................34 
9.6.1. 
Urine Pregnancy Test .................................................................................................35 
9.6.2. 
Sample Collection, Storage, and Shipping .................................................................35 
9.7. 
Other Safety Measurements ........................................................................................35 
9.7.1. 
Tolerability .................................................................................................................35 
9.8. 
Adverse Events ...........................................................................................................36 
9.8.1. 
Method of Determining Adverse Events ....................................................................36 
9.8.2. 
Adverse Event Definitions ..........................................................................................36 
9.8.2.1. 
Adverse Events ...........................................................................................................36 
9.8.2.2. 
Serious Adverse Events ..............................................................................................37 
9.8.2.3. 
Severity of Adverse Events ........................................................................................37 
9.8.2.4. 
Relationship of Adverse Events to Study Treatments ................................................38 
9.8.2.5. 
Adverse Events Expectedness ....................................................................................38 
9.8.3. 
Reporting Adverse Events ..........................................................................................38 
9.8.4. 
Adverse Event Follow-up ...........................................................................................38 
9.8.4.1. 
Pregnancy reporting ....................................................................................................39 
9.8.5. 
Clinically Significantly Abnormal Laboratory Results ..............................................39 
9.9. 
Appropriateness of Safety Measurement ....................................................................39 
10. 
STATISTICAL DESIGN AND ANALYSIS .............................................................40 
10.1. 
Statistical Analysis Plan .............................................................................................40 


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10.2. 
Determination of Sample Size ....................................................................................40 
10.3. 
Analysis Populations ..................................................................................................41 
10.4. 
Efficacy Endpoints ......................................................................................................42 
10.4.1. 
Primary Efficacy Endpoints ........................................................................................42 
10.4.2. 
Secondary Efficacy Endpoints ....................................................................................43 
10.4.3. 
Tertiary efficacy endpoints .........................................................................................43 
10.5. 
Safety endpoints ..........................................................................................................43 
10.5.1. 
Adverse Events ...........................................................................................................43 
10.5.2. 
Vital Signs ..................................................................................................................44 
10.5.3. 
Physical Examinations ................................................................................................44 
10.5.4. 
Clinical Laboratory Results ........................................................................................44 
10.6. 
Statistical Analysis ......................................................................................................44 
10.6.1. 
Interim Analysis ..........................................................................................................44 
10.6.2. 
Subject Accounting, Demographic, and Baseline Characteristics ..............................44 
10.6.3. 
Efficacy Analysis ........................................................................................................44 
10.6.4. 
Safety Analysis ...........................................................................................................45 
11. 
STUDY MANAGEMENT .........................................................................................46 
11.1. 
Monitoring ..................................................................................................................46 
11.2. 
Protocol Amendments ................................................................................................46 
11.3. 
Protocol Deviations ....................................................................................................47 
11.4. 
Withdrawal of Subjects ...............................................................................................47 
11.5. 
Termination of the Study ............................................................................................48 
11.6. 
Publication Policy .......................................................................................................48 
12. 
ETHICS ......................................................................................................................48 
12.1. 
Conduct of the Study ..................................................................................................48 
12.2. 
Institutional Review Boards (IRB) .............................................................................48 
12.3. 
Written Informed Consent ..........................................................................................48 
12.4. 
Subject Confidentiality ...............................................................................................49 
12.5. 
Records Retention .......................................................................................................49 
12.6. 
Financing ....................................................................................................................50 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................50 
14. 
DATA HANDLING AND RECORD KEEPING ......................................................50 
15. 
REFERENCE LIST ....................................................................................................51 


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16. 
APPENDICES ............................................................................................................52 
16.1. 
Appendix 1 – Subjects Satisfaction Questionnaire .....................................................52 
16.2. 
Appendix 2 – Protocol Amendments ..........................................................................53 
16.2.1. 
Amendment 1 ..............................................................................................................53 
16.2.2. 
Amendment 2 ..............................................................................................................61 


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List of Tables 
Table 1: Schedule of Procedures - Study FX2014-05  – Part 1 .....................................................19 
Table 2: Schedule of Procedures - Study FX2014-05  – Part 2 .....................................................24 
Table 3: IGA Scale for Acne Vulgaris ...........................................................................................32 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition 
AE 
Adverse event 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
eCRF 
Electronic case report form 
EKG 
Electrocardiogram 
FDA 
Food & Drug Administration 
GCP 
Good Clinical Practice 
HEENT 
Head, eyes, ears, nose, and throat 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System (IWRS) 
LOCF 
Last-observation-carried-forward 
ITT 
Intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed-Cases 
P. acnes 
Propionibacterium acnes 
PP 
Per protocol 
TEAE 
Treatment-emergent adverse event 
SAE 
Serious adverse event 
SOC 
System organ class 
 
 
 
 
 
 
 
 
 


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STUDY ADMINISTRATIVE STRUCTURE 
Name 
Affiliation / Address /  
Telephone Number 
Responsibility 
Foamix Pharmaceuticals, Inc 
520 U.S. Highway 22, Suite 305 
Bridgewater, NJ 08807 
Sponsor 
TKL Research, Inc. 
 
365 West Passaic Street, Suite 550 
Rochelle Park, NJ 07662 
CRO 
 
TKL Research, Inc. 
 
 
TKL Research, Inc. 
 
 
PPD
PPD
PPD
PPD


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2. 
INTRODUCTION 
Acne vulgaris is a common disease of both males and females, usually manifesting initially 
during adolescence.  The primary pathologic events are initiated in the pilo-sebaceous units, 
especially of sebaceous-gland-bearing areas of the face, chest, and back as a result of increased 
androgen stimulation initiated at adrenarche or puberty.  As a result of both abnormal 
keratinization of the infra-infundibular portion of the pilo-sebaceous follicle and increased 
sebum produced in the gland, a blockage of the duct results in the inapparent clinical lesion of 
the microcomedone.  Continued blockage, colonization of the follicle by Propionibacterium 
acnes (P. acnes), and generation of multiple chemoattractant and proinflammatory moieties may 
result in non-inflammatory clinical lesions, comedones, and inflammatory lesions: papules, 
pustules, nodules, and cysts.1 
FMX-101, 4% is a minocycline containing topical foam being developed as a treatment for acne 
vulgaris.  Antibiotics, especially erythromycin, minocycline, and doxycycline, have been 
prescribed as acne treatments for many years.  These antibiotics effectively control the signs of 
inflammatory acne while patients continue to use them.  Nonclinical studies have demonstrated 
that FMX-101, 4% exhibits favorable characteristics.  
Foamix has conducted 2 Phase 1 and 1 Phase 2 study of FMX-101, 4% to assess its safety and 
tolerability.  FMX-101, 4% has been shown to be effective and well tolerated at the 4% dose that 
is being utilized in this study.  The Investigator’s Brochure should be consulted for summaries of 
the results of these studies.  
This Phase 3 study (Study FX2014-05 ) will assess the efficacy, safety and long-term safety of 
FMX-101, 4% for the treatment of moderate to severe facial acne vulgaris. 
3. 
 STUDY OBJECTIVES  
The objectives of this study are: 
 To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX-
101, 4% administered daily for 12 weeks 
 To evaluate the safety compared to vehicle of topical FMX-101, 4% administered 
daily for 12 weeks 
 To evaluate the long-term safety of topical FMX-101, 4% administered daily for up to 
an additional 40 weeks 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
The one-year study will have 2 parts.  The first 12 weeks will be double-blind treatment with 
FMX-101, 4% or vehicle foam.  The remaining 40 weeks will involve open-label treatment with 
FMX-101, 4% by any subjects who complete the first part of the study. 


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4.1.1. 
Part 1 – Double-blind  
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy over 12 weeks of FMX-101 minocycline foam, 4%, compared to vehicle, in 
the treatment of subjects with moderate to severe facial acne vulgaris. 
Qualified subjects will be randomized to receive 1 of the following 2 treatments: 
 FMX-101, 4%  minocycline foam 
 Vehicle foam 
Subjects with qualifying lesion counts (Section 8.1.2) and Investigator’s Global Assessments 
(IGA, Section 8.1.1) of acne severity scores and will be assigned to 1 of 2 treatments according 
to the randomization schedule.  Subjects will apply the assigned study drug topically once daily 
for 12 weeks as directed.  Subjects will be advised to apply the study drug at approximately the 
same time each day, preferably in the evening before bedtime.  Both the Investigator and subject 
will be blinded to the study drug identity. 
Subjects will return for visits at Weeks 1, 3, 6, 9, and 12.  Efficacy evaluations (acne lesion 
counts and IGAs will be performed at Weeks 3, 6, 9, and 12 during the study.  Other assessments 
will be performed as described in Sections 8.2 and 9. 
4.1.2. 
Part 2 – Open-label  
At the Week 12 Visit, subjects may be invited to continue into the open-label part of this study 
for an additional 9 months of treatment.  Subjects will be enrolled in this phase of the study until 
a total of approximately 400 subjects from Studies FX2014-04 and FX2014-05 have elected to 
continue in the open-label portion of their respective study.  Subjects who elect to continue into 
the open-label part of this study will receive supplies of active FMX-101, 4% minocycline foam.   
Treatment during this part of the study will be guided by each subject’s clinical response.  The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas.  Even if the treatment is partially or completely 
temporarily suspended, the subject will continue in the study and make all scheduled clinic visits.  
If at any time the acne 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.   
4.2. 
Rationale for Study Design and Dose Selection 
A randomized, multicenter, double-blind, vehicle-controlled study design has been selected in 
order to assess the efficacy of the study drug in accordance with the FDA Guidance.2  The 
subjects will be selected according to predefined entry criteria.  The study will have a 12-week 
treatment duration.    
FMX-101 foam, 4% is a novel minocycline formulation that has been shown to have efficacy in 
once daily use in a Phase 2 study.  The once daily dosing regimen is appropriate given the 
pharmacokinetic characteristics of FMX-101, 4%. 


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Because of the mode of action of tetracycline drugs, the primary efficacy endpoints will be the 
effect on inflammatory lesion count and IGA (Section 8.1.1).  The effect on noninflammatory 
lesions will be the most important secondary endpoint.  
The extension of the study for an additional 40 weeks is necessary to obtain safety information 
about the long-term use of FMX-101, 4% to treat acne, which is a chronic condition.  The design 
of the study is expected to provide sufficient safety information to fulfill the ICH E1 guideline. 
5. 
STUDY POPULATION 
The planned enrollment is 450 subjects.  Subjects will be randomized to active or vehicle in a 2:1 
ratio.  Approximately 300 and 150 subjects will be assigned to the FMX-101, 4% or vehicle 
treatment groups, respectively. 
5.1. 
Inclusion Criteria 
A male or female subject will be considered eligible for participation in the study if all of the 
following inclusion criteria are satisfied prior to randomization: 
1. Has completed and signed an appropriately administered Informed Consent Form (ICF) 
prior to any study-related procedures.  Subjects less than 18 years of age (or as required 
by state law) must sign an Assent Form for the study and a parent or legal guardian must 
sign the ICF.  
2. Is 9 years of age or greater,  
3. Has facial acne vulgaris with: 
 20 to 50 inflammatory lesions (papules, pustules, and nodules) 
 25 to 100 noninflammatory lesions (open and closed comedones) 
 No more than 2 nodules on the face 
 IGA score of moderate (3) to severe (4) 
4. If women of child-bearing potential, have a negative urine pregnancy test 
5. For women of child-bearing potential at risk of becoming pregnant, agree to an effective 
method of contraception (Sections 7.7 and 7.8) 
6. Willing to use only the supplied non-medicated cleanser 
 
and to refrain from use of any other acne medication, medicated cleanser, excessive sun 
exposure, and tanning booths for the duration of the study 
5.2. 
Exclusion Criteria 
Subjects who have any of the following will be excluded from the study: 
1. Female who is pregnant or lactating, or is planning a pregnancy during the study 
2. Acne conglobata, acne fulminans, secondary acne (chloracne, drug induced acne) or any 
dermatological condition of the face or facial hair (eg, beard, sideburns, mustache) that 
could interfere with the clinical evaluations 
CCI


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3. Sunburn on the face  
4. Severe systemic disease, which might interfere with the conduct of the study or the 
interpretation of the results. 
5. Abnormal baseline laboratory values that are considered clinically significant. 
6. Currently participating, or has participated within 30 days prior to this study, in an 
investigational drug or device study 
7. Inability to fully comply with the study requirements 
Subjects who have a history of any of the following will be excluded: 
8. Allergy to tetracycline-class antibiotics or to any ingredient in the study drug 
9. Pseudomembranous colitis or antibiotic-associated colitis 
10. Hepatitis or liver damage or renal impairment 
11. Known or suspected premalignant or malignant disease (excluding successfully treated 
skin cancers)  
12. Subjects who have used the following medications (topical refers only to the facial area) 
will not be eligible: 
Within 1 week prior to randomization:  
 Medicated facial cleansers 
 Topical acne treatments (other than those listed below) 
Within 4 weeks prior to randomization: 
 Topical retinoids 
 Topical anti-inflammatories and corticosteroids 
 Systemic antibiotics 
 Systemic acne treatments 
Within 12 weeks prior to randomization:  
 Systemic retinoids 
 Systemic corticosteroids 
13. Drug addiction or alcohol abuse (within the last 2 years). 
14. Current or significant past history of depression. 
 


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6. 
STUDY PROCEDURES 
Potential subjects will be assessed for eligibility at Screening.  During this visit, the purpose, 
timing, procedures, and risks of the study will be explained to the subject, including 
requirements for enrollment and participation in the study, medication restrictions during the 
study, and requirements for washout of certain medications that the subject may already be 
taking.  
The eligible subject who is willing to participate in the study will then sign an appropriately 
administered Informed Consent Form (ICF) prior to any study-related procedures.  Subjects less 
than 18 years of age (or per state law) must sign an Assent Form for the study and a parent or 
legal guardian must sign the ICF. 
Procedures at the Screening Visit will include obtaining blood and urine samples for clinical 
laboratory tests.  These results must be no more than 30 days old at the time of Baseline Visit  
randomization.   
If a subject, who has agreed to participate in the study and signed the ICF or Assent Form, is 
currently undergoing acne therapy identified in Exclusion Criterion 12, they must first enter a 
washout period, before beginning the Screening procedures.   
A summary of study assessments and the time point at which they will be performed during the 
study is presented in Table 1.  If a subject prematurely withdraws from the study before the 
Week 12 Visit, the subject should return to the study site for a withdrawal visit, during which all 
evaluations described under Visit 6/Week 12 must be performed. 
See  
Table 2 and Section 6.2 for descriptions of the procedures required during the open-label part of 
the study. 


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Table 1: Schedule of Procedures - Study FX2014-05  – Part 1 
 
Assessment 
 
Screening 1 
 
Baseline 1 
 
Visits 
“Final” 
Visit 2 
Visit 
 
1 
2 
3 
4 
5 
6 
Week 
 
 
1 
3 
6 
9 
12 
Informed Consent/Assent 
X 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
Assign identification number 
X 
 
 
 
 
 
 
Medical/Surgical/Medication 
(prior/concomitant) History 
X 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
X 
 
 
 
 
 
Physical Exam, height, weight 3,4 
 
X  
 
 
 
 
X 
Blood Pressure/heart rate 5 
 
X 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
X 
 
 
X 
 
 
X 
Urine pregnancy test (females of 
childbearing potential only)6 
 
X 
 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
 
X 
X 
X 
X 
Lesion Count 
X 
X 
 
X 
X 
X 
X 
Photography 
 
X 
 
 
X 
 
X 
Subject Satisfaction Questionnaire 
 
 
 
 
 
 
X 
Randomization  
 
X 
 
 
 
 
 
Concomitant Medication  
 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
Tolerability Assessments 
 
 
X 
X 
X 
X 
X 
Perform drug accountability 
 
 
X 
X 
X 
X 
X 
Collect empty canisters 
 
 
X 
X 
X 
X 
X 
Dispense Study Drug 
 
X 
X 
X 
X 
X 
X7 
Schedule/Confirm Next Visit 
X 
X 
X 
X 
X 
X 
X 
                                                 
1 The duration of Screening is variable but if there are medications to be discontinued it can not be less than the time indicated in 
Exclusion Criterion 12. The procedures required at these visits can be combined.  However, drug should not be dispensed until 
all inclusion and exclusion criteria are met. 
2 Subject may continue into open-label phase of study. If a subject is not continuing into open-label phase for any reason 
(see Section 4.1.2, all evaluations described under Visit 6/Week 12 must be performed.   
3 Height to be measured only at Baseline 
4 Including 12-lead EKG at Screening in subjects over 39 years of age 
5 Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest 
6 Perform urine pregnancy test at indicated visits.  Also dispense home urine pregnancy test at Week 12 if subject is 
continuing into open-label treatment 
7 If subject is continuing into open-label treatment phase, dispense appropriate Study Drug Kit 


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6.1. 
Part 1 – Double-Blind 
6.1.1. 
Screening Visit  
 Obtain a signed and dated, written Informed Consent Form (ICF) prior to any study-
related procedures; subjects less than 18 years of age (or as required by state law) 
must sign an Assent Form for the study and a parent or legal guardian must sign the 
ICF.  (Subjects must be at least 9 years of age at the time of assent/consent) 
 Obtain demographic data 
 Assign the subject a unique subject identification number 
 Obtain medical history  
 Obtain surgical history 
 Obtain history of prior and concomitant medication usage (including previous use of 
acne medications); record start and stop dates of any medications used in the last 
3 months  
 Perform IGA (Section 8.1.1) 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
(Section 8.1.2)  
 Record regions beyond face affected by acne 
 Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory (Section 9.6)  
 If subject wears make-up, remind the subject not to wear any make-up at future visits. 
 Record AEs 
 Schedule/confirm the next study visit.  Remind subject to avoid sun overexposure. 
6.1.2. 
Baseline Visit, Visit 1 
The procedures required at this visit can be combined with Screening.  However, drug should not 
be dispensed until all inclusion and exclusion criteria are met.   
 Confirm/reconfirm eligibility according to the inclusion/exclusion criteria and 
o Perform IGA  
o Perform facial lesion count of inflammatory, noninflammatory, and nodular 
lesions  
 Perform photography (Section 8.2) 
 Measure blood pressure and heart rate (Section 9.4)  
 Perform physical examination including height and weight (Section 9.5) 
 Perform 12-lead EKG if subject is over 39 years of age 


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 Perform urine pregnancy test in females of childbearing potential 
 Randomize the subject using the IWRS system, when all criteria have been met  
 Record concomitant medications 
 Record AEs 
 Dispense 1 kit (2 canisters) of study drug  
 Dispense cleanser 
     
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 
6.1.3. 
Visit 2, Week 1 
 Measure blood pressure and heart rate 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
 Collect previously dispensed study drug canister(s) if applicable 
 Dispense 1 kit (2 canisters) of study drug  
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 
6.1.4. 
Visit 3, Week 3 
 Measure blood pressure and heart rate 
 Perform urine pregnancy test in females of childbearing potential 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory (Section 9.6)  
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
 Collect previously dispensed study drug canister(s) if applicable 
 Dispense 1 kit (2 canisters) of study drug  
 Determine if additional drug or cleanser needs to be dispensed.   
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 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 
6.1.5. 
 Visit 4, Week 6 
 Measure blood pressure and heart rate 
 Perform urine pregnancy test in females of childbearing potential 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Perform photography 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
 Collect previously dispensed study drug canister(s) if applicable 
 Dispense 1 kit (2 canisters) of study drug  
 Determine if additional drug or cleanser needs to be dispensed.   
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 
6.1.6. 
Visit 5, Week 9  
 Measure blood pressure and heart rate 
 Perform urine pregnancy test in females of childbearing potential 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
 Collect previously dispensed study drug canister(s) if applicable 
 Dispense 1 kit (2 canisters) of study drug  
 Determine if additional drug or cleanser needs to be dispensed.   
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 


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6.1.7. 
Visit 6, Week 12 End of Double-Blind or Continuation in Open Label / Early 
Termination   
 Perform physical examination including weight 
 Measure blood pressure and heart rate 
 Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory 
 Perform urine pregnancy test in females of childbearing potential 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Perform photography 
 Administer Subject Satisfaction Questionnaire 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Assess product use to confirm that subject continues to use properly; confirm that 
only provided cleanser is being used. 
 Collect previously dispensed study drug canister(s) 
 If subject is continuing into the open-label phase of the study (see Section 4.1.2), 
dispense 2 kit (4 canisters) of FMX-101, 4% minocycline foam 
o If subjects facial acne is “clear” or “almost clear,” consider withholding 
treatment with FMX-101, 4% at this time but continue subject in study and 
schedule next visit. 
 Schedule/confirm the next study visit and remind subject to avoid overexposure to 
sunlight 


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6.2. 
Part 2 – Open-label 
A summary of study assessments and the time point at which they will be performed during the 
Part 2 of this study is presented in 
Table 2.  If a subject prematurely withdraws from the study, the subject should return to the 
study site at which time all evaluations described under Final Visit 13/Week 52 must be 
performed. 
 
Table 2: Schedule of Procedures - Study FX2014-05  – Part 2 
 
Assessment 
 
 Visits 
Final 
Visit 1 
Visit 
7 
8 
9 
10 
11 
12 
13 
Week 
16 
22 
28 
34 
40 
46 
52 
Physical Exam, weight, 
 
 
 
 
 
 
X 
Blood Pressure/heart rate 2 
X 
X 
X 
X 
X 
X 
X 
Blood and urine samples for clinical 
laboratory tests  
 
 
X 
 
 
 
X 
Urine pregnancy test (females of 
childbearing potential only)3 
X 
X 
X 
X 
X 
X 
X 
Investigator’s Global Assessment 
X 
X 
X 
X 
X 
X 
X 
Lesion Count 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medication  
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
Tolerability Assessment 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction Questionnaire 
 
 
 
 
 
 
X 
Perform drug accountability 
X 
X 
X 
X 
X 
X 
X 
Collect empty canisters 
X 
X 
X 
X 
X 
X 
X 
Dispense Study Drug 
X 
X 
X 
X 
X 
X 
 
Schedule/Confirm Next Visit 
X 
X 
X 
X 
X 
X 
 
 
                                                 
1 If a subject prematurely withdraws from the study, all evaluations described under Final Visit 13/Week 52 must be performed.   
2 Measure blood pressure and heart rate after the subject has been sitting for at least 5 minutes at rest 
3 Home pregnancy tests will be dispensed at each visit to all female subjects of a childbearing potential and will be performed at 
least monthly and whenever there is a suspicion of pregnancy (e.g., a missed period). Perform urine pregnancy test at Final visit. 


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6.2.1. 
Visit 7 - Week 16 
 Measure blood pressure and heart rate 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Assess product use to confirm that subject continues to use study drug properly 
 Collect empty study drug canister(s) 
 Dispense 2 kits (4 canisters) of FMX-101, 4% minocycline foam if required 
 Dispense Home pregnancy kit to all female subjects of childbearing potential 
 Schedule/confirm the next study visit  
o If subjects facial acne is “clear” or “almost clear,” consider withholding 
treatment with FMX-101, 4% at this time but continue subject in study and 
schedule next visit.  
o If treatment has been interrupted, consider restarting treatment if clinically 
indicated 
6.2.2. 
Visits 8, 9, 10, 11 and 12 – Weeks 22, 28, 34, 40 and 46 
 Measure blood pressure and heart rate 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 At Visit 9 (Week 28) only - Collect blood and urine samples for clinical laboratory 
tests and send to the central laboratory (Section 9.6)  
 Assess product use to confirm that subject continues to use study drug properly 
 Collect empty study drug canister(s) 
 Dispense 2 kits (4 canisters) of FMX-101, 4% minocycline foam if required 
 Dispense Home pregnancy kit to all female subjects of childbearing potential 
 Schedule/confirm the next study visit  
o If subjects facial acne is “clear” or “almost clear,” consider withholding 
treatment with FMX-101, 4% at this time but continue subject in study and 
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o If treatment has been interrupted, consider restarting treatment if clinically 
indicated 
6.2.3. 
Visit 13, Final Visit – Week 52 
 Measure blood pressure and heart rate 
 Perform physical examination including weight 
 Collect blood and urine samples for clinical laboratory tests and send to the central 
laboratory 
 Perform urine pregnancy test in females of childbearing potential 
 Perform IGA 
 Perform facial lesion count of inflammatory, noninflammatory, and nodular lesions 
 Record concomitant medications 
 Record AEs and Tolerability Assessment 
 Administer Subject Satisfaction Questionnaire 
 Collect previously dispensed study drug canister(s) 
7. 
STUDY TREATMENTS 
FMX-101, 4% and vehicle will be supplied as identical canisters.  All study drug will be stored, 
inventoried, reconciled, and destroyed according to US regulations. 
7.1. 
Treatments Administered 
The description of study drug kits and treatments is shown below.  
7.1.1. 
Part 1 (double-blind) – Weeks 1 to 12 
Dosage form description Active kit: FMX-101 minocycline foam, 4%;  
Vehicle kit: Matching vehicle foam 
Package description 
Active kit: 2 canisters of FMX-101, 4% dispensed as foam when actuator is depressed 
Vehicle kit: 2 canisters dispensing vehicle foam when actuator is depressed 
Daily dose 
Approximately 0.5 gm of FMX-101, 4% (containing 40 mg minocycline per gram of foam; 0 mg 
for vehicle subjects); applied to face topically each day.  Additional drug product may be applied 
to other acne-affected areas 
Cumulative maximal 
dose 
Approximately 1,680 mg of minocycline (0 mg for vehicle subjects) assuming application of 0.5 
gm of foam daily to the face for 84 days. Maximum total amount of drug dispensed contains 14 
gm of minocycline.  
Dispensing 
1 Kit (2 canisters) dispensed at Baseline and Weeks 1, 3, 6, and 9.  Total of 5 kits (10 canisters) 
dispensed to the subject for the study. 


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7.1.2. 
Part 2 (open-label) – Weeks 13 to 52 
Dosage form description FMX-101 minocycline foam, 4%;  
Package description 
Active kit: 2 canisters of FMX-101, 4% dispensed as foam when actuator is depressed 
Daily dose 
Approximately 0.5 gm of FMX-101, 4% (containing 40 mg minocycline per gram of foam) 
applied to face topically each day.  Additional drug product may be applied to other acne-affected 
areas 
Cumulative maximal 
dose 
Up to approximately 5,600 mg of minocycline assuming application of 0.5 gm of FMX-101 foam 
daily to the face for 280 days. Maximum total amount of drug dispensed contains 39.2 gm of 
minocycline. 
Dispensing 
Up to 2 Kits (4 canisters) dispensed at Weeks 12, 16, 22, 28, 34, 40 and 46 depending on rate of 
usage. Up to a total of 14 kits (28 canisters) dispensed to the subject for the study. 
7.1.3. 
Dosing Instructions 
7.1.3.1. 
Part 1 – Double-blind 
The dosing regimen will be the same for both treatment groups.  
After shaking the canister well, a small amount of foam (about 1/2 gram or a cherry-sized 
amount) should be expressed from the canister onto the fingertips of the hand and then rubbed 
into acne-affected parts of the face.  This should be repeated as needed until all acne-affected 
parts of the face are treated.  If acne is present on other parts of the subject’s body (neck, 
shoulders, arms, back or chest) additional amounts (up to a total of 4g) of foam should also be 
applied to these areas. The foam should be applied at approximately the same time each day 
preferably in the evening at bedtime. The subject should not bathe, shower or swim for at least 1 
hour after application of the product. 
Study kits of blinded drug supplies will be dispensed at Baseline and Weeks 1, 3, 6 and 9 to 
ensure continuous dosing in case the subject is late for subsequent visits.  
Dose adjustments are not permitted in this part of the study.  Subjects who require a dose 
adjustment or discontinuation of study drug must be withdrawn from the study (Section 11.4). 
7.1.3.2. 
Part 2 – Open-label 
At the Week 12 Visit, subjects who elect to continue into the open-label part of this study will 
receive supplies of active FMX-101, 4% minocycline foam.   
Treatment during this part of the study will be guided by each subject’s clinical response.  The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas.  Even if the treatment is partially or completely 
temporarily suspended, the subject will be continued in the study and make all scheduled clinic 
visits.  If at any time the acne recurs or worsens, retreatment of the affected areas may be 
resumed. At each visit, the changes in treatment will be documented.  
Sufficient product will be dispensed at each visit to allow continuation of treatment as required. 
Subjects may be discontinued from the study at any time if their disease becomes refractory or 
they become intolerant of the product.   


