Conditions: Acne Vulgaris
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 601
Healthy volunteers: no

Brief summary:
This is a multi-center, open label long-term safety (LTS) study to be conducted in approximately 600 subjects with acne vulgaris.

Detailed description:
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term Safety of SB204 Once Daily in the Treatment of Acne Vulgaris.

Arms:
arm 1: All subjects received SB204 4% once daily (QD) in this open label study. Subjects assigned to SB204 4% QD in the parent study (NI-AC301/302) continued to receive SB204 for 40 more weeks. Subjects assigned to Vehicle Gel in the parent study (NI-AC301/302) received SB204 4% QD in this open label study.

Interventions: intervention 1: SB204 4%
Intervention descriptions: intervention 1: Open label, topical SB204 4%

Protocol document:
Prot_000.pdf: 
 
 
Confidential and Proprietary, Novan, Inc. 
  
 
 
 
 
STUDY TITLE 
A Phase 3 Multi-Center, Open Label Study Evaluating 
the Long Term Safety of SB204 Once Daily in the 
Treatment of Acne Vulgaris 
PROTOCOL NO. 
NI-AC303 
SPONSOR 
Novan, Inc. 
4222 Emperor Blvd., Suite 200 
Durham, NC 27703 
Tel.: 919-485-8080 
VERSION DATE 
9 November 2015 
VERSION 
1.0 
 
The study will be conducted in compliance with the obligations as detailed in this 
protocol and all applicable regulations and guidelines (e.g., International Conference on 
Harmonisation, Good Clinical Practices guidelines). 
 
 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is provided to you in confidence as an Investigator, 
potential Investigator, or consultant for review by you, your staff, and an applicable Institutional 
Review Board.  The information is only to be used by you in connection with authorized clinical studies 
of the investigational product described in the protocol.  You may not disclose any of the information 
contained within to others without written authorization, except to the extent necessary to obtain 
informed consent from those persons to whom the investigational product may be administered. 
 




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 INFORMATION PAGE 
Sponsor Contact Information: 
 
Novan, Inc. 
4222 Emperor Blvd., Suite 200 
Durham, NC 27703 
Tel:  919-485-8080 
Fax:  919-237-9212 
 
CRO Contact Information: 
 
Chiltern  
4000 CentreGreen Way 
Suite 300 
Cary, NC 27513 
Tel: 919-462-8867 
 
PROJECT MANAGER: 
Sandra Boehnke 
Tel: 423-990-0281 
Mobile: 512-963-0193 
Fax: 888-697-9147 
E-mail: sandra.boehnke@chiltern.com 
 
MEDICAL MONITOR: 
William R Welder, MD, MPH 
Tel: 423-990-0471 
Fax: 888-833-6865 
E-mail: Bill.Welder@Chiltern.com 
 
 
 
 
Serious Adverse Event (SAE) and Safety Contact Information: 
SAE Hotline: 1-888-SAE CHIL (888-723-2445) 
Email:GlobalSAEInbox@Chiltern.com 
Fax: 1-800-468-2288                             
 
 


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INVESTIGATOR’S AGREEMENT 
I have carefully read the protocol entitled: “A Phase 3 Multi-Center, Open Label Study Evaluating 
the Long Term Safety of SB204 Once Daily in the Treatment of Acne Vulgaris” and,  
 
I agree that the protocol contains the necessary information required to conduct the study. I also 
agree to conduct this study as outlined in and according to the obligations of Clinical Investigators 
and all other pertinent requirements in the International Conference on Harmonisation (ICH) Good 
Clinical Practice (GCP) guideline. 
 
I agree to obtain approval of the protocol and informed consent prior to the start of the study by an 
Institutional Review Board (IRB). 
 
I agree to obtain formal written informed consent in accordance with applicable federal and local 
regulations and international guidelines from all subjects prior to their entry into the study. 
 
I have received and reviewed the Investigator’s Brochure including the potential risks and side 
effects of the product and instructions for use. 
 
I agree to report to Novan, Inc. or designee adverse events that occur during the course of the study 
in accordance with the ICH GCP guideline and the protocol. 
 
I agree to ensure that all associates, colleagues and employees assisting me with the conduct of the 
study are informed of their responsibilities in meeting the above commitments and the 
commitments set forth in this Investigator’s Agreement. 
 
I agree to maintain adequate and accurate records and to make those records available for 
inspection in accordance with the ICH GCP guideline, and federal and local requirements. 
 
The Investigator, agreeing to be fully bound, hereby executes this agreement on the date as set 
forth below. 
 
 
Investigator Signature 
 
 
 
 
 
 
Printed Name 
 
Date 
Address 
 
 
 
 
Phone Number 


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
Novan, Inc. 
Name of Finished Product: 
SB204 
Name of Active Ingredient: 
NVN1000 
Title 
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term 
Safety of SB204 Once Daily in the Treatment of Acne Vulgaris 
Study Objectives 
The primary objective of this study is to evaluate the safety of SB204 4% 
in subjects with acne vulgaris for up to 40 weeks of treatment. 
Treatment 
Regimens 
Eligible subjects at the Baseline visit will be assigned to SB204 QD and 
treated for up to 40 weeks to acne affected areas including the face, chest, 
back and upper shoulders.  
Formulation 
Investigational Drug:  SB204, containing NVN1000 Gel and hydrogel 
Study Period 
Subjects will be dosed in the study for up to 40 weeks. 
Study Design 
This is a multi-center, open label long-term safety (LTS) study to be 
conducted in approximately 600 subjects with acne vulgaris. Subjects 
eligible to enroll in this study will have completed one of the Phase 3 
pivotal studies with SB204, NI-AC301 or NI-AC302.  
Subjects who satisfy the entry criteria at the Baseline visit will be 
enrolled to receive open-label SB204. Investigational drug will be 
delivered from a double barrel single pump dispenser. The pump 
dispenses product (NVN1000 Gel and a hydrogel) from two chambers 
which will be mixed together quickly (about 5 seconds) by the subject 
and applied to the acne affected areas including the face, chest, back and 
upper shoulders once daily. No other acne treatments will be permitted 
during the study. Tolerability and safety assessments include cutaneous 
tolerability evaluation, adverse event collection, physical exams 
including blood pressure and pulse rate, and urine pregnancy tests 
(UPTs). Subjects will return for post-baseline evaluation at Weeks 4, 12, 
24, 36 and 40.   
Diagnosis and 
Criteria for 
Inclusion/Exclusion 
Male and female subjects who completed one of the two SB204 Phase 3 
pivotal studies will be eligible for participation in the study. The last visit 
in the Phase 3 pivotal study may serve as the first visit for the long-term 
safety study. Subjects must enroll in the LTS study within 7 days of 
completion of NI-AC301 or NI-AC302. Any subject who terminated 
early from one of these studies for any reason will not be eligible to enroll 


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in this long-term safety study. 
 
Inclusion criteria: 
 Have no more than two nodules on the face; 
 Completed 12 weeks of treatment in NI-AC301 or NI-AC302 
Exclusion Criteria: 
 Terminated early from an SB204 Phase 3 pivotal study for any 
reason;  
 Have any dermatological conditions on the face that could 
interfere with clinical evaluations such as acne conglobata, acne 
fulminans, acne secondary to medications or other medical 
conditions, perioral dermatitis, clinically significant rosacea, or 
gram-negative folliculitis; 
 Have an on-going adverse event at the Week 12 visit for NI-
AC301 or NI-AC302 that warrants stopping study drug 
application; 
 Have facial hair, tattoos or other facial markings that would 
interfere with efficacy and safety assessments; 
 Have any underlying disease(s) or some other dermatological 
condition of the face that requires the use of interfering topical or 
systemic therapy or makes evaluations and lesion count 
inconclusive; 
 Have used medications or vitamins during the 12 weeks 
immediately preceding Baseline which are reported to exacerbate 
acne (e.g. azathioprine, haloperidol, halogens such as iodides or 
bromides, lithium, anabolic steroids, systemic corticosteroids, 
phenytoin and phenobarbital). Daily use of a multi-vitamin is 
acceptable. 
Sample Size 
Approximately 600 subjects will be entered into the study.   
Safety and 
Tolerability 
Evaluation 
Safety and tolerability assessments will be collected beginning at the 
Baseline visit for NI-AC303. The subject must enroll in NI-AC303 
within 7 days of completion of NI-AC301 or NI-AC302. Demographics 
and the subject’s Week 12 visit values from NI-AC301 or NI-AC302 for 
blood pressure, pulse, urine pregnancy test, physical exam findings, 
lesion counts and tolerability will be used as the Baseline values for NI-
AC303. Adverse events will be assessed and collected at each evaluation 
beginning at Baseline. A brief physical exam will be collected at Week 
40/Early Termination (ET). Blood pressure and pulse will be collected 
at each visit through Week 40/ET. Urine pregnancy tests in women of 


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child-bearing potential (WOCBP) will be conducted at each visit.  
Subjects will be assessed at each visit through Week 40 for cutaneous 
tolerability on the face. Tolerability will be assessed on a scale of 0 to 3 
where 0=none, 1=mild, 2=moderate, and 3=severe for erythema, scaling, 
dryness, pruritus, and burning/stinging. 
The body surface area (BSA) treated (based on locations) will be 
collected at each visit for each subject   Extent of exposure will be 
calculated for each subject based on the number of treatments and 
treatment area.  Extent of exposure will also be summarized on a unit 
day which will be defined as total exposure divided by the total number 
of days enrolled. 
Endpoints 
Safety endpoints will include adverse events, changes in physical 
examination and changes in vital sign measurements. Any clinically 
significant changes noted during the physical exam as well as from the 
vital sign measurements will be recorded as adverse events and 
included in the comparison. Urine pregnancy tests in women of child-
bearing potential will be conducted at each visit. 
Tolerability endpoints will include the investigator’s assessment of 
erythema, scaling, dryness, and the subject’s report of pruritus and 
burning/stinging based on the preceding 24 hours. 
Statistical Methods 
All statistical processing will be performed using statistical analysis 
software (SAS®) unless otherwise stated. Safety analyses will be 
performed using the safety population. 
Safety Analyses 
Adverse Events 
All AEs occurring during the study will be recorded and classified on the 
basis of the Medical Dictionary for Regulatory Authorities (MedDRA) 
terminology.  Descriptions of AEs will include the date of onset, the date 
the AE ended, the severity of the AE, the relationship to study 
medication, and the outcome. All reported AEs that occurred on or after 
the Baseline date will be included in the summaries and analysis. 
Summaries will be presented to describe the characteristics of the 
adverse events reported and will include the number and percentage of 
subjects who report at least one AE and the number of events reported 
by severity, seriousness, and relationship to study medication. A 
summary of adverse event system organ class (SOC) and preferred terms 
(PTs) will also be presented. A subject will be counted only once under 


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each SOC and PT. For the summary by severity, subjects will only be 
counted once for a specific SOC or PT under the worst severity. For the 
summary by relationship to study medication, subjects will only be 
counted once for a specific SOC or PT under the highest relationship. 
If multiple serious adverse events (SAEs) are reported, a table 
summarizing the SAEs characteristics will be provided. 
All information pertaining to AEs noted during the study will be listed 
by subject, detailing verbatim given by the Investigator, preferred term, 
system organ class, start date, stop date, severity, seriousness, and 
relationship to study medication. The AE onset will also be shown 
relative (in number of days) to the day of initial dose of the open label 
study medication. A summary of adverse events that lead to a subject’s 
discontinuation of study medication usage will also be provided. 
 
Physical Examinations 
Any clinically significant changes from Baseline will be documented as 
an AE. 
 