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7.1.4. 
Manufacturer 
The manufacturer of the investigational product is 
 
. 
7.1.5. 
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:  
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. 
7.1.6. 
Storage of Study Drug 
FMX-101, 4% and vehicle canisters must be stored at 2°C – 8°C until being dispensed to the 
subjects.  Subsequently, they must be stored at 20°C – 25°C (refer to USP Controlled Room 
Temperature).  The investigator will be responsible for the suitable storage of the investigational 
product in compliance with the storage instructions and must restrict access to the study 
personnel only. 
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7.2. 
Study Drug Accountability 
The Investigator will have overall responsibility for the use of the study drug.  The Investigator 
or designee will verify the contents of the drug shipment and confirm receipt of the study drug in 
the Interactive Web Response System (IWRS) system.  In addition, an accurate study drug 
dispensing record that specifies the date and amount dispensed to each subject must be kept.  
This inventory record must be available for inspection by representatives of the Sponsor and is 
subject to regional regulatory authority inspection at any time.  At the conclusion of the study, 
the Investigator must provide a copy of this record to the Sponsor.  In addition, the weight of 
each canister will be determined prior to being dispensed to the subjects and each canister that 
has been retrieved from the subject will be returned to the vendor to be weighed. 
Under no circumstances will the Investigator allow the investigational drugs to be used other 
than as directed by this protocol.  Qualified study personnel must use the IWRS to assign and 
dispense kits to the subjects.  Reasons for digression from the expected dispensing regimen must 
also be recorded. 
7.3. 
Handling and Disposal of Study Drug 
The study drug must be protected from unauthorized access (eg, in a locked storage facility). 
Any unused, partially used, or empty bottles of study drug will be returned to the Sponsor or 
designee by the time of the site’s close-out visit.  Receipt, distribution, and return of the study 
drug must be properly documented on forms provided by the Sponsor or designee. 
7.4. 
Method of Assignment of Study Drug 
7.4.1. 
Part 1 – Double- blind 
After pretreatment clinical evaluations and all other screening procedures have been completed, 
authorized site personnel will acknowledge that the applicable subject met all the specified 
inclusion criteria and none of the exclusion criteria.  Assignment to a treatment group will then 
follow a predetermined list of randomization numbers, with each successive number receiving 
1 of the 2 treatments in random order.  Authorized site personnel will use the IWRS system to 
assign a kit number that corresponds to the randomization schedule.  The kit box with the 
assigned kit number will be dispensed to the subject.  
The randomization code will be provided by TKL.  
7.4.2. 
Part 2 – Open-label 
All subjects who elect to continue into the second part of the study will receive FMX-101, 4% 
minocycline foam as described in Section 7.1.3.2.        
7.5. 
Selection and Timing of Doses in the Study 
The 4% minocycline concentration of FMX-101 was shown to be more effective than 1% in a 
Phase 2 study.  The once-daily dosing regimen is appropriate given the pharmacokinetic 
characteristics of minocycline. 


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7.6. 
Blinding 
The first part of this study is double-blind with limited access to the randomization code.  The 
randomization code will be held in confidence until after the study database is locked and a 
memo documenting the database lock has been issued.  Every effort will be made to retain the 
integrity of the blind.  When issued to the sites, the study drug will be identical in appearance for 
all subjects, regardless of treatment assignment. 
The treatment each subject receives will not be disclosed to the Investigator, study site personnel, 
subjects, monitors, or the Sponsor staff except as required for the purposes of conducting this 
study. 
In the event that emergency identification of study drug is required (eg, if the Investigator 
believes that the information is necessary to properly treat a subject with an AE), the study drug 
identity can be obtained by the Investigator through the IRT system. 
Before breaking the blind for a subject, the Investigator should determine that the information is 
necessary (ie, that it will alter the subject’s immediate course of treatment and will contribute to 
the management of the AE).  In many cases, particularly when the emergency is clearly not 
related to study drug, the problem may be effectively managed by assuming that the subject is 
receiving active study drug without the need for unblinding.  Every effort should be made to alert 
the Medical Monitor before requesting that the blind be broken.  If this is not possible, the 
Medical Monitor should be immediately notified of the breaking of the blind.  The Investigator 
will record the unblinding procedures in the subject’s source documents. 
If unblinding is necessary, the subject will be withdrawn from the study and Week 12 Visit 
assessments will be completed. 
7.7. 
Prior and Concomitant Therapy   
Subjects should use the cleanser, 
 (provided by the Sponsor).  An 
alternative, non-medicated, cleanser may be used if agreed to by the Sponsor. 
The use of or change in the dose of any and all concomitant medication, either prescription or 
over-the-counter, during the study will be recorded. The reason for use or change of dose of a 
concomitant therapy may need to be reported as an AE.  Therapies (medication and non-
medication therapies) not restricted by the protocol may be used.  Non-prohibited chronic 
therapies being used at Baseline may be continued. If a subject is using an oral contraceptive 
product, she should have been on the same product for at least 3 months and she should continue 
using the same or equivalent product for the duration of the double-blind portion of the study. 
If a subject is taking anticoagulant therapy, the subject should be advised that they may require a 
downward adjustment of their anticoagulant dosage. 
All topical or systemic medications listed in the exclusion criteria are prohibited during the 
double-blind part of this study (through Week 12).  Similarly, no other topical medications are 
permitted to be used on the face during this period.  Subjects requiring systemic antibiotics not 
known to affect acne will be considered on a case-by-case basis.  During the open-label part of 
the study, concomitant acne medications are permitted; their use should be properly recorded. 
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See the Investigators’ Brochure for information about tetracyclines and possible drug-drug 
interactions 
7.8. 
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 or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea > 12 
consecutive months).  Females of childbearing potential must have a negative urine pregnancy 
test and, if they are sexually active or become sexually active during the study, must use an 
effective method of birth control such as those listed below during the course of the study.  The 
following is not an all-inclusive list; the subject must discuss with the Investigator the most 
appropriate form of birth control: 
 Hormonal methods 
o Oral contraceptives – (Topical 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 
 Abstinence 
7.9. 
Treatment Compliance 
Each subject is to be instructed on the importance of following the dosing schedule and returning 
all kits (empty/used/unused) at the appropriate visits.  The study personnel will question the 
subject on the history of study drug use since the last visit. A subject who deviates significantly 
from the prescribed dosage will be counseled.  


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8. 
EFFICACY ASSESSMENTS 
8.1. 
Primary Efficacy Assessments 
The primary efficacy assessments will be the IGA and lesion counts. 
8.1.1. 
Investigator Global Assessment Score (IGA) 
Table 3 displays the IGA scale for acne vulgaris, which will be used by the investigators to 
assess the severity of a subject’s acne vulgaris.  The Case Report Forms (CRFs) will allow for 
Investigators to report lesions worsening beyond Grade 4 with treatment.    The IGA must be 
performed prior to the lesion count. 
The same evaluator should perform all evaluations for a subject; when this is not possible, 
another approved evaluator may perform the evaluations. 
Table 3: IGA Scale for Acne Vulgaris 
Score 
Grade 
  Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
 
1 
Almost clear 
Rare noninflammatory lesions may be present, with rare non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink- red) 
2 
Mild 
Some noninflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Many noninflammatory lesions.  Multiple inflammatory lesions evident with several 
to many papules/pustules, and there may be one small nodulocystic lesion 
4 
Severe 
Inflammatory lesions are more apparent, many comedones and papules/pustules, there 
may be a few nodulocystic lesions 
5 
Very Severe 
Highly inflammatory lesions predominate, variable number of comedones, many 
papules/pustules and many nodulocystic lesions 
8.1.2. 
Lesion Counts 
Subjects are eligible for enrollment if they have: 
 20 to 50 inflammatory lesions (papules, pustules, and nodules) 
 25 to 100 noninflammatory lesions (open and closed comedones) 
 No more than 2 nodules can be present on the face at Screening 
Lesions will be characterized as inflammatory or non-inflammatory using the following criteria: 
 Inflammatory lesions: 
Papule – a solid, elevated lesion less than 0.5 cm in diameter 
Pustule – an elevated lesion containing pus less than 0.5 cm in diameter 
Nodule – palpable solid lesion greater than 0.5 cm in diameter; has depth, not 
necessarily elevated 
 
 


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 Noninflammatory lesions: 
Open comedones (blackhead) – non-infected plugged hair follicle with 
dilated/open orifice; black in color 
Closed comedones (whitehead) – non-infected plugged hair follicle: small 
(microscopic) opening at skin surface 
Facial lesion counts will be made for the forehead, left and right cheeks, nose and chin at each 
visit.  Total inflammatory lesions (pustules, papules, and nodular lesions) and noninflammatory 
lesions (open and closed comedones) will be counted and recorded separately.  Lesion counts 
will be repeated at Weeks 3, 6, 9 and 12. 
8.2. 
Photography 
Photography of the face will be performed at Baseline and at Weeks 6 and 12 using recognized 
methods.  The equipment and techniques for this photography and for archiving the images are 
described in the Study Manual.  Photographs will be reviewed at the site and by the sponsor for 
quality.  Photographs will not be used to assess the lesion counts or the Investigator’s assessment 
of global severity but will be archived to be available for subsequent review, if required, by the 
sponsor, auditors or the FDA. 
8.3. 
Subject Satisfaction Questionnaire 
A satisfaction questionnaire will be administered at Visit 6, Week 12 and Visit 13, Week 52 (see 
Section 16.1, Appendix 1). 
9. 
SAFETY ASSESSMENTS 
The safety assessments in this study are standard safety measures in clinical studies, including 
physical examinations, the monitoring of vital signs, AEs (volunteered, observed, and elicited by 
general questioning in a non-suggestive manner), and clinical laboratory test results.  In addition, 
skin assessments at the drug application site(s) will be performed. 
9.1. 
Medical/Surgical History 
A complete medical and surgical history will be obtained at Screening, which will include 
diseases of the head, ears, eyes, nose and throat; respiratory diseases; cardiovascular diseases; 
gastrointestinal diseases, hepatic diseases, genitourinary diseases, musculoskeletal diseases, 
endocrine diseases, neurological diseases, psychiatric diseases, skin diseases, allergies, 
hematological diseases, and other abnormalities. 
9.2. 
Medication History 
A history of medication usage (including previous use of acne medications and non-medication 
therapies) will be recorded at Screening.  The start and stop dates of previous use of medications 
in the last 3 months will be recorded. 


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9.3. 
Concomitant Medications 
All medication that the subject is currently taking or any change in medication or dosage since 
the last visit will be documented throughout the study. 
9.4. 
Vital Signs 
Heart rate and blood pressure will be measured at all post-Baseline visits.  All blood pressure 
measurements will be made using a sphygmomanometer with an appropriate cuff size for the 
individual subject.  Measurements will be administered while the subject is seated after at least 
5 minutes at rest. 
9.5. 
Physical Examination 
A complete physical examination will include an evaluation of general appearance, skin, 
HEENT, neck, lymph nodes, lungs, heart, abdomen, musculoskeletal system, and neurologic 
system. A standard 12-lead EKG (after at least 5 minutes rest) will be performed at Baseline in 
subjects over 39 years of age. 
Weight will be recorded at the Baseline Visit, Visit 6 (Week 12) and Final Visit (Week 52).  
Height will be measured at Baseline, only. 
9.6. 
Clinical Laboratory Tests 
Serum chemistry, hematology and urinalysis will be evaluated at Baseline, Week 12/ Final Visit 
of the double-blind phase of the Study, and at Week 28 and Week 52/Final Visit of the open-
label phase of the Study. Serum chemistry, hematology, and urinalysis tests will be performed at 
a central laboratory. 
Refer to the manual from the central laboratory for detailed instructions on collecting, 
processing, and shipping of samples.  


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Hematology 
Urinalysis 
Serum chemistry 
Hematocrit 
Hemoglobin 
MCH 
MCHC 
MCV 
MPV 
Platelet count 
RBC 
RDW 
WBC 
Reticulocyte count  
WBC differential  (% & 
absolute) : 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocytes esterase 
pH 
Protein 
Specific gravity 
 
Urine pregnancy 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 
Triglycerides 
Uric acid 
9.6.1. 
Urine Pregnancy Test 
A urine pregnancy test will be performed on all females of childbearing potential at Baseline, 
Week 3, Week 6, Week 9 and Week 12 of the double-blind phase of the Study and Final Visit or 
when a subject prematurely withdraws from the study. 
Home pregnancy kits will be provided at each visit to all female subjects of childbearing 
potential in the open-label phase of the Study and are to be used at least monthly and if a 
pregnancy is suspected between visits (e.g., if a subject misses a period). A urine pregnancy test 
will be performed at Week 52/ Final Visit. 
 
9.6.2. 
Sample Collection, Storage, and Shipping 
Sample collection kits, requisition slips, and shipping boxes will be supplied by the central 
laboratory. Sample collection procedures and shipping instructions will be detailed in the 
laboratory manual. Study centers must be equipped to store the samples according to the 
laboratory manual procedures before shipping samples to the central laboratory. 
9.7. 
Other Safety Measurements 
9.7.1. 
Tolerability 
Erythema, dryness, hyperpigmentation and skin peeling at the sites of study drug application will 
be assessed by the investigator at each study visit on a scale of 0 to 3 (0=none; 1=mild; 
2=moderate; 3=severe). Itching will be assessed using the same scale based on the subjects’ 
subjective assessment.  The intensity and location of each finding will be recorded.  These signs 


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and symptoms should not be recorded as AEs unless they require concomitant treatment or lead 
to the subject’s discontinuation from the study. 
9.8. 
Adverse Events 
9.8.1. 
Method of Determining Adverse Events 
Safety assessments will include recording AEs reported spontaneously by the subject or observed 
by the Investigator.  AEs will be recorded at each visit throughout the study on the appropriate 
CRF. Every attempt should be made to describe the AE in terms of a diagnosis.  If a clear 
diagnosis has been made, individual signs and symptoms will not be recorded unless they 
represent atypical or extreme manifestations of the diagnosis, in which case they should be 
reported as separate events.  If a clear diagnosis cannot be established, each sign and symptom 
must be recorded individually. 
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 over-the-counter) 
 Were admitted to a hospital or had any accidents 
 Developed unusual headaches or changes in vision 
All questions should be of a general nature and should not suggest symptoms. 
When an AE is suspected, all relevant evaluations will be carried out and appropriate treatment 
provided.  Additional follow-up will be done as necessary (Section 9.8.4) and recorded in the 
subject’s source documents, and the results will be provided to the Sponsor. 
For AE definitions and reporting requirements, refer to Section 9.8.2 and Section 9.8.3, 
respectively. 
9.8.2. 
Adverse Event Definitions 
9.8.2.1. 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended sign, symptom, or disease that appears 
or worsens in a subject after the subject signs the ICF (and/or Assent Form) 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 


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increase in the severity of the pre-existing condition/illness during the study.  Planned or elective 
surgical procedures for pre-existing conditions that have not worsened are not AEs.  However, 
any complication that occurs during a planned or elective surgery is an AE.  (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. 
9.8.2.2. 
Serious Adverse Events 
A “serious adverse event” (SAE) is any AE that: 
 Results in death 
 Is life-threatening 
(Note: The term “life-threatening” refers to any AE that, as it occurs, puts the subject 
at immediate risk of death.  It does not refer to an AE that hypothetically might have 
caused death if it were more severe.) 
 Results in hospitalization or prolongation of current hospitalization (not including 
hospitalization for a pre-existing condition that has not increased in severity or 
frequency from the subject’s underlying medical condition prior to entry into the 
study) 
 Results in persistent or significant disability/incapacity 
 Is a congenital anomaly/birth defect in the offspring of a subject 
 Is another serious (important medical events) events 
 
(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. 
9.8.2.3. 
Severity of Adverse Events 
“Severity” of the AE refers to the extent to which an AE affects the subject’s daily activities and 
differs from “Serious,” which is a regulatory classification.  Severity will be categorized 
according to the following criteria: 
 Mild:  The symptom has a negligible effect or no impairing effect on the subject’s 
normal function. 
 Moderate:  The symptom impairs the subject’s normal function to some extent. 
 Severe:  The symptom has an obvious, significantly impairing effect on the subject’s 
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9.8.2.4. 
Relationship of Adverse Events to Study Treatments 
“Causality” refers to the relationship of the AE to study drug and will be categorized according 
to the following criteria: 
 Unlikely:  There is no medical evidence to suggest that the AE may be related to 
study drug usage, or there is another more probable medical explanation. 
 Possible:  There is medical evidence to suggest that there is a reasonable possibility 
that the AE may be related to study drug usage. However, other medical explanations 
cannot be excluded as a possible cause. 
 Probable:  There is strong medical evidence to suggest that the AE is related to study 
drug usage. 
9.8.2.5. 
Adverse Events Expectedness 
Expected AEs are defined as those described in the Investigator’s Brochure.  If an event 
increases in intensity or severity from that described in the IB, it will be considered unexpected. 
9.8.3. 
Reporting Adverse Events 
AEs that occur from the time of informed consent/assent through completion of the last study 
visit should be reported.  Any AE that the Investigator becomes aware of that occurs within 30 
days of study completion or withdrawal should also be reported. 
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 individually. 
Any serious AEs occurring in a subject receiving study drug must be reported to the Sponsor or 
designee within 24 hours of the site being informed of the event, even if the event does not 
appear to be drug-related.  The report must be made by sending a completed Serious Adverse 
Event (SAE) Report form to the Sponsor or designee.  Any pertinent follow-up information 
should be provided in a similar manner.  Contact information is provided below:  
TKL Clinical Pharmacovigilance 
 
9.8.4. 
Adverse Event Follow-up 
Adverse events, and tolerability signs and symptoms greater than zero (0), that are ongoing when 
a subject withdraws from or completes the study will be followed until resolution or stabilization 
(in the opinion of the Investigator), or for 30 days, whichever is shorter.  Investigators and the 
Sponsor will decide if longer follow-up is appropriate on a case-by-case basis.  Subjects who 
experience any clinically significant AE will remain under medical supervision until the 
Investigator or the Sponsor’s Medical Monitor deems the AE to be resolved, stabilized, or no 
longer serious enough to warrant follow-up. 
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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 resolved or stabilized. 
9.8.4.1. 
Pregnancy reporting 
Prior to study enrollment, females of childbearing potential must be advised of the importance of 
avoiding pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy.  The Informed Consent or Assent Form that the subject signs must document this 
discussion.  
If a subject or Investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug must be withheld until the results of laboratory pregnancy testing 
are available.  If pregnancy is confirmed, the subject must not receive study drug and must not be 
enrolled in the study. 
A urine pregnancy test will be performed on all females of childbearing potential at Baseline, 
Week 3, Week 6, Week 9 and Week 12 of the double-blind phase of the Study and Final Visit or 
when a subject prematurely withdraws from the study. 
Home pregnancy kits will be provided at each visit to all female subjects of childbearing 
potential in the open-label phase of the Study and are to be used at least monthly and if a 
pregnancy is suspected between visits (e.g., if a subject misses a period). A urine pregnancy test 
will be performed at Week 52/Final Visit. 
During the study, all females of childbearing potential should be instructed to contact the 
Investigator immediately if they suspect they might be pregnant (eg, missed or late menstrual 
period).  If a subject or Investigator suspects that the subject may be pregnant at any time before 
or during the study, the study drug must be withheld until the results of laboratory pregnancy 
testing are available.  The Sponsor and Site Monitor must be notified and available information 
captured on a “Suspected Pregnancy” 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) but the 
pregnancy will not be captured as an AE. 
The subject should be followed until the outcome of the pregnancy is known. 
9.8.5. 
Clinically Significantly Abnormal Laboratory Results  
All laboratory values that are outside of the normal range for that parameter will be so flagged 
when reported to the site.  The Investigator will determine which out-of-range laboratory test 
results should be characterized as clinically significant and will so annotate the laboratory report.  
If a clinically significant laboratory abnormality requires treatment or is the reason for a subject 
being discontinued from the study, the abnormal result must also be classified as an AE. 
9.9. 
Appropriateness of Safety Measurement 
The safety assessments in this study are standard safety measures in clinical trials. 
 


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10. 
STATISTICAL DESIGN AND ANALYSIS 
10.1. 
Statistical Analysis Plan 
A detailed statistical analysis plan will be finalized prior to breaking of the study blind. 
Descriptive statistics for qualitative variables (eg, race) will include the number and percentage 
of subjects with the qualitative response.  Missing responses will be enumerated, but the 
calculation of percentages will exclude missing responses.  For quantitative variables (eg, age), 
descriptive statistics will include the number of subjects with non-missing data, mean, standard 
deviation, median, minimum value and maximum value.  All hypothesis testing will be 
conducted using two-sided tests with α=0.05 level of significance unless otherwise specified. 
All study data will be presented in listings. 
10.2. 
Determination of Sample Size 
In a phase 2 study, the proportion of subjects with an IGA score of 0 or 1 after 12 weeks of 
treatment was 20% in the minocycline 4% foam group compared to 2% in the vehicle group. The 
following table provides a few alternate assumptions and corresponding sample sizes. Power was 
set to 90% and type-1 error to two-sided 0.05. Sample size was calculated based on Fisher’s 
Exact test. 
Vehicle IGA (0,1) Minocycline 4% 
foam IGA (0,1) 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
Assuming 12% dropout rate, 
 subjects on active, and 
 subjects on vehicle will provide at 
least 90% power for a statistically significant difference on IGA 0 or 1. In the same phase 2 
study, the change from baseline in inflammatory lesions was 
 in the minocycline 4% foam 
versus 
 in the vehicle group. The standard deviation in change from baseline was 
approximately 9.2. The following table shows alternate assumptions and corresponding sample 
sizes, for 90% power and a two-sided type 1 error of 0.05. The sample sizes were calculated 
using a t-test. 
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Vehicle mean 
inflammatory 
lesion reduction 
Minocycline 4% foam 
mean inflammatory 
lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
To summarize, using some conservative estimates of the effect on minocycline 4% foam versus 
the vehicle for both IGA and change in inflammatory lesions at week 
 subjects on active, 
and 
 on vehicle will provide > 90% power for s statistically significant difference. 
Another consideration for the sample size must be given to the secondary endpoint of 
noninflammatory lesions which will be compared to the vehicle for non-inferiority. The margin 
for non-inferiority will be 30% of the change from baseline to week 12. In a phase 2 study, 
change from baseline in noninflammatory lesions at week 9 was 
 for the vehicle group with 
a standard deviation of 18. Assuming approximately the same reduction at week 12, a 30% non-
inferiority margin is about 
 lesions. The following table provides approximate sample sizes 
for alternate assumptions for 90% power to show non-inferiority. 
Vehicle mean 
noninflammatory 
lesion reduction 
Minocycline 4% foam 
mean noninflammatory 
lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
 
If Minocycline 4% foam has the same effect on noninflammatory lesions as vehicle, 
 subjects 
on vehicle and 
 on 4% foam will be needed for 90% power to show non-inferiority. If 
Minocycline 4% foam has a slightly less effect on noninflammatory lesions (
 lesion 
reduction versus 
 in vehicle), there will be about 90% power to show non-inferiority. 
10.3. 
 Analysis Populations 
The Intent-to-Treat (ITT) population will include all randomized subjects. The ITT population 
will be the primary population for all efficacy analyses. 
The Safety population will include all randomized subjects who took at least one dose of study 
drug.  Subjects who have no post-Baseline assessments will be included in the Safety population 
unless all dispensed study drug is returned unused. 
The Per Protocol (PP) population is defined as the subset of the ITT population without any 
protocol deviations that may have an impact on the efficacy assessments.  The subjects to be 
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included in the PP population will be determined by the Sponsor/CRO prior to the unblinding of 
the study.  The PP population will be secondary for the co-primary endpoints only. 
Subjects may be excluded from the PP population if any of the following are met:  
 Did not meet inclusion/exclusion criteria 
 Have administered any interfering concomitant medications 
 Have not, in the opinion of the investigator, been compliant with the treatment 
regimen (e.g. reported frequent missed doses) 
Prior to breaking the blind, additional criteria for exclusion from the PP population may be 
included to accommodate for unforeseen events that occurred during the conduct of the study.  
10.4. 
Efficacy Endpoints 
The primary population for all efficacy analyses will be the ITT population.  Subjects will be 
analyzed according to their randomized treatment.  The primary method of handling missing data 
will be the last observation carried forward (LOCF) approach.   Sensitivity analyses using 
multiple imputations and baseline observation carried forward (BOCF) will be performed on the 
co-primary endpoints only. 
Supportive efficacy analyses will also be performed on the PP population.  All analyses using the 
PP population will use the Observed-Cases (OC) approach.  i.e., there will be no imputation for 
missing data at any time point. 
Changes from Baseline lesion count will be calculated as the Baseline value minus the post-
Baseline value.  Thus, a positive change will reflect a reduction in lesion count.  The percent 
change from Baseline lesion count will be calculated as the Baseline value minus the post-
Baseline value divided by the Baseline value, expressed as a percentage.  Thus, a positive 
percent change will reflect a reduction in lesion count. 
10.4.1. 
Primary Efficacy Endpoints 
The co-primary efficacy endpoints are: 
 The absolute change from Baseline in the inflammatory lesion count at Week 12 
 Treatment Success (dichotomized as Yes/No) at Week 12, where success is defined 
as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from 
Baseline 
The null hypotheses of the equality of the FMX-101 4% and vehicle means for absolute change 
from Baseline to Week 12 in the inflammatory lesion count and the equality of IGA success rates 
at Week 12 will each be tested at a two-sided 0.05 level of significance. Change from baseline in 
inflammatory lesion count will be analyzed using an Analysis of Covariance (ANCOVA), with 
Treatment as a main effect, baseline inflammatory lesion count as a covariate, and 
investigational site a blocking factor. Investigational site by Treatment interaction will be tested 
at 0.1 level, and if significant, it will further be explored. The dichotomized IGA will be 
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10.4.2. 
Secondary Efficacy Endpoints 
 The absolute change from Baseline in the noninflammatory lesion count at Week 12 
 The absolute change from Baseline in the inflammatory lesion count and IGA 
Treatment Success at the interim visit at Week 9 
 The absolute change from Baseline in the inflammatory lesion count and IGA 
Treatment Success at the interim visit at Week 6 
10.4.3. 
Tertiary efficacy endpoints 
 The percent change from Baseline in the inflammatory lesion count at Weeks 3, 6, 9 
and 12 
 The absolute change from Baseline in the inflammatory and noninflammatory lesions, 
and the IGA Treatment Success at Week 3 
 The absolute change from Baseline in the noninflammatory lesion count at Weeks 3, 
6, 9 and 12 
 The percent change from Baseline in the noninflammatory lesion count at Weeks 3, 6, 
9 and 12 
Secondary efficacy endpoint will be tested sequentially in the order listed above, at 0.05 level of 
significance, only if the co-primary efficacy endpoints are significant. 
10.5. 
Safety endpoints   
Treatment-emergent adverse events (TEAEs), vital signs, physical examinations, and clinical 
laboratory measurements will be reported on the Safety population.  Subjects will be reported 
according to the treatment they actually received.  No statistical tests will be performed for any 
of the safety assessments. 
Baseline for vital signs, physical examinations, and clinical laboratory measurements is defined 
as the last non-missing value prior to the first dose of study drug. 
10.5.1. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to system organ class (SOC) and preferred term. 
TEAEs will be defined as events that emerge during treatment having been absent pre-treatment, 
or worsen relative to the pre-treatment state.  Summaries of AEs will be limited to TEAEs.  The 
number and percentage of subjects reporting each SOC and preferred term will be summarized 
for each treatment group and by the Study Period.  At each level of summarization, a subject will 
be counted once if he/she reported one or more events.  The severity of TEAEs and relationship 
to study drug will be summarized in a similar manner.  For summaries of relationship to study 
drug, a subject will be classified according to the closest relationship.  For summaries of TEAE 
severity, a subject will be classified according to the highest severity. 
Summaries of SAEs and subjects who prematurely withdraw from the study due to AEs will be 
presented. 


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10.5.2. 
Vital Signs  
Vital sign parameters will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point.  Changes from Baseline will also be summarized.  Baseline is defined 
as the last non-missing value prior to the first dose of study drug. 
10.5.3. 
Physical Examinations 
Physical examinations will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point.  Shifts from Baseline will also be summarized.  Baseline is defined as 
the last non-missing value prior to the first dose of study drug. 
10.5.4. 
Clinical Laboratory Results  
Baseline is defined as the last non-missing value prior to the first dose of study drug. 
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 each post-baseline time point.  
A listing of subjects with pre-treatment and treatment-emergent clinically significant abnormal 
laboratory values will be presented for each treatment group. Clinical significance is based on 
the Investigator’s judgment.  
10.6. 
Statistical Analysis 
10.6.1. 
Interim Analysis  
No interim analysis is planned. 
10.6.2. 
Subject Accounting, Demographic, and Baseline Characteristics 
Demographic, baseline characteristics, and prior and concomitant medications will be 
summarized by treatment.  Study completion status and reasons for discontinuation will also be 
displayed by treatment.   
Medical and surgical history will only be presented in the listings. 
10.6.3. 
Efficacy Analysis 
The co-primary endpoint of absolute change from Baseline in inflammatory lesions at Week 12 
will be analyzed using an Analysis of Covariance (ANCOVA) model with main effect treatment 
and investigational site as a covariate.  The treatment by investigational site interaction will be 
tested separately at 0.1 level of significance, and if significant, will be further be explored.  A 
95% confidence interval will be calculated on the difference in mean changes from baseline 
between FMX-101 4% and vehicle. 
The co-primary endpoint of IGA Treatment Success rate at Week 12 will be analyzed using a 
Cochran–Mantel–Haenszel (CMH) test with investigational site as the stratification factor.  If the 
overall IGA Treatment Success rate is less than 10%, a Fisher’s Exact test will be used to 


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corroborate the CMH test.  A 95% confidence interval will be constructed on the difference in 
IGA Treatment Success rates between FMX-101 4% and vehicle. 
If FMX-101, 4% is found superior to vehicle (one-sided p<=0.025) for both co-primary 
endpoints, the secondary endpoints will be tested sequentially. The first secondary endpoint of 
noninflammatory lesions at Week 12 will be tested initially as a non-inferiority comparison of 
FMX-101, 4% to vehicle. Non-inferiority margin is defined as 30% of the noninflammatory 
lesion reduction in the vehicle group at Week 12. A lower 97.5% confidence limit will be 
calculated for µa-0.6×µv, where µa and µv are the mean reduction of noninflamatory lesions of 
FMX-101, 4% and vehicle respectively. If the confidence limit is above 0, non-inferiority will be 
concluded. If non-inferiority is concluded, the superiority of FMX-101, 4% to vehicle for 
noninflammatory lesions at Week 12 will be tested. The sequential testing will proceed 
according to the order in Section 10.4.2.1.  Testing of secondary efficacy endpoints at an earlier 
timepoint for each type of lesion and IGA Treatment Success will be performed only if 
superiority (one-sided p<=0.025) is seen at the later timepoint.  
Secondary efficacy parameters will be analyzed similar to the appropriate co-primary efficacy 
parameter. 
Absolute change from baseline in inflammatory lesion count and the IGA assessments in the 
open-label phase of the study will be summarized. No statistical testing will be performed for the 
open label efficacy data. 
10.6.4. 
Safety Analysis 
The Medical Dictionary for Regulatory Activities (MedDRA) terminology will be used to 
classify all AEs with respect to system organ class (SOC) and preferred term. 
TEAEs will be defined as events that emerge during treatment having been absent pre-treatment, 
or worsen relative to the pre-treatment state.  Summaries of AEs will be limited to TEAEs.  The 
number and percentage of subjects reporting each SOC and preferred term will be summarized 
for each treatment group.  At each level of summarization, a subject will be counted once if 
he/she reported one or more events.  The severity of TEAEs and relationship to study drug will 
be summarized in a similar manner.  For summaries of relationship to study drug, a subject will 
be classified according to the closest relationship.  For summaries of TEAE severity, a subject 
will be classified according to the highest severity. 
Summaries of SAEs and subjects who prematurely withdraw from the study due to AEs will be 
presented. 
Vital sign parameters will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point.  Changes from Baseline will also be summarized. 
Physical examinations will be summarized using descriptive statistics at Baseline and for the 
final visit.  Shifts from Baseline will also be summarized. 
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. 


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A listing of subjects with pre-treatment and treatment-emergent clinically significant abnormal 
laboratory values will be presented for each treatment group. Clinical significance is based on 
the Investigator’s judgment. 
11. 
STUDY MANAGEMENT 
11.1. 
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 IRB to have direct access to all documents pertaining to the study.  The Investigator is to 
immediately notify the Sponsor or the Sponsor’s representative of any regulatory authority 
inspections.  The Investigator will be informed about the outcome of any Sponsor audit. 
This study will be monitored regularly, by or under supervision of a monitor from the Sponsor.  
The frequency of monitoring visits will be agreed upon by the Sponsor’s representative and the 
study site.  
Monitoring visits will take place on a regular basis according to the enrollment rate and number 
of subjects enrolled at each investigational site.  During these visits, the monitor will check the 
completion of the CRF entries, compliance with the study protocol and with GCP-ICH, and the 
agreement of key entries with the source data.  The monitor will also verify the correct use of the 
study drug.  At the Final Visit or at an agreed to time prior to 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 
or the Sponsor’s representative’s clinical research associate, as needed, regarding study concerns 
and/or questions.  Contact information is provided in the Study Binder for the site. 
11.2. 
Protocol Amendments 
The Sponsor may propose to amend this protocol at any time. 
No change to the protocol will be implemented until the Sponsor and the IRB have reviewed and 
approved the amendment. 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety.  All such procedures must have written documentation and be 
promptly reported to the Sponsor. 
Amendments to the protocol, if any, are included in Section 16.2, page 53.  This protocol version 
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11.3. 
Protocol Deviations 
A protocol deviation is any change, divergence or departure from the IRB-approved protocol by 
the study staff (intentional or unintentional).  All deviations are to be documented at the site and 
reported to the IRB according to the IRB’s guidelines. 
In the event of an emergency, the Investigator shall implement any medical procedures deemed 
appropriate for subject safety.  All such procedures must have written documentation and be 
promptly reported to the Sponsor. 
11.4. 
Withdrawal of Subjects 
Withdrawn subjects are those who do not complete all evaluations and procedures outlined in the 
protocol.  Subjects who discontinue taking study drug for any reason must also be withdrawn 
from the study.  Subjects may be withdrawn from the study because of one 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 9.8.4. 
 Abnormal Laboratory Result:  Any clinically significant laboratory abnormality 
that requires withdrawal of the subject from the study should be considered an AE 
leading to withdrawal.  If possible, laboratory tests will be repeated for any results 
that were clinically significantly abnormal until the abnormality is resolved or 
stabilized to the satisfaction of the Investigator in consultation with the Medical 
Monitor. 
 Lost to Follow-up:  Confirmed at minimum by 2 phone calls and a traceable letter 
without response. 
 Subject Request:  Subject requests, for any reason (eg, AE), to be withdrawn or 
withdraws his/her consent. 
 Poor protocol adherence:  A subject may be withdrawn from the study at the 
discretion of the Investigator or Sponsor due to poor compliance with protocol 
requirements that may compromise the study results or subject safety. 
 Other:  Other reasons include but are not limited to: Investigator decision that it is in 
the subject’s best interest to be withdrawn, administrative reasons, relocation of 
subject, etc.  If a subject becomes pregnant during the study, the subject will be 
withdrawn from the study and followed through conclusion of the pregnancy. 
If a subject is withdrawn from the study following the start of study drug during Period 1 of the 
study, all Week 12 assessments should be completed.  If a subject is withdrawn from the study 
following the start of study drug during Period 2 of the study, all Final Visit assessments should 
be completed.  Subjects withdrawn from the study will not be replaced. 


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11.5. 
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. 
11.6. 
Publication Policy 
The data obtained in this study are the property of the Sponsor, which will make reasonable 
efforts to assure that the results are published in a peer-reviewed journal.  As some of the 
information concerning the investigational product and development activities at the Sponsor 
may be of strictly confidential nature, any manuscript or other presentation of data must first be 
reviewed by the Sponsor before its submission. 
12. 
ETHICS 
12.1. 
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. 
12.2. 
Institutional Review Boards (IRB) 
This protocol (and any changes), all consent/assent 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 doctor-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 apply place followed by IRB approval. 
Review and approval by the IRB for continuation of the study must apply place at least once a 
year. 
12.3. 
Written Informed Consent 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration and the potential benefits and risks of participation to each 
subject prior to his/her entry into the study (ie, before examinations and procedures associated 
with selection for the study are initiated).  Each subject will have ample opportunity to ask 
questions and will be informed about the right to withdraw from the study at any time without 
any disadvantage and without having to provide reasons for this decision. 


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Following this informative discussion, the subject will be asked if he/she is willing to sign a 
statement of informed consent.  Only subjects who voluntarily sign the Informed Consent Forms 
(ICF) may enter the study. Subjects less than 18 years of age (or as required by state law) must 
sign an Assent Form for the study and a parent or legal guardian must sign the ICF. 
The ICF and Assent Form must be reviewed and approved by the Sponsor and the IRB prior to 
their use. 
The original signed ICF and Assent Form will remain in the Investigator’s files.  The 
Investigator or designee will indicate in each subject’s source documents that he / she has 
informed the subject about the study and its procedures, the subject has signed and dated the 
ICF/Assent Form, 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 subjects’ 
willingness to continue in the study. 
12.4. 
Subject Confidentiality 
The Sponsor ensures that the following have permission to review all study-related documents: 
monitor, auditor, IRB and regulatory authorities.  The subject’s identity and study-related records 
will remain confidential throughout the duration of the study data collection and reporting 
process. 
A unique subject identification code is assigned 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. 
12.5. 
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, source 
documentation corresponding to all information contained in the CRFs, signed informed consent 
and assent forms, relevant correspondence, and all other supporting documentation) until at least 
2 years after the last approval of a marketing application in an ICH region and until there are no 
pending or contemplated marketing applications in an ICH region, or at least 2 years after the 
formal discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted.  Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same time period. Custody of the records may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies.  Written notice of 
transfer must be submitted to the Sponsor.  The Investigator must contact the Sponsor prior to 
disposing of any study records. 


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12.6. 
Financing 
Funding for this study will be agreed between the Investigator and the Sponsor and will be 
confirmed in writing before the study starts. 
Completion of Financial Disclosure Forms will be required before the study starts.  Any 
additions to the primary site personnel will necessitate the completion of new Financial 
Disclosure Forms.  This information will also be collected at site closure and one year after the 
completion of the study. 
Disclosure Forms.  Investigators will be informed that they must report any new information to 
the sponsor or designate at site closure and one year after the completion of the study. 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor and Investigator will apply all steps possible to ensure the accuracy, consistency, 
completeness, and reliability of the data, including participating in an Investigator meeting 
and/or site initiation visit, routine site monitoring, review of CRFs against source documents, and 
quality control checks.  
In addition, a representative from the Sponsor’s Clinical Quality Assurance (CQA) Department 
or designee may conduct periodic audits of the study processes, including, but not limited to, 
auditing the clinical site, laboratories, vendors and CROs, the clinical database, and the final 
study report. 
14. 
DATA HANDLING AND RECORD KEEPING 
This study will use web-based, electronic case report forms (eCRFs) developed through a 
validated, Electronic Records / Electronic Signatures-compliant platform (US Title 21 CFR Part 
11).  Foamix Clinical Data Management department or designee will create the electronic CRFs 
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 user name and password.  Only the person who owns 
the user name and password will enter the system using that user name 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 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 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. 


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15. 
REFERENCE LIST 
1. Brown SK, Shalita A R; Acne Vulgaris, Follicutitis, and Acne Rosacea. Lancet 
351:1871-76, 1998 
2. Guidance for Industry: “Acne Vulgaris: developing Drugs for Treatment ” September 
2005 FDA Draft Guidance 
 


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16. 
APPENDICES 
16.1. 
Appendix 1 – Subjects Satisfaction Questionnaire 
 
The following 8 questions will be asked of the subject at Visit 6, Week12 and Visit 13, Week 52: 
1. How satisfied are you with this product in treating your acne? 
2. How satisfied are you with how easy this product is to use? 
3. How satisfied are you with this product compared to other products you have previously 
used for acne, such as gels and creams? 
4. How satisfied are you with how this product feels on your skin after treatment? 
5. How satisfied are you with the odor of this product after treatment? 
6. How satisfied are you with the color of this product after treatment? 
7. Overall, how satisfied are you with this product? 
8. Overall, how likely are you to recommend this product to a friend? 
 
Answers to Questions 1-7 will be selected from the following: 
1=Very Satisfied 
2=Satisfied 
3=Somewhat Satisfied 
4=Dissatisfied 
5=Very Dissatisfied 
 
Answer to Question 8 will be selected from the following: 
1=Very Likely 
2=Likely 
3=Somewhat Likely 
4=Unlikely 
5=Very Unlikely 
 


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16.2. 
Appendix 2 – Protocol Amendments 
This appendix describes the amendment(s) that have been made to the protocol for Study 
FX2014-0. 
Section 16.2.1 describes the changes made to Protocol FX2014-05  Version 1 issued January 19, 
2016, via Amendment 1 effective February 26, 2016. 
Section 16.2.2 describes the changes made to Protocol FX2014-05  Version 2 issued February 
26, 2016, via Amendment 2 effective April 6, 2016.   
16.2.1. 
Amendment 1, effective February 26, 2016 
The following is the summary of the changes that were made to Protocol FX2014-05  Version 1 
issued 19-JAN-2016. 
Administrative changes: 
Section  
Revision 
    Title Page 
Added: 
 
    Signature Page 
Added 
    Study Administrative 
Structure 
Added: 
 
 
    SAE Reporting Information Added: TKL Clinical Pharmacovigilance 
 
 
Content changes:  
New or changed test is bolded. 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
1.10.1. Efficacy 
 . . Weeks 1, 3, 6, 9 and 12  
. Weeks 3, 6, 9 and 12.  
Correction 
1.11  Statistical 
Methods 
IGA score at Week 12 
(where success is defined as 
at least a 2-grade decrease 
from Baseline). 
IGA Treatment Success 
(dichotomized as Yes/No) 
at Week 12, where success 
is defined as an IGA score 
of 0 or 1, and at least a 2-
grade decrease from 
Baseline.   
Modified as per FDA 
suggestion 
At least a 2-grade 
improvement (decrease) 
from Baseline in the IGA 
score will be analyzed 
using . . . 
The IGA Treatment 
Success rates will be 
compared between the 
treatment groups using . . . 
PPD
PPD
CCI


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Section 
Revision 
Rationale 
Old Text 
New Text 
 
6.  Study 
Procedures 
Inserted 
Procedures at the 
Screening Visit will include 
obtaining blood and urine 
samples for clinical 
laboratory tests.  These 
results must be no more 
than 30 days old at the 
time of Baseline Visit  
randomization. 
Clarification of timing of 
laboratory tests during 
Screening 
6.  Study 
Procedures – 
Table 1 
Inserted 
“X” for Tolerability 
Assessment at all post-
Baseline visits  
Added at request of FDA 
“X” for Blood and urine 
samples at Baseline 
“X” for Blood and urine 
samples at Screening 
Sampling moved to earlier 
timepoint 
Inserted 
“X” for Blood and urine 
samples at Week 3  
Added at request of FDA 
Inserted  
“X” for Dispense study drug 
at Week 1 
Correction  
Inserted 
“X” to Confirm next visit 
Correction 
Footnote inserted  
Footnote 6  -  Home 
pregnancy tests will be 
dispensed to all female 
subjects at risk of 
becoming pregnant and 
will be performed 
whenever there is a 
suspicion of pregnancy 
(e.g., a missed period) 
Added at request of FDA 
6.  Study 
Procedures – 
Table 1 
Footnote 2 
If a subject prematurely 
withdraws from the study, 
all evaluations described 
under Visit 6/Week 12 must 
be performed.   
Subject may continue into 
open-label phase of study. 
If a subject is not 
continuing into open-label 
phase for any reason (see 
Section 4.1.2), all 
evaluations described under 
Visit 6/Week 12 must be 
performed.   
Clarification of process at 
Visit 6 
6.1 – 6.2   Study 
Procedures 
at Visits 3 – 14 
Record AEs  
Record AEs and 
Tolerability Assessments  
Changed at all post-Baseline 
Visits at request of FDA  
6.1.1  Screening 
Visit 
Using the Interactive Web 
Response system (IWRS), 
assign the subject a . . . 
Assign the subject a  . . . 
Screening number will not 
be assigned by IWRS 


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Section 
Revision 
Rationale 
Old Text 
New Text 
 
Inserted  
•   Collect blood and urine 
samples for clinical 
laboratory tests . . . 
Lab tests moved from 
Baseline to Screening Visit 
6.1.2  Baseline 
Visit, Visit 1 
• Confirm eligibility 
none 
Deleted repetition 
• Collect blood and urine 
samples for clinical 
laboratory tests . . . 
deleted 
Lab tests moved from 
Baseline to Screening Visit 
6.1.3    Visit 2, 
Week 1  
Inserted  
• 
Dispense 1 kit (2 
canisters) of study drug 
Correction 
6.1.4. Visit 3, 
Week 3 
inserted 
• Collect blood and urine 
samples for clinical . . . 
Added per FDA request 
• 
Confirm that subject 
continues to use the drug 
product and only provided 
cleanser correctly 
Deleted 
Redundant 
6.1.7. Visit 6, 
Week 12  
End of Double-Blind or 
Early Termination   
End of Double-Blind or 
Continuation in Open 
Label / Early Termination   
Title changed for clarity 
6.2   Part 2 – 
Open-label  Table 
2 
Footnote inserted  
Footnote 3  -  Home 
pregnancy tests will be 
dispensed to all female 
subjects at risk of 
becoming pregnant and 
will be performed 
whenever there is a 
suspicion of pregnancy 
(e.g., a missed period) 
Added at request of FDA 
Inserted 
“X” for Tolerability 
Assessment at all post-
Baseline visits  
Added at request of FDA 
Inserted 
“X” for Blood and urine 
samples at Week 28 
Added at request of FDA 
6.2.1   Visit 7 – 
Week 16 
Dispense 1 kits (2 canisters) 
of FMX-101, 4% 
minocycline foam if required 
Dispense 2 kits (4 canisters) 
of FMX-101, 4% 
minocycline foam if required 
Correction 
6.2.2  Visit 9, 
Week 28 
inserted 
• At Visit 9 (Week 28) only 
– Collect blood and urine . 
. . 
Added per FDA request 
7.1.3.1  Part 1 – 
Double-blind 
none 
After shaking the canister 
well . . . 
Added text to include 
instruction to shake 
 . . .supplies will be 
dispensed at Baseline and 
Weeks 3, 6 and 9 . . . 
. . . supplies will be 
dispensed at Baseline and 
Weeks 1, 3, 6 and 9 . . . 
Correction 


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Section 
Revision 
Rationale 
Old Text 
New Text 
 
7.1.5  Labeling of 
Study Drug 
none 
“Shake well before using” 
Added text to label about 
shaking  
7.1.6  Storage of 
Drug 
FMX-101, 4% and vehicle 
canisters must be stored at 
20°C – 25°C  . . . 
FMX-101, 4% and vehicle 
canisters must be stored at 
2°C – 8°C until being 
dispensed to the subjects.  
Subsequently, they must be 
stored at 20°C – 25°C . . . 
Inclusion of instruction that 
site must keep drug 
refrigerated until it is 
dispensed 
7.2   Study Drug 
Accountability 
Inserted 
 
In addition, the weight of 
each canister will be 
determined prior to being 
dispensed to the subjects 
and each canister that has 
been retrieved from the 
subject will be returned to 
the vendor to be weighed 
Added per FDA request 
7.7  Prior and 
Concomitant 
Therapy  
Inserted 
 
If a subject is taking 
anticoagulant therapy, the 
subject should be advised 
that they may require a 
downward adjustment of 
their anticoagulant dosage. 
Tetracyclines may decrease 
plasma prothrombin activity 
7.8  Use of 
Contraception 
• 
Hormonal methods 
o 
Oral contraceptives  
. . . birth control must be 
utilized in subjects using 
topical contraceptives) 
• 
Hormonal methods 
o 
Oral contraceptives  
. . . birth control must be 
utilized in subjects using 
oral contraceptives) 
Correction 
8.1.1  IGA 
Table 3 
See a) below 
See b) below 
Removal of quantitative 
description of non-
inflammatory lesions 


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Section 
Revision 
Rationale 
Old Text 
New Text 
 
8.1.2  Lesion 
counts 
Facial lesion counts . . . 
Inflammatory lesions 
(pustules, papules, and 
nodular lesions) and 
noninflammatory lesions 
(open and closed 
comedones) will be counted 
for each area and recorded 
separately.  The totals of 
inflammatory and non-
inflammatory lesions will 
be calculated from these 
regional lesion counts.   
Lesion counts will be 
repeated at Weeks 3, 6, 9 
and 12. Totals do not need 
to be calculated at these 
visits. 
Facial lesion counts  . . .  
Total inflammatory lesions 
(pustules, papules, and 
nodular lesions) and 
noninflammatory lesions 
(open and closed 
comedones) will be counted 
and recorded separately.   
Lesion counts will be 
repeated at Weeks 3, 6, 9 
and 12.  
Counting method modified 
and addressed in Data 
Management Plan 
9.2  Medication 
History 
A history of medication 
usage . . . medications in the 
last 3 months (6 months for 
acne medications) will be 
recorded. 
A history of medication 
usage . . . medications in the 
last 3 months will be 
recorded. 
Consistency with Section 
6.1.1. 
9.4  Vital Signs 
Heart rate and blood 
pressure will be measured at 
all visits.   
Heart rate and blood 
pressure will be measured at 
all post-Baseline visits.   
Correction 
9.8.1   Method of 
Determining 
Adverse Events 
inserted 
•  Developed unusual 
headaches or changes in 
vision 
Queried at each visit as per 
FDA request 
9.8.3.  Reporting 
Adverse Events 
Any serious AEs . . . must be 
reported to the Sponsor 
within . . . 
Any serious AEs . . . must be 
reported to the Sponsor or 
designee within . . . 
Correction of omission 
10.2  
Determination of 
Sample Size  
None 
See text at c) below  
Modified as per FDA 
suggestion 
10.4.1  Primary 
Efficacy 
Endpoints  
IGA score at Week 12 
(where success is defined as 
at least a 2-grade decrease 
from Baseline). 
Treatment Success 
(dichotomized as Yes/No) 
at Week 12, where success 
is defined as an IGA score 
of 0 or 1, and at least a 2-
grade improvement 
(decrease) from Baseline.   
Modified as per FDA 
suggestion 


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Section 
Revision 
Rationale 
Old Text 
New Text 
 
10.4.2. Secondary 
Efficacy 
Endpoints 
 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 12 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA at the interim visit 
at Week 9 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 9 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA Treatment Success 
at the interim visit at Week 6 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 6 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Week 12 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA Treatment 
Success at the interim visit 
at Week 9 
• 
The absolute change 
from Baseline in the 
inflammatory lesion count 
and IGA Treatment 
Success at the interim visit 
at Week 6 
Modified as per FDA 
suggestion 
10.4.3. Tertiary 
Efficacy 
Endpoints 
 
• 
The percent change from 
Baseline in the inflammatory 
lesion count at Weeks 3, 6, 9 
and 12 
• 
The percent change 
from Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, 9 and 
12 
• 
The absolute change 
from Baseline in the 
inflammatory and 
noninflammatory lesions, 
and the dichotomized IGA 
score, (where success is 
defined as at least a 2-
grade decrease from 
Baseline), at Week 3 
• 
The percent change from 
Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, 9 and 
12 
• 
The percent change from 
Baseline in the inflammatory 
lesion count at Weeks 3, 6, 9 
and 12 
• 
The absolute change 
from Baseline in the 
inflammatory and 
noninflammatory lesions, 
and the IGA Treatment 
Success at Week 3 
• 
The absolute change 
from Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, and 9 
• 
The percent change from 
Baseline in the 
noninflammatory lesion 
count at Weeks 3, 6, 9 and 
12 
Modified as per FDA 
suggestion 


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Section 
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Rationale 
Old Text 
New Text 
 
10.6.3 Efficacy 
Analysis 
The co-primary endpoint of 
at least a 2-grade 
improvement (decrease) 
from Baseline in the IGA 
score at Week 12 will be 
analyzed . . . overall IGA 
response rates are less than 
10% . . . on the difference in 
IGA success rates between 
FMX-101 4% and vehicle. 
The co-primary endpoint of 
IGA Treatment Success 
rate at Week 12 will be 
analyzed . . . overall IGA 
Treatment Success rate is 
less than 10% . . . on the 
difference in IGA 
Treatment Success rates 
between FMX-101 4% and 
vehicle. 
Modified as per FDA 
suggestion 
. . .Testing of secondary 
efficacy endpoints at an 
earlier timepoint for each 
type of lesion and IGA will 
be performed only if 
superiority (one-sided 
p<=0.025) is seen at the later 
timepoint. 
.  Testing of secondary 
efficacy endpoints at an 
earlier timepoint for each 
type of lesion and IGA 
Treatment Success will be 
performed only if superiority 
(one-sided p<=0.025) is seen 
at the later timepoint. 
Modified as per FDA 
suggestion 
11.1  Monitoring 
Monitoring visits will apply 
place . . . 
Monitoring visits will take 
place 
Correction  
 . . . Sponsor . . . 
. . . Sponsor or Sponsor’s 
representative . . . 
Multiple corrections 
 
 
 


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a) Old Table 3 – IGA Scale 
 
Table 3: IGA Scale for Acne Vulgaris 
Score 
Grade 
Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
1 
Almost clear 
Rare noninflammatory lesions present; rare (eg, <5) non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink-
red) 
2 
Mild 
Some noninflammatory lesions are present; few (eg, <10) inflammatory 
lesions (papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Many noninflammatory lesions; multiple (eg, between 25 and 40) 
inflammatory lesions present; many papules/pustules; there may or may not 
be a few nodulocystic lesions 
4 
Severe 
Inflammatory lesions predominate, many papules/pustules (eg, between 40 and 75); 
there may be a few nodulocystic lesions 
5 
Very Severe 
Highly inflammatory lesions predominate, variable number of comedones, many 
papules/pustules and many nodulocystic lesions 
 
b) New Table 3 – IGA Scale 
 
Table 3: IGA Scale for Acne Vulgaris 
Score 
Grade 
  Description 
0 
Clear 
Normal, clear skin with no evidence of acne vulgaris 
 
1 
Almost clear 
Rare noninflammatory lesions may be present, with rare non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink- red) 
2 
Mild 
Some noninflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulocystic lesions) 
3 
Moderate 
Many noninflammatory lesions.  Multiple inflammatory lesions evident with 
several to many papules/pustules, and there may be one small nodulocystic lesion 
4 
Severe 
Inflammatory lesions are more apparent, many comedones and papules/pustules, 
there may be a few nodulocystic lesions 
5 
Very Severe 
Highly inflammatory lesions predominate, variable number of comedones, many 
papules/pustules and many nodulocystic lesions 
 
 
c) 
Inserted in Section 10.2 
Another consideration for the sample size must be given to the secondary endpoint of 
noninflammatory lesions which will be compared to the vehicle for non-inferiority. The margin 
for non-inferiority will be 30% of the change from baseline to week 12. In a phase 2 study, 
change from baseline in noninflammatory lesions at week 9 was 22.8 for the vehicle group with 
a standard deviation of 18. Assuming approximately the same reduction at week 12, a 30% non-
inferiority margin is about 6.8 lesions. The following table provides approximate sample sizes 
for alternate assumptions for 90% power to show non-inferiority. 