Vital Signs 
Blood pressure and pulse will be summarized from Baseline through 
Week 40. Additionally, change from Baseline in vital signs will be 
summarized at Weeks 4, 12, 24, 36 and 40. Clinically significant changes 
from Baseline will be documented as an AE. 
 
Urine Pregnancy Tests 
Urine pregnancy test results for WOCBP will be presented in data 
listings by subject. 
 
Tolerability Analyses 
Cutaneous tolerability assessments (erythema, scaling, dryness, pruritus, 
burning/stinging) will be summarized with frequency counts and 
percentages at each evaluation.  
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE 
Adverse Event 
BSA 
Body Surface Area 
EDC 
Electronic Data Capture 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
MedDRA 
Medical Dictionary for Regulatory Activities 
NOVAN 
Novan, Inc. 
OTC 
Over-the-Counter 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment Emergent Adverse Events 
UPT 
Urine Pregnancy Test 
WOCBP 
Women of Child-Bearing Potential 
 


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TABLE OF CONTENTS 
INFORMATION PAGE ................................................................................................................3 
INVESTIGATOR’S AGREEMENT ............................................................................................4 
PROTOCOL SYNOPSIS ..............................................................................................................5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................9 
TABLE OF CONTENTS ............................................................................................................10 
LIST OF FIGURES .....................................................................................................................13 
LIST OF TABLES .......................................................................................................................13 
1. INTRODUCTION..................................................................................................................14 
1.1 Background .....................................................................................................................14 
1.2 Investigational Product ...................................................................................................14 
1.3 Nonclinical Studies with NVN1000 Gel.........................................................................15 
1.4 Clinical Studies with NVN1000 Gel...............................................................................15 
1.5 Summary of Benefits and Risks ......................................................................................16 
2. RATIONALE AND OBJECTIVES .....................................................................................17 
2.1 Study Rationale ...............................................................................................................17 
2.2 Study Objectives .............................................................................................................17 
3. STUDY DESIGN ....................................................................................................................17 
3.1 Study Endpoints ..............................................................................................................18 
3.1.1 Safety Endpoints .................................................................................................18 
3.1.2 Tolerability Endpoints ........................................................................................18 
3.1.3 Extent of Exposure..............................................................................................18 
3.1.4 Efficacy endpoints ..............................................................................................18 
3.2 Structure ..........................................................................................................................18 
3.3 Duration ..........................................................................................................................18 
3.4 Dosage/Dose Regimen ....................................................................................................19 
3.5 Visit Schedule .................................................................................................................19 
3.6 Study Population .............................................................................................................19 
3.7 Eligibility Criteria ...........................................................................................................20 
3.7.1 Informed Consent and Authorization to Release Health Information ................20 
3.7.2 Inclusion Criteria ................................................................................................20 
3.7.3 Exclusion Criteria ...............................................................................................21 
4. STUDY PROCEDURES AND METHODS ........................................................................22 
4.1 Subject Entry Procedures ................................................................................................22 
4.1.1 Baseline ...............................................................................................................25 


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4.1.2 Weeks 4, 12, 24 and 36 (Days 28, 84, 168, 252) ................................................25 
4.1.3 Week 40/ET (Day 280) .......................................................................................26 
4.1.4 Discontinuation/Withdrawal Procedures ............................................................26 
4.2 Tolerability Assessments ................................................................................................28 
4.3 Safety Assessments .........................................................................................................29 
4.3.1 Adverse Events ...................................................................................................29 
4.3.2 Physical Exam.....................................................................................................30 
4.3.3 Vital Signs...........................................................................................................30 
4.3.4 Pregnancy Testing...............................................................................................30 
4.4 Efficacy Assessments......................................................................................................30 
4.4.1 Lesion Counts .....................................................................................................30 
4.5 Screen Failures ................................................................................................................31 
4.6 Protocol Deviations .........................................................................................................31 
5. PROHIBITED THERAPIES AND MEDICATIONS ........................................................31 
6. EVALUATION OF ADVERSE EVENTS ...........................................................................32 
6.1 Definitions.......................................................................................................................32 
6.1.1 Adverse Event Severity Grades ..........................................................................33 
6.1.2 Investigational Product Causality .......................................................................33 
6.2 Reporting Adverse Events ..............................................................................................34 
6.3 Immediately Reportable Events ......................................................................................34 
6.4 Pregnancy ........................................................................................................................35 
6.5 Follow-Up of Adverse Events ........................................................................................36 
6.5.1 Follow-Up of Non-Serious Adverse Events .......................................................36 
6.5.2 Follow-Up of Post Study Serious Adverse Events .............................................36 
6.6 Overdosage .....................................................................................................................36 
6.7 Discontinuation of Individual Subjects from the Study ..................................................37 
7. STATISTICAL ANALYSIS .................................................................................................37 
7.1 General Considerations ...................................................................................................37 
7.2 Populations ......................................................................................................................37 
7.2.1 Safety Population ................................................................................................37 
7.3 Demographic and Baseline Characteristics ....................................................................37 
7.4 Descriptive Statistics .......................................................................................................37 
7.5 Safety ..............................................................................................................................38 
7.5.1 Adverse Events ...................................................................................................38 
7.5.2 Physical Examination .........................................................................................38 
7.5.3 Vital Signs...........................................................................................................38 
7.5.4 Urine Pregnancy Tests ........................................................................................38 


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7.6 Tolerability ......................................................................................................................39 
7.7 Extent of exposure ..........................................................................................................39 
7.8 Efficacy Analysis ............................................................................................................39 
7.9 Sample Size and Power Considerations ..........................................................................39 
8. INVESTIGATIONAL PRODUCT MANAGEMENT .......................................................39 
8.1 Receipt of Investigational Product ..................................................................................39 
8.2 Storage of Investigational Product ..................................................................................39 
8.3 Treatment Assignment and Blinding ..............................................................................40 
8.4 Investigational Product Accountability ...........................................................................40 
8.5 Returns and Destruction ..................................................................................................40 
9. RECORDS MANAGEMENT ...............................................................................................41 
9.1 Data Collection ...............................................................................................................41 
9.2 File Management at the Study Site .................................................................................42 
9.3 Records Retention at the Study Site................................................................................42 
10. MONITORING, COMPLIANCE, AND QUALITY ..........................................................43 
10.1 Quality Assurance Audits and Quality Control ..............................................................44 
11. ETHICS AND RESPONSIBILITY ......................................................................................44 
12. CONFIDENTIALITY ...........................................................................................................44 
13. AMENDMENT POLICY ......................................................................................................45 
14. USE OF INFORMATION AND PUBLICATION..............................................................45 
15. REFERENCES .......................................................................................................................46 
16. APPENDICES ........................................................................................................................47 
16.1 APPENDIX 1:  List of Restricted Medications: .............................................................47 
 


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LIST OF FIGURES 
Figure 1: Study Diagram .................................................................................................18 
 
LIST OF TABLES 
Table 1: 
Dosing Amount by Area ..................................................................................19 
Table 2: 
Schedule of Visits and Procedures ...................................................................24 
 
 
 
 


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1. INTRODUCTION 
1.1 BACKGROUND 
Acne vulgaris is a chronic skin disease characterized by open and closed comedones, papules, 
pustules, and cysts. Current acne therapies include oral and topical antibiotics, topical keratolytics, 
and oral contraceptives.  
Nitric oxide is a free radical gas naturally produced by the human body which has antimicrobial 
and anti-inflammatory activity. Novan, Inc. has developed a topical gel containing NVN1000, a 
drug which releases nitric oxide to the skin after topical application. SB204, an admixture of an 
alcoholic NVN1000 Gel with an aqueous hydrogel, is in development for the treatment of acne 
vulgaris. In randomized, double-blind, placebo-controlled, 12-week, Phase 2 studies, treatment 
with SB204 decreased inflammatory and non-inflammatory lesion counts and improved the 
Investigator Global Assessment (IGA) in subjects with acne and was well tolerated.  
To date, approximately 400 subjects have been treated with NVN1000 Gel, including SB204, and 
approximately 200 subjects have been treated with the Vehicle Gel.  
1.2 INVESTIGATIONAL PRODUCT  
SB204 is an alcohol-based topical gel containing NVN1000 and the formulation will be dispensed 
from a dual chamber pump with hydrogel.  
Investigational Product 
Name of Active Ingredient 
NVN1000 
Drug Name/Concentration 
SB204 4%  
Manufacturer 
Ei, LLC  
Packaging 
Pump designed to deliver 1:1 
Hydrogel: NVN1000 Gel to yield 
final concentration of SB204 4%  
Storage Requirements 
Refrigerated, 2-8 °C until dispensed. 
Appearance Post-Mixing 
Opaque white gel  
Dosing Schedule 
Once daily 
Route of Administration 
Topical Application 


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1.3 NONCLINICAL STUDIES WITH NVN1000 GEL 
Novan has conducted over 30 nonclinical studies to evaluate the local safety and tolerance of 
NVN1000 (drug substance and formulated product) following dermal administration to support 
the acne development program. Repeat dose dermal toxicology studies have included 4-week and 
13-week GLP dermal toxicology studies in miniature swine, and a 13-week dermal toxicology 
study in both rats and mice. A 39-week miniature swine study has completed the in-life portion; 
data from that study will be available prior to initiation of this long-term safety study. In completed 
studies in both the miniature swine and mice, doses of NVN1000 far in excess in both 
concentration and applied surface area of projected clinical doses have not demonstrated any 
significant toxicological effects. The most relevant and persistent finding has been a transient 
dermal erythema that is concentration dependent and believed to be a consequence of a vascular 
dilation, “flushing” effect. Additional safety studies in rabbits and guinea pigs showed no effects 
on acute dermal irritation or skin sensitization. As expected, due to the alcohol-based formulation, 
NVN1000 was found to be an ocular irritant. From a genotoxicity perspective, NVN1000 was 
positive in a standard in vitro AMES assay but negative in three in vivo mutagenicity assays. 
Additionally, in SEG I and II reproductive toxicology studies in rats and rabbits, oral 
administration of NVN1000 resulting in high systemic levels of nitrate and hMAP3, a key 
structural component of NVN1000, showed the requisite maternal toxicological effects upon dose 
escalation as a complication of high methemoglobin concentrations, but minimal effects on fertility 
or fetal development. 
For additional information refer to the Investigator’s Brochure. 
1.4 CLINICAL STUDIES WITH NVN1000 GEL 
The topical administration of NVN1000 Gel to healthy volunteers or subjects with acne vulgaris 
has generally been well-tolerated with no safety concerns identified. In nine completed clinical 
studies, approximately 400 subjects have been treated with NVN1000 Gel or SB204 and 
approximately 200 subjects have been treated with Vehicle Gel. One unrelated SAE has been 
reported and the systemic AE profile has been similar in subjects treated with active (NVN1000 
Gel or SB204) and vehicle in the acne development program. Asymptomatic, transient erythema 
has been observed in some subjects.  There have been no clinically significant changes in 
laboratory results including methemoglobin, or changes in physical examinations.  
A cross-over pharmacokinetic (PK) study was conducted in 18 subjects with moderate to severe 
acne. Subjects were randomized to treatment with SB204 8% or Vehicle Gel to the face, chest, 
upper back, and shoulders (~17% BSA) in two treatment periods. In this study, there was no 
detectable plasma hMAP3 (LLOQ 5 ng/ml), a component of NVN1000 and no difference in 
plasma nitrate levels in subjects treated with SB204 versus Vehicle Gel. One subject withdrew 
during the second dosing period due to contact dermatitis.  A 4 period, double-dummy, cross-over 
study in subjects with moderate to severe acne is ongoing to assess effects of therapeutic and 


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supratherapeutic doses of SB204 on ECG parameters. The thorough ECG study will be completed 
prior to dosing in the Phase 3 pivotal program.  
In the Phase 2 clinical development program, the topical application of SB204 in subjects with 
acne vulgaris resulted in significant decreases in inflammatory and non-inflammatory lesion 
counts and improvement in the Investigator Global Assessment (IGA) when compared to vehicle. 
Once daily treatment was as effective as twice daily treatment. 
A summary of the clinical studies conducted to date in subjects with acne is in the Investigator’s 
Brochure.  
1.5 SUMMARY OF BENEFITS AND RISKS 
The pathogenesis of acne vulgaris includes several mechanisms which are potential targets for 
nitric oxide. Nitric oxide has been demonstrated to inhibit several inflammatory pathways relevant 
in acne, decrease P. acnes, and decrease sebum production. In two completed Phase 2 studies, 
SB204 4% administered in subjects with acne decreased inflammatory and non-inflammatory 
lesion counts at the end of treatment and improved IGA scores. Once daily treatment was as 
effective as twice daily treatment. In the studies conducted to date, the systemic AE profile was 
similar between subjects treated with NVN1000 Gel, SB204, and subjects treated with Vehicle 
Gel. SB204 4% has been generally well tolerated and has not been associated with a safety or 
tolerability signal. In PK studies, there was no detectable systemic exposure to the parent 
compound, NVN1000, or changes in plasma nitrate. 
Dermal toxicology studies in mice and minipigs have demonstrated minimal evidence of toxicity 
with mild-moderate dermal changes most frequently reported. In reproductive toxicology studies, 
findings were limited to toxicities associated with high methemoglobinemia at supra-therapeutic 
doses. 
Based on the known mechanism of action of nitric oxide, theoretical risks from systemic exposure 
following topical administration of NVN1000 Gel or SB204 include hypotension and headache. 
Methemoglobin has been monitored in previous clinical studies with NVN1000 Gel and SB204 
and no significant changes in methemoglobin levels have been observed. 
Inadvertent administration to the eyes may result in ocular irritation due to the excipients and 
should be avoided. Should the product be accidently instilled in the eye(s), prompt flushing with 
copious amount of normal saline or water is recommended.  
A transient (approximately 5-10 minutes), asymptomatic erythema has been observed in some 
subjects shortly after application of NVN1000 Gel or SB204 which is a physiologic response 
(vasodilation) to local nitric oxide release. Topical application has been associated with local 
application-site reactions including erythema, scaling, dryness, and burning/stinging. These local 


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application-site reactions may occur due to the active agent (NVN1000) or the vehicle. In other 
development programs, local application-site reactions that led to treatment discontinuations were 
observed following application of alcoholic NVN1000 Gel or Vehicle Gel under occlusion in 
subjects with psoriasis or to the genital/perianal area in subjects with genital/perianal warts. 
Based on available data, Novan anticipates that the risks to subjects enrolling in this Phase 3 study 
at which the maximum strength of SB204 will be 4% once daily on up to 17% body surface area 
are minimal, and that appropriate monitoring is in place to assess safety. Some subjects may have 
a clinical benefit in this long-term, open label study.  
2. RATIONALE AND OBJECTIVES 
2.1 STUDY RATIONALE 
Novan is conducting this study to evaluate the long term safety of SB204 4% administered once 
daily. Subjects will dose once daily for up to 40 weeks (280 days) with SB204 4% to acne affected 
areas. Based on the previous human safety data with SB204 at up to 8% and Vehicle Gel as well 
as the nonclinical safety data including dosing with and without hydrogel, this dose is expected to 
be safe and well tolerated. 
2.2 STUDY OBJECTIVES 
The primary objective of this study is to evaluate the long term safety of SB204 4% once daily for 
up to 40 weeks in subjects with acne vulgaris.  
3. STUDY DESIGN 
Figure 1 depicts the overall study design for this 40-week, open label study in subjects with acne 
vulgaris dosed once daily with SB204 4%. Subjects must have completed participation in one of 
the pivotal acne trials (NI-AC301 or NI-AC302) to be eligible to participate in this long term safety 
trial. Subjects will be treated chronically or repeatedly as recommended by the Investigator for up 
to 40 weeks. The Investigator may stop treatment if the subject’s acne is in remission and re-initiate 
treatment if the subject’s acne recurs. Any subject who is determined to be clear will remain 
enrolled in the study until study completion or termination. The total time on study will be counted 
as the days from enrollment until the subject discontinues or the study terminates. 


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Figure 1: 
Study Diagram 
Baseline 
 
SB204 4%  
(N=600) 
 
Study 
Visits 
 
 
Week 
(Day)      
 (0) 
4
(28)
 
12 
(84) 
 
 
 
24 
(168) 
 
 
36 
(252) 
    40/ET 
(280) 
 
 
ET = Early termination 
3.1 STUDY ENDPOINTS  
3.1.1 SAFETY ENDPOINTS 
Safety endpoints will include adverse events, changes in physical examination and changes in vital 
sign measurements. Any clinically significant changes noted during the physical exam as well as 
from the vital sign measurements will be recorded as adverse events and included in the 
comparison. Urine pregnancy tests in women of child-bearing potential will be conducted at each 
visit. 
3.1.2 TOLERABILITY ENDPOINTS 
The cutaneous tolerability assessments include the investigator’s assessment of erythema, scaling, 
dryness, and the subject’s report of pruritus and burning/stinging based on the preceding 24 hours. 
3.1.3 EXTENT OF EXPOSURE 
Extent of exposure will be calculated based on total number of days of study drug application 
and the body surface area treated (face, upper back, upper chest/shoulders). 
3.1.4 EFFICACY ENDPOINTS 
Efficacy endpoints will include change in inflammatory and non-inflammatory lesion counts from 
baseline at each study visit.  
3.2 STRUCTURE 
This is a multi-center, open label study. Eligible subjects will have completed either NI-AC301 or 
NI-AC302, regardless of which treatment arm they were assigned to receive in the original study. 
3.3 DURATION  
Subjects will be in the study for a maximum of 40 weeks; the Week 12 visit from the pivotal study 
will serve as the Baseline Visit for this study.  


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3.4 DOSAGE/DOSE REGIMEN 
SB204 will be dispensed from a dual-chamber pump designed to deliver approximately equal 
amounts of NVN1000 Gel and hydrogel. NVN1000 Gel will be opaque and the hydrogel will be 
clear. The subject will instantly mix the two substances in the palm of the hand and then 
immediately massage a thin layer over the acne affected areas once daily after washing. The 
product should be mixed for about 5 seconds until thoroughly combined with a uniform opaque 
appearance then applied with the fingertips. Subjects should apply SB204 prior to bedtime.  
Up to 2.7 g of SB204 4% will be applied evenly over the acne affected area, including the face, 
chest, back, and upper shoulders once a day for a period of up to 40 weeks (280 days). The amount 
of SB204 per application will vary depending on the areas to be treated as shown in Table 1 below. 
One pump stroke (0.9 g) will be used for the face.  Application to the face, upper back and upper 
chest/shoulders will require up to 2.7 g (three (3) pump strokes).  
Table 1: 
Dosing Amount by Area 
Area (BSA) 
Number of Pump Strokes 
Amount of Product 
Face (3%) 
1 
0.9 g 
Upper Back (6%) 
1 
0.9 g 
Upper Chest/Shoulders (8%) 
1 
0.9 g 
 
3.5 VISIT SCHEDULE 
The Week 12 visit for the pivotal studies NI-AC301 or NI-AC302 will serve as the Baseline Visit 
for this long term safety study. Subjects must have completed the full 12 weeks of treatment in 
one of the pivotal studies to enroll in the long term safety study. Subjects may enter the long term 
safety study up to 7 calendar days after their Week 12 visit in the pivotal study. Study visits will 
take place after the first four weeks then at Weeks 4, 12, 24, 36 and 40.  
3.6 STUDY POPULATION 
Approximately 600 healthy male and female subjects with acne vulgaris on the face, chest, 
shoulders or back will be allowed to participate in the study if they have successfully completed 
12 weeks in either NI-AC301 or NI-AC302.   
A subject whose facial acne cleared during NI-AC301 or NI-AC302 is eligible to enroll if all other 
inclusion criteria and none of the exclusion criteria are met.  If a subject enters the pivotal study at 
age 40 and is 41 at the time they complete participation in the pivotal study, they are eligible for 
the long term safety study as long as they meet all other study inclusion criteria and none of the 
exclusion criteria. 


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3.7 ELIGIBILITY CRITERIA 
3.7.1 INFORMED CONSENT AND AUTHORIZATION TO RELEASE HEALTH 
INFORMATION 
Written informed consent/assent will be obtained from all subjects before any study-related 
procedures are performed. The Investigator may discuss the study and the possibility for entry with 
a potential subject without first obtaining consent/assent. A subject wishing to participate must 
give written informed consent/assent prior to any study-related procedures being conducted.  The 
Investigator has both the ethical and legal responsibility to ensure that each subject being 
considered for inclusion in this study has been given a full explanation of the procedures and 
expectations for study participation. The Week 12 assessments for the pivotal study NI-AC301 or 
NI-AC302 should be done prior to consenting the subject for participation in this long term safety 
study.  
The site-specific informed consent and assent forms must be forwarded to Chiltern for approval 
prior to submission to an Institutional Review Board (IRB) as appropriate. Each subject will sign 
the consent form that has been approved by the same IRB responsible for protocol approval. Each 
informed consent document must adhere to the ethical principles stated in the Declaration of 
Helsinki and will include the elements required by the Food and Drug Administration (FDA) 
regulations in 21 CFR as well as the International Conference on Harmonisation (ICH) Good 
Clinical Practice (GCP) guidelines, and applicable federal and local regulatory requirements. The 
consent form(s) must also include a statement that Novan, Chiltern (or their designees) and 
auditing regulatory agencies will have direct access to the subject’s records and medical history.  
Once the appropriate essential information has been provided to the subject and parent or legal 
guardian (where applicable) and fully explained by the Investigator (or a qualified designee) and 
it is felt that the subject understands the implications and risks of participating in the study, the 
IRB approved consent and assent (where applicable) document(s) shall be signed and dated by 
both the subject and parent or legal guardian (where applicable) and the person obtaining consent 
(Investigator or designee), and by any other parties required by the IRB or other regulatory 
authorities. A subject under 18 years of age (or the age of majority in their state) must sign a written 
informed assent and be accompanied by the parent or legal guardian at the time of consent/assent 
signing. If a subject becomes 18 years of age during the study, the subject must provide written 
informed consent at the next study visit to continue study participation. The subject will be given 
a copy of the signed informed consent document with the original kept on file by the Investigator. 
All of the above activities must be completed before any study related procedures are conducted.  
3.7.2 INCLUSION CRITERIA 
Each subject must fulfill all of the following inclusion criteria to participate in the study: 