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Vehicle mean 
noninflammatory 
lesion reduction 
Minocycline 4% foam 
mean noninflammatory 
lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
 
If Minocycline 4% foam has the same effect on noninflammatory lesions as vehicle, 
 subjects 
on vehicle and 
 on 4% foam will be needed for 90% power to show non-inferiority. If 
Minocycline 4% foam has a slightly less effect on noninflammatory lesions (
 lesion 
reduction versus 
 in vehicle), there will be about 90% power to show non-inferiority. 
16.2.2. 
Amendment 2, effective April 6, 2016 
The following is the summary of the changes that were made to Protocol FX2014-05  Version 2 
issued February 26, 2016. 
 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
5.2 Exclusion Criteria 
2. Dermatological condition 
of the face or facial hair 
(eg, beard, sideburns, 
mustache) that could 
interfere with the clinical 
evaluations 
 2. Acne conglobata, acne 
fulminans, secondary 
acne (chloracne, drug 
induced acne) or any 
dermatological condition.  
Specific exclusions added 
for clarity 
6. Study Procedures 
Table 1: Schedule of 
Procedures 
 
 
 
 
 
 
 
 
Footnote 3 
 
 
Urine pregnancy test 
(females, only) 
Urine pregnancy test 
(females of childbearing 
potential only) 
Clarification  
Inserted 
“X” for pregnancy tests to 
be performed at Week 3, 6 
and 9 
Modified per FDA 
Inserted 
New line and “X” for 
Subject Satisfaction 
Questionnaire for Week 12 
Procedure added 
. . . This visit and the 
procedures required at this 
visit can be combined with 
Screening. . . 
. . . The procedures required 
at these visits can be 
combined . . . 
Clarification  
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Page 62 of 65 
 
 
CONFIDENTIAL 
 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
 
Footnote 6 
Home pregnancy tests will 
be dispensed to all female 
subjects at risk of becoming 
pregnant and will be 
performed whenever there 
is a suspicion of pregnancy 
(e.g., a missed period) 
Perform urine pregnancy 
test at indicated visits.  
Also dispense home urine 
pregnancy test at Week 12 
if subject is continuing 
into open-label treatment 
Modified per FDA 
6.1.2. Baseline Visit, 
Visit 1 
 
. . . This visit and the 
procedures required at this 
visit can be combined with 
Screening. . . 
. . . The procedures required 
at this visit can be 
combined with Screening . . 
. 
Clarification 
Perform urine pregnancy 
test 
Perform urine pregnancy 
test in females of 
childbearing potential 
Clarification 
6.1.4. Visit 3, Week 3; 
6.1.5. Visit 4, Week 6; 
6.1.6. Visit 5, Week 9 
Inserted 
 
Perform urine pregnancy 
test in females of 
childbearing potential 
Modified per FDA 
6.1.7. Visit 6, Week 12 Collect a urine sample from 
female subjects for a urine 
pregnancy test  
Perform urine pregnancy 
test in females of 
childbearing potential 
Clarification 
Inserted 
• 
Administer Subject 
Satisfaction 
Questionnaire 
Procedure added 
• 
If subject is continuing 
. . . dispense 1 kit (2 
canisters) of FMX-101 . . . 
• 
If subject is continuing 
. . . dispense 2 kits (4 
canisters) of FMX-101 . 
Correction 
6.2 Part 2 – Open-label 
Table 4: Schedule of 
Procedures 
 
 
 
 
Footnote 3  
 
 
 
Inserted 
“X” for pregnancy tests to 
be dispensed at Weeks 16, 
22, 28, 34, 40 and 46. 
Modified per FDA 
Inserted 
New line and “X” for 
Subject Satisfaction 
Questionnaire for Week 52 
Procedure added 
Home pregnancy tests will 
be dispensed to all female 
subjects at risk of becoming 
pregnant whenever . . . 
Home pregnancy tests will 
be dispensed at each visit 
to all female subjects of 
childbearing potential and 
will be performed at least 
monthly and whenever . . . 
Perform urine pregnancy 
test at Final Visit. 
Modified per FDA 
 


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CONFIDENTIAL 
 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
6.2.1. Visit 7, Week 16 Inserted 
 
Dispense Home 
pregnancy kit to all 
female subjects of 
childbearing potential 
Modified per FDA 
 
6.2.2. Visits 8 – 12, 
Weeks 22 - 46 
Inserted 
 
Dispense Home 
pregnancy kit to all 
female subjects of 
childbearing potential 
Modified per FDA 
 
6.2.3. Visit 13, Final 
Visit – Week 52 
Collect a urine sample from 
female subjects for a urine 
pregnancy test 
Perform urine pregnancy 
test in females of 
childbearing potential 
Clarification 
Inserted 
• 
Administer Subject 
Satisfaction 
Questionnaire 
Procedure added 
7.1.3.1. Part 1 – 
Double-blind 
 
After shaking . . . , a small 
amount of foam should be 
expressed . . . . additional 
amounts of foam should 
also be applied . . 
.approximately the same 
time each day preferably in 
the evening. 
After shaking . . .a small 
amount of foam (about 1/2 
gram or a cherry-sized 
amount) should be 
expressed . . .  additional 
amounts (up to a total of 
4g) of foam should also be 
applied . . .the same time 
each day preferably in the 
evening at bedtime. 
Clarification of amounts 
and timing 
8.3. Subject 
Satisfaction 
Questionnaire 
 
Inserted 
A satisfaction 
questionnaire will be 
administered at Visit 6, 
Week 12 and Visit 13, 
Week 52 (see Section 16.1, 
Appendix 1). 
Procedure added 
9.6. Clinical 
Laboratory Tests 
Serum chemistry, 
hematology and 
urinalysis will be 
evaluated at Baseline, 
Week 12 and Final Visit. 
Serum chemistry, 
hematology and 
urinalysis will be 
evaluated at Baseline, 
Week 12/ Final Visit of 
the double-blind phase 
of the Study, and at 
Week 28 and Week 
52/Final Visit of the 
open-label phase of the 
Study. 
Modified per FDA 
 


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CONFIDENTIAL 
 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
9.6.1. Urine Pregnancy 
Test 
A urine sample will be 
collected from all female 
subjects for a urine 
pregnancy test at 
Baseline, Week 12 and 
Final Visit or when a 
subject prematurely 
withdraws from the 
study. 
A urine pregnancy test 
will be performed on all 
females of childbearing 
potential at Baseline, 
Week 3, Week 6, Week 
9 and Week 12 of the 
double-blind phase of 
the Study and Final Visit 
or when a subject 
prematurely withdraws 
from the study. 
Home pregnancy kits 
will be provided at each 
visit to all female 
subjects of childbearing 
potential in the open-
label phase of the Study 
and are to be used at 
least monthly and if a 
pregnancy is suspected 
between visits (e.g., if a 
subject misses a 
period). A urine 
pregnancy test will be 
performed at Week 52/ 
Final Visit. 
Modified per FDA 
 
9.7.1. Tolerability 
 . . pigmentation . . . 
. . .hyperpigmentation . . . 
Correction 
9.8.4. Adverse Event 
Follow-up 
Adverse events that are 
ongoing when a subject 
withdraws from or 
completes the study will 
be followed until 
resolution or stabilization 
(in the opinion of the 
Investigator), or for 30 
days, whichever is 
shorter.   
Adverse events, and 
tolerability signs and 
symptoms greater than 
zero (0), that are ongoing 
when a subject 
withdraws from or 
completes the study will 
be followed until 
resolution or stabilization 
(in the opinion of the 
Investigator), or for 30 
days, whichever is 
shorter.   
Modified as per FDA 
suggestion 


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CONFIDENTIAL 
 
Section 
Revision 
Rationale 
Old Text 
New Text 
 
9.8.4.1. Pregnancy 
reporting 
A urine pregnancy test will 
be performed . . . at 
Baseline and 
Week 12/Final Visit of the 
double-blind phase of the 
Study or when a subject 
prematurely withdraws . . . 
A urine pregnancy test will 
be performed . . .at 
Baseline, Week 3, Week 6,  
Week 9 and Week 12/Final 
Visit of the double-blind 
phase of the Study or when 
a subject prematurely 
withdraws . . . 
Modified as per FDA 
suggestion 
Home pregnancy kits will 
be provided to all female 
subjects at risk of becoming 
pregnant and are to be used 
if a pregnancy is suspected 
between visits (e.g., if a 
subject misses a period). 
 
Home pregnancy kits will 
be provided to all female 
subjects of childbearing 
potential in the open-label 
phase of the Study and are 
to be used at least monthly 
and if a pregnancy is 
suspected between visits 
(e.g., if a subject misses a 
period). A urine pregnancy 
test will be performed at 
Final Visit. 
10.3 Analysis 
Populations 
• 
Have not been 
compliant with the dosing 
regimen (ie, subjects 
missed more than 5 
consecutive days of dosing 
and took less than 80% of 
expected doses) 
• 
Have not, in the 
opinion of the 
investigator, been 
compliant with the 
treatment regimen (e.g. 
reported frequent missed 
doses) 
Modify definition of Per 
Protocol Population 
10.6.3  Efficacy 
Analysis 
Non-inferiority margin is 
defined as 40% of the 
noninflammatory lesion 
reduction in the vehicle 
group at Week 12 
Non-inferiority margin is 
defined as 30% of the 
noninflammatory lesion 
reduction in the vehicle 
group at Week 12 
Correction 
16.1.  Appendix 1 – 
Subjects Satisfaction 
Questionnaire 
Inserted 
See Appendix 1 (p.52) 
Procedure added 
 

SAP_001.pdf: 
A Randomized, Double-Blind Study to Compare the Efficacy, 
Safety and Long-Term Safety of Topical Administration of 
FMX-101 for 1 Year in the Treatment of Moderate-to-Severe Acne 
Vulgaris, Study FX2014-05
ClinicalTrials.gov Identifier: NCT02815280 
Date of Statistical Analysis Plan: 03 February 2017 
Statistical Analysis Plan, Open-Label Phase: 19 October 2017 
Statistical Analysis Plan, Open-Label Phase Amendment 1: 07 December 2017 


Privileged and Confidential 
Clinical Study Report FX2014-05 
16.1.9 
Documentation of Statistical Methods 
Statistical Analysis Plan, 03 Feb 2017 
Statistical Analysis Plan, Open-Label Phase, 19 Oct 2017 
Statistical Analysis Plan, Open-Label Phase Amendment 1, 07 Dec 2017 
Note to File, 08 October 2018




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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
Table of Contents 
Table of Contents ...........................................................................................................................2 
List of Abbreviations and Definitions of Terms ..........................................................................4 
1. 
INTRODUCTION ..................................................................................................................5 
2. 
STUDY OBJECTIVES ..........................................................................................................5 
3. 
STUDY DESIGN ....................................................................................................................5 
4. 
HARDWARE AND SOFTWARE ........................................................................................6 
5. 
DATABASE CLOSURE .......................................................................................................6 
6. 
SAMPLE SIZE DETERMINATION ...................................................................................7 
7. 
ANALYSIS POPULATIONS ...............................................................................................8 
8. 
HANDLING OF MISSING DATA ......................................................................................8 
9. 
DATA CONVENTIONS FOR ANALYSIS .......................................................................10 
9.1 General Statistical Principles ..............................................................................................10 
9.2 Study Day ..............................................................................................................................10 
9.3 Baseline and Change from Baseline ...................................................................................10 
9.4 Analysis Visit Window .........................................................................................................10 
10. STATISTICAL EVALUATION .........................................................................................11 
10.1 Interim Analysis .........................................................................................................11 
10.2 Subject Disposition.....................................................................................................11 
10.3 Protocol Deviation ......................................................................................................11 
10.4 Demographic and Baseline Characteristics .............................................................12 
10.5 Study Medication Exposure and Compliance .........................................................12 
10.6 Prior and Concomitant Medications ........................................................................12 
10.7 Medical/Surgical History...........................................................................................12 
10.8 Efficacy Analyses .......................................................................................................13 
10.8.1 Primary Efficacy Endpoints......................................................................................13 
10.8.2 Secondary Efficacy Endpoints ..................................................................................13 
10.8.3 Tertiary Efficacy Endpoints......................................................................................13 
10.9 Efficacy Analyses .......................................................................................................13 
10.9.1 Primary Efficacy Analyses ........................................................................................13 
10.9.2 Secondary Efficacy Analyses ....................................................................................14 
10.9.3 Subject Satisfaction Questionnaire ..........................................................................15 


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10.10 Safety Analysis ...........................................................................................................15 
10.10.1 
Adverse Events ...............................................................................................15 
10.10.2 
Vital Signs .......................................................................................................16 
10.10.3 
Physical Examinations ..................................................................................16 
10.10.4 
Clinical Laboratory Results ..........................................................................16 
10.10.5 
Tolerability .....................................................................................................17 
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES .........................17 
12. HEADINGS ..........................................................................................................................17 
13. ARCHIVING AND RETENTION OF DOCUMENTS ....................................................17 
14. REFERENCES .....................................................................................................................18 
 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
CFR 
Code of Federal Regulations 
eCRF 
Electronic case report form 
EOS 
End of study 
FDA 
Food and Drug Administration 
IGA 
Investigator’s global assessment 
ITT 
Intent-to-treat (population) 
IWRS 
Interactive web-based response (system) 
MedDRA 
Medical Dictionary for Regulatory Activities 
PI 
Principal investigator 
PP  
Per protocol (population) 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
TEAE 
Treatment emergent adverse event 
UPT 
Urine pregnancy test 
US  
United States 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the study Protocol Version 4 dated October 14, 
2016. This document provides additional details concerning the statistical analyses outlined in 
the protocol and reflects any changes to the protocol from any amendments. This plan will not 
repeat all the definitions given in the protocol but will provide further details of the summaries 
and analyses planned therein.   
2. STUDY OBJECTIVES 
The objectives of this study are:  
 To evaluate the efficacy in the treatment of acne compared to vehicle of topical FMX-
101, 4% administered daily for 12 weeks  
 To evaluate the safety compared to vehicle of topical FMX-101, 4% administered daily 
for 12 weeks  
 To evaluate the long-term safety of topical FMX-101, 4% administered daily for up to 40 
additional weeks  
3. STUDY DESIGN 
The one-year study will have 2 parts. The first 12 weeks will be double-blind (DB) treatment 
with FMX-101, 4% or vehicle foam. The remaining 40 weeks will involve open-label (OL) 
treatment with FMX-101, 4% by any subjects who complete the first part of the study. 
Part 1 – Double-blind 
This is a randomized, multicenter, double-blind, vehicle-controlled, 2-arm study to evaluate the 
safety and efficacy over 12 weeks of FMX-101 minocycline foam, 4%, compared to vehicle, in 
the treatment of subjects with moderate to severe facial acne vulgaris.  
Qualified subjects will be randomized to receive 1 of the following 2 treatments:  
 FMX-101, 4% minocycline foam  
 Vehicle foam  
Subjects with qualifying lesion counts and Investigator’s Global Assessments (IGA) of acne 
severity scores and will be assigned to 1 of 2 treatments according to the randomization 
schedule. Subjects will apply the assigned study drug topically once daily for 12 weeks as 
directed. Subjects will be advised to apply the study drug at approximately the same time each 
day, preferably in the evening before bedtime. Both the Investigator and subject will be blinded 
to the study drug identity.  


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
Subjects will return for visits at Weeks 1, 3, 6, 9, and 12. Efficacy evaluations (acne lesion 
counts and IGAs will be performed at Weeks 3, 6, 9, and 12 during the study.  
Part 2 – Open-label 
At the Week 12 Visit, subjects may be invited to continue into the open-label part of this study 
for an additional 9 months of treatment. Subjects will be enrolled in this phase of the study until 
a total of approximately 400 subjects from Studies FX2014-04 and FX2014-05 have elected to 
continue in the open-label portion of their respective study. Subjects who elect to continue into 
the open-label part of this study will receive supplies of active FMX-101, 4% minocycline foam. 
Treatment during this part of the study will be guided by each subject’s clinical response. The 
Investigator may elect to suspend treatment of some or all areas if there is clinical improvement 
or resolution of the acne in those areas. Even if the treatment is partially or completely 
temporarily suspended, the subject will continue in the study and make all scheduled clinic visits. 
If at any time the acne 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. 
4. HARDWARE AND SOFTWARE 
Statistical analysis will be performed following Novella/TKL standard operating procedures and 
on the Novella/TKL computer network. All statistical analysis will be performed using SAS 
Version 9.2 with program code prepared specifically for the project by qualified Novella Clinical 
statisticians and SAS programmers. 
The SAS programs will generate rich-text-formatted (RTF) output with the “RTF” extension 
using the SAS Output Delivery System (ODS). The summary tables and listings will be 
formatted using the Times New Roman 9-point font. The RTF output is included in report 
documents prepared with Microsoft Word and converted to PDF format without typographical 
change. 
Datasets will be created and taken as input to validated SAS programs to generate the report-
ready tables, listings, and figures. Each output display will show the names of the data sets and 
SAS program used to produce it.  
5. DATABASE CLOSURE 
The database closure will occur after the completion of each part of the study. 
After completion of all data review procedures, validation of the project database, and approval 
of the data review document by the study sponsor, the clinical database will be closed. Any 
change to the clinical database after this time will require written authorization, with explanation, 
by the Sponsor and the Biostatistician.    


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
6. SAMPLE SIZE DETERMINATION 
In a phase 2 study, the proportion of subjects with an IGA score of 0 or 1 after 12 weeks of 
treatment was 20% in the minocycline 4% foam group compared to 2% in the vehicle group. The 
following table provides a few alternate assumptions and corresponding sample sizes. Power was 
set to 90% and type-1 error to two-sided 0.05. Sample size was calculated based on Fisher’s 
Exact test.  
Vehicle IGA (0,1) Minocycline 4% foam IGA (0,1) Sample sizes (vehicle, active) 
 
 
 
 
 
 
 
 
 
Assuming 12% dropout rate, 
 subjects on active, and 
 subjects on vehicle will provide at 
least 90% power for a statistically significant difference on IGA 0 or 1. In the same phase 2 
study, the change from baseline in inflammatory lesions was 
 in the minocycline 4% foam 
versus 
 in the vehicle group. The standard deviation in change from baseline was 
approximately 9.2. The following table shows alternate assumptions and corresponding sample 
sizes, for 90% power and a two-sided type 1 error of 0.05. The sample sizes were calculated 
using a t-test.  
 
Vehicle mean 
inflammatory lesion 
reduction 
Minocycline 4% foam mean 
inflammatory lesion reduction 
Sample sizes 
(vehicle, active) 
 
 
 
 
 
 
 
 
 
To summarize, using some conservative estimates of the effect on minocycline 4% foam versus 
the vehicle for both IGA and change in inflammatory lesions at week 12, 
 subjects on active, 
and 
 on vehicle will provide > 90% power for s statistically significant difference.  
Another consideration for the sample size must be given to the secondary endpoint of 
noninflammatory lesions which will be compared to the vehicle for non-inferiority. The margin 
for non-inferiority will be 15% of the percent change from baseline to week 12. The standard 
deviation (SD) of percent change from baseline in noninflammatory lesions is projected to be 
approximately 45%. With a 15% non-inferiority margin, there will be approximately 90% power 
to show non-inferiority with sample sizes of 
 and 150 in the Minocycline 4% foam and 
vehicle groups respectively. The margin of 15% appears to be reasonable given that the non-
inflammatory lesions is a secondary endpoint. Any smaller margin will require a larger sample 
size for the secondary endpoint than for the primary endpoint. 
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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
The assumption for the SD of percentage change from baseline in non-inflammatory lesions was 
confirmed by a blinded review of 
 subjects completing week 12, which reported an SD of 
 
7. ANALYSIS POPULATIONS 
The following populations will be defined for analysis: 
 Intent-To-Treat (ITT) population: all randomized subjects.  
 Per Protocol (PP) population: defined as the subset of the ITT population without any 
protocol deviations that may have an impact on the efficacy assessments. Subjects to be 
included in the PP population will be determined by the Sponsor/CRO prior to the 
unblinding of the study.  
Subjects may be excluded from the PP population if any of the following are met: 
o Failure to meet Inclusion/Exclusion criteria; 
o Have administered any interfering concomitant medications  
o Have not, in the opinion of the investigator, been compliant with the treatment 
regimen (e.g. reported frequent missed doses)  
o Randomization error 
Prior to breaking the blind, additional criteria for exclusion from the PP population 
may be included to accommodate for unforeseen events that occurred during the 
conduct of the study. 
 Safety Population: all randomized subjects who take any study product. Subjects who 
have no post-Baseline assessments will be included in the Safety population unless all 
dispensed study drug is returned unused. 
The ITT population will be the primary population for efficacy analysis. The PP population will 
be secondary for the co-primary endpoints only. The Safety population will be used for the 
analyses of safety endpoints.  
All efficacy analyses will be conducted according to the randomized treatment assignment; all 
safety analyses will be conducted according to the treatment actually received.  
8. HANDLING OF MISSING DATA  
The primary population for all efficacy analyses will be the ITT population. For the analyses of 
the co-primary and secondary efficacy endpoints based on the ITT population, a variety of 
methods will be used to impute missing data, including multiple imputation (MI), last-
observation-carried forward (LOCF), and baseline observation carried forward (BOCF). MI will 
be the primary imputation method. Sensitivity analyses using LOCF and BOCF will be 
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performed to assess the robustness of alternate imputation assumptions. All analyses using the 
PP population will use the Observed-Cases (OC) approach. i.e., there will be no imputation for 
missing data at any time point. No other imputations will be made unless otherwise specified.  
The imputation procedures for post-baseline missing inflammatory lesion counts and missing 
IGA scores are described below. 
 LOCF: The last observed value will be carried forward for any subsequent missing 
values. Baseline values will not be carried forward. 
 BOCF: The baseline value will be used for any missing post-baseline values. 
 MI: Multiple imputations is a simulation based approach where missing values are 
replaced by multiple Bayesian draws from the conditional distribution of missing data 
given the observed data and covariates, creating multiple completed data sets. These 
completed datasets can then be analyzed using standard analysis methods.  
MI procedures for inflammatory lesion counts: 
Intermittent missing values of inflammatory lesion counts will be imputed separately for 
each treatment group using the Markov Chain Monte Carlo (MCMC) method. 500 copies 
of the dataset with monotonic missing pattern will be generated. 
For each of the 500 datasets, missing values at scheduled visits (Weeks 3, 6, 9, and 12) 
will be imputed sequentially using an analysis of covariance (ANCOVA) model 
including treatment, baseline inflammatory lesion count, and inflammatory lesion counts 
at the previous scheduled visits. Specifically, missing values at Week 3 will be imputed 
based on the above mentioned model where the baseline value is included as a covariate. 
Missing values at Week 6 will be imputed where both the baseline value and Week 3 
value, which might be imputed, are included as covariates. Missing values at each 
scheduled visit will be imputed in this manner until values at Week 12 are obtained. SAS 
Proc MI using the monotone regression method will be used. 
MI procedures for IGA Treatment Success: 
The imputation of post-baseline IGA scores will be performed following a similar 
approach as described above for inflammatory lesion counts. Intermittent missing IGA 
scores will be imputed separately for each treatment group where 500 copies of the 
dataset with monotonic missing pattern will be generated. For each of the 500 datasets, 
missing values at scheduled visits (Weeks 3, 6, 9, and 12) will be imputed sequentially 
using an ANCOVA model including treatment, baseline IGA score, and IGA scores at 
the previous scheduled visits. The logistic regression method for monotone data will be 
used for the imputation. IGA Treatment Success status (Yes/No) will then be derived 
based on the imputed dataset.  
A pre-specified seed number of 
 will be used in all imputation procedures as 
described above. 
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9. DATA CONVENTIONS FOR ANALYSIS 
9.1 General Statistical Principles 
All statistical processing will be performed using the SAS system (Version 9.2 or higher).  
All observed and derived variables (e.g., change from baseline, percentage change from baseline, 
Treatment Success) used in the summaries of analyses will be presented in by-subject listings. 
Descriptive statistics will be used to provide an overview of the efficacy and safety results. For 
categorical parameters, the number and percentage of subjects in each category will be 
presented. Missing responses will be enumerated, but the calculation of percentages will exclude 
missing responses. For quantitative variables (e.g., age), descriptive statistics will include 
number of subjects with non-missing data, mean, standard deviation (SD), median, minimum 
value and maximum value. 
All efficacy analyses will be conducted according to the subject’s randomized treatment; all 
safety analyses will be conducted according to the actual treatment received. 
All hypothesis testing will be conducted using two-sided tests with α=0.05 level of significance 
unless otherwise specified. No adjustments for multiple comparisons are planned. 
9.2 Study Day 
Day 1 is defined as the date of first study drug administration. Study day is calculated relative to 
the date of Day 1.   
9.3 Baseline and Change from Baseline 
Baseline value is defined as the last non-missing value prior to the first dose of study drug. 
Changes from Baseline in lesion count will be calculated as the Baseline value minus the post-
Baseline value. Thus, a positive change will reflect a reduction in lesion count. The percent 
change from Baseline lesion count will be calculated as the Baseline value minus the post-
Baseline value divided by the Baseline value, expressed as a percentage. Thus, a positive percent 
change will reflect a reduction in lesion count. 
 
 
9.4 Analysis Visit Window 
Efficacy endpoints will be analyzed according to their windowed visits defined by actual study 
day. If more than one visit occurs within a single visit window, then the analysis will take the 
one closest to the target day. The following analysis visit windows will apply: 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
 
 
Visit 
Week 
Target Day 
Efficacy Assessment Window 
Double-Blind Phase 
2 
1 
7 
Post-dose ─ Day 14 
3 
3 
21 
15 ─ 31 
4 
6 
42 
32 ─ 52 
5 
9 
63 
53 ─ 73 
6 
12 
84 
74 ─ 94 
Open-Label Phase 
7 
16 
112 
95 ─ 133 
8 
22 
154 
134 ─ 175 
9 
28 
196 
176 ─ 217 
10 
34 
238 
218 ─ 259 
11 
40 
280 
260 ─ 301 
12 
46 
322 
302 ─ 343 
13 
52 
364 
344 ─ 384 
10. STATISTICAL EVALUATION  
10.1 
Interim Analysis 
No interim analysis is planned. 
10.2 
Subject Disposition 
The number and percentage of subjects who are screened, randomized, included in each analysis 
population, who complete the study, withdraw from the study (overall and by reason for 
withdrawal), and who are excluded from the PP population (overall and by reason for exclusion) 
will be summarized, overall, by treatment group and by sites.  
A by-subject enrollment and disposition listing will be presented for all randomized subjects. 
Subjects who are screen failures and subjects who are not randomized will also be presented in a 
separate listing. 
10.3 
Protocol Deviation 
Protocol deviations will be presented in a by-subject listing.  


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
10.4 
Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarized overall and by treatment for the 
ITT, PP and Safety populations. The following demographic and baseline variables will be 
included: 
 Age (years) 
 Age group (9-<13 years , ≥13-<18 years, ≥18 years) 
 Sex 
 Race  
 Ethnicity  
 Baseline lesion count (inflammatory, noninflammatory, total) 
 Baseline IGA score (moderate=3, severe=4) 
10.5 
Study Medication Exposure and Compliance 
The following parameters of study medication exposure will be summarized by treatment group 
and study period for the ITT and PP populations: 
 Total number of days of exposure to study drug, defined as the date of last dose of study 
drug minus date of first dose of study drug plus 1; 
 Amount of drug dispensed 
 Amount of drug used 
 Amount of drug per day 
 
Amount of drug used is defined as the difference in weight between the returned and dispensed 
canisters, where weight of dispensed canisters will be calculated as the product of total number 
of dispense canister and the unit weight per canister. 
Investigator’s assessment of subject’s compliance (Yes, No) with the treatment regimen at each 
visit will be summarized by treatment using frequency counts and percentages.  
10.6 
Prior and Concomitant Medications 
Prior (with stop dates prior to Day 1) and concomitant medications (ongoing or with stop dates 
on or after Day 1) for all randomized subjects will be provided in a by-subject listing.  
10.7 
Medical/Surgical History 
Past and current medical conditions for all randomized subjects will be provided in a by-subject 
listing. Surgical history will also be provided in a by-subject listing. 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
10.8 
Efficacy Analyses 
10.8.1 Primary Efficacy Endpoints 
The co-primary efficacy endpoints are:  
 The absolute change from Baseline in the inflammatory lesion count at Week 12  
 Treatment Success (dichotomized as Yes/No) at Week 12, where success is defined as an 
IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from Baseline  
10.8.2 Secondary Efficacy Endpoints 
The secondary efficacy endpoints will include the following: 
 The percent change from Baseline in the noninflammatory lesion count at Week 12 
 The absolute change from Baseline in the inflammatory lesion count and IGA Treatment 
Success at the interim visit at Week 9 
 The absolute change from Baseline in the inflammatory lesion count and IGA Treatment 
Success at the interim visit at Week 6 
10.8.3 Tertiary Efficacy Endpoints 
The tertiary efficacy endpoints will include the following: 
 The percent change from Baseline in the inflammatory lesion count at Weeks 3, 6, 9 and 
12 
 The absolute change from Baseline in the inflammatory and noninflammatory lesions, 
and the IGA Treatment Success at Week 3 
 The absolute change from Baseline in the noninflammatory lesion count at Weeks 3, 6, 9 
and 12 
 The percent change from Baseline in the noninflammatory lesion count at Weeks 3, 6, 9 
and 12 
10.9 
Efficacy Analyses 
10.9.1 Primary Efficacy Analyses 
In order to attain the primary efficacy goal of FMX-101 4% to be considered superior to vehicle, 
both co-primary efficacy endpoints must be significant (i.e., attaining significance at the two-
sided 0.05 level without adjustment for multiplicity). The null hypotheses of the equality of 
FMX-101 4% and vehicle are: 
 H01: the absolute changes from Baseline in inflammatory lesion count at Week 12  in the 
two treatment groups are equal 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
 H02: the IGA success rates at Week 12 in the two treatment groups are equal 
The primary efficacy analyses will be based on the ITT population using MI and are as follows: 
 Absolute change from baseline in inflammatory lesion count: 
For each of the multiple imputed datasets, change from baseline in inflammatory lesion 
count will be analyzed using an ANCOVA model, with treatment as a main effect, 
baseline inflammatory lesion count as a covariate, and investigational site a blocking 
factor. The difference in the mean change from baseline between FMX-101 4% and 
vehicle, along with its estimated standard error (SE) will be reported. These results will 
be combined in Proc MIANALYZE using Rubin’s formula and the resulting p-value will 
be used for inference at the 0.05 level of significance. The combined estimated mean 
difference in change from baseline (FMX-101 4% minus vehicle) and the associated 95% 
confidence interval (CI) will be reported. 
 Dichotomized IGA Success Rate: 
For each of the multiple imputed datasets, the dichotomized IGA (Yes/No) will be 
analyzed using a Cochran-Mantel-Haenszel (CMH) test, stratified by investigational site. 
The Mantel-Haenszel risk ratio, along with its estimated SE, 95% CI and the associated 
p-value will be reported.  
These results will be combined in Proc MIANALYZE and the resulting p value will be 
used for inference at the 0.05 level. The combined estimated log of the risk ratio (FMX-
101 4% / vehicle) and associated 95% confidence limits will be back-transformed.  
If the overall IGA Treatment Success rate is less than 10%, the simple proportion of 
responders in each treatment group, the proportion difference, along with the estimated 
SE will be reported and combined in Proc MIANALYZE. The resulting p-value, 
proportions, proportion difference and their 95% CIs will be presented. 
 
Sensitivity analyses of the co-primary efficacy endpoints will be performed using the same 
method as described above for each MI dataset. Sensitivity analyses will include: 
 ITT population (OC, LOCF, and BOCF)  
 PP population (OC) 
Homogeneity among investigational sites will be assessed by including an investigational site by 
treatment interaction in the ANCOVA model of the ITT OC analysis of the absolute change from 
baseline in inflammatory lesion counts. Investigational site by treatment interaction will be tested 
at 0.1 level, and if significant, it will further be explored.  
10.9.2 Secondary Efficacy Analyses 
Secondary efficacy endpoints will be analyzed similar to the appropriate co-primary efficacy 
parameter.  
Secondary efficacy endpoints will be tested sequentially at 0.05 level of significance, only if both 
co-primary efficacy endpoints are significant in the primary analyses. 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
The first secondary endpoint of noninflammatory lesions at Week 12 will be tested initially as a 
non-inferiority comparison of FMX-101, 4% to vehicle. The non-inferiority margin is defined as 
15% of the noninflammatory lesion percent reduction in the vehicle group at Week 12. A lower 
97.5% confidence limit will be calculated for μa-0..85×μv, where μa and μv are the mean percent 
reduction of noninflammatory lesions of FMX-101, 4% and vehicle respectively. If the 
confidence limit is above 0, non-inferiority will be concluded. If non-inferiority is concluded, the 
superiority of FMX-101, 4% to vehicle for noninflammatory lesions at Week 12 will be tested.  
The sequential testing will proceed according to the order in Section 10.8.2. Testing of secondary 
efficacy endpoints at an earlier timepoint for each type of lesion and IGA Treatment Success will 
be performed only if superiority (one-sided p<=0.025) is seen at the later timepoint. 
Absolute change from baseline in inflammatory lesion count and noninflammatory lesion count, 
and the IGA assessments will be summarized for each study period. No statistical testing will be 
performed for the open label efficacy data. 
10.9.3 Subject Satisfaction Questionnaire 
Answers to subject satisfaction questionnaire (Q1-Q8) will be summarized using frequency 
counts and percentages at Visit 6, Week 12 and Visit 13, Week 52. 
10.10 Safety Analysis 
All safety analyses will be based on the Safety Population according to the treatment received. 
No statistical tests will be performed for any of the safety assessments. 
10.10.1 Adverse Events 
AE terms will be coded using MedDRA dictionary. AEs that occur after informed consent but 
before administration of the study product will be recorded as medical history. A treatment-
emergent AE (TEAE) is defined as an AE that merges during treatment having been absent pre-
treatment, or worsen relative to the pre-treatment state. In particular, for subjects entering the OL 
phase, all AEs starting on or after the date of the first application of study medication of the DB 
phase, but before the date of the first application of the OL phase will be considered as TEAEs of 
the DB phase. All AEs starting on or after the first application of the OL phase will be 
considered as TEAEs of the OL phase. If relationship to treatment is missing, the event will be 
conservatively summarized as being related to study drug. If severity is missing, a separate 
category of missing severity will be included in the summary table, and no imputation of severity 
will be performed. Through the data cleaning process, all attempts will be made to avoid missing 
values for relationship and severity. 
All AEs will be presented in a by-treatment and by-subject listing, detailing the verbatim term 
given by the investigator, the preferred term (PT), system organ class (SOC), onset date and 
time, end date and time, severity, outcome, relationship to study drug, action taken with study 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
drug, other action taken, seriousness and criteria for seriousness. Serious AEs (SAEs) and 
TEAEs leading to study discontinuation will also be presented in a separate listing.  
An overall summary of AEs will be presented by treatment and overall for each Study Period. 
The summary will include the total number of events, frequency counts and percentages with: 
 Any AE 
 Any TEAE 
 Any serious TEAE 
 Any treatment-related TEAE  
 Any TEAE leading to study discontinuation 
For each Study Period, summaries of the incidence of TEAEs, SAEs, and TEAEs leading to 
study discontinuation will be displayed by treatment according to the following: 
 All TEAEs by PT in descending order of frequency (the combined frequency of both 
treatments) 
 All TEAEs by SOC, PT, and maximum severity (mild, moderate, or severe) 
 All TEAEs by SOC, PT, and maximum causality (not related, related) to the study 
drug 
At each level of summarization, a subject will be counted once if he/she reported one or more 
events. The severity of TEAEs and relationship to study drug will be summarized in a similar 
manner. For summaries of relationship to study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE severity, a subject will be classified according to 
the highest severity.  
10.10.2 Vital Signs 
Vital sign parameters will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point. Changes from Baseline will also be summarized.  
10.10.3 Physical Examinations 
Physical examinations will be summarized using descriptive statistics at Baseline and at each 
post-baseline time point. Shifts from Baseline will also be summarized. Abnormal physical 
examination findings will be displayed in a by-subject listing. 
10.10.4 Clinical Laboratory Results 
Absolute values and changes from baseline will be summarized for clinical laboratory 
(chemistry, hematology) results using descriptive statistics. 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 


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Protocol No. FX2014-05 
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Novella Clinical No. CT991715 
laboratory range (high) at baseline with the number of subjects with low, normal or high values 
at each post-baseline time point. 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. 
A listing of subjects with pre-treatment and treatment-emergent clinically significant abnormal 
laboratory values will be presented for each treatment group. Clinical significance is based on 
the Investigator’s judgment. 
Urine pregnancy test will be presented in a by-subject listing.     
10.10.5 Tolerability  
Erythema, dryness, hyperpigmentation and skin peeling at the sites of study drug application will 
be assessed at each study visit on a scale of 0 to 3 (0=none; 1=mild; 2=moderate; 3=severe). 
Itching will be assessed using the same scale based on the subjects’ subjective assessment. The 
intensity and location of each finding will be recorded. 
Erythema, dryness, hyperpigmentation, skin peeling, and itching will be summarized using 
frequency counts and percentages by location (facial, non-facial) at each visit. 
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES 
Not applicable. 
12. HEADINGS 
Each page of the analysis will show the sponsor’s name, the investigational product, and the 
protocol number. Report tables will be embedded in the MS Word report document from SAS 
program output without change. The footer of each table will show the name of the SAS program 
module which generated it, the names of all data sets providing input data in the program and the 
date and time the table was generated. 
13. ARCHIVING AND RETENTION OF DOCUMENTS 
After finalization of the analysis, the following will be archived at Novella Clincial and/or with 
the study sponsor: 
 SAP and any amendments 
 All SAS code used in the project for statistical analysis, report tables generation, and 
analysis data set creation 
 Tables, listings and figures as included in the clinical study report 
 SAS study data tabulation model (SDTM) and analysis dataset model (ADaM) datasets 


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14. REFERENCES 
Rubin, D.B. (1987). Multiple Imputation for Nonresponse in Surveys. New York: Wiley. 




Foamix Pharamaceuticals, Inc.   
                             
Protocol No. FX2014-05  
 
                                   October 19, 2017 
Novella Clinical No. CT991715 
 
 
Tables – Open-Label Phase 
14.1 
Summary of Disposition, Demographic, and Baseline Data Summary Tables  
14.1.1.1.1 
Summary of Subject Enrollment and Disposition, All Subjects Entering Open-Label Phase 
14.1.2.1.1 
Summary of Subject Demographics and Baseline Characteristics, Safety Population Entering Open-Label Phase 
14.1.3.1.1 
Summary of Concomitant Medications by Anatomical Therapeutic Chemical Class (ATC) and Preferred Term, Safety Population Entering Open-Label Phase 
14.2 
Summary of Efficacy Endpoints 
14.2.4.1.1 
Summary of Inflammatory Lesion Counts, Safety Population Entering Open-Label Phase 
14.2.5.1.1 
Summary of Non-Inflammatory Lesion Count, Safety Population Entering Open-Label Phase 
14.2.6.1.1 
Summary of Investigator’s Global Assessment (IGA),Frequency Counts by Study Visit, Safety Population Entering Open-Label Phase 
14.2.7.1 
Summary of Subject Satisfaction Questionnaire at Week 52, Safety Population Entering Open-Label Phase 
14.3 
Summary of Safety Tables 
14.3.1.1.1 
Overall Summary of Adverse Events, Safety Population Entering Open-Label Phase, All AEs Starting in Open-Label Phase 
14.3.1.2.1.1 
Summary of Treatment-Emergent Adverse Events,by System Organ Class and Preferred Term in Descending Frequency, Safety Population Entering Open-Label 
Phase 
14.3.1.2.2.1 
Summary of Treatment-Emergent Adverse Events,by Preferred Term in Descending Frequency, Safety Population Entering Open-Label Phase 
14.3.1.2.3.1 
Summary of Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity, Safety Population Entering Open-Label Phase 
14.3.1.2.4.1 
Summary of Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Causality,Safety Population Entering Open-Label 
Phase,All SAEs Starting in Open-Label Phase 
14.3.1.3.1.1 
Summary of Serious Adverse Events by System Organ Class and Preferred Term in Descending Frequency, Safety Population Entering Open-Label Phase,All 
SAEs Starting in Open-Label Phase 
14.3.1.3.2.1 
Summary of Serious Adverse Events by System Organ Class, Preferred Term, and Maximum Severity, Safety Population Entering Open-Label Phase, All SAEs 
Starting in Open-Label Phase 
14.3.1.3.3.1 
Summary of Serious Adverse Events by System Organ Class, Preferred Term, and Maximum Causality,Safety Population Entering Open –Label Phase,All SAEs 
Starting in Open-Label Phase 
14.3.1.4.1.1 
Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term in Descending Frequency, Safety 
Population Entering Open-Label Phase  
14.3.1.4.2.1 
Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation by System Organ Class, Preferred Term and Maximum Severity, Safety 
Population Entering Open-Label Phase  
14.3.1.4.3.1 
Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation by System Organ Class ,Preferred Term and Maximum Causality, Safety 
Population Entering Open-Label Phase  
14.3.2.1.1.1 
Summary of Clinical Laboratory Results by Visit, Hematology , Safety Population Entering Open-Label Phase  
14.3.2.2.1.1 
Summary of Clinical Laboratory Results by Visit, Chemistry , Safety Population Entering Open-Label Phase  
14.3.3.1.1 
Summary of Vital Signs by Visit, Safety Population Entering Open-Label Phase  
14.3.3.2.1.1 
Summary of Physical  Exam by Study Visit, Safety Population Entering Open-Label Phase  with Abnormal findings 
14.3.3.2.2.1 
Shifts in Physical  Exam Result from Baseline to Week 52 , Safety Population Entering Open-Label Phase  
14.3.4.1 
Summary of Tolerability Assessment, Safety Population Entering Open-Label Phase  


Foamix Pharamaceuticals, Inc.   
                             
Protocol No. FX2014-05  
 
                                   October 19, 2017 
Novella Clinical No. CT991715 
 
 
Listings – Open-Label Phase 
16.1.1 
All Ongoing Concomitant Medications at the End of Double-Blind Phase, All Subjects 
16.1.2 
All Adverse Events Ongoing at the End of Double-Blind Phase, All Subjects 
16.2.1.2.1 
Subject Disposition, Safety Population Entering Open-Label Phase 
16.2.2.1 
Protocol Deviations, Safety Population Entering Open-Label Phase 
16.2.4.4.1 
Concomitant Medications Started in Open-Label Phase, All Subjects Entering Open-Label Phase 
16.2.5.1.1 
Study Medication Exposure and Compliance, All Subjects Entering Open-Label Phase 
16.2.5.2.1 
Study Medication Accountability, All Subjects Entering Open-Label Phase 
16.2.6.1.1.1 
Lesion Counts, All Subjects Entering Open-Label Phase 
16.2.6.1.2.1 
Total Inflammatory/Noninflammatory Lesion Counts, All Subjects Entering Open-Label Phase 
16.2.6.2.1 
Investigator’s Global Assessment and Treatment Success, All Subjects Entering Open-Label Phase 
16.2.6.3.1 
Subject Satisfaction Questionnaire at Week 12 and Week 52, All Subjects Entering Open-Label Phase 
16.2.7.1.1 
Adverse Events Started in Open-Label Phase, All Subjects Entering Open-Label Phase 
16.2.7.2.1 
Serious Adverse Events Leading to Study Discontinuation, All Subjects Entering Open-Label Phase 
16.2.7.3.1 
Treatment-Emergent Adverse Events Leading to Study Discontinuation, All Subjects Entering Open-Label Phase 
16.2.8.1.1 
Urine Pregnancy Test, All Subjects Entering Open-Label Phase 
16.2.8.1.2 
Home Pregnancy Test, All Subjects Entering Open-Label Phase 
16.2.8.2.1.1.1 
Clinical Laboratory Tests, Hematology, All Subjects Entering Open-Label Phase 
16.2.8.2.1.2.1 
Clinical Laboratory Tests , Chemistry, All Subjects Entering Open-Label Phase 
16.2.8.2.1.3.1 
Clinical Laboratory Tests , Urinalysis, All Subjects Entering Open-Label Phase 
16.2.8.2.2.1 
Clinically Significant Clinical Laboratory Tests for  Hematology, Chemistry and Urinalysis, All Subjects Entering Open-Label Phase 
16.2.8.2.3.1 
Out-of-Range (Abnormal) Clinical Laboratory Test Results for  Hematology, Chemistry and Urinalysis, All Subjects Entering Open-Label Phase 
16.2.8.3.1 
Vital Signs, All Subjects Entering Open-Label Phase 
16.2.8.4.1 
Physical  Exam, All Subjects Entering Open-Label Phase 
16.2.8.5.1 
Tolerability Assessment for Face, All Subjects Entering Open-Label Phase 
16.2.8.5.2 
Tolerability Assessment for Non-facial Areas, All Subjects Entering Open-Label Phase 
  
 


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Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                            Page X of Y 
Protocol No. FX2014-05,  Open-Label Phase 
 
Table 14.1.1.1.1: Summary of Subject Enrollment and Disposition 
All Subjects Entering Open-Label Phase 
 
  
  
DB-FMX-101, 4%  
DB-Vechicle Foam 
Overall 
 
 
 
Number of Subjects Entering Open-Label 
XXX 
XXX 
XXX 
         Number of Subjects in Safety Population, n (%) 
XXX (100) 
XXX (100) 
XXX (100) 
 
 
 
 
Number of Subjects Completing the Open-Label Phase, n (%)[1] 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Number of Subjects Discontinued from the Open-Label Phase, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Reason for Discontinuation, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          Adverse Event (including a clinically significant abnormal lab 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) 
          Poor Protocol Adherence 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Administrative, Other 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Other 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
 
 
Note: DB=Double-Blind phase. 
[1] Subject are identified as completing the open-label phase if they rolled into the open-label phase and did not discontinue. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


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Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals Inc.                                                                                                                                                                                                              Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.1.2.1.1: Summary of Subject Demographics and Baseline Characteristics  
Safety Population Entering Open-Label Phase 
 
 
DB-FMX-101, 4%  
(N=XXX) 
DB-Vechicle Foam  
(N=XXX) 
Overall 
(N=XXX) 
Age (years) 
 
 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Age Group, n (%) 
 
9─ < 13 years 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
≥13-<18 years 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
≥ 18 years 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
Sex, n (%) 
 
  Female 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Male 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
Race, n (%) 
 
  White 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Black or African American 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Asian 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  American Indian or Alaska Native 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Native Hawaiian or Other Pacific Islander 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Multiple Races Reported 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
Ethnicity, n (%) 
 
  Hispanic or Latino 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Not Hispanic or Latino 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
DB=Double-Blind Phase; IGA=Investigator’s Global Assessment; SD=Standard deviation. 
Note:  Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase. 
 
Generated on XX/XX/XX:XXXX  by XXXXXX / Uses: XXXX / Reference: Data Listings XXXX


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Foamix Pharmaceuticals Inc.                                                                                                                                                                                                              Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.1.2.1.1: Summary of Subject Demographics and Baseline Characteristics (Continued)  
 Safety Population Entering Open-Label Phase 
 
 
DB-FMX-101, 4%  
(N=XXX) 
DB-Vechicle Foam  
(N=XXX) 
Overall 
(N=XXX) 
Baseline Inflammatory Lesion Counts 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Baseline Noninflammatory Lesion Counts 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Baseline Total Lesion Counts 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Baseline IGA Score, n (%) 
 
  2 – Moderate 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  3 – Severe 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
DB=Double-Blind Phase; IGA=Investigator’s Global Assessment; SD=Standard deviation.  
Note: Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase. 
 
Generated on XX/XX/XX:XXXX  by XXXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


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Foamix Pharamaceuticals                                                                                                                                              
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
Table 14.1.3.1.1: Summary of Concomitant Medications 
by Anatomical Therapeutic Chemical Class (ATC) and Preferred Term 
Safety Population Entering Open-Label Phase 
  
 
  
Anatomical Therapeutic Chemical Class 
DB-FMX-101, 4%  
DB-Vechicle Foam  
Overall 
          Preferred Term 
(N=XXX) 
(N=XXX) 
(N=XXX) 
 
  
  
  
Subjects with any Concomitant Medication, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
<< Anatomical Therapeutic Chemical Class >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
<< Anatomical Therapeutic Chemical Class >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
  
  
  
DB=Double-Blind 
 
 
 
Concomitant = ongoing or with stop dates on or after first day in the Open-Label phase. Counts reflect number of subjects in each treatment group reporting one or more 
concomitant medication that map to the WHO Drug anatomical therapeutic chemical or preferred term. A subject may be counted once only in each row of the table. 
 
Generated on  XX/XX/XX:XXXX  by XXXXXX  / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 8 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
14.2.4.1.1: Summary of Inflammatory Lesion Counts 
Safety Population Entering Open-Label Phase (Observed-Cases) 
 
  
  
DB-FMX-101, 4% (N=XXX) 
  
DB-Vehicle Foam (N=XXX)  
Analysis Visit 
  
N 
Mean (SD) 
Median 
Min, Max 
N 
Mean (SD) 
Median 
Min, Max 
  
 
 
 
 
 
 
 
 
 
Baseline/Visit  
 
 
 
 
 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
 
 
 
 
 
Visit 3/Week 3 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 4/Week 6 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 5/Week 9 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
  
 <<<< Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
DB=Double-Blind phase; SD=Standard deviation. 
 
 
 
 
 
 
Note: Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value. Percent change from baseline is calculated as the baseline value minus the post-baseline 
value divided by the baseline value, expressed as a percentage 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 9 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
14.2.5.1.1: Summary of Non-Inflammatory Lesion Count  
Safety Population Entering Open-Label Phase (Observed-Cases) 
  
  
  
DB-FMX-101, 4% (N=XXX) 
  
DB-Vehicle Foam (N=XXX)  
Visit 
  
N 
Mean (SD) 
Median 
Min, Max 
N 
Mean (SD) 
Median 
Min, Max 
  
 
 
 
 
 
 
 
 
 
Baseline/Visit 1 
 
 
 
 
 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
 
 
 
 
 
Visit 3/Week 3 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 4/Week 6 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 5/Week 9 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
  
  
<<<< Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>>  
  
 
DB=Double-Blind phase; SD=Standard deviation. 
Note: Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value. Percent change from baseline is calculated as the baseline value minus the post-baseline 
value divided by the baseline value, expressed as a percentage 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 10 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc. 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
14.2.6.1.1: Summary of Investigator’s Global Assessment (IGA) 
Safety Population Entering Open-Label Phase (Observed-Cases) 
 
 
 
  
DB-FMX-101, 4% 
(N=XXX) 
DB-Vehicle Foam 
(N=XXX) 
 
 
 
Baseline/Visit 1, n (%)  
 
 
N  
XXX 
XXX 
3-Moderate 
XXX (XX.X) 
XXX (XX.X) 
4-Severe 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
Visit 3/Week 3, n (%) 
 
N  
XXX 
XXX 
0-Clear 
XXX (XX.X) 
XXX (XX.X) 
1-Almost Clear 
XXX (XX.X) 
XXX (XX.X) 
2-Mild 
XXX (XX.X) 
XXX (XX.X) 
3-Moderate 
XXX (XX.X) 
XXX (XX.X) 
4-Severe 
XXX (XX.X) 
XXX (XX.X) 
5-Very Severe 
XXX (XX.X) 
XXX (XX.X) 
IGA Treatment Success 
XXX (XX.X) 
XXX (XX.X) 
<Continue for Visit 4/Week 6,  Visit 5/Week 9, Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22,  Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 
46 and Visit 13/Week 52> 
  
DB=Double-Blind phase. 
Note: IGA treatment success is a score of ‘clear’ (0) or “almost clear” (1) at least 2 grade decrease from Baseline.  
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 11 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc. 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
14.2.7.1: Summary of Subject Satisfaction Questionnaire at Week 52 
Safety Population Entering Open-Label Phase  
 
 
 
  
 
Overall  
(N=XXX) 
 
 
 
Q1: How satisfied are you with this product in treating your acne? 
N  
 
XXX 
1-Very Satisfied 
 
XXX (XX.X) 
2- Satisfied 
 
XXX (XX.X) 
3-Somewhat Satisfied 
 
XXX (XX.X) 
4-Dissatisfied 
 
XXX (XX.X) 
5-Very Dissatisfied 
 
XXX (XX.X) 
 
 
<Continue for :> 
 
Q2: How satisfied are you with how easy this product is to use? 
Q3: How satisfied are you with this product compared to other products you have previously used for acne, such as gels and creams? 
Q4: How satisfied are you with how this product feels on your skin after treatment? 
Q5: How satisfied are you with the odor of this product after treatment? 
Q6: How satisfied are you with the color of this product after treatment? 
Q7: Overall, how satisfied are you with this product? 
 
Q8: Overall, how likely are you to recommend this product to a friend? 
N  
 
XXX 
1-Very Likely 
 
XXX (XX.X) 
2- Likely 
 
XXX (XX.X) 
3-Somewha Likely 
 
XXX (XX.X) 
4-Unliklely 
 
XXX (XX.X) 
5-Very Unlikely 
 
XXX (XX.X) 
 
 
 
 
 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 12 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.                                                                                                
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.1.1: Overall Summary of Adverse Events  
Safety Population who entered Open-Label Phase 
All AEs Starting in Open-Label Phase 
  
  
  
  
  
 
Overall 
 
 
(N =XXX) 
 
 
 
 
 
Subjects with any treatment-emergent AE (TEAE), n (%) [1] 
 
XX (XX.X) 
 
          Number of treatment-emergent AEs 
 
XXX 
 
 
 
 
 
Subjects with any serious TEAE (SAE), n (%) 
 
XXX (XX.X) 
 
          Number of serious TEAEs (SAE) 
 
XXX 
 
 
 
 
 
Subjects with any treatment-related TEAE, n (%) 
 
XXX (XX.X) 
 
          Number of treatment-related TEAEs 
 
XXX 
 
 
 
 
 
Subjects with any TEAE leading to study discontinuation, n (%) 
 
XXX (XX.X) 
 
          Number of TEAEs leading to study discontinuation 
 
XXX 
 
  
 
  
 
  
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. A subject may be counted once only in each row of the table. 
[1] All AEs staring on or after the first application of the Open-Label phase will be considered as TEAEs of the Open-Label phase.  
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 13 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.2.1.1: Summary of Treatment-Emergent Adverse Events  
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population Entering Open-Label Phase 
  
System Organ Class 
  
 
  
Overall 
 
          Preferred Term 
 
(N=XXXX) 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
  
  
  
  
  
  
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only 
in each row of the table. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase.  
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 14 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.2.2.1: Summary of Treatment-Emergent Adverse Events  
by Preferred Term in Descending Frequency 
Safety Population Entering Open-label Phase 
  
System Organ Class 
  
 
  
Overall 
 
          Preferred Term 
 
(N=XXX) 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
  
  
  
  
  
  
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA preferred term. A subject may be counted once only in each row of the 
table. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase.  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 15 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                                                            Page X of Y 
Protocol No. FX2014-05, Open-Label Phase  
Table 14.3.1.2.3.1: Summary of Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population Entering Open-Label Phase 
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Mild  
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest severity. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 16 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharamaceuticals, Inc                                                                                                                                                                                                                         Page X of Y 
Protocol No. FX2014-05, Open-Label Phase  
Table 14.3.1.2.4.1: Summary of Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population Entering Open-Label Phase  
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest causality. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 17 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.3.1.1: Summary of Serious Adverse Events  
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population who entered Open-Label Phase 
All SAEs Starting in Open-Label Phase 
  
System Organ Class 
 
Overall 
 
          Preferred Term 
 
(N=XXX) 
 
 
 
 
 
Subjects with any SAE, n (%) 
 
XXX (XX.X) 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
 
 
 
 
  
  
  
  
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only in 
each row of the table. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 18 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.                                               
 
 
 
 
  Page X of Y 
Protocol No. FX2014-05, Open-Label Phase  
 
 
 
 
 
 
Table 14.3.1.3.2.1: Summary of Serious Adverse Events  
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population  Entering Open –Label Phase 
All SAEs Starting in Open-Label Phase 
  
System Organ Class 
Severity 
  
 
Overall  
 
          Preferred Term 
 
(N = XXX) 
 
 
 
 
 
 
 
Subjects with any SAE, n (%) [1] 
Total 
 
 
XXX (XX.X) 
 
 
Mild  
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
  
  
  
  
  
  
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at 
the highest severity. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 19 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharamaceuticals, Inc                                                                                                                                                                                                                        Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.3.3.1: Summary of Serious Adverse Events 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population Entering Open –Label Phase 
All SAEs Starting in Open-Label Phase 
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any SAE, n (%) 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest causality. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 20 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.4.1.1: Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation  
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population Entering Open-Label Phase  
 
  
System Organ Class 
  
 
Overall 
 
          Preferred Term 
 
(N=XXX) 
 
 
 
 
  
 
Subjects with any TEAE, n (%)  
 
 
XXX (XX.X) 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
 
 
  
  
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only in 
each row of the table. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 21 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                                                           Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.4.2.1: Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation 
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population Entering Open-Label Phase  
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Mild  
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest severity. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 22 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharamaceuticals, Inc                                                                                                                                                                                                                        Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.4.3.1: Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population Entering Open-Label Phase  
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall  
 (N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest causality. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 23 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
Table 14.3.2.1..X.1: Summary of Clinical Laboratory Results by Visit 
[Hematology] [Chemistry] 
Safety Population Entering Open-Label Phase  
 
  
 
DB-FMX-101, 4% (N=XXX) 
DB-Vehicle Foam (N=XXX) 
 
Observed Values 
Change from  
Observed Values 
Change from  
Baseline  
Baseline  
Parameter 1 (units) 
 
 
 
 
Baseline/Visit 1  
 
 
 
 
N 
XXX 
-- 
XXX 
-- 
Mean (SD) 
XX.X (XX.X) 
-- 
XX.X (XX.X) 
-- 
Median 
XX.X 
-- 
XX.X 
-- 
Min, Max 
XX.X, XX.X 
-- 
XX.X, XX.X 
-- 
 
 
 
 
 
 
 
 
 
 
Visit 3/Week3 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
Visit 6/Week12 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
<Continue for Visit 9/Week 28, Visit 13/Week 52 and for Parameter 2, 3, ….> 
 
 
 
 
 
 
 
 
  
Note: DB=Double-Blind phase. Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value. 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 24 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
Table 14.3.3.1.1: Summary of Vital Signs by Visit  
Safety Population Entering Open-Label Phase  
 
  
 
DB-FMX-101, 4% (N=XXX) 
DB-Vehicle Foam (N=XXX) 
 
Observed Values 
Change from  
Observed Values 
Change from  
Baseline  
Baseline  
 
 
 
 
 
Weight (kg) 
 
 
 
 
Baseline/Visit 1  
 
 
 
 
N 
XXX 
- 
XXX 
- 
Mean (SD) 
XX.X (XX.X) 
- 
XX.X (XX.X) 
- 
Median 
XX.X 
- 
XX.X 
- 
Min, Max 
XX.X, XX.X 
- 
XX.X, XX.X 
- 
 
 
 
 
 
Visit 6/Week 12 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
Visit 13/Week 52 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
  
Note: DB=Double Blind phase. Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
[Programming note: add page break between Weight and Blood pressure] 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 25 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.  
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
Table 14.3.3.1.1: Summary of Vital Signs by Visit (Continued) 
 
Safety Population Entering Open-Label Phase  
  
 
DB-FMX-101, 4% (N=XXX) 
DB-Vehicle Foam (N=XXX) 
 
Observed Values 
Change from Baseline  
Observed Values 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
 
 
 
 
Baseline/Visit 1 [1] 
 
 
 
 
N 
XXX 
-- 
XXX 
-- 
Mean (SD) 
XX.X (XX.X) 
-- 
XX.X (XX.X) 
-- 
Median 
XX.X 
-- 
XX.X 
-- 
Min, Max 
XX.X, XX.X 
-- 
XX.X, XX.X 
-- 
 
 
 
 
 
 
Visit 3/Week 3 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
Visit 4/Week 6 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
<Continue for Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52> 
<Continue for Diastolic Blood Pressure (mmHg), Pulse Rate (beats/minute)> 
 
 
Note: DB=Double-Blind phase.  Baseline value is defined as the last non-missing value prior to the first dose of study drug in the double-blind phase. 
Change from baseline is calculated as baseline value minus post-baseline value  
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
  
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 26 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.   
 