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1. Have a signed written informed consent form. Subjects less than 18 years of age or the age 
of majority in their state must sign an assent form for the study and a parent or a legal 
guardian must sign the informed consent; 
2. Have completed the full 12 weeks of treatment in NI-AC301 or NI-AC302; 
3. Be in good general health; 
4. Have no more than two nodules or cysts on the face; 
5. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test 
(UPT) prior to enrollment; 
6. WOCBP must agree to use an effective method of birth control during the course of the 
study and for 30 days after their final study visit; 
7. Be willing and able to follow study instructions and likely to complete all study 
requirements. Subjects under 18 years of age or age of majority must be accompanied by 
the parent or legal guardian at the time of assent/consent signing. 
3.7.3 EXCLUSION CRITERIA 
Subjects will not be enrolled if they meet any of the following exclusion criteria: 
1. Have any dermatological conditions on the face that could interfere with clinical evaluations 
such as acne conglobata, acne fulminans, acne secondary to medications or other medical 
conditions, perioral dermatitis, clinically significant rosacea, or gram-negative folliculitis;  
2. Have any underlying disease(s) or some other dermatological condition of the face that 
requires the use of interfering topical or systemic therapy or makes evaluations and lesion 
count inconclusive; 
3. Have an on-going adverse event at the Week 12 visit for NI-AC301 or NI-AC302 that 
warrants stopping study drug application; 
4. Are transgender persons who are taking testosterone (female to male) or estrogen (male to 
female); 
5. Have facial hair, tattoos or other markings that could interfere with assessments or 
application of study drug; 
6. Have a history of experiencing significant burning or stinging when applying any facial 
treatment (e.g., make-up, soap, masks, washes, sunscreens, etc.) to their face; 
7. Female subjects who are pregnant, nursing mothers, or planning to become pregnant during 
the study; 


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8. Intend to use a tanning booth or sunbathe during the study; 
9. Are members of the same household where a subject is enrolled in NI-AC301, NI-AC302, 
or NI-AC303; 
10. Are immediate family members of study site personnel directly involved in NI-AC301, NI-
AC302, or NI-AC303; 
11. Have any condition or situation which, in the Investigator’s opinion, puts the subject at 
significant risk, could confound the study results, or may interfere significantly with the 
subject’s participation in the study;  
12. Are unable to communicate or cooperate with the Investigator due to language problems, 
poor mental development, or impaired cerebral function; 
13. Concurrently participating in a different interventional research study. 
4. STUDY PROCEDURES AND METHODS 
4.1 SUBJECT ENTRY PROCEDURES 
Prospective subjects as defined by the eligibility criteria in Sections 3.7.2 and 3.7.3 
(Inclusion/Exclusion Criteria) will be considered for entry into this study. Subjects’ informed 
consent/assent must be obtained prior to conducting any procedures for this study and after 
completion of the Week 12 assessments for NI-AC301 or NI-AC302. 
Some baseline procedures (i.e., review of inclusion/exclusion criteria, brief physical exam, blood 
pressure and pulse rate, lesion counts, cutaneous tolerability, adverse event assessment, 
concomitant medication review and UPT) must be completed prior to dispensing open label study 
medication.  
WOCBP having a positive UPT at baseline may not be randomized into the study. Women of 
childbearing potential must agree to use an effective form of contraception during participation in 
the study and for 30 days after their final study visit. Effective contraception is defined as stabilized 
on oral contraceptive for at least three months (90 days), intrauterine device (IUD), condom with 
spermicide, diaphragm with spermicide, implant, NuvaRing®, medroxyprogesterone injection, 
transdermal patch or abstinence with a documented second acceptable method of birth control 
should the subject become sexually active. Females taking hormonal contraceptives must have 
taken the same type for at least three months (90 days) prior to entering the study and must not 
change type during the study. Subjects who had used hormonal contraception and stopped must 
have stopped no less than three months prior to the start of the study.  


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A female is considered to be of childbearing potential UNLESS she is post-menopausal (no menses 
for 24 consecutive months), surgically sterilized, or without a uterus and/or both ovaries. Pre-
menarchal girls are considered to be of childbearing potential. 
After the required procedures are completed and study eligibility is confirmed, study drug will be 
dispensed to the subject. The subject will be trained on the mixing, application, and storage of the 
study drug. All study drug applications will be done at home. 


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Table 2: 
Schedule of Visits and Procedures 
Study visits should occur at approximately the same time of day throughout the study. 
 
PROCEDURES 
Visit 11 
 
Baseline 
(Day 0) 
Visit 23 
Week 4 
±5 days 
(Day 28) 
Visit 3 
Week 12 
±7 days 
(Day 84) 
Visit 4 
Week 24 
±7 days 
(Day 168) 
Visit 5 
Week 36 
±7 days 
(Day 252) 
Visit 64 
Week 40/ET 
±7 days 
(Day 280) 
Informed 
Consent/Assent 
X 
 
 
 
 
 
Demographics  
X2 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
Medication History  
X 
 
 
 
 
 
Inclusion/ 
Exclusion Criteria 
X 
 
 
 
 
 
Brief Physical 
Examination 
X2 
 
 
 
 
X 
Urine Pregnancy Test 
(all WOCBP) 
X2 
X 
X 
X 
X 
X 
Blood Pressure and 
Pulse 
X2 
X 
X 
X 
X 
X 
Lesion Counts 
X2 
X 
X 
X 
X 
X 
Cutaneous Tolerability 
Evaluation 
X2 
X 
X 
X 
X 
X 
Instruct on Study Drug 
Application and 
Provide Subject 
Instructions  
X 
 
 
 
 
 
Record application 
areas since last visit 
 
X 
X 
X 
X 
X 
Study Drug 
Dispensed/Retraining 
on mixing and 
application 
X 
X 
X 
X 
X 
 
Study Drug Collected 
 
X 
X 
X 
X 
X 
Subject Study Drug 
Use Reviewed 
 
X 
X 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
¹Data for the Baseline Visit for this study will be the Week 12 data from the Phase 3 pivotal study for completing, eligible 
subjects. 
2Demographics and assessments from the Week 12 visit from the preceding Phase 3 study including the physical examination, 
blood pressure and pulse, UPT, tolerability, and lesion counts do not need to be repeated. 
3All visit dates are in reference to Baseline, e.g., Visit 2 occurs four weeks (28 days) after Baseline visit. 
4All Week 40 procedures should be completed for subjects who prematurely discontinue. 


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4.1.1 BASELINE  
The following procedures were performed as Week 12 assessments in NI-AC301 or NI-AC302 
and will be used for baseline values for this study: 
1. Collect blood pressure and pulse rate after the subject has been sitting quietly for 5 minutes. 
2. Perform a brief physical examination. 
3. Obtain pregnancy test (WOCBP only) and evaluate results. If pregnancy test is positive, 
the subject may not participate in the study. 
4. Perform Cutaneous Tolerability Evaluation on the face only. 
5. Perform lesion counts on the face only. Inflammatory and non-inflammatory lesion counts 
will be performed on the entire face and reported separately.  
The following procedures must be performed and recorded at the Baseline visit:  
1. Review study procedures and information regarding the study including the potential risk 
and benefits of SB204 with the subject and obtain written informed consent/assent. 
2. Review subject’s concomitant medication information. 
3. Verify appropriate contraception being used for WOCBP per Section 6.4. 
4. Review prohibited medications, acne treatments, and supplements that should not be used 
during the trial. 
5. Confirm subject meets eligibility criteria. 
6. Dispense subject diary and study drug. Instruct subject on dispensing, mixing, and 
application of study product and diary completion. 
7. Collect AEs related to study procedures performed since signing of informed consent. 
8. Confirm the study schedule with the subject. 
4.1.2 WEEKS 4, 12, 24 AND 36 (DAYS 28, 84, 168, 252) 
The following procedures must be performed and recorded at the Weeks 4, 12, 24, and 36 visits: 
1. Update concomitant medication information. 
2. Update AE information and record any new AEs if applicable. 
3. Obtain UPT (WOCBP only) and evaluate results. 
4. Collect blood pressure and pulse rate after the subject has been sitting quietly for 5 minutes. 


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5. Perform cutaneous tolerability evaluation (face only). 
6. Perform lesion counts (face only). 
7. Record areas treated since last visit (face, upper back, upper chest/shoulders). 
8. Collect returned study drug and diary, perform accountability, and review study drug 
compliance with subject.  
9. Review subject diary for completion. 
10. Dispense new study drug and diary.   
11. Review and confirm the study schedule with the subject. 
4.1.3 WEEK 40/ET (DAY 280) 
The following procedures must be performed and recorded at the Week 40/ET visit: 
1. Update concomitant medication information. 
2. Perform a brief physical exam. 
3. Update AE information and record any new AEs. 
4. Obtain UPT (WOCBP only) and evaluate results. 
5. Collect blood pressure and pulse rate after the subject has been sitting quietly for 5 minutes. 
6. Perform cutaneous tolerability evaluation (face only). 
7. Perform lesion counts (face only). 
8. Record areas treated since last visit (face, upper back, upper chest/shoulders). 
9. Collect returned study drug and diary, perform accountability, and review study drug 
compliance with subject.  
10. Review subject diary for completion.  
4.1.4 DISCONTINUATION/WITHDRAWAL PROCEDURES 
A subject may voluntarily withdraw from study participation at any time. If the subject withdraws 
consent and discontinues from the study, the Investigator will attempt to determine the reason for 
discontinuation and record the reason in the subject’s study records and in the study database. If a 
subject is withdrawn because of an AE, that AE should be indicated as the reason for withdrawal. 
In the event of early discontinuation, (i.e., prior to Week 40/Day 280 visit) and whenever possible, 
the subject should be asked to return to the study center to complete the Week 40/ET evaluations. 
Subjects who withdraw from the study will not be replaced. 


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If at any time during the study the Investigator determines that it is not in the best interest of the 
subject to continue, the subject will be discontinued from participation. The Investigator can 
discontinue a subject at any time if medically necessary. The Investigator may discontinue a 
subject’s participation if the subject has failed to follow study procedures or to keep follow-up 
appointments. Appropriate documentation in the subject’s study record and the study database 
regarding the reason for discontinuation must be completed.  
All subjects who fail to return to the study center for the Week 40/ET visit will be contacted by 
telephone to determine the reason(s) why the subject failed to return for the necessary visit or 
elected to discontinue from the study. If a subject is unreachable by telephone after a minimum of 
two documented attempts (one attempt on two different days), a certified letter will be sent 
requesting that the subject contact the Investigator. 
Reasons for an Investigator’s withdrawal of a subject may include, but are not limited to, the 
following: 
 Safety (e.g., severe adverse reactions, pregnancy); 
 Lack of efficacy as determined by the Investigator; 
 When the requirements of the protocol are not respected (e.g., significant issues with study 
visit compliance); 
 When a concomitant medication or treatment likely to interfere with the results of the study 
is reported, or required, by the subject (the Investigator will decide, in consultation with 
Chiltern, whether the subject is to be withdrawn); 
 When a subject is lost to follow-up. The Investigator will try twice to reach the subject by 
telephone and will send a certified follow-up letter before considering that the subject is 
lost-to-follow-up. These actions will be reported on the subject’s study record and a copy 
of the follow-up letter maintained in the Investigator's file. 
Refer to Section 6.7 for a discussion of criteria for discontinuation of individual subjects from the 
study. 
All premature discontinuations and their causes must be carefully documented by the Investigator 
on the subject’s study record and in the study database. In no case will a subject who has been 
assigned a study number and entered into the study be replaced by another. 
All Week 40/ET evaluations should be performed at the time of premature discontinuation. All 
data gathered on the subject prior to termination will be made available to Chiltern. 