                                                                                                                                                                            Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.3.2.1.1: Summary of Physical Exam by Study Visit 
Safety Population Entering Open-Label Phase  
with Abnormal Findings 
  
  
  
  
  
  
  
  
  
  
  
  
DB-FMX-101, 4%  
(N=XXX) 
DB-Vehicle Foam  
(N=XXX) 
  
  
  
  
  
Baseline/Visit 1 
(N=XXX)  
Visit 6/Week 12 
(N=XXX) 
Visit 13/Week 52 
(N=XXX) 
  
Baseline/Visit 1 
(N=XXX) 
Visit 6/Week 12 
(N=XXX) 
Visit 13/Week 52 
(N=XXX) 
Abnormal, n/N (%) 
General Appearance Assessment 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Dermatology Assessment 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
HEENT Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Lymphatic Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Respiratory Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Cardiovascular Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Abdominal Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Musculoskeletal Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Neurological Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  
 
Note: DB=Double-Blind phase.   
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 27 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.   
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
            Table 14.3.3.2.2.1: Shifts in Physical  Exam Result from Baseline to Week 12 and  Week 52  
                                                  Safety Population Entering Open-Label 
  
  
  
DB-FMX-101, 
4%  
DB-Vehicle Foam 
(N=XXX) 
(N=XXX) 
Any Body System  
  
 
Visit 6/Week 12 
 
  N [1]  
XXX 
XXX 
  Abnormal to Normal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
  Normal to Abnormal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
Visit 13/ Week 52 
 
 
  N [2]  
XXX 
XXX 
  Abnormal to Normal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
  Normal to Abnormal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
<Continue for General Appearance, Dermatology, HEENT, Lymphatic, Respiratory, Cardiovascular, Abdominal, Musculoskeletal and Neurological   Assessment > 
  
 
  
  
Note: DB=Double-Blind phase. Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase 
[1] Number of subjects in the safety population with physical exam for both baseline and week 12 within treatment group. 
[2] Number of subjects in the safety population with physical exam for both baseline and week 52 within treatment group. 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 28 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.4.1: Summary of Tolerability Assessment 
Safety Population Entering Open-Label 
  
  
  
DB-FMX-101, 4% (N=XXX) 
  
DB-Vehicle Foam (N=XXX) 
 
  
0=None 
1=Mild 
2=Moderate 
3=Severe 
0=None 
1=Mild 
2=Moderate 
3=Severe 
  
  
  
  
  
  
 
 
 
  
Visit 2/ Week 1  
 
 
 
 
 
 
 
 
 
Face, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Erythema 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Dryness 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Hyperpigmentation 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Skin Peeling 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Itching 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
Non-facial Sites, n (%) 
 
 
 
 
 
 
 
 
Erythema 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Dryness 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Hyperpigmentation 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Skin Peeling 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Itching 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
< Continue for Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, and Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 
11/Week 40, Visit 12/Week 46 and Visit 13/Week 52> 
 
 
 
 
 
 
 
 
Note: DB=Double Blind phase. 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 29 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.                                                                                                                            
 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
                             Data Listing 16.1.1: All Ongoing Concomitant Medications at the End of Double-Blind Phase 
                                                                                        All Subjects 
                                                                             
 
 
 
  
  
  
  
Site/ 
Double-Blind Phase 
Treatment Group 
WHO Preferred Term 
(Verbatim Term) /  
Indication 
Dose/ 
Frequency/ 
Start Date  (Day)/ 
Ongoing? 
Subject 
 
ATC Classification 
Dose Unit 
Route 
Stop Date  (Day) [1] 
 
 
  
  
 
  
  
 
XX/XX
X  
 
xxxxxxxxx(xxxxxxx) 
xxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/ 
Y 
FMX-101,4% 
/ 
 
xxxxxxxxxxxxx 
ddMMMyyyy  (XX)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
  
  
  
  
  
 
  
  
  
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
  
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 30 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharamaceuticals 
                                                                                                                                                                           Page X of Y  
Protocol No. FX2014-05, Open-Label Phase 
 
Data Listing 16.1.2.: All Adverse Events Ongoing at the End of Double-Blind Phase  
All Subjects  
 
 
Site/ 
Subject 
Double-Blind 
Phase 
Treatment 
Group 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment Area 
Treatment-emergent? [1] 
Onset Date (Day) –  
End Date (Day) [2] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken / 
SAE? SAE Criteria 
 
 
XX/XX
X 
FMX-101,4% XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XX
X 
FMX-101,4% XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX)  –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
XXX 
 
 
 
 
 
[1] TEAEs of double-blind phase are defined as AEs starting on or after the date of first application of study medication of the double-blind phase, but before the date of the first 
application of the open-label phase. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 31 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  Page X of Y 
Page X of Y  
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.1.2.1: Subject Disposition 
Safety Population Entering Open-Label Phase 
 
 
 
 
 
 
 
 
Site/Subject  
DB Treatment 
Group 
Date of First  
Dose in DB  [1] 
Date (Day) of First 
Dose in OL [2] 
Date (Day) of  Last 
Dose in OL [3] 
Date (Day) of Last 
Visit  
Date (Day) of Last 
Contact  
Completion 
Status / With 
drawl Reason 
 
 
 
 
 
 
 
 
XX/XXX 
FMX-101,4% 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
Completed 
XX/XXX 
FMX-101,4% 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
Lost to Follow-
up 
XX/XXX 
Vehicle Foam 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
XXXXXXX 
XX/XXX 
Vehicle Foam  
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
XXXXXXX 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
DB= Double- Blind. OL=Open-Label 
Note: Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
[1] First dose administration ( Day 1) 
 
 
 
 
 
[2] First report of drug administration after rolling into the open-label phase 
[3] Last report of  drug administrated during the open-label phase 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 32 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc. 
              Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Data Listing 16.2.2.1: Protocol Deviations 
All Subjects with Deviations in the Open-Label phase 
 
Site/ 
Subject 
 
Type 
  
Description 
 
Action Taken 
 
 
 
 
  
 
 
 
 
XX/XXX  
Study product use 
  
XXXXXXXXX 
 
Retrained on protocol 
 
 
 
 
  
 
 
 
 
XX/XXX  
Missed Visit 
  
XXXXXXXXX 
 
Other: XXXX 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by  XXXXX / Uses: XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 33 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharamaceuticals, Inc.  
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
                                            Data Listing 16.2.4.4.1: Concomitant Medications starting in the Open-Label Phase 
 
                                                                     All Subject Entering Open-Label Phase 
 
 
 
  
  
  
  
Site/ 
Double Blind 
Treatment 
Group 
WHO Preferred 
Term (Verbatim 
Term) /  
Indication 
Dose/ 
Frequency/ 
Start Date  (Day)/ 
Ongoing? 
Subject 
 
ATC Classification 
Dose Unit 
Route 
Stop Date  (Day) [1] 
 
 
  
  
 
  
  
 
XX/XXX  
 
xxxxxxxxx(xxxxxxx) 
xxxxxxxxxxxxxxx
xxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/ 
Y 
          FMX-101,4% 
/ 
 
xxxxxxxxxxxxx 
ddMMMyyyy  (XX)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
  
  
  
  
  
 
  
  
  
Note: Concomitant = ongoing or with stop dates on or after Day 1. 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase.. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 34 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.                            
 
 
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.5.1.1: Study Medication Exposure and Usage 
 
 
All Subjects Entering Open-Label phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
Site/Subject  
Double-Blind 
Treatment 
Group 
Date of First 
Dose in DB  
Date (Day) of 
Last Dose in OL 
[1]  
Total Days 
of 
Exposure 
[2] 
Visit 
# 
Canisters 
Dispensed 
# 
Canisters 
Returned 
Kit 
Number 
Dispensed 
Regions Beyond the 
Face where Study Drug 
was Applied 
01/002 
FMX-101,4% 
ddMMMyyy(XX) 
ddMMMyyy(XX) 
92 
Baseline/Visit 1 
2 
  
19197 
NONE 
 
 
 
 
 
Visit 2/Week 1 
2 
2 
19197 
NONE 
 
 
 
 
 
Visit 3/Week 3 
2 
0 
13345 
NONE 
 
 
 
 
 
Visit 4/Week 6 
2 
2 
19818 
NONE 
 
 
 
 
 
Visit 5/Week 9 
2 
2 
14092 
NONE 
 
 
 
 
 
Visit 6/Week 12 
2 
2 
90047 
NONE 
 
 
 
 
 
Visit 6/Week 12 
2 
2 
90048 
NONE 
 
 
 
 
 
 
 
 
 
 
<< Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>> 
  
  
DB= Double-Blind; OL= Open-Label 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
[1]Total number of days to exposure to study drug is defined as the date of last dose of the study drug minus the first dose of study drug plus 1. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 35 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.      
 
 
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
  
 
 
 
 
 
 
 
Data Listing 16.2.5.2.1: Study Medication Accountability 
All Subjects Entering Open-Label Phase 
 
Site/ 
 Double Blind  
Treatment 
Group 
  
Kit 
Number of  
Amount 
Amount 
  
Subject 
Number 
Canisters  
Returned 
Applied 
  
Dispensed 
Returned in Kit 
(g) 
(g) [1] 
XX/XXX 
FMX-101,4% 
 
XXXXX 
X 
XX.X 
XX.X 
 
 
 
 
XXXXX 
X 
XX.X 
XX.X 
 
 
 
 
XXXXX 
X 
XX.X 
XX.X 
 
 
 
 
XXXXX 
X 
XX.X 
XX.X 
 
 
 
 
XXXXX 
X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
[1] Weight of applied medication is defined as the difference in weight of returned and dispensed canisters. Sealed canisters will be assumed to be 0 g. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
<< Display for only unique kit numbers>> 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 36 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.                                                                                                   
 
 
 
 
 
Pag X of Y 
Protocol No.FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.1.1.1: Lesion Counts   
All Subjects Entering Open-Label Phase 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inflammatory Lesions (IL) 
Noninflammatory Lesions (NIL) 
  
 
Site/Subject  
DB 
Treatment 
Group 
Analysis Visit 
Date (Day) [1] 
Papules 
Pustules 
Nodules 
Total 
IL 
Open 
Comedones 
Closed 
Comedones 
Total 
NIL 
Total 
[2] 
Non Facial 
Area [3] 
  
  
  
  
  
  
  
  
  
  
  
  
  
XX/XXX 
FMX-
101,4% 
Screening 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX,XX 
 
 
Baseline/Visit 1  
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 2/Week 1 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 3/Week 3 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 4/Week 6 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 5/Week 9 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 6/Week 12 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
< Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46 and Visit 13/Week 52> 
  
  
  
  
  
  
  
  
  
  
  
  
  
DB=Double-Blind 
 
 
 
 
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
[2] Total includes inflammatory and noninflammatory. 
[3] Regions beyond the face affected by acne. 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 37 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
 
 
 
Page X of Y 
Protocol No.FX2014-05, Open- Label Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.1.2.1: Total Inflammatory and Noninflammatory Lesion 
Counts 
 
 
 
 
All Subjects Entering Open-Label Phase 
 
 
 
Site/Subject 
Double-Blind 
Phase 
Analysis Visit 
Date (Day) [1] 
 Type 
Total Inflammatory 
Total 
Noninflammatory 
Treatment 
Group 
  
  
  
  
  
  
  
XX/XXX 
FMX-101,4% 
Screening 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
Baseline/Visit 1  
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
Visit 2/Week 16 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
 
 
Change From Baseline 
XX 
XX 
 
 
 
 
Percent Change from Baseline  
XX.X 
XX.X 
 
 
Visit 3/Week 22 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
 
 
Change From Baseline 
XX 
XX 
 
 
 
 
Percent Change from Baseline  
XX.X 
XX.X 
 
 
Visit 4/Week 28 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
 
Change From Baseline 
XX 
XX 
 
 
 
Percent Change from Baseline  
XX.X 
XX.X 
 
 
 
 
 
 
< Continue for Visit 6/Week 40, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46 and Visit 13/Week 52>  
 
 
Change from baseline is calculated as baseline value minus post-baseline value. Percent change from baseline is calculated as baseline value minus post-baseline value divided by 
the baseline value expressed as a percent. 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 38 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
 
 
 
 
 
 
Page X of Y 
Protocol No.FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.2.1: Investigator’s Global Assessment and Treatment Success 
 
 
 
 
 
All Subjects Entering Open-Label Phase 
 
 
 
  
  
  
  
  
  
Site/Subject 
Double-Blind Phase 
 Treatment Group 
Analysis Visit 
Date (Day)  [1] 
IGA 
Treatment Success 
 
  
  
  
  
  
XX/XXX 
FMX-101,4% 
Screening 
ddMMMyyyy (XX) 
3 
- 
 
 
Baseline/Visit 1 
ddMMMyyyy (XX) 
3 
- 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
3 
No 
 
 
Visit 4/Week 6 
ddMMMyyyy (XX) 
3 
No 
 
 
Visit 5/Week 9 
ddMMMyyyy (XX) 
1 
Yes 
 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
1 
Yes 
 
 
 
 
 
 
  
  
<< Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>> 
  
  
 
IGA= Investigator’s Global Assessment 
  
  
  
  
  
  
  
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 39 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.   
 
 
 
Page X of Y 
Protocol No.FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.3.1: Subject Satisfaction Questionnaire  
 
 
 
                     All Subjects Entering Open-Label Phase 
 
 
 
 
 
 
 
 
  
 
 
 
 
Site/Subject  
Double-
Blind 
Treatment 
Group 
Visit  
Date (Day) [1] 
Question  
Response  
XX/XXX 
FMX-
101,4% 
Visit 6/Week 12 
ddMMMyyyy (XX) 
Q1: How satisfied are you with this product in treating your acne? 
1=Very Satisfied 
 
 
 
 
 
 
 
 
Q2: How satisfied are you with how easy this product is to use? 
1=Very Satisfied 
 
 
Q3: How satisfied are you with this product compared to other products you 
1=Very Satisfied 
 
 
       have previously used for acne, such as gels and creams? 
 
 
Q4: How satisfied are you with how this product feels on you skin after      
       treatment 
1=Very Satisfied 
 
 
Q5: How satisfied are you with the odor of this product after treatment? 
1=Very Satisfied 
 
 
Q6: How satisfied are you with the color of this product after treatment? 
1=Very Satisfied 
 
 
Q7: Overall, how satisfied are you with this product? 
1=Very Satisfied 
 
 
Q8: Overall, how likely are you to recommend this product to a friend? 
1=Very Likely 
XX/XXX 
FMX-
101,4% 
Visit 13/Week 52 
ddMMMyyyy (XX) 
Q1: How satisfied are you with this product in treating your acne? 
1=Very Satisfied 
 
 
        Q2: How satisfied are you with how easy this product is to use? 
1=Very Satisfied 
 
                            Q3: How satisfied are you with this product compared to other products you 
1=Very Satisfied 
 
                             have previously used for acne, such as gels and creams? 
1=Very Satisfied 
 
                            Q4: How satisfied are you with how this product feels on you skin after  
                              treatment 
1=Very Satisfied 
 
                            Q5: How satisfied are you with the odor of this product after treatment? 
1=Very Satisfied 
 
                            Q6: How satisfied are you with the color of this product after treatment? 
1=Very Satisfied 
 
                            Q7: Overall, how satisfied are you with this product? 
                    1=Very Satisfied 
                                                          Q8: Overall, how likely are you to recommend this product to      
 
                    1=Very Likely 
  
  
  
  
  
  
  
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 40 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharamaceuticals 
                                                                                                                                                                                           Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Data Listing 16.2.7.1.1: All Adverse Events Started in Open-Label Phase 
All Subjects Entering Open-Label Phase 
 
Site/ 
Subject 
Double-
Blind Phase 
Treatment 
Group 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment Area Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken / 
SAE? SAE Criteria 
 
 
XX/XXX FMX-101,4% XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX FMX-101,4% XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX)  –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
XXX 
 
 
 
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
 Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 41 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharamaceuticals, Inc. 
       Page X of Y  
Protocol No. FX2014-05, Open-Label Phase 
Data Listing 16.2.7.2.1: Serious Adverse Events Leading to Study Discontinuation 
 All Subjects who entered Open-Label Phase 
 
Site/ 
Subject 
Double-Blind Phase 
Treatment Group 
MedDRA SOC Term/ 
MedDRA Preferred Term 
/ 
(Verbatim Term) / 
Location of AE to 
Treatment Area 
Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken 
/ 
SAE? SAE Criteria 
 
 
XX/XXX 
FMX-101,4% 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment 
Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
FMX-101,4% 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
 [1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 42 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharamaceuticals, Inc. 
            Page X of Y  
Protocol No. FX2014-05, Open-Label Phase 
Data Listing 16.2.7.3.1: Treatment-Emergent Adverse Events Leading to Study Discontinuation 
 All Subjects who Entered Open-Label Phase 
 
Site/ 
Subject 
Double-Blind Phase 
Treatment Group 
MedDRA SOC Term/ 
MedDRA Preferred Term 
/ 
(Verbatim Term) / 
Location of AE to 
Treatment Area 
Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken 
/ 
SAE? SAE Criteria 
 
 
XX/XXX 
FMX-101,4% 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment 
Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
FMX-101,4% 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
 [1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 43 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.  
 
             Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Data Listing 16.2.8.1.1: Urine Pregnancy Test 
All Subjects Entering Open-Label Phase 
 
 
Site/ 
Double-Blind Phase 
Treatment Group 
Childbearing Potential 
Visit 
Date of Test (Day)[1] 
Result 
Subject 
 
 
 
 
 
 
XX/XXX 
FMX-101,4% 
XXXXXXX 
Baseline/Visit 1  
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 2/Week 1 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 4/Week 6 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 5/Week 9 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 13/Week 52 
ddMMMyyyy (XX) 
Negative 
 
 
 
 
 
 
XX/XXX 
FMX-101,4% 
Male 
-- 
-- 
-- 
 
 
<<<<Include all available visits>>> 
  
  
  
  
 
 
 [1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 44 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
Foamix Pharmaceuticals, Inc.  
 
 
 
 
 
Page X of Y 
Protocol No.FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.1.2: Home Pregnancy Test  
 
 
 
 
 
    All Subjects Entering Open-Label Phase 
 
 
Site/Subject 
Double-Blind Phase 
Childbearing 
 Potential 
Analysis Visit 
Date (Day) [1] 
Was a Home 
Pregnancy Test 
dispensed? 
Positive 
Pregnancy Test 
since last Visit? 
Date of 
Positive 
Pregnancy 
Test 
  
  
  
  
 
  
  
 
XX/XXX 
FMX-101,4% 
XXXXX 
Visit 6/ Week 12 
ddMMMyyyy (XX) 
XXX 
- 
- 
 
 
 
Visit 7/Week 16 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 8/Week 22 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 9/Week 28 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 10/Week 34 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 11/Week 40 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 12/Week 46 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 13/Week 52 
ddMMMyyyy (XX) 
         XXX 
XXX 
- 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 
 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 45 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
 
 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                                                         Page X of Y 
Protocol No. FMX2014-04, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.2.1.X.1:  Clinical Laboratory Tests 
All Subjects Entering Open-Label Phase   
[Hematology][Chemistry][Urinalysis] 
 
 
 
 
 
 
 
 
Site/Subject 
Double-
Blind 
Phase 
Treatment 
Group 
Visit 
Test 
Name 
Test Date (Day)[1] 
Result (Unit) 
Abnormal? 
Clinically 
Significant? 
Reference Range 
 
 
 
 
 
 
 
 
 
XX/XXX 
FMX-
101,4% 
Baseline/Visit 1  
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Normal 
 
xxxx, xxxx 
 
 
 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Normal 
 
xxxx, xxxx 
 
 
 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Low 
No 
xxxx, xxxx 
 
 
 
<< Include for Visit 2/Week 1, Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week 12, Visit 1 Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 
10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 46 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
 
 
 
 
Foamix Pharmaceuticals, Inc.  
                                    Page X of Y 
Protocol No. FMX2014-04, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.2.2.1:  Clinically Significant Clinical Laboratory Tests for Hematology, Chemistry and Urinalysis 
 
All Subjects Entering Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
Site/Subject 
Double-
Blind 
Phase 
Treatment 
Group 
Visit 
Category of      
Laboratory 
Test 
Test Name 
Test Date (Day)[1] 
Result (Unit) 
Abnormal? 
Reference 
Range 
 
 
 
 
 
 
 
 
XX/XXX 
FMX-
101,4% 
Baseline/Visit 1 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
xxxx, xxxx 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
xxxx, xxxx 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Low 
xxxx, xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
<< Include for Visit 2/Week 1, Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week 12, Visit 1 Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 
10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 47 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
                 Page X of Y 
 
 
 
 
Foamix Pharmaceuticals, Inc.  
 
Protocol No. FMX2014-04, Open-Label Phase 
 
 
 
 
 
 
Data Listing 16.2.8.2.3.1: Out-of-Range (Abnormal) Clinical Laboratory Test Results for  Hematology, Chemistry and Urinalysis 
All Subjects Entering Open-Label Phase 
 
 
 
 
 
 
  
 
 
 
Site/Subject 
Double-Blind 
Phase 
Treatment 
Group 
Visit 
Category of      
Laboratory 
Test 
Test Name 
Test Date (Day)[1] 
Result (Unit) 
Abnormal? 
Clinically 
Significant 
 
 
 
 
 
 
 
 
XX/XXX 
FMX-101,4% 
Baseline/Visit1 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
No 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
No 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Low 
No 
 
 
 
 
 
 
 
 
 
 
 
 
<< Include for Visit 2/Week 1, Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week 12, Visit 1 Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 
28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
 
  
 [1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
  Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 48 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.     
 
 
 
 
 
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 Data Listing 16.2.8.3.1:  Vital Signs  
All Subjects Entering Open-Label Phase   
  
Site/ 
Double-Blind 
Phase 
Analysis Visit 
Date (Day) [1] 
Weight (kg) 
Systolic Blood  
Diastolic Blood  
Pulse Rate  
Subject 
Treatment 
Group 
Pressure (mmHg) 
Pressure (mmHg) 
(beats/minute) 
  
  
Observed 
CFBL 
Observed 
CFBL 
Observed 
CFBL 
Observed 
CFBL 
 
  
 
 
 
  
  
  
  
  
XX/XXX 
FMX-101,4% 
Baseline/Visit 1  
ddMMMyyyy (XX) 
xxx.x 
-- 
xxx 
-- 
xxx 
-- 
xx 
-- 
 
 
Visit 2/Week 1 
ddMMMyyyy (XX) 
-- 
-- 
xxx 
-- 
xxx 
-- 
xx 
-- 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
-- 
-- 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
 
Visit 4/Week 6 
ddMMMyyyy (XX) 
-- 
-- 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
 
Visit 5/Week 9 
ddMMMyyyy (XX) 
-- 
-- 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
xxx.x 
xxx.x 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
< <<Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46 and Visit 13/Week 52>>> 
  
  
  
  
  
  
  
  
  
  
 
CFBL=Change from Baseline 
  
  
  
Note: Baseline value is defined as the last non-missing value prior to the first dose of study drug.  Change from baseline is calculated as baseline value minus post-baseline value 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 49 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
 
Foamix Pharmaceuticals, Inc.   
 
 
                        Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.4.1: Physical  Exam  
Subjects Entering Open-Label Phase with Abnormal Results  
  
  
  
  
  
  
  
Site/ 
Double-Blind Phase 
Analysis Visit 
Date (Day) [1] 
Body System 
Result 
Comment 
Subject 
Treatment Group 
  
  
  
  
  
  
XX/XXX 
FMX-101,4% 
Baseline/Visit 1  
ddMMMyyyy (XX) 
General Appearance 
Abnormal 
 XXXXXXXXX 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
Dermatological 
Abnormal  
XXXXXXXXX 
 
 
Visit 13/Week 52 
ddMMMyyyy (XX) 
Dermatological 
Abnormal  
XXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
[1]  Study day is calculated relative to the date of Day 1, the date of first study drug administration 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 50 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
 
 
 
 
 
 
Foamix Pharmaceuticals, Inc.   
 
 
 
 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.5.1: Tolerability Assessment for Face 
 
All Subjects Entering Open-Label Phase   
  
 
  
  
  
  
  
 
Site/ 
Double-Blind Phase 
Treatment Group 
Analysis Visit 
Date (Day) [1] 
Symptoms 
 
Intensity 
Comment 
Subject 
 
 
 
 
 
 
 
XX/XXX 
Vehicle Foam 
Visit 2/Week1 
ddMMMyyyy (XX) 
Erythema 
 
1=Mild 
 XXXXX 
 
Dryness 
 
1=Mild 
 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
 
 
 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
Erythema 
 
1=Mild 
 XXXXX 
 
 
 
Dryness 
 
1=Mild 
 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
<Continue for  Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week12, Visit 7/Week16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 
46, Visit 13/Week 52> 
  
 
  
  
  
  
  
  
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 51 of 51 
Protocol No. FX2014-05  
 
  
October 19, 2017 
Novella Clinical No. CT991715 
 
 
 
 
Foamix Pharmaceuticals, Inc.   
 
 
 
 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.5.2: Tolerability Assessment for Non-Facial Areas 
 
All Subjects Entering Open-Label Phase   
  
 
  
  
  
  
  
 
Site/ 
Double-Blind Phase 
Treatment Group 
Analysis Visit 
Date (Day) [1] 
Symptoms 
Affected Area [2] 
Intensity[3] 
Comment 
Subject 
 
 
 
 
 
 
 
XX/XXX 
Vehicle Foam 
Visit 2/Week1 
ddMMMyyyy (XX) 
Erythema 
Non-face: Neck 
1=Mild 
 XXXXX 
 
Dryness 
 
1=Mild 
XXXXX 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
 
 
 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
Erythema 
Non-face: Neck 
1=Mild 
 XXXXX 
 
 
 
Dryness 
 
1=Mild 
XXXXX 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
<Continue for  Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week12, Visit 7/Week16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 
46, Visit 13/Week 52> 
  
 
  
  
  
  
  
  
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
[2] For non-face area, region affected maximally is reported 
[3] For non-face area, maximum intensity is reported 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 




Foamix Pharamaceuticals, Inc.   
                             
Protocol No. FX2014-05  
 
                                   December 7, 2017 
Novella Clinical No. CT991715 
 
 
Tables – Open-Label Phase 
14.1 
Summary of Disposition, Demographic, and Baseline Data Summary Tables  
14.1.1.1.1 
Summary of Subject Enrollment and Disposition, All Subjects Entering Open-Label Phase 
14.1.2.1.1 
Summary of Subject Demographics and Baseline Characteristics, Safety Population Entering Open-Label Phase 
14.1.3.1.1 
Summary of Concomitant Medications starting in Open-Label Phase,  by Anatomical Therapeutic Chemical Class (ATC) and Preferred Term, Safety Population Entering Open-
Label Phase 
14.2 
Summary of Efficacy Endpoints 
14.2.4.1.1 
Summary of Inflammatory Lesion Counts, Safety Population Entering Open-Label Phase (Observed-Cases) 
14.2.5.1.1 
Summary of Non-Inflammatory Lesion Count, Safety Population Entering Open-Label Phase (Observed-Cases) 
14.2.6.1.1 
Summary of Investigator’s Global Assessment (IGA),Frequency Counts by Study Visit, Safety Population Entering Open-Label Phase (Observed-Cases) 
14.2.7.1 
Summary of Subject Satisfaction Questionnaire at Week 52, Safety Population Entering Open-Label Phase 
14.3 
Summary of Safety Tables 
14.3.1.1.1 
Overall Summary of Adverse Events, Safety Population Entering Open-Label Phase, All AEs Starting in Open-Label Phase 
14.3.1.2.1.1 
Summary of Treatment-Emergent Adverse Events,by System Organ Class and Preferred Term in Descending Frequency, Safety Population Entering Open-Label Phase 
14.3.1.2.2.1 
Summary of Treatment-Emergent Adverse Events,by Preferred Term in Descending Frequency, Safety Population Entering Open-Label Phase 
14.3.1.2.3.1 
Summary of Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity, Safety Population Entering Open-Label Phase 
14.3.1.2.4.1 
Summary of Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Causality,Safety Population Entering Open-Label Phase,All SAEs 
Starting in Open-Label Phase 
14.3.1.3.1.1 
Summary of Serious Adverse Events by System Organ Class and Preferred Term in Descending Frequency, Safety Population Entering Open-Label Phase,All SAEs Starting in 
Open-Label Phase 
14.3.1.3.2.1 
Summary of Serious Adverse Events by System Organ Class, Preferred Term, and Maximum Severity, Safety Population Entering Open-Label Phase, All SAEs Starting in 
Open-Label Phase 
14.3.1.3.3.1 
Summary of Serious Adverse Events by System Organ Class, Preferred Term, and Maximum Causality,Safety Population Entering Open –Label Phase,All SAEs Starting in 
Open-Label Phase 
14.3.1.4.1.1 
Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term in Descending Frequency, Safety Population 
Entering Open-Label Phase  
14.3.1.4.2.1 
Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation by System Organ Class, Preferred Term and Maximum Severity, Safety Population 
Entering Open-Label Phase  
14.3.1.4.3.1 
Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation by System Organ Class ,Preferred Term and Maximum Causality, Safety Population 
Entering Open-Label Phase  
14.3.2.1.1.1 
Summary of Clinical Laboratory Results by Visit, Hematology , Safety Population Entering Open-Label Phase  
14.3.2.2.1.1 
Summary of Clinical Laboratory Results by Visit, Chemistry , Safety Population Entering Open-Label Phase  
14.3.3.1.1 
Summary of Vital Signs by Visit, Safety Population Entering Open-Label Phase  
14.3.3.2.1.1 
Summary of Physical  Exam by Study Visit, Safety Population Entering Open-Label Phase  with Abnormal findings 
14.3.3.2.2.1 
Shifts in Physical  Exam Result from Baseline to Week 52 , Safety Population Entering Open-Label Phase  
14.3.4.1 
Summary of Tolerability Assessment, Safety Population Entering Open-Label Phase  
 


Foamix Pharamaceuticals, Inc.   
                             
Protocol No. FX2014-05  
 
                                   December 7, 2017 
Novella Clinical No. CT991715 
 
 
Listings  
16.2.1.2.1 
Subject Disposition, Safety Population Entering Open-Label Phase 
16.2.2.1 
Protocol Deviations, Safety Population Entering Open-Label Phase 
16.2.4.4.1 
Concomitant Medications used at Any Time During the Study, All Randomized Subjects 
16.2.4.4.2 
Concomitant Medications used during Double-Blind Phase, All Randomized Subjects 
16.2.4.4.3 
Concomitant Medications starting in the Open-Label Phase, All Randomized Subjects 
16.2.5.1.1 
Study Medication Exposure and Compliance, All Subjects Entering Open-Label Phase 
16.2.5.2.1 
Study Medication Accountability, All Randomized Subjects  
16.2.6.1.1.1 
Lesion Counts, All Randomized Subjects  
16.2.6.1.2.1 
Total Inflammatory/Noninflammatory Lesion Counts, All Randomized Subjects  
16.2.6.2.1 
Investigator’s Global Assessment and Treatment Success, All Randomized Subjects 
16.2.6.3.1 
Subject Satisfaction Questionnaire at Week 12 and Week 52, All Randomized Subjects 
16.2.7.1.1 
Adverse Events at Any Time During the Study , All Randomized Subjects  
16.2.7.1.2 
Adverse Events during the Double-Blind Phase, All Randomized Subjects  
16.2.7.1.3 
Adverse Events starting in the Open-Label Phase, All Randomized Subjects 
16.2.7.2.1 
Serious Adverse Events Starting in to Open-Label Phase Leading to Study Discontinuation, All Subjects Entering Open-Label Phase 
16.2.7.3.1 
Treatment-Emergent Adverse Events Starting in to Open-Label Phase Leading to Study Discontinuation, All Subjects Entering Open-Label Phase 
16.2.8.1.1 
Urine Pregnancy Test, All Randomized Subjects 
16.2.8.1.2 
Home Pregnancy Test, All Randomized Subjects 
16.2.8.2.1.1.1 
Clinical Laboratory Tests, Hematology, All Randomized Subjects 
16.2.8.2.1.2.1 
Clinical Laboratory Tests , Chemistry, All Randomized Subjects 
16.2.8.2.1.3.1 
Clinical Laboratory Tests , Urinalysis, All Randomized Subjects 
16.2.8.2.2.1 
Clinically Significant Clinical Laboratory Tests for  Hematology, Chemistry and Urinalysis, All Randomized Subjects 
16.2.8.2.3.1 
Out-of-Range (Abnormal) Clinical Laboratory Test Results for  Hematology, Chemistry and Urinalysis, All Randomized Subjects 
16.2.8.3.1 
Vital Signs, All Randomized Subjects 
16.2.8.4.1 
Physical  Exam, All Subjects Entering Open-Label Phase 
16.2.8.5.1 
Tolerability Assessment for Face, All Randomized Subjects 
16.2.8.5.2 
Tolerability Assessment for Non-facial Areas, All Randomized Subjects 
  
 


Foamix Pharamaceuticals, Inc.   
                             
Protocol No. FX2014-05  
 
                                   December 7, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                            
Page X of Y 
Protocol No. FX2014-05,  Open-Label Phase 
 
Table 14.1.1.1.1: Summary of Subject Enrollment and Disposition 
All Subjects Entering Open-Label Phase 
 
  
  
DB-FMX-101, 4%  
DB-Vechicle Foam 
Overall 
 
 
 
Number of Subjects Entering Open-Label 
XXX 
XXX 
XXX 
         Number of Subjects in Safety Population, n (%) 
XXX (100) 
XXX (100) 
XXX (100) 
 
 
 
 
Number of Subjects Completing the Open-Label Phase, n (%)[1] 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Number of Subjects Discontinued from the Open-Label Phase, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Reason for Discontinuation, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          Adverse Event (including a clinically significant abnormal lab 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) 
          Poor Protocol Adherence 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Administrative, Other 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Other 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
 
 
Note: DB=Double-Blind phase. 
[1] Subject are identified as completing the open-label phase if they rolled into the open-label phase and did not discontinue. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
Protocol No. FX2014-05  
 
                                   December 7, 2017 
Novella Clinical No. CT991715 
 
 
Foamix Pharmaceuticals Inc.                                                                                                                                                                                                                            Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.1.2.1.1: Summary of Subject Demographics and Baseline Characteristics  
Safety Population Entering Open-Label Phase 
 
 
DB-FMX-101, 4%  
(N=XXX) 
DB-Vechicle Foam  
(N=XXX) 
Overall 
(N=XXX) 
Age (years) 
 
 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Age Group, n (%) 
 
9─ < 13 years 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
≥13-<18 years 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
≥ 18 years 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
Sex, n (%) 
 
  Female 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Male 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
Race, n (%) 
 
  White 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Black or African American 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Asian 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  American Indian or Alaska Native 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Native Hawaiian or Other Pacific Islander 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Multiple Races Reported 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
Ethnicity, n (%) 
 
  Hispanic or Latino 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  Not Hispanic or Latino 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
DB=Double-Blind Phase; IGA=Investigator’s Global Assessment; SD=Standard deviation. 
Note:  Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase. 
 
Generated on XX/XX/XX:XXXX  by XXXXXX / Uses: XXXX / Reference: Data Listings XXXX


Foamix Pharamaceuticals, Inc.   
                             
  
Page 6 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals Inc.                                                                                                                                                                                                              Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.1.2.1.1: Summary of Subject Demographics and Baseline Characteristics (Continued)  
 Safety Population Entering Open-Label Phase 
 
 
DB-FMX-101, 4%  
(N=XXX) 
DB-Vechicle Foam  
(N=XXX) 
Overall 
(N=XXX) 
Baseline Inflammatory Lesion Counts 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Baseline Noninflammatory Lesion Counts 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Baseline Total Lesion Counts 
 
  N  
XXX 
XXX 
XXX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
Baseline IGA Score, n (%) 
 
  2 – Moderate 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  3 – Severe 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
DB=Double-Blind Phase; IGA=Investigator’s Global Assessment; SD=Standard deviation.  
Note: Baseline value is defined as the last non-missing value on or prior to the day of the first dose of study drug during the double-blind phase. 
 
Generated on XX/XX/XX:XXXX  by XXXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 7 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharamaceuticals                                                                                                                                              
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
Table 14.1.3.1.1: Summary of Concomitant Medications starting in Open-Label Phase 
by Anatomical Therapeutic Chemical Class (ATC) and Preferred Term 
Safety Population Entering Open-Label Phase 
  
 
  
Anatomical Therapeutic Chemical Class 
DB-FMX-101, 4%  
DB-Vechicle Foam  
Overall 
          Preferred Term 
(N=XXX) 
(N=XXX) 
(N=XXX) 
 
  
  
  
Subjects with any Concomitant Medication, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
<< Anatomical Therapeutic Chemical Class >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
<< Anatomical Therapeutic Chemical Class >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          << Concomitant Medication Preferred Term >> 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
  
  
  
DB=Double-Blind 
 
 
 
[1] Concomitant medications starting on or after the first dose in the Open-Label Phase . Counts reflect number of subjects in each treatment group reporting one or more 
concomitant medication that map to the WHO Drug anatomical therapeutic chemical or preferred term. A subject may be counted once only in each row of the table. 
 
Generated on  XX/XX/XX:XXXX  by XXXXXX  / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 8 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
14.2.4.1.1: Summary of Inflammatory Lesion Counts 
Safety Population Entering Open-Label Phase (Observed-Cases) 
 
  
  
DB-FMX-101, 4% (N=XXX) 
  
DB-Vehicle Foam (N=XXX)  
Analysis Visit 
  
N 
Mean (SD) 
Median 
Min, Max 
N 
Mean (SD) 
Median 
Min, Max 
  
 
 
 
 
 
 
 
 
 
Baseline/Visit  
 
 
 
 
 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
 
 
 
 
 
Visit 3/Week 3 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 4/Week 6 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 5/Week 9 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
  
 <<<< Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
DB=Double-Blind phase; SD=Standard deviation. 
 
 
 
 
 
 
Note: Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value. Percent change from baseline is calculated as the baseline value minus the post-baseline 
value divided by the baseline value, expressed as a percentage 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 9 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
14.2.5.1.1: Summary of Non-Inflammatory Lesion Count  
Safety Population Entering Open-Label Phase (Observed-Cases) 
  
  
  
DB-FMX-101, 4% (N=XXX) 
  
DB-Vehicle Foam (N=XXX)  
Visit 
  
N 
Mean (SD) 
Median 
Min, Max 
N 
Mean (SD) 
Median 
Min, Max 
  
 
 
 
 
 
 
 
 
 
Baseline/Visit 1 
 
 
 
 
 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
 
 
 
 
 
Visit 3/Week 3 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline  
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 4/Week 6 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
 
 
 
 
 
 
Visit 5/Week 9 
 
 
 
 
Absolute Value 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
XXX 
XX.X (XX.X) 
XX.X 
XX,XX 
 
Percent Change from Baseline 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
XXX 
XX.X (XX.X) 
XX.X 
XX.X,XX.X 
  
  
<<<< Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>>  
  
 
DB=Double-Blind phase; SD=Standard deviation. 
Note: Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value. Percent change from baseline is calculated as the baseline value minus the post-baseline 
value divided by the baseline value, expressed as a percentage 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 10 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc. 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
14.2.6.1.1: Summary of Investigator’s Global Assessment (IGA) 
Safety Population Entering Open-Label Phase (Observed-Cases) 
 
 
 
  
DB-FMX-101, 4% 
(N=XXX) 
DB-Vehicle Foam 
(N=XXX) 
 
 
 
Baseline/Visit 1, n (%)  
 
 
N  
XXX 
XXX 
3-Moderate 
XXX (XX.X) 
XXX (XX.X) 
4-Severe 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
Visit 3/Week 3, n (%) 
 
N  
XXX 
XXX 
0-Clear 
XXX (XX.X) 
XXX (XX.X) 
1-Almost Clear 
XXX (XX.X) 
XXX (XX.X) 
2-Mild 
XXX (XX.X) 
XXX (XX.X) 
3-Moderate 
XXX (XX.X) 
XXX (XX.X) 
4-Severe 
XXX (XX.X) 
XXX (XX.X) 
5-Very Severe 
XXX (XX.X) 
XXX (XX.X) 
IGA Treatment Success 
XXX (XX.X) 
XXX (XX.X) 
<Continue for Visit 4/Week 6,  Visit 5/Week 9, Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22,  Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 
46 and Visit 13/Week 52> 
  
DB=Double-Blind phase. 
Note: IGA treatment success is a score of ‘clear’ (0) or “almost clear” (1) and at least 2 grade decrease from Baseline.  
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 11 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc. 
 
 
  Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
14.2.7.1: Summary of Subject Satisfaction Questionnaire at Week 52 
Safety Population Entering Open-Label Phase 
  
  
  
  
  
DB-FMX-101, 4% 
DB-Vehicle  
Overall 
(N= XXX) 
(N=XXX) 
(N=XXX) 
 
 
 
 
Q1: How satisfied are you with this product in treating your acne? 
N  
XXX 
XXX 
XXX 
1-Very Satisfied 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
2- Satisfied 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
3-Somewhat Satisfied 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
4-Dissatisfied 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
5-Very Dissatisfied 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
<Continue for :> 
 
 
Q2: How satisfied are you with how easy this product is to use? 
Q3: How satisfied are you with this product compared to other products you have previously used for acne, such as gels and creams? 
Q4: How satisfied are you with how this product feels on your skin after treatment? 
Q5: How satisfied are you with the odor of this product after treatment? 
Q6: How satisfied are you with the color of this product after treatment? 
Q7: Overall, how satisfied are you with this product? 
 
Q8: Overall, how likely are you to recommend this product to a friend? 
N  
XXX 
 
XXX 
1-Very Likely 
XXX (XX.X) 
 
XXX (XX.X) 
2- Likely 
XXX (XX.X) 
 
XXX (XX.X) 
3-Somewha Likely 
XXX (XX.X) 
 
XXX (XX.X) 
4-Unliklely 
XXX (XX.X) 
 
XXX (XX.X) 
5-Very Unlikely 
XXX (XX.X) 
 
XXX (XX.X) 
  
  
  
  
 DB= Double-Blind 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 12 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.                                                                                                
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.1.1: Overall Summary of Adverse Events  
Safety Population who entered Open-Label Phase 
All AEs Starting in Open-Label Phase 
  
  
  
  
  
DB-FMX-101, 4%  
DB-Vehicle 
Overall 
(N =XXX) 
(N =XXX) 
(N =XXX) 
 
 
 
 
Subjects with any treatment-emergent AE (TEAE), n (%) [1] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
          Number of treatment-emergent AEs 
XXX 
XXX 
XXX 
 
 
 
 
Subjects with any serious TEAE (SAE), n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          Number of serious TEAEs (SAE) 
XXX 
XXX 
XXX 
 
 
 
 
Subjects with any treatment-related TEAE, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          Number of treatment-related TEAEs 
XXX 
XXX 
XXX 
 
 
 
 
Subjects with any TEAE leading to study discontinuation, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
          Number of TEAEs leading to study discontinuation 
XXX 
XXX 
XXX 
  
 
  
 
 DB=Double-Blind 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. A subject may be counted once only in each row of the table. 
[1] All AEs staring on or after the first application of the Open-Label phase will be considered as TEAEs of the Open-Label phase.  
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 13 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.2.1.1: Summary of Treatment-Emergent Adverse Events  
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population Entering Open-Label Phase 
  
System Organ Class 
  
 
  
Overall 
 
          Preferred Term 
 
(N=XXXX) 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
  
  
  
  
  
  
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only 
in each row of the table. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase.  
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 14 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.2.2.1: Summary of Treatment-Emergent Adverse Events 
by Preferred Term in Descending Frequency 
Safety Population Entering Open-label Phase 
 
System Organ Class 
  
 
  
Overall 
 
          Preferred Term 
 
(N=XXX) 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
  
  
  
  
  
  
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA preferred term. A subject may be counted once only in each row of the 
table. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase.  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 15 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                                                            Page X of Y 
Protocol No. FX2014-05, Open-Label Phase  
Table 14.3.1.2.3.1: Summary of Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population Entering Open-Label Phase 
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Mild  
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest severity. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 16 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharamaceuticals, Inc                                                                                                                                                                                                                         Page X of Y 
Protocol No. FX2014-05, Open-Label Phase  
Table 14.3.1.2.4.1: Summary of Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population Entering Open-Label Phase  
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest causality. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 17 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.3.1.1: Summary of Serious Adverse Events  
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population who entered Open-Label Phase 
All SAEs Starting in Open-Label Phase 
  
System Organ Class 
 
Overall 
 
          Preferred Term 
 
(N=XXX) 
 
 
 
 
 
Subjects with any SAE, n (%) 
 
XXX (XX.X) 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
XXX (XX.X) 
 
 
 
 
 
  
  
  
  
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only in 
each row of the table. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 18 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.                                               
 
 
 
 
  Page X of Y 
Protocol No. FX2014-05, Open-Label Phase  
 
 
 
 
 
 
Table 14.3.1.3.2.1: Summary of Serious Adverse Events  
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population  Entering Open-Label Phase 
All SAEs Starting in Open-Label Phase 
  
System Organ Class 
Severity 
  
 
Overall  
 
          Preferred Term 
 
(N = XXX) 
 
 
 
 
 
 
 
Subjects with any SAE, n (%) [1] 
Total 
 
 
XXX (XX.X) 
 
 
Mild  
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
  
  
  
  
  
  
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at 
the highest severity. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 19 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharamaceuticals, Inc                                                                                                                                                                                                                        Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.3.3.1: Summary of Serious Adverse Events 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population Entering Open-Label Phase 
All SAEs Starting in Open-Label Phase 
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any SAE, n (%) 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest causality. 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 20 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.    
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.4.1.1: Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation  
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population Entering Open-Label Phase  
 
  
System Organ Class 
  
 
Overall 
 
          Preferred Term 
 
(N=XXX) 
 
 
 
 
  
 
Subjects with any TEAE, n (%)  
 
 
XXX (XX.X) 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
<< Adverse Event Preferred Term >> 
 
 
XXX (XX.X) 
 
 
 
  
  
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only in 
each row of the table. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 21 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                                                           Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.4.2.1: Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation 
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population Entering Open-Label Phase  
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Mild  
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Mild 
 
 
 
XXX (XX.X) 
 
 
Moderate 
 
 
 
XXX (XX.X) 
 
 
Severe 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest severity. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 22 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharamaceuticals, Inc                                                                                                                                                                                                                        Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.1.4.3.1: Summary of Treatment-emergent Adverse Events Leading to Study Discontinuation 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population Entering Open-Label Phase  
 
System Organ Class 
          Preferred Term 
Severity 
 
 
 
Overall  
 (N=XXX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%)  
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Total 
 
 
 
XXX (XX.X) 
 
 
Related  
 
 
 
XXX (XX.X) 
 
 
Not Related 
 
 
 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at the 
highest causality. TEAEs of the Open-Label phase are defined as AEs starting on or after the first application of the Open-Label phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 23 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
Table 14.3.2.1.X.1: Summary of Clinical Laboratory Results by Visit 
[Hematology] [Chemistry] 
Safety Population Entering Open-Label Phase  
 
  
 
DB-FMX-101, 4% (N=XXX) 
DB-Vehicle Foam (N=XXX) 
 
Observed Values 
Change from  
Observed Values 
Change from  
Baseline  
Baseline  
Parameter 1 (units) 
 
 
 
 
Baseline/Visit 1  
 
 
 
 
N 
XXX 
-- 
XXX 
-- 
Mean (SD) 
XX.X (XX.X) 
-- 
XX.X (XX.X) 
-- 
Median 
XX.X 
-- 
XX.X 
-- 
Min, Max 
XX.X, XX.X 
-- 
XX.X, XX.X 
-- 
 
 
 
 
 
 
 
 
 
 
Visit 3/Week3 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
Visit 6/Week12 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
<Continue for Visit 9/Week 28, Visit 13/Week 52 and for Parameter 2, 3, ….> 
 
 
 
 
 
 
 
 
  
Note: DB=Double-Blind phase. Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value. 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 24 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.  
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
Table 14.3.3.1.1: Summary of Vital Signs by Visit  
Safety Population Entering Open-Label Phase  
 
  
 
DB-FMX-101, 4% (N=XXX) 
DB-Vehicle Foam (N=XXX) 
 
Observed Values 
Change from  
Observed Values 
Change from  
Baseline  
Baseline  
 
 
 
 
 
Weight (kg) 
 
 
 
 
Baseline/Visit 1  
 
 
 
 
N 
XXX 
- 
XXX 
- 
Mean (SD) 
XX.X (XX.X) 
- 
XX.X (XX.X) 
- 
Median 
XX.X 
- 
XX.X 
- 
Min, Max 
XX.X, XX.X 
- 
XX.X, XX.X 
- 
 
 
 
 
 
Visit 6/Week 12 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
Visit 13/Week 52 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
  
Note: DB=Double Blind phase. Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase.  
Change from baseline is calculated as baseline value minus post-baseline value 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
[Programming note: add page break between Weight and Blood pressure] 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 25 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.  
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
Table 14.3.3.1.1: Summary of Vital Signs by Visit (Continued) 
Safety Population Entering Open-Label Phase  
  
 
DB-FMX-101, 4% (N=XXX) 
DB-Vehicle Foam (N=XXX) 
 
Observed Values 
Change from Baseline  
Observed Values 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
 
 
 
 
Baseline/Visit 1 [1] 
 
 
 
 
N 
XXX 
-- 
XXX 
-- 
Mean (SD) 
XX.X (XX.X) 
-- 
XX.X (XX.X) 
-- 
Median 
XX.X 
-- 
XX.X 
-- 
Min, Max 
XX.X, XX.X 
-- 
XX.X, XX.X 
-- 
 
 
 
 
 
 
Visit 3/Week 3 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
Visit 4/Week 6 
 
 
 
 
N 
XXX 
XXX 
XXX 
XXX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
<Continue for Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52> 
<Continue for Diastolic Blood Pressure (mmHg), Pulse Rate (beats/minute)> 
 
 
Note: DB=Double-Blind phase.  Baseline value is defined as the last non-missing value prior to the first dose of study drug in the double-blind phase. 
Change from baseline is calculated as baseline value minus post-baseline value  
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
  
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 26 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.   
 
                                                                                                                                                                                       Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.3.2.1.1: Summary of Physical Exam by Study Visit 
Safety Population Entering Open-Label Phase  
with Abnormal Findings 
  
  
  
  
  
  
  
  
  
  
  
  
DB-FMX-101, 4%  
(N=XXX) 
DB-Vehicle Foam  
(N=XXX) 
  
  
  
  
  
Baseline/Visit 1 
(N=XXX)  
Visit 6/Week 12 
(N=XXX) 
Visit 13/Week 52 
(N=XXX) 
  
Baseline/Visit 1 
(N=XXX) 
Visit 6/Week 12 
(N=XXX) 
Visit 13/Week 52 
(N=XXX) 
Abnormal, n/N (%) 
General Appearance Assessment 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Dermatology Assessment 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
HEENT Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Lymphatic Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Respiratory Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Cardiovascular Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Abdominal Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Musculoskeletal Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Neurological Results 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
  
 
Note: DB=Double-Blind phase.   
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 27 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.   
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
 
 
 
 
            Table 14.3.3.2.2.1: Shifts in Physical  Exam Result from Baseline to Week 12 and  Week 52  
                                                  Safety Population Entering Open-Label 
  
  
  
DB-FMX-101, 4%  
DB-Vehicle Foam 
(N=XXX) 
(N=XXX) 
Any Body System  
  
 
Visit 6/Week 12 
 
  N [1]  
XXX 
XXX 
  Abnormal to Normal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
  Normal to Abnormal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
 
Visit 13/ Week 52 
 
 
  N [2]  
XXX 
XXX 
  Abnormal to Normal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
  Normal to Abnormal, n (%) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
<Continue for General Appearance, Dermatology, HEENT, Lymphatic, Respiratory, Cardiovascular, Abdominal, Musculoskeletal and Neurological   Assessment > 
  
 
  
  
Note: DB=Double-Blind phase. Baseline value is defined as the last non-missing value prior to the first dose of study drug during the double-blind phase 
[1] Number of subjects in the safety population with physical exam for both baseline and week 12 within treatment group. 
[2] Number of subjects in the safety population with physical exam for both baseline and week 52 within treatment group. 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 28 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No. FX2014-05, Open-Label Phase 
 
Table 14.3.4.1: Summary of Tolerability Assessment 
Safety Population Entering Open-Label 
  
  
  
DB-FMX-101, 4% (N=XXX) 
  
DB-Vehicle Foam (N=XXX) 
 
  
0=None 
1=Mild 
2=Moderate 
3=Severe 
0=None 
1=Mild 
2=Moderate 
3=Severe 
  
  
  
  
  
  
 
 
 
  
Visit 2/ Week 1  
 
 
 
 
 
 
 
 
 
Face, n (%) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Erythema 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Dryness 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Hyperpigmentation 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Skin Peeling 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Itching 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
Non-facial Sites, n (%) 
 
 
 
 
 
 
 
 
Erythema 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Dryness 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Hyperpigmentation 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Skin Peeling 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
Itching 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
XXX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
< Continue for Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, and Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 
40, Visit 12/Week 46 and Visit 13/Week 52> 
 
  
 
 
 
 
 
 
Note: DB=Double Blind phase. If more than one non-face area is affected (neck, chest, back, right shoulder, right arm, left shoulder, left arm 
and other), the region affected maximally is reported and the maximum intensity is reported 
 
 
Generated on XX/XX/X XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference: Data Listing XXXXXXXXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 29 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.   
Page X of Y  
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.1.2.1: Subject Disposition 
All Randomized Subjects 
Randomized Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
 
 
 
Site/Subject  
 
Date of First  
Dose in DB  [1] 
Date (Day) of First 
Dose in OL [2] 
Date (Day) of  Last 
Dose in OL [3] 
Date (Day) of Last 
Visit  
Date (Day) of Last 
Contact  
Completion Status / With 
drawl Reason 
 
 
 
 
 
 
 
 
XX/XXX 
 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
Completed 
XX/XXX 
 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
Lost to Follow-up 
XX/XXX 
 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
XXXXXXX 
XX/XXX 
 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
ddMMMyyyy (XX) 
XXXXXXX 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
DB= Double- Blind. OL=Open-Label 
Note: Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
[1] First dose administration ( Day 1) 
 
 
 
 
 
[2] First report of drug administration after rolling into the open-label phase 
[3] Last report of  drug administrated during the open-label phase 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 30 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc. 
                     Page X of Y 
Protocol No. FX2014-05 
 
Data Listing 16.2.2.1: Protocol Deviations 
All Randomized Subjects with Protocol Deviations 
Randomized Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
Site/ 
Subject  
Type 
  
Description 
 
Action Taken 
 
 
 
 
  
 
 
 
 
XX/XXX  Study product use   
XXXXXXXXX 
 
Retrained on protocol 
 
 
 
 
  
 
 
 
 
XX/XXX  
Missed Visit 
  
XXXXXXXXX 
 
Other: XXXX 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by  XXXXX / Uses: XXXX 
 
 
 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 31 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharamaceuticals, Inc.  
 