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Study completion or reason(s) for discontinuation as listed in the study record will be entered into 
the study database as follows: 
 Completed  
 Adverse Event  
 Lack of Efficacy  
 Withdrawal by Subject 
 Physician Decision  
 Protocol Violation 
 Lost to Follow-Up 
 Pregnancy 
 Worsening of condition 
 Other 
Novan has the right to terminate or stop the study at any time. Should this be necessary, the 
Investigator will ensure that proper study discontinuation procedures are completed. 
4.2 TOLERABILITY ASSESSMENTS 
The evaluator will assess the subject’s face at baseline and each study visit. The cutaneous 
tolerability scores from Week 12 of NI-AC301 or NI-AC302 will be the subject’s baseline 
tolerability. The cutaneous tolerability assessment should be performed at least 30 minutes after 
study drug application. Cutaneous tolerability evaluations will include erythema, scaling, dryness, 
pruritus and burning/stinging. Pruritus and burning/stinging will be based on the subject’s report 
for the previous 24 hours. Cutaneous tolerability endpoints will not be reported as an AE unless 
they reach severe and/or result in subject’s discontinuation from the study. Subjects who develop 
intolerance to the product as defined by scores of 3 (severe) on two or more categories of 
tolerability (erythema, scaling, dryness, pruritus, burning/stinging) shall be discontinued from the 
study. Cutaneous tolerability assessments will be performed according to the following scales: 
 
Erythema 
Score 
Description 
0-None 
No evidence of erythema present 
1-Mild 
Slight pink coloration 
2-Moderate 
Definite redness 
3-Severe 
Marked erythema, bright red to dusky dark red in color 


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Scaling 
Score 
Description 
0-None 
No scaling 
1-Mild 
Fine scales present to limited areas of the face, barely perceptible 
2-Moderate 
Fine scale generalized to all areas of the face 
3-Severe 
Scaling and peeling of skin over all areas of the face 
Dryness 
Score 
Description 
0-None 
No dryness 
1-Mild 
Slight but definite roughness 
2-Moderate 
Moderate roughness 
3-Severe 
Marked roughness 
Pruritus 
Score 
Description 
0-None 
No itching 
1-Mild 
Slight itching, not very bothersome 
2-Moderate 
Moderate amount of itching, somewhat bothersome 
3-Severe 
Severe amount of itching, definite discomfort and sleep may be disturbed 
Burning/Stinging 
Score 
Description 
0-None 
No burning/stinging 
1-Mild 
Slight warm, burning/stinging sensation; not very bothersome 
2-Moderate 
Definite warm, burning/stinging sensation that is somewhat bothersome 
3-Severe 
Hot, tingling/sensation that has caused definite discomfort and may have 
disturbed sleep 
4.3 SAFETY ASSESSMENTS 
Adverse events will be collected beginning with the Baseline Visit for this study.  Adverse 
events that began during NI-AC301 or NI-AC302 that are ongoing at the conclusion of either 
study will be reported as AEs at Baseline in this long-term safety study (NI-AC303) and 
followed.  The physical exam, vital signs and pregnancy test results from the Week 12 visit of 
NI-AC301 or NI-AC302 will be used as the subject’s Baseline assessments for this long term 
safety study and be collected during the study. 
4.3.1 ADVERSE EVENTS 
AEs will be collected starting after the subject has signed the informed consent and completed 
any study assessment until the end of the final study visit. The date of onset, date ended, severity, 


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relationship to study drug, therapy required, and action taken regarding study drug and study 
participation will be reported for each AE.  
See Section 6 for additional information regarding the evaluation of adverse events. 
4.3.2 PHYSICAL EXAM 
A brief physical exam will be performed at Week 40/ET. If clinically significant changes in the 
physical examination from Baseline are noted at the Week 40/ET visit, these will be recorded as 
adverse events.  
4.3.3 VITAL SIGNS  
Blood pressure and pulse rate will be collected at Weeks 4, 12, 24, 36 and 40/ET. Any clinically 
significant changes in vital signs from Baseline will be recorded as adverse events whether or not 
drug related. 
4.3.4 PREGNANCY TESTING 
All WOCBP must have a UPT at Weeks 4, 12, 24, 36 and 40/ET and if the result is positive, the 
subject will not be allowed to continue in the study. Refer to Section 6.4 for further information. 
4.4 EFFICACY ASSESSMENTS 
The same evaluator should perform lesion counting at Weeks 4, 12, 24, 36, and 40/ET. This should 
be the same evaluator that performed the Week 12 assessments for the NI-AC301 or NI-AC302 
study. In the event that this is not possible due to unforeseen circumstances, a different evaluator 
may evaluate the subject. However, the same evaluator should evaluate subjects at the Baseline 
and Week 40/ET evaluations. The subject’s Week 12 lesion counts from NI-AC301 or NI-AC302 
will be considered the Baseline value for this study. 
4.4.1 LESION COUNTS 
The facial area lesion counts will be taken from the forehead, right and left cheeks, chin and nose. 
The lesion count groups will be inflammatory and non-inflammatory. Facial inflammatory lesions 
(pustules, papules, nodules and cysts) will be counted and recorded. Non-inflammatory lesions 
(open and closed comedones) will be counted and recorded.   The following are definitions of each 
lesion type:  
Inflammatory lesions are defined as follows: 
 
Papule –A small, superficial, circumscribed, palpable lesion elevated above the skin surface, less 
than 10 mm in diameter 


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Pustule –A superficial elevated lesion that contains yellow fluid (pus) within or beneath the 
epidermis  
Nodule –A firm (indurated) lesion greater than 10 mm in diameter and that is thicker or deeper 
than the average papule  
Cyst - Spherical swelling that contains fluid or semisolid material 
 
Non-inflammatory lesions are defined as follows: 
 
Open comedones (blackhead) –Plugged follicular units with brown/black central debris 
Closed comedones (whitehead) –Plugged follicular units with white central debris 
4.5 SCREEN FAILURES 
A screen failure subject will be a person from whom informed consent is obtained but who does 
not meet the study eligibility requirements. Subjects will not be allowed to rescreen. 
4.6 PROTOCOL DEVIATIONS 
This study will be conducted as described in this protocol, except for an emergency situation in 
which the protection, safety, and well-being of the subject requires immediate intervention, based 
on the judgment of the Investigator (or a responsible, appropriately trained professional designated 
by the Investigator). In the event of a significant deviation from the protocol due to an emergency, 
accident, or mistake, the Investigator or designee must contact Chiltern at the earliest possible time 
by telephone. 
5. PROHIBITED THERAPIES AND MEDICATIONS 
Concomitant medications are any prescription or over-the-counter (OTC) preparations. Use of 
concomitant medications will be recorded on the concomitant medications study record and study 
database beginning at the Baseline Visit until the final evaluation (Week 40/ET).  
Subjects will be permitted to apply non-comedogenic moisturizer or sunscreen on an as-needed 
basis. Moisturizer must not contain antibacterials and the subject must not change moisturizer 
and/or sunscreen used during the course of the study. If used, moisturizers and sunscreen must be 
applied at least 30 minutes after study drug application. 
Subjects must not have used anti-acne treatments including topical or systemic antibiotics or 
retinoids as described in Section 3.7.3 prior to Baseline. These medications are also prohibited 
during the trial. Short term courses of antibiotics (≤ 14 days) for non-acne related illnesses and 
inhaled or intranasal steroids are permitted during the trial.  


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Subjects may not be concurrently on drugs associated with exacerbating acne vulgaris (Appendix 
16.1). Subjects must not participate in a different interventional research study during the study 
period.  
Any medication/therapy used by the subject following first application of study product will be 
considered a concomitant medication/therapy (e.g., aspirin, acetaminophen, birth control pills, 
vitamins, etc.). Every attempt should be made to keep concomitant medication/therapy dosing 
constant during the study. Any change to concomitant medications/therapies should be noted on 
the subject’s study record and in the study database. When applicable, an AE should be completed 
for any subject starting a concomitant medication/therapy after enrollment into the study. 
6. EVALUATION OF ADVERSE EVENTS  
6.1 DEFINITIONS 
An adverse event (AE) is any untoward medical occurrence (e.g., sign, symptom, disease, 
syndrome, intercurrent illness, clinically significant abnormal laboratory finding, injury or 
accident) whether or not considered drug related. Any AE that emerges or worsens following 
administration of the informed consent and until the end of study participation will be collected. 
A pre-existing condition is one that is present prior to the start of the study and is to be reported as 
part of the subject’s medical history unless it began as an AE in NI-AC301 or NI-AC302. Adverse 
events that began during NI-AC301 or NI-AC302 that are ongoing at the conclusion of either study 
will be reported as AEs at Baseline in this long-term safety study (NI-AC303) and followed.  Prior 
conditions should be reported as an AE if the frequency, intensity, or the character of the condition 
worsens during the study or if the condition persists. 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigator’s Brochure or is not listed at the specificity or severity that has been observed. 
A serious adverse event (SAE) includes any event, if in the view of either the investigator or the 
Medical Monitor results in any of the following outcomes: 
 Death 
 Life-threatening event (i.e., the subject was, in the opinion of the Investigator, at immediate 
risk of death from the event as it occurred. It does not apply to an AE that hypothetically 
might have caused death if it were more severe) 
 Persistent or significant disability/incapacity (i.e., the AE results in a substantial disruption 
of the subject’s ability to carry out normal life functions) 
 Requires in-patient hospitalization or prolongs hospitalization (i.e., the AE required at least 
a 24-hour in-patient hospitalization or prolonged a hospitalization beyond the expected 


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length of stay; hospitalizations for elective medical/surgical procedures, scheduled 
treatments, or routine check-ups are not SAEs by this criterion) 
 Congenital anomaly/birth defect (i.e., an adverse outcome in a child or fetus of a subject 
exposed to the molecule or investigational product before conception or during pregnancy) 
 Does not meet any of the above serious criteria but may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the outcomes listed above (i.e., is 
a significant or important medical event) 
6.1.1 ADVERSE EVENT SEVERITY GRADES 
The Investigator is responsible for evaluating all AEs and determining the severity of the event.  
Severity will be categorized according to the following definitions: 
 Mild:  Event may be noticeable to subject; does not influence daily activities; usually does 
not require intervention. 
 Moderate: Event may be of sufficient severity to make subject uncomfortable; performance 
of daily activities may be influenced; intervention may be needed. 
 Severe:  Event may cause severe discomfort; usually interferes with daily activities; subject 
may not be able to continue in the study; treatment or other intervention usually needed.  
The Investigator will follow all subjects who experience AEs until there is a return to the subject’s 
baseline condition or until a clinically satisfactory resolution is achieved or the subject is lost to 
follow-up. 
6.1.2 INVESTIGATIONAL PRODUCT CAUSALITY 
Relationship of an AE to investigational product will be assessed as follows: 
 Definite:  There is a clinically plausible time sequence between the onset of the AE and 
the application of investigational product; when the event responds to withdrawal of 
investigational product and recurs with re-administration of investigational product. 
 Probable:  There is a clinically plausible time sequence between the onset of the AE and 
the application of investigational product; the AE is unlikely to be caused by the 
concurrent/underlying illness, other drugs or procedures. 
 Possible:  There may or may not be a clinically plausible time sequence between the 
onset of the AE and the application of investigational product and a cause cannot be ruled 
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 Unlikely:  There is no reasonable temporal association between the test material and the 
suspected event and the event could have been produced by the subject's clinical state or 
other modes of therapy administered to the Subject. 
 Unrelated:  This term should be reserved for those events that cannot be even remotely 
related to study participation. 
6.2 REPORTING ADVERSE EVENTS 
For the purpose of AE reporting the trial period is defined as the period after the subject signs the 
informed consent/assent to the end of subject’s last visit. 
The Investigator will assess subjects at each scheduled study visit for the occurrence of AEs. In 
order to avoid bias in eliciting AEs, subjects should be asked the following non-leading question:  
“How have you felt since your last visit?” All AEs (serious and non-serious) reported by the subject 
must be recorded on the subject’s study record and entered into the study database. 
In addition, Chiltern must be notified within 24 hours of the Investigator’s knowledge of the event 
by telephone or email of any immediately reportable events according to the procedure outlined 
below. Special attention should be paid to recording hospitalizations and concomitant therapies 
and medications. 
6.3 IMMEDIATELY REPORTABLE EVENTS 
Serious adverse events (SAEs) are considered immediately reportable events. Any SAE, whether 
deemed drug-related or not, must be reported to Chiltern telephone, fax, or email as soon as 
possible after the Investigator or coordinator has become aware of its occurrence. The 
Investigator/coordinator must complete a Serious Adverse Event (SAE) Form and email it to 
Chiltern within 24 hours of notification of the event. When appropriate, Novan will notify the 
appropriate regulatory body of drug related Serious Adverse Events. 
Serious Adverse Event (SAE) and Safety Contact Information: 
Phone: SAE Hotline: 1-888-SAE CHIL (1-888-723-2445)  
Email: GlobalSAEInbox@Chiltern.com 
Fax: 1-800-468-2288 
 
If a subject experiences an SAE or pregnancy the Investigator must: 
1. Report the SAE or pregnancy by telephone, fax, or email immediately (within 24 hours) 
after the Investigator becomes aware of the event. 
2. Complete an SAE or Pregnancy Notification Form and email, fax, or overnight courier to 
Chiltern within 24 hours of knowledge of the event. 


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3. Obtain and maintain all pertinent medical records, information and medical judgments of 
medical personnel who assisted in subject’s treatment and follow-up and document as 
appropriate. 
4. Provide a more detailed report to both Chiltern and the IRB, if applicable, no later than 
seven days after the Investigator discovers the event as further information becomes 
available, and when necessary update the information with follow-up information 
including outcomes. This report should include a statement as to whether the event was 
or was not related to the use of investigational product. 
5. The Investigator will notify the IRB of the SAE or pregnancy according to specific IRB 
requirements. 
6. The Investigator will collect information on SAEs until the subject’s health has returned to 
baseline status, until all parameters have returned to normal, or remaining health issues 
have otherwise been explained. 
6.4 PREGNANCY 
Women of child-bearing potential (WOCBP) must use an effective method of birth control during 
the course of the study and for 30 days following their final study visit. Allowable methods of birth 
control include stabilized on oral contraceptive for at least three months (90 days), IUD, condom 
with spermicide, diaphragm with spermicide, implant, NuvaRing®, injection, transdermal patch 
or abstinence with a documented second acceptable method of birth control should the subject 
become sexually active. Females taking hormonal contraceptives must have taken the same type 
for at least three months (90 days) prior to entering the study and must not change type during the 
study. Those who have used birth control pills or hormonal contraception in the past and stopped 
must have discontinued usage at least three months (90 days) prior to the start of the study. 
A female is considered to be of childbearing potential unless she is post-menopausal (no menses 
for 24 consecutive months), surgically sterilized, or without a uterus and/or both ovaries. 
Premenarchal females are considered to be of childbearing potential. 
 
Before enrolling any subject in this clinical trial, the Investigator must review guidelines about 
study participation including the topics below: 
 Informed consent document 
 Pregnancy prevention information 
 Risks to unborn child(ren) 
 Any drug interactions with hormonal contraceptives 
 Contraceptives in current use 


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 Guidelines for the follow-up of a reported pregnancy 
Prior to study enrollment, all subjects must be advised of the importance of avoiding pregnancy 
during participation in this clinical study and the potential risk factors for an unintentional 
pregnancy. The subject must sign an informed consent document stating that the above-mentioned 
risk factors and the consequences were discussed. 
During the study, WOCBP should be instructed to contact the Investigator immediately if they 
suspect they might be pregnant (e.g., missed or late menstrual cycle). The Investigator must 
immediately notify Chiltern of any female subject who becomes pregnant any time during study 
participation, record the information on the Pregnancy Notification Form and email/fax the form 
to Chiltern. Subjects found to be pregnant prior to Week 40 will be discontinued from the study. 
Chiltern will ask the site to follow-up with the subject periodically during the pregnancy for 
ongoing health and safety information through term, as applicable. Protocol-required procedures 
for the Week 40/ET evaluation must be performed for the subject. 
6.5 FOLLOW-UP OF ADVERSE EVENTS  
6.5.1 FOLLOW-UP OF NON-SERIOUS ADVERSE EVENTS 
Non-serious AEs that are not resolved at the time of the last scheduled study visit (Week 40/ET) 
must be recorded in the study database as ongoing/not recovered/not resolved. 
6.5.2 FOLLOW-UP OF POST STUDY SERIOUS ADVERSE EVENTS 
Serious adverse events that are identified on the last scheduled contact (Week 40/ET) must be 
recorded in the study database and reported to Chiltern according to the reporting procedures 
outlined in Sections 6.2 and 6.3. This may include unresolved previously reported SAEs, or new 
SAEs. The Investigator should follow these SAEs until the events are resolved, or the subject is 
lost to follow-up. The Investigator should continue to report any significant follow-up information 
to Chiltern and the IRB up to the point the event has been resolved. Resolution means the subject 
has returned to the baseline state of health, or the Investigator does not expect any further 
improvement or worsening of the subject’s condition. 
Any new SAEs reported by the subject to the Investigator that occur after the last scheduled contact 
and are determined by the Investigator to be reasonably associated with the application of 
investigational product should be reported to Chiltern and the IRB. 
6.6 OVERDOSAGE 
There is no specific antidote for nitric oxide. In the event of an overdose, best supportive care 
should be utilized. Methylene blue may be used to treat subjects exhibiting methemoglobinemia. 


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6.7 DISCONTINUATION OF INDIVIDUAL SUBJECTS FROM THE STUDY  
Subjects who develop intolerance to the product as defined by scores of 3 (severe) on 2 or more 
categories of tolerability (erythema, scaling, dryness, pruritus, burning/stinging) shall be 
discontinued from the study. 
If a subject is determined to be pregnant prior to Week 40, the subject will be discontinued from 
the study but followed until term. 
7. STATISTICAL ANALYSIS  
7.1 GENERAL CONSIDERATIONS 
All statistical processing will be performed using SAS® unless otherwise stated.  A detailed 
description of the statistical methodology and data reporting for this study will be provided in the 
Statistical Analysis Plan (SAP). The SAP will be finalized before the database is locked and 
released to Novan. Any deviations from the SAP will be justified in the clinical study report. 
7.2 POPULATIONS 
7.2.1 SAFETY POPULATION  
The safety population will include all subjects that have been dispensed study drug. 
7.3 DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
Subject demographic and baseline characteristics will be summarized. For continuous variables 
(e.g., age), mean, median, standard deviation, minimum and maximum will be presented. 
Categorical variables (e.g., ethnicity, race) will be summarized with frequency count and 
percentage. 
7.4 DESCRIPTIVE STATISTICS 
Safety data will be summarized as indicated below for the safety population. 
Continuous data will be summarized with sample size (N), mean, median, standard deviation, 
minimum and maximum. Categorical data will be summarized with N, frequency counts, and 
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7.5 SAFETY 
7.5.1 ADVERSE EVENTS 
All AEs that occur during the study or continue after enrollment into this study will be recorded 
and classified on the basis of MedDRA terminology. Treatment-emergent adverse events (TEAEs) 
are defined as AEs reported on or after the first day of enrollment in this long term safety study. 
All information pertaining to an AE noted during the study will be listed by subject, detailing 
verbatim term given by the PI or designee, preferred term, system organ class (SOC), onset date, 
resolution date, severity, seriousness, action taken, outcome, and drug relatedness. The event onset 
will also be shown relative (in number of days) to date of first dose in this study. 
Treatment-emergent AEs will be summarized by the number of subjects reporting a TEAE, SOC, 
preferred term, severity, relationship to study drug (causality), and seriousness. When 
summarizing AEs by severity and relationship, each subject will be counted only once within a 
system organ class or a preferred term by using the event with the highest severity and greatest 
relationship within each classification. 
Adverse events will also be summarized by windows of exposure to study drug.  The windows 
will include but are not limited to: 1) within the first 24 hours of exposure, 2) up to 1 month of 
exposure, 3) up to 3 months of exposure, 4) up to 6 months of exposure and 5) up to 12 months of 
exposure. 
AEs will also be summarized based on extent of exposure as described in Section 7.7 
Serious AEs will be summarized by severity, and relationship to study drug, and individual SAEs 
will be listed by subject. In addition, a list of subjects who prematurely discontinue from the study 
due to an AE will be provided. 
7.5.2 PHYSICAL EXAMINATION 
Any clinically significant changes from Baseline will be documented as an AE. 
7.5.3  VITAL SIGNS  
Blood pressure and pulse will be summarized from Baseline through Week 40. Additionally, 
change from Baseline in vital signs will be summarized at Week 4, 12, 24, 36, and 40.  Clinically 
significant changes from Baseline will be documented as an AE. 
7.5.4 URINE PREGNANCY TESTS 
Urine pregnancy tests results for WOCBP will be presented in data listings by subject. 


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7.6 TOLERABILITY 
Distribution and shift in cutaneous tolerability assessments (erythema, scaling, dryness, pruritus, 
burning/stinging) will be summarized from Baseline to Week 40. 
7.7 EXTENT OF EXPOSURE 
Extent of exposure will be based on days of treatment and the body surface area treated (face, 
upper back, and/or upper chest/shoulders) as collected at each visit for each subject. AEs will also 
be summarized by extent of exposure to determine if there is a safety signal due to duration of 
exposure or total body area exposed. 
7.8 EFFICACY ANALYSIS  
Lesion counts will be summarized at each evaluation from Baseline through Week 40. Absolute 
and percent change in lesion counts will be summarized at Weeks 4, 12, 24, 36 and 40. 
7.9 SAMPLE SIZE AND POWER CONSIDERATIONS 
Approximately 600 subjects who completed treatment in either the NI-AC301 or NI-AC302 will 
be enrolled into the study from approximately 100 sites in North America. The main objective of 
this study is to evaluate the long term safety of SB204, therefore, no sample size or power 
calculations were performed. 
8. INVESTIGATIONAL PRODUCT MANAGEMENT 
8.1 RECEIPT OF INVESTIGATIONAL PRODUCT 
Novan, or designee, will provide all investigational products to the study sites. 
8.2 STORAGE OF INVESTIGATIONAL PRODUCT 
Upon receipt from Novan, or Novan’s designee, a study staff member will place all study supplies 
in a temperature-controlled area. The pumps should be refrigerated (2-8 °C). Access to study 
supplies should be strictly limited to the study staff. Neither the Investigator nor any member of 
the study staff will distribute any of the study supplies to any person not participating in this study. 
If a study staff member becomes aware that the study supplies have not been properly handled 
(i.e., supply arrives and was not placed in refrigerator upon receipt), the Chiltern CRA or designee 
must be contacted immediately. In such an event, study supplies should be quarantined and not be 
administered to any subject until Novan provides further direction. 
The investigational product will be dispensed at the discretion and by the direction of the 
Investigator in accordance with the conditions specified in this protocol. It is the Investigator’s 


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responsibility to ensure that accurate records of investigational product issuance and return are 
maintained. 
It is expected that the site staff will maintain refrigerator temperature logs in the investigational 
product storage area, recording the temperature at least once each working day. Excursions in 
temperature during storage should be discussed with the Chiltern CRA or designee immediately 
and study supplies should be quarantined and not administered until Novan provides approval for 
use. Other supplies will be stored at room temperature. 
8.3 TREATMENT ASSIGNMENT AND BLINDING 
Subjects will receive open label SB204 4%. The evaluator and subject will be not be blinded to 
the subject’s treatment.  
8.4 INVESTIGATIONAL PRODUCT ACCOUNTABILITY 
A trained study staff member will maintain an inventory of investigational product components.  
This will include: 
 Dates and initials of person designated as responsible for the inventory of the 
investigational product 
 Amount received including date 
 Amount currently in refrigerator, 2-8 °C storage 
 Pumps dispensed to each subject, identified at a minimum by a unique subject number 
 Amount transferred to another location within the study site or destroyed; this should not 
occur without prior notification to Chiltern 
 Non-study disposition (e.g., wasted, broken) 
 Amount returned to Novan’s designee, if applicable 
 Amount destroyed, if applicable 
All investigational product accountability forms and treatment logs must be retained in the 
Investigator’s permanent study file. These records must be available for inspection by Novan and 
Chiltern, their designees, or regulatory agencies at any time. 
8.5 RETURNS AND DESTRUCTION 
Upon completion or termination of the study, the site will be instructed on return or destruction of 
clinical supplies. 


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9. RECORDS MANAGEMENT 
9.1 DATA COLLECTION 
The full details of procedures for data handling will be documented in the data management plan. 
Source study records will be collected for each study subject and a study database will be 
maintained for all enrolled study subjects. Screen failures will not be entered in the electronic data 
capture (EDC) system. 
Novan requires that the study database be verifiable with the subject’s source study record. This 
requirement necessitates access to all original recordings and other records for each subject. The 
Investigator must therefore agree to allow access to subjects’ records, and source data must be 
made available for all study data. Subjects (or their legal representatives) must also allow access 
to the subject’s medical records. Subjects will be informed of the importance of increased record 
access and permission granted by signature on the informed consent document prior to any study 
procedures being performed. 
Before the study database is formally submitted to Novan, the study monitor, Chiltern Medical 
Monitor or Novan staff may request copies of the subject’s source study record for preliminary 
medical review. 
The Investigator must keep written or electronic source documents for every subject participating 
in the clinical study. These records must include: 
 Name Contact information 
 Date of birth 
 Sex 
 Medical history 
 Concomitant diseases 
 Concomitant therapies/medication 
 Study visit dates 
 Performed examinations, evaluations, and clinical findings 
 Investigational product administration 
 AEs, SAEs, or pregnancy (as applicable) 
Additionally, any other documents with source data must be included in the subject’s source 
documents and must include the subject’s initials, study number and the date of the evaluation. 


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The data recorded during the course of the study will be documented in the study database. 
Subjects will authorize the use of their protected health information during the informed consent 
process in accordance with the applicable privacy requirements. Subjects who deny permission to 
use and disclose protected health information will not be eligible to participate in the study. The 
Investigator will ensure that the study records and any other documents forwarded to Chiltern 
contain no mention of subject names. 
Any amendments and corrections necessary will be undertaken in both the study records and the 
study database. 
Regulatory authorities, Investigational Review Boards, Novan, and Chiltern may request access to 
all study records and other study documentation for on-site audit or inspection. The Investigator 
must guarantee direct access to these documents. The original set of study records will be kept by 
the site or an authorized designee in a secured area. Clinical data will be recorded in an electronic 
format for subsequent statistical analyses. Data files will be stored on electronic media with a final 
master data file kept by Novan after descriptive and statistical analyses and reports have been 
generated and are complete. 
9.2 FILE MANAGEMENT AT THE STUDY SITE 
It is the responsibility of the Investigator to ensure that the study center file is maintained in 
accordance with Section 8 – Essential Documents for the Conduct of a Clinical Trial of the ICH 
Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance and 21 CFR Part 312. 
9.3 RECORDS RETENTION AT THE STUDY SITE 
It is a Novan requirement that all Investigators participating in clinical studies maintain detailed 
clinical data for one of the following periods, whichever is longest: 
 Country-specific requirements; or 
 A period of at least two years following the last approval of a marketing application 
approved by a Regulatory Authority in an ICH region or until there are no pending or 
contemplated marketing applications in an ICH region; or, 
 A period of two years after Novan notifies the Investigator that the data will not be 
submitted for review by any Regulatory Authority. 
The Investigator must not dispose of any records or essential documents relevant to this study 
without either (1) written permission from Novan, or (2) providing an opportunity for Novan to 
collect such records. The Investigator shall take responsibility for maintaining adequate and 
accurate electronic or hard copy source documents of all observations and data generated during 
this study. Such documentation is subject to inspection by Novan or their designees and relevant 


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regulatory agencies. If the Investigator withdraws from the study (e.g., relocation, retirement), all 
study-related records should be transferred to a mutually agreed-upon designee. Notice of such 
transfer will be provided to Novan in writing. 
10. MONITORING, COMPLIANCE, AND QUALITY 
All aspects of the study will be monitored by Chiltern according to Good Clinical Practices and 
Standard Operating Procedures (SOPs) for compliance with applicable government regulations, 
(i.e., informed consent regulations, (21 C.F.R. § 50.20, 1999), and Institutional Review Board 
regulations, (21 C.F.R. § 56.103, 1981)). Access to all records, both during the trial and after trial 
completion, should be made available to Chiltern at any time for review and audit to ensure the 
integrity of the data. The Investigator must notify Chiltern immediately if the responsible IRB has 
been disqualified or if proceedings leading to disqualification have begun. 
The Investigator must conduct the protocol in accordance with applicable GCP regulations and 
guidelines, applicable informed consent regulations (21 C.F.R. § 50.20, 1999), and in compliance 
with the principles in the Declaration of Helsinki. Every attempt must be made to follow the 
protocol and to obtain and record all data requested for each subject at the specified times. If data 
is not recorded per protocol, the reason(s) must be clearly documented on the study records. 
Before study initiation, at a site initiation visit or at a meeting with the Investigator(s), a Novan or 
Chiltern representative will review the protocol and study records with the Investigator(s) and their 
staff. During the study, the Chiltern study monitor will visit the site regularly to check the 
completeness of subject records, the accuracy of entries into the study database, the adherence to 
the protocol and to GCP, the progress of enrollment, to ensure that consent is being sought and 
obtained in compliance with applicable regulations, and that the investigational product is being 
stored, dispensed and accounted for according to specifications. The Investigator and key trial 
personnel must be available to assist the monitor during these visits. 
The Investigator must give the monitor access to relevant hospital or clinical records to confirm 
their consistency with the study database entries. No information in these records about the identity 
of the subjects will leave the study center. Monitoring standards require full verification for the 
presence of informed consent, adherence to the inclusion/exclusion criteria, documentation of 
SAEs and the recording of safety variables. A reduced source data verification model will be 
deployed for this study in order to focus on the critical data for analysis and this will be executed 
per the study specific monitoring plan. Additional checks of the consistency of the study records 
with the study database will be performed according to the study-specific monitoring plan. 
The Investigator or designee must promptly enter the data into the study database after the subject’s 
visit. The monitor is responsible for reviewing them and clarifying and resolving any data queries. 
A copy of the study records will be retained by the Investigator who must ensure that it is stored 


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in a secure place with other study documents, such as the protocol, the Investigator’s Brochure and 
any protocol amendments. 
The Investigator must provide Chiltern and the responsible IRB with a study summary shortly after 
study completion. 
10.1 QUALITY ASSURANCE AUDITS AND QUALITY CONTROL 
In addition to the routine monitoring procedures, audits of clinical research activities in accordance 
with SOPs may be performed to evaluate compliance with the principles of GCP. A regulatory 
authority may also wish to conduct an inspection (during the study or even after its completion). 
If a regulatory authority requests an inspection, the Investigator must inform Chiltern immediately 
that this request has been made. 
Study conduct may be assessed during the course of the study by a Quality Assurance 
representative(s) to ensure that the study is conducted in compliance with the protocol and GCP. 
He/she will be permitted to inspect the study documents (study protocol, study records, 
investigational product, original, study-relevant medical records). All subject data will be treated 
confidentially.  
11. ETHICS AND RESPONSIBILITY 
This study must be conducted in compliance with the protocol, the ICH Guidance for Industry E6 
Good Clinical Practice: Consolidated Guidance and the applicable regulatory requirements. The 
Investigator must submit all essential regulatory documentation, as required by local and national 
regulations (including approval of the protocol and informed consent/assent form by an IRB) to 
Chiltern before investigational product will be shipped to the study site. The Investigator will 
review the final study results to confirm that to the best of his knowledge, it accurately describes 
the conduct and results of the study.  
12. CONFIDENTIALITY 
All information generated in this study must be considered highly confidential and must not be 
disclosed to any persons not directly concerned with the study without written prior permission 
from Novan. Authorized regulatory officials, Novan and Chiltern personnel (or their 
representatives) will be allowed full access to inspect and copy the records. All study 
investigational products, subject bodily fluids, and/or other materials collected shall be used solely 
in accordance with this protocol, unless otherwise agreed to in writing by Novan. 
Subjects will be identified at a minimum by unique subject numbers in the study database.  


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13. AMENDMENT POLICY 
Only Novan may modify the protocol. Amendments may be approved by all applicable national 
and local committees including, but not limited to, the government regulatory authorities and/or 
regional IRB before implementation. The only exception is when an Investigator considers that a 
subject may be harmed and immediate action is necessary. Under these circumstances, approval 
of the chairman of the IRB, or an authorized designee must be sought immediately. The 
Investigator should inform Chiltern and the full IRB no later than five working days after the 
emergency occurs. Protocol-specified safety reporting requirements must be adhered to 
independent of any other variables. All amendments that have an impact on subject risk, the study 
objectives or that require revision of the informed consent document must be approved by the IRB 
before implementation. Administrative changes to the protocol and/or changes that do not impact 
subject safety, risk or comfort may be implemented prior to IRB approval if local institutional 
policy permits. A copy of the written approval of the IRB, which becomes part of the essential 
study documents file, must be given to the study monitor. Examples of amendments requiring such 
approval are: 
 A significant change in the study design 
 An increase in the number of invasive procedures to which subjects are exposed 
 An addition or deletion of a test procedure 
The Principal Investigator at each study site must sign the Investigator’s Agreement page of the 
amended protocol. 
14. USE OF INFORMATION AND PUBLICATION 
It is understood by the Investigator that the information generated in this study will be used by 
Novan in connection with the development of the product and therefore may be disclosed to 
government agencies in various countries. To allow for the use of information derived from the 
study, it is understood that the Investigator is obliged to provide Novan with complete test results, 
all study data and access to all study records. 
Investigators may not report the results of this clinical study in any publication, poster or other 
public forum without express authorization from Novan.  
 
 


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15. REFERENCES  
Guideline for Good Clinical Practice.  ICH Harmonised Tripartite Guideline. 1996.   
Protection of Human Subjects.  Code of Federal Regulation. 1999. Part 50, Title 21, Section 20.   
Institutional Review Boards.  Code of Federal Regulation. 1981. Part 56, Title 21, Section 103. 


Protocol NI-AC303 
 
Version 1.0 
Novan, Inc. 
 
 09 November 2015 
Confidential and Proprietary, Novan, Inc. 
 
47 
16. APPENDICES 
16.1  APPENDIX 1:  LIST OF RESTRICTED MEDICATIONS: 
 Anti-acne medications 
 Anabolic steroids 
 Azathioprine  
 Bromides 
 Corticosteroids (oral) 
 Chloroquine 
 Flutamide 
 Halides 
 Lithium 
 Phenobarbital 
 Phenytoin 
 Vitamin A (> 10,000 IU/day) 
 
 

SAP_001.pdf: 
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Statistical Analysis Plan  
  
  
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term Safety of SB204 Once 
Daily in the Treatment of Acne Vulgaris   
  
Novan, Inc.  
4105 Hopson Road 
Morrisville, NC 27560  
  
  
  
  
  
  
Author(s):  
Melissa Hays  
Document Status:  
Final  
Version Date:  
Version 1.0 12Apr2017 
  
  
  
  
  
  
  
  
 
 


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Contents 
Abbreviations ................................................................................................................................ 3 
1 
Introduction ....................................................................................................................... 4 
2 
Study Objectives ............................................................................................................... 4 
2.1 
Safety Endpoints .............................................................................................................. 4 
2.2 
Tolerability Endpoints ...................................................................................................... 4 
2.3 
Extent of Exposure ........................................................................................................... 4 
2.4 
Efficacy Endpoints ........................................................................................................... 4 
3 
Study Design ...................................................................................................................... 4 
3.1 
Study Design .................................................................................................................... 4 
3.2 
Study Treatment ............................................................................................................... 5 
3.3 
Study Schedule ................................................................................................................. 6 
3.4 
Concomitant Medication .................................................................................................. 7 
3.5 
Populations ....................................................................................................................... 7 
3.5.1 
Safety Population .......................................................................................................... 7 
3.6 
Sample Size ...................................................................................................................... 7 
4 
Statistical Methodology .................................................................................................... 8 
4.1 
Planned Analyses ............................................................................................................. 8 
4.2 
Disposition of Subjects ..................................................................................................... 8 
4.3 
Baseline and Demographic Characteristics ...................................................................... 8 
4.4 
Extent and Duration of Exposure ..................................................................................... 8 
4.5 
Safety ................................................................................................................................ 9 
4.5.1 
Adverse Events .............................................................................................................. 9 
4.5.2 
Prior and Concomitant Medications .......................................................................... 10 
4.5.3 
Physical Examination ................................................................................................. 10 
4.5.4 
Vital Signs ................................................................................................................... 10 
4.5.5 
Urine Pregnancy Tests ............................................................................................... 10 
4.6 
Tolerability ..................................................................................................................... 10 
4.7 
Efficacy Analysis ........................................................................................................... 11 
4.8 
Deviations from SAP ..................................................................................................... 11 
 
 
  
 
 


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Abbreviations  
  
Abbreviation  
Definition  
AE  
Adverse Event  
ATC  
Anatomical and Therapeutic Class 
ET  
Early Termination  
g  
gram 
IRB  
Institutional Review Board 
LTS  
Long-Term Safety 
MedDRA  
Medical Dictionary for Regulatory Activities  
NOVAN  
Novan, Inc.  
OCP  
Oral Contraceptive Pill 
PT  
Preferred Term 
SAE  
Serious Adverse Event  
SAF  
Safety Population  
SAP  
Statistical Analysis Plan  
SAS  
Statistical Analysis Software  
SOC  
System Organ Class  
TEAE  
Treatment Emergent Adverse Events  
UPT  
Urine Pregnancy Test  
WHO  
World Health Organization 
WOCBP  
Women of Child-Bearing Potential  
 
 


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1 Introduction  
This document presents the statistical analysis plan (SAP) for Novan Inc., Protocol No. NI-AC303: 
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term Safety of SB204 Once Daily 
in the Treatment of Acne Vulgaris. 
The SAP provides the detailed description of the planned statistical analysis of data from protocol 
NI-AC303.  
  
2 Study Objectives  
The primary objective of this study is to evaluate the safety of SB204 4% once daily in subjects 
with acne vulgaris for up to 40 weeks of treatment. The Week 12 visit from the pivotal studies (NI-
AC301 and NI-AC302) will serve as the Baseline Visit for this study. 
2.1 Safety Endpoints  
Safety endpoints will include adverse events, changes in physical examination and changes in vital 
sign measurements. Any clinically significant changes noted during the physical exam as well as 
from the vital sign measurements will be recorded as adverse events and included in the 
comparison. Urine pregnancy tests in women of child-bearing potential will be conducted at each 
visit. 
2.2 Tolerability Endpoints  
 
The cutaneous tolerability assessments include the investigator’s assessment of erythema, scaling, 
dryness, and the subject’s report of pruritus and burning/stinging based on the preceding 24 hours. 
  
2.3 Extent of Exposure 
  
Duration, days of, and extent of exposure for each subject will be determined based on the stop 
and start dates of use of SB204, the total number of days of study drug application, and the areas 
treated (face, upper back, upper chest, and shoulders). 
2.4 Efficacy Endpoints  
  
Efficacy endpoints will include absolute and percent change in inflammatory and non-
inflammatory facial area lesion counts from baseline at each study visit.  
 
3 Study Design  
3.1 Study Design  
This is a multi-center, open label long-term safety (LTS) study to be conducted in approximately 
600 subjects with acne vulgaris. Subjects will be enrolled into the study from approximately 100 


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sites in North America. Subjects eligible to enroll in this study will have completed one of the 
Phase 3 pivotal studies with SB204, NI-AC301 or NI-AC302, and meet study inclusion and 
exclusion criteria. 
Subjects who satisfy the entry criteria at the Baseline visit will be enrolled to receive open-label 
SB204. Investigational drug will be delivered from a double barrel single pump dispenser. The 
pump dispenses product (NVN1000 Gel and a hydrogel) from two chambers which will be 
mixed together quickly (about 5 seconds) by the subject and applied once daily to the acne 
affected areas identified by the Investigator.  Areas that could be treated include the face, upper 
chest, upper back and shoulders. No other acne treatments will be permitted during the study.  
Subjects will return for post-baseline evaluation at Weeks 4, 12, 24, 36 and 40/ET.   
3.2 Study Treatment  
The amount of SB204 per application will vary depending on the areas to be treated as shown in 
Table 1 below. Subjects are allowed to specify ‘Other’.  If the other specification is jaw or neckline, 
it is assumed that the same pump stroke used to apply drug to face is being used for the jaw and/or 
neckline application. One pump stroke will likely be used for each application area.  For example, 
application to the face, upper back and upper chest will require up to 2.7 g (three (3) pump strokes).   
Table 1: 
Dosing Amount by Area 
Area (BSA) 
Number of Pump Strokes 
Amount of Product 
Face, including jaw line and 
or neck if indicated 
1 
0.9 g 
Upper Back  
1 
0.9 g 
Upper Chest  
1 
0.9 g 
Shoulders 
1 
0.9 g 
 
 


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3.3 Study Schedule  
 
Study visits should occur at approximately the same time of day throughout the study.   
 
PROCEDURES 
Visit 11 
 
Baseline 
(Day 0) 
Visit 23 
Week 4 
±5 days 
(Day 28) 
Visit 3 
Week 12 
±7 days 
(Day 84) 
Visit 4 
Week 24 
±7 days 
(Day 168) 
Visit 5 
Week 36 
±7 days 
(Day 252) 
Visit 64 
Week 40/ET
±7 days 
(Day 280) 
Informed 
Consent/Assent 
X 
 
 
 
 
 
Demographics  
X2 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Medication History 
X 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
Brief Physical 
Examination 
X2 
 
 
 
 
X 
Urine Pregnancy Test 
(all WOCBP) 
X2 
X 
X 
X 
X 
X 
Blood Pressure and 
Pulse 
X2 
X 
X 
X 
X 
X 
Lesion Counts 
X2 
X
X
X
X 
X
Cutaneous Tolerability 
Evaluation 
X2 
X 
X 
X 
X 
X 
Instruct on Study Drug 
Application and 
Provide Subject 
Instructions  
X 
 
 
 
 
 
Record application 
areas since last visit 
 
X 
X 
X 
X 
X 
Study Drug 
Dispensed/Retraining 
on mixing and 
application 
X 
X 
X 
X 
X 
 
Study Drug Collected 
 
X 
X 
X 
X 
X 
Subject Study Drug Use
Reviewed 
 
X 
X 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X
X
X
X 
X
¹Data for the Baseline Visit for this study will be the Week 12 data from the Phase 3 pivotal study for completing, eligible subjects. 
2Demographics and assessments from the Week 12 visit from the preceding Phase 3 study including the physical examination, blood 
pressure and pulse, UPT, tolerability, and lesion counts do not need to be repeated. 
3All visit dates are in reference to Baseline, e.g., Visit 2 occurs four weeks (28 days) after Baseline visit. 
4All Week 40 procedures should be completed for subjects who prematurely discontinue, if possible. 
 


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3.4 Concomitant Medication  
  
Subjects will be permitted to apply non-comedogenic moisturizer or sunscreen on an as-needed 
basis. Moisturizer must not contain antibacterials and the subject must not change moisturizer 
and/or sunscreen used during the course of the study. If used, moisturizers and sunscreen must be 
applied at least 30 minutes after study drug application.  
Subjects must not have used anti-acne treatments including topical or systemic antibiotics or 
retinoids (as described in Section 3.7.3 of the protocol) prior to Baseline. These medications are 
also prohibited during the trial. Short term courses of antibiotics (≤ 14 days) for non-acne related 
illnesses and inhaled or intranasal steroids are permitted during the trial. 
Subjects may not be concurrently on drugs associated with exacerbating acne vulgaris (see 
Appendix 16.1 of the protocol). Subjects must not participate in a different interventional research 
study during the study period.  
Any medication/therapy used by the subject following first application of study product will be 
considered a concomitant medication/therapy (e.g., aspirin, acetaminophen, birth control pills, 
vitamins, etc.). Every attempt should be made to keep concomitant medication/therapy dosing 
constant during the study. Any change to concomitant medications/therapies should be noted on 
the subject’s study record and in the study database. When applicable, an AE should be completed 
for any subject starting a concomitant medication/therapy after enrollment into the study.  
3.5 Populations  
  
3.5.1 Safety Population  
  
The safety population (SAF) will include all subjects that have received at least one dose of SB204. 
For the summaries, we are defining two subject categories, based on the subject’s status at the start 
of the LTS: 
 SB204 Experienced: subjects allocated to SB204 in the previous study 
 SB204 Naїve: subjects allocated to vehicle in the previous study 
 
3.6 Sample Size  
  
The main objective of this study is to evaluate the long term safety of SB204, therefore, no sample 
size or power calculations were performed. 


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4 Statistical Methodology  
4.1 Planned Analyses  
All statistical processing will be performed using statistical analysis software (SAS®) unless 
otherwise stated. Safety analyses will be performed using the safety population. 
Continuous data will be summarized with sample size (N), mean, median, standard deviation, 
minimum and maximum.  Categorical data will be summarized with N, frequency counts, and 
percentages, based on N.  
4.2 Disposition of Subjects  
The number of subjects in the Safety Population, who completed the study and the reasons for any 
premature discontinuation from the study, will be presented. Listings will indicate whether subjects 
met all inclusion and exclusion criteria, and, if not, which criteria were not met.   
A summary and a listing of protocol deviations will be presented.   
4.3 Baseline and Demographic Characteristics  
Subject baseline and demographic characteristics, including age, race, ethnicity, and gender, will 
be summarized, as well as which previous Novan study the subject was enrolled in (NI-AC301 or 
NI-AC302) and previous treatment assignment (SB204 or Vehicle).  
 
For female subjects the following summaries will be included: child-bearing potential, 
contraceptive use at baseline. Medical history will be summarized for each treatment group by 
SOC and PT and presented in listings. Adverse events ongoing at end of pivotal study will be 
carried forward to this study, will not be considered treatment-emergent for this study, and will be 
summarized separately by SOC, PT, and relatedness. 
  
4.4 Extent and Duration of Exposure  
 
Summaries of the duration of exposure, days of exposure, and extent of exposure (calculated total 
grams) to study drug will be presented, overall and by whether previously randomized to SB204 
(SB204 experienced) or randomized to Vehicle (SB204 naïve).  This information plus study drug 
management details will be listed as well.  All exposure endpoints will take into account whether 
the subject received SB204 in the previous study (NI-AC301 or NI-AC302). 
 
Duration of exposure will be defined as:  
 