 
 
Page X of Y 
Protocol No. FX2014-05  
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.4.4.1: Concomitant Medications used at Any Time During the Study 
All Randomized Subject 
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
 
  
  
  
  
  
  
Site/Subject 
WHO Preferred Term (Verbatim Term) / ATC 
Classification 
Indication 
Dose/ Dose 
Unit 
Frequency/ Route 
Start Date  (Day)/ 
Stop Date  (Day) [1] 
  
  
  
  
  
  
 
  
  
 
  
  
XX/XXX  
xxxxxxxxx(xxxxxxx)/ xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/ 
ddMMMyyyy  (XX)  
 
 
 
 
 
 
XX/XXX  
xxxxxxxxx(xxxxxxx)/ xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/ 
ddMMMyyyy  (XX)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
Note: Concomitant = ongoing or with stop dates on or after Day 1. 
 
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 32 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharamaceuticals, Inc.  
 
 
 
Page X of Y 
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.4.4.2: Concomitant Medications used during Double-Blind Phase 
 
All Randomized Subject 
 
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
 
Site/Subject 
WHO Preferred Term 
(Verbatim Term) / ATC 
Classification 
Indication 
Dose/ Dose Unit 
Frequency/ 
Route 
Start Date  (Day)/ Stop 
Date  (Day) [1] 
Ongoing at end 
of Double-Blind 
Phase? 
  
  
  
  
  
  
 
 
  
  
 
  
  
 
XX/XXX  
xxxxxxxxx(xxxxxxx)/ 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/  
--  
                Y 
 
 
 
 
 
 
 
XX/XXX  
xxxxxxxxx(xxxxxxx)/ 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/ 
ddMMMyyyy  (XX)  
                N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
 
  
  
  
  
  
 
Note: Includes concomitant medications ongoing or with stop dates on or after Day 1 but start date prior to first dose in Open-Label Phase. 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. If end date is missing the concomitant 
medication is ongoing.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 
<<<<Programmer note: if stop date is not provided include a “/” after the start date to clarify >>>> 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 33 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharamaceuticals, Inc.  
 
 
 
Page X of Y 
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.4.4.3: Concomitant Medications starting in the Open-Label Phase 
All Randomized Subject  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
  
  
  
  
  
  
Site/Subject 
WHO Preferred Term (Verbatim Term) / ATC 
Classification 
Indication 
Dose/ Dose 
Unit 
Frequency/ Route 
Start Date  (Day)/ 
Stop Date  (Day) [1] 
  
  
  
  
  
  
 
  
  
 
  
  
XX/XXX  
xxxxxxxxx(xxxxxxx)/ xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/  
-- 
 
 
 
 
 
 
XX/XXX  
xxxxxxxxx(xxxxxxx)/ xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxx/xxx 
xxx/xxxxx 
ddMMMyyyy  (XX)/ 
ddMMMyyyy  (XX)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
Note: Includes concomitant medications starting on or after the first dose in the Open-Label Phase. 
 
 
 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 
<<<<Programmer note: if no stop date is provided include a “/” after the start date to clarify >>>> 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 34 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.                            
 
 
 
 
 
Page X of Y 
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                          Data Listing 16.2.5.1.1: Study Medication Exposure and Usage 
 
 
 
                                                                  All Randomized Subjects  
                                              Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
Site/Subject  
Date of First Dose 
in DB  
Date (Day) of 
Last Dose [1]     
Phase of 
Last Dose  
Total 
Days of 
Exposure 
[2] 
          Visit 
# 
Canisters 
Dispensed 
# 
Canisters 
Returned 
Kit 
Number 
Dispensed 
Regions Beyond 
the Face where 
Study Drug was 
Applied 
XX/XXX 
 
ddMMMyyy(XX) 
ddMMMyyy(XX) 
Double-
Blind 
92 
Baseline/Visit 1 
2 
  
19197 
NONE 
 
 
 
 
 
 
Visit 2/Week 1 
2 
2 
19197 
NONE 
 
 
 
 
 
 
Visit 3/Week 3 
2 
0 
13345 
NONE 
 
 
 
 
 
 
Visit 4/Week 6 
2 
2 
19818 
NONE 
 
 
 
 
 
 
Visit 5/Week 9 
2 
2 
14092 
NONE 
 
 
 
 
 
 
Visit 6/Week 12 
2 
2 
90047 
NONE 
 
 
 
 
 
 
Visit 6/Week 12 
2 
2 
90048 
NONE 
 
 
 
 
 
 
 
 
 
 
 
 
<< Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>> 
  
 
  
DB= Double-Blind; OL= Open-Label 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
[1]Total number of days to exposure to study drug is defined as the date of last dose of the study drug minus the first dose of study drug plus 1. 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 35 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.      
 
 
Page X of Y 
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
Data Listing 16.2.5.2.1: Study Medication Accountability 
All Randomized Subjects  
Randomized Treatment: [DB-FMX-101, 4%][ DB-Vehicle Foam] 
Site/ 
Kit 
Number of  
Amount 
Amount 
Subject 
Number 
Canisters  
Returned 
Applied 
  
Dispensed 
Returned in Kit 
(g) 
(g) [1] 
XX/XXX 
XXXXX 
X 
XX.X 
XX.X 
 
XXXXX 
X 
XX.X 
XX.X 
 
XXXXX 
X 
XX.X 
XX.X 
 
XXXXX 
X 
XX.X 
XX.X 
 
XXXXX 
X 
XX.X 
XX.X 
  
  
  
  
  
 
 
 
 
 
[1] Weight of applied medication is defined as the difference in weight of returned and dispensed canisters. Sealed canisters will be assumed to be 0 g. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 36 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.                                                                                                   
 
 
 
 
 
Page X of Y 
Protocol No.FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.1.1.1: Lesion Counts   
All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
  
  
  
  
Inflammatory Lesions (IL) 
Noninflammatory Lesions (NIL) 
  
 
Site/Subject  
 
Analysis Visit [1] 
Date (Day) [2] 
Papules 
Pustules 
Nodules 
Total 
IL 
Open 
Comedones 
Closed 
Comedones 
Total 
NIL 
Total 
[3] 
Non Facial 
Area [4] 
  
  
  
  
  
  
  
  
  
  
  
  
  
XX/XXX 
 
Screening 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX,XX 
 
 
Baseline/Visit 1  
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 2/Week 1 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 3/Week 3 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 4/Week 6 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 5/Week 9 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
Visit 6/Week 12 
ddMMMyyy (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
< Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46 and Visit 13/Week 52> 
  
  
  
  
  
  
  
  
  
  
  
  
  
DB=Double-Blind 
 
 
 
 
 
 
Note: If more than one visit occurs within a single analysis visit window, then the analysis will take the one closest to the target day. Values with * are not used in analysis. 
[1] The 'unassigned' analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
[3] Total includes inflammatory and noninflammatory. 
[4] Regions beyond the face affected by acne. 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 37 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.  
Page X of Y 
Protocol No.FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.1.2.1: Total Inflammatory and Noninflammatory Lesion Counts 
 
 
 
 
All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
Site/Subject 
 
Analysis Visit [1] 
Date (Day) [2] 
 Type 
Total Inflammatory 
Total 
Noninflammatory 
 
  
  
  
  
  
  
  
XX/XXX 
 
Screening 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
Baseline/Visit 1  
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
Visit 2/Week 16 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
 
 
Change From Baseline 
XX 
XX 
 
 
 
 
Percent Change from Baseline  
XX.X 
XX.X 
 
 
Visit 3/Week 22 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
 
 
Change From Baseline 
XX 
XX 
 
 
 
 
Percent Change from Baseline  
XX.X 
XX.X 
 
 
Visit 4/Week 28 
ddMMMyyyy (XX) 
Absolute Value 
XX 
XX 
 
 
 
Change From Baseline 
XX 
XX 
 
 
 
Percent Change from Baseline  
XX.X 
XX.X 
 
 
 
 
 
 
< Continue for Visit 6/Week 40, Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46 and Visit 13/Week 52>  
 
 
Note: If more than one visit occurs within a single analysis visit window, then the analysis will take the one closest to the target day. Values with * are not used in analysis. 
Change from baseline is calculated as baseline value minus post-baseline value. Percent change from baseline is calculated as baseline value minus post-baseline value divided by 
the baseline value expressed as a percent. 
 
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
  [2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 38 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.  
 
 
Page X of Y 
Protocol No.FX2014-05 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.2.1: Investigator’s Global Assessment and Treatment Success 
All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
  
  
  
  
  
Site/Subject 
Analysis Visit [1] 
Date (Day)  [2] 
IGA 
Treatment Success 
  
 
  
  
 
 
 
  
  
 
XX/XXX 
Screening 
ddMMMyyyy (XX) 
3 
- 
 
Baseline/Visit 1 
ddMMMyyyy (XX) 
3 
- 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
3 
No 
 
Visit 4/Week 6 
ddMMMyyyy (XX) 
3 
No 
 
Visit 5/Week 9 
ddMMMyyyy (XX) 
1 
Yes 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
1 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<< Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>> 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
IGA= Investigator’s Global Assessment 
 
 
Note: If more than one visit occurs within a single analysis window, then the analysis will take the one closest to the target day. Value with * are not used in analysis  
[1] The 'unassigned' analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 39 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.   
 
 
 
Page X of Y 
Protocol No.FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.6.3.1: Subject Satisfaction Questionnaire  
 
 
 
                     All Randomized Subjects  
 
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
  
 
 
 
 
Site/Subject  
 
Analysis Visit [1]  
Date (Day) [2] 
Question  
Response  
XX/XXX 
 
    Visit 6/Week 12 
ddMMMyyyy (XX) 
Q1: How satisfied are you with this product in treating your acne? 
1=Very Satisfied 
 
 
 
 
 
 
 
 
Q2: How satisfied are you with how easy this product is to use? 
1=Very Satisfied 
 
 
Q3: How satisfied are you with this product compared to other products you 
1=Very Satisfied 
 
 
       have previously used for acne, such as gels and creams? 
 
 
Q4: How satisfied are you with how this product feels on you skin after      
       treatment 
1=Very Satisfied 
 
 
Q5: How satisfied are you with the odor of this product after treatment? 
1=Very Satisfied 
 
 
Q6: How satisfied are you with the color of this product after treatment? 
1=Very Satisfied 
 
 
Q7: Overall, how satisfied are you with this product? 
1=Very Satisfied 
 
 
Q8: Overall, how likely are you to recommend this product to a friend? 
1=Very Likely 
XX/XXX 
 
   Visit 13/Week 52 
ddMMMyyyy (XX) 
Q1: How satisfied are you with this product in treating your acne? 
1=Very Satisfied 
 
 
        Q2: How satisfied are you with how easy this product is to use? 
1=Very Satisfied 
 
                           Q3: How satisfied are you with this product compared to other products you 
1=Very Satisfied 
 
                             have previously used for acne, such as gels and creams? 
1=Very Satisfied 
 
                            Q4: How satisfied are you with how this product feels on you skin after  
                              treatment 
1=Very Satisfied 
 
                            Q5: How satisfied are you with the odor of this product after treatment? 
1=Very Satisfied 
 
                            Q6: How satisfied are you with the color of this product after treatment? 
1=Very Satisfied 
 
                            Q7: Overall, how satisfied are you with this product? 
                    1=Very Satisfied 
                                                          Q8: Overall, how likely are you to recommend this product to                          1=Very Likely 
  
  
  
  
  
  
  
 
[1] The 'unassigned' analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 40 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharamaceuticals 
                                                                                                                                                                                       Page X of Y 
Protocol No. FX2014-05 
 
Data Listing 16.2.7.1.1: Adverse Events at Any Time During the Study  
All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
Site/ 
Subject 
 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment Area 
Treatment-emergent?[1]/  
Onset Date (Day) –  
End Date (Day) [2] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken 
/ 
SAE? SAE Criteria 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX)  –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
XXX 
 
 
 
 
 
[1]TEAEs are defined as AEs starting on or after the date of the first application of study medication. 
  [2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
 Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 41 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharamaceuticals 
Protocol No. FX2014-05 
                                                                                                                                                                                           Page X of Y 
 
Data Listing 16.2.7.1.2: Adverse Events Starting in the Double-Blind Phase 
All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
Site/ 
Subject 
 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment 
Area 
Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken / 
SAE? SAE Criteria 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
ddMMMyyyy (XX)  –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
XXX 
 
 
 
 
 
Note: Adverse Events starting in Double-Blind Phase are AEs with a start date on or after first dose in Double-Blind Phase but prior to first dose in Open-Label Phase. 
[1]Study day is calculated relative to the date of Day 1, the date of first study drug administration. An AE with end date greater than Day 84 generally continued into the open-label 
phase.   
  
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 42 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
 
Foamix Pharamaceuticals 
                                                                                                                                                                                           Page X of Y 
Protocol No. FX2014-05 
 
Data Listing 16.2.7.1.3:Adverse Events Starting in the Open-Label Phase  
All Randomized Subjects Entering Open-Label Phase  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
Site/ 
Subject 
 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment Area Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken / 
SAE? SAE Criteria 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
ddMMMyyyy (XX)  –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
XXX 
 
 
 
 
 
Note: Adverse Events starting in Open-Label Phase are AEs with a start date on or after first dose in Open-Label Phase. 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
 Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 43 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
 
 
 
 
 
 
Foamix Pharamaceuticals, Inc. 
      Page X of Y  
Protocol No. FX2014-05 
Data Listing 16.2.7.2.1: Serious Adverse Events Starting in Open-Label Phase Leading to Study Discontinuation 
All Randomized Subjects Entering Open-Label Phase 
Actual Treatment: [ DB-FMX-101,4%][ DB-Vehicle Foam] 
 
Site/ 
Subject 
 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment Area 
Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken 
/ 
SAE? SAE Criteria 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
 Note: Adverse Events starting in Open-Label Phase are AEs with a start date on or after first dose in Open-Label Phase. 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 44 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharamaceuticals, Inc. 
             Page X of Y  
Protocol No. FX2014-05 
Data Listing 16.2.7.3.1: Treatment-Emergent Adverse Events Starting in Open-Label Phase Leading to Study Discontinuation 
 All Randomized Subjects Entering Open-Label Phase  
Actual Treatment: [FMX-101,4%][Vehicle Foam] 
 
Site/ 
Subject 
 
MedDRA SOC Term/ 
MedDRA Preferred Term / 
(Verbatim Term) / 
Location of AE to Treatment 
Area 
Onset Date (Day) –  
End Date (Day) [1] 
Severity / 
Relationship  / 
Outcome 
Action Taken / 
Other Action Taken 
/ 
SAE? SAE Criteria 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Outside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
No 
 
 
XX/XXX 
 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Inside Treatment Area 
Y / 
ddMMMyyyy (XX) –  
ddMMMyyyy (XX) 
XXXXXXXX /  
XXXXXXXX /  
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX /  
Yes: XXXX 
 
 
Note: Adverse Events starting in Open-Label Phase are AEs with a start date on or after first dose in Open-Label Phase. 
[1] Study day is calculated relative to the date of Day 1, the date of first study drug administration during double-blind phase. 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 45 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
Foamix Pharmaceuticals, Inc.  
 
             Page X of Y 
Protocol No. FX2014-05 
 
Data Listing 16.2.8.1.1: Urine Pregnancy Test 
All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
Site/ 
 
Childbearing Potential 
Analysis Visit [1] 
Date of Test (Day)[2] 
Result 
Subject 
 
 
 
 
 
 
XX/XXX 
 
XXXXXXX 
Baseline/Visit 1 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 2/Week 1 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 4/Week 6 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 5/Week 9 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
Negative 
 
 
 
Visit 13/Week 52 
ddMMMyyyy (XX) 
Negative 
 
 
 
 
 
 
XX/XXX 
 
           Male 
-- 
-- 
-- 
 
 
<<<<Include all available visits>>> 
  
  
  
  
 
 
 [1] The 'unassigned' analysis visit indicates a visit that did not fall into an analysis window. 
 [2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 46 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.  
 
 
 
 
 
Page X of Y 
Protocol No.FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.1.2: Home Pregnancy Test          
 
 
 
 
 
               All Randomized Subjects  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
Site/Subject 
 
Childbearing 
 Potential 
Analysis Visit [1] 
Date (Day) [2] 
Was a Home 
Pregnancy Test 
dispensed? 
Positive 
Pregnancy 
Test since last 
Visit? 
Date of 
Positive 
Pregnancy 
Test 
  
  
 
  
 
  
  
 
XX/XXX 
 
XXXXX 
Visit 6/ Week 12 
ddMMMyyyy (XX) 
XXX 
- 
- 
 
 
 
Visit 7/Week 16 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 8/Week 22 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 9/Week 28 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 10/Week 34 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 11/Week 40 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 12/Week 46 
ddMMMyyyy (XX) 
XXX 
XXX 
- 
 
 
 
Visit 13/Week 52 
ddMMMyyyy (XX) 
         XXX 
XXX 
- 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
[1] The 'unassigned' analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration during the double-blind phase. 
 
 
 
 
 
   Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 47 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
 
 
 
 
Foamix Pharmaceuticals, Inc.                                                                                                                                                                                                                         Page X of Y 
Protocol No. FMX2014-04 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.2.1.X.1:  Clinical Laboratory Tests 
All Randomized Subjects   
[Hematology][Chemistry][Urinalysis] 
Actual Treatment: [ DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
 
 
 
Site/Subject 
 
Analysis Visit [1] 
Test Name 
Test Date (Day)[2] 
Result (Unit) 
Abnormal? 
Clinically 
Significant? 
Reference Range 
 
 
 
 
 
 
 
 
 
XX/XXX 
 
Baseline/Visit 1  
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Normal 
 
xxxx, xxxx 
 
 
 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Normal 
 
xxxx, xxxx 
 
 
 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Low 
No 
xxxx, xxxx 
 
 
 
<< Include for Visit 2/Week 1, Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week 12, Visit 1 Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 
10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
 
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 48 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
 
 
 
 
Foamix Pharmaceuticals, Inc.  
                                    Page X of Y 
Protocol No. FMX2014-04 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.2.2.1:  Clinically Significant Clinical Laboratory Tests for Hematology, Chemistry and Urinalysis 
 
All Randomized Subjects   
Actual Treatment: [DB-FMX-101,4%][DB-Vehicle Foam] 
 
 
 
 
 
 
 
 
 
 
Site/Subject 
 
 
Analysis Visit [1] 
Category of      
Laboratory 
Test 
Test Name 
Test Date (Day)[2] 
Result (Unit) 
Abnormal? 
Reference 
Range 
 
 
 
 
 
 
 
 
 
XX/XXX 
Baseline/Visit 1 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
xxxx, xxxx 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
xxxx, xxxx 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Low 
xxxx, xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
<< Include for Visit 2/Week 1, Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week 12, Visit 1 Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 
10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 49 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
                 Page X of Y 
 
 
 
 
Foamix Pharmaceuticals, Inc.  
 
Protocol No. FMX2014-04 
 
 
 
 
 
 
Data Listing 16.2.8.2.3.1: Out-of-Range (Abnormal) Clinical Laboratory Test Results for  Hematology, Chemistry and Urinalysis 
All Randomized Subjects    
Actual Treatment: [ DB-FMX-101,4%][ DB-Vehicle Foam] 
 
 
 
 
 
 
  
 
 
 
Site/Subject 
 
Analysis Visit [1] 
Category of      
Laboratory 
Test 
Test Name 
Test Date (Day)[1] 
Result (Unit) 
Abnormal? 
Clinically 
Significant 
 
 
 
 
 
 
 
 
XX/XXX 
Baseline/Visit1 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
No 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
High 
No 
 
 
 
Chemistry 
xxxx 
ddMMMyyyy (XX) 
xxxx (xxxx) 
Low 
No 
 
 
 
 
 
 
 
 
 
 
 
 
<< Include for Visit 2/Week 1, Visit 3/Week 3, Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week 12, Visit 1 Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 
28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46, Visit 13/Week 52>>> 
 
 
  
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
  Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 50 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.    
 
 
 
 
 
Page X of Y 
Protocol No. FX2014-05 
 
 Data Listing 16.2.8.3.1:  Vital Signs  
All Randomized Subjects   
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
  
Site/ 
Analysis Visit [1] 
Date (Day) [2] 
Height (cm) 
Weight (kg) 
Systolic Blood  
Diastolic Blood  
Pulse Rate  
Subject 
Pressure (mmHg) 
Pressure (mmHg) 
(beats/minute) 
  
Observed 
Observed 
CFBL 
Observed 
CFBL 
Observed 
CFBL 
Observed 
CFBL 
 
 
 
 
 
 
 
 
 
 
XX/XXX 
Baseline/Visit 1 
ddMMMyyyy (XX) 
xxx.x 
xxx x 
-- 
xxx 
-- 
xxx 
-- 
xx 
-- 
 
Visit 2/Week 1 
ddMMMyyyy (XX) 
-- 
-- 
-- 
xxx 
-- 
xxx 
-- 
xx 
-- 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
-- 
-- 
-- 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
Visit 4/Week 6 
ddMMMyyyy (XX) 
-- 
-- 
-- 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
Visit 5/Week 9 
ddMMMyyyy (XX) 
-- 
-- 
-- 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
-- 
xxx x 
xxx x 
xxx 
xxx.x 
xxx 
xxx x 
xx 
xx.x 
  
   
< <<Continue for Visit 7/Week 16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 46 and Visit 13/Week 
52>>>  
 
  
 
  
  
CFBL=Change from baseline 
Note: If more than one visit occurs within a single analysis visit window, then the analysis will take the one closest to the target day. Values with * are not used in analysis. 
Baseline value is defined as the last non-missing value prior to the first dose of study drug. Change from baseline is calculated as baseline value minus post-baseline value. 
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by LSTVS / Uses: XX 
 
 
 
 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 51 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
Foamix Pharmaceuticals, Inc.   
 
 
                        Page X of Y 
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.4.1: Physical  Exam  
All Randomized Subjects Abnormal Results  
Actual Treatment: [DB-FMX-101,4%][ DB-Vehicle Foam] 
  
  
  
  
  
  
  
Site/ 
 
Analysis Visit [1] 
Date (Day) [2] 
Body System 
Result 
Comment 
Subject 
 
 
  
  
  
  
  
XX/XXX 
 
Baseline/Visit 1  
ddMMMyyyy (XX) 
General Appearance 
Abnormal 
 XXXXXXXXX 
 
Visit 6/Week 12 
ddMMMyyyy (XX) 
Dermatological 
Abnormal  
XXXXXXXXX 
 
 
Visit 13/Week 52 
ddMMMyyyy (XX) 
Dermatological 
Abnormal  
XXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 52 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
 
 
 
 
 
Foamix Pharmaceuticals, Inc.   
 
 
 
   
Page X of Y  
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.5.1: Tolerability Assessment for Face 
 
All Randomized Subjects  
Actual Treatment: [ DB-FMX-101,4%][ DB-Vehicle Foam]   
  
 
  
  
  
  
  
 
Site/ 
 
Analysis Visit [1] 
Date (Day) [2] 
Symptoms 
 
Intensity 
Comment 
Subject 
 
 
 
 
 
 
 
XX/XXX 
 
Visit 2/Week1 
ddMMMyyyy (XX) 
Erythema 
 
1=Mild 
 XXXXX 
 
Dryness 
 
1=Mild 
 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
 
 
 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
Erythema 
 
1=Mild 
 XXXXX 
 
 
 
Dryness 
 
1=Mild 
 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
<Continue for  Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week12, Visit 7/Week16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 
46, Visit 13/Week 52> 
  
 
  
  
  
  
  
  
 
 
Note: If more than one visit occurs within a single analysis visit window, then the analysis will take the one closest to the target day. Values with * are not used in analysis. 
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 


Foamix Pharamaceuticals, Inc.   
                             
  
Page 53 of 53 
Protocol No. FX2014-05  
 
  
December 7, 2017 
Novella Clinical No. CT991615 
 
 
 
 
Foamix Pharmaceuticals, Inc.   
 
 
 
Page X of Y  
Protocol No. FX2014-05 
 
 
 
 
 
 
 
 
 
Data Listing 16.2.8.5.2: Tolerability Assessment for Non-Facial Areas 
 
All Randomized Subjects   
Actual Treatment: [ DB-FMX-101,4%][ DB-Vehicle Foam]   
  
 
  
  
  
  
  
 
Site/ 
 
Analysis Visit [1] 
Date (Day) [2] 
Symptoms 
Affected Area 
[3] 
Intensity
[4] 
Comment 
Subject 
 
 
 
 
 
 
 
XX/XXX 
 
Visit 2/Week1 
ddMMMyyyy (XX) 
Erythema 
Non-face: Neck 
1=Mild 
 XXXXX 
 
Dryness 
 
1=Mild 
XXXXX 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
 
 
 
 
 
Visit 3/Week 3 
ddMMMyyyy (XX) 
Erythema 
Non-face: Neck 
1=Mild 
 XXXXX 
 
 
 
Dryness 
 
1=Mild 
XXXXX 
 
 
 
Hyper-Pigmentation 
 
1=Mild 
 
 
 
 
 
Skin Peeling 
 
1=Mild 
 
 
 
 
 
Itching 
 
1=Mild 
 
 
 
 
 
<Continue for  Visit 4/Week 6, Visit 5/Week 9, Visit 6/Week12, Visit 7/Week16, Visit 8/Week 22, Visit 9/Week 28, Visit 10/Week 34, Visit 11/Week 40, Visit 12/Week 
46, Visit 13/Week 52> 
  
 
  
  
  
  
  
  
 
 
 
 
Note: If more than one visit occurs within a single analysis visit window, then the analysis will take the one closest to the target day. Values with * are not used in analysis. 
 
[1] The “unassigned” analysis visit indicates a visit that did not fall into an analysis window. 
 
[2] Study day is calculated relative to the date of Day 1, the date of first study drug administration. 
[3] For non-face area, region affected maximally is reported 
[4] For non-face area, maximum intensity is reported 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX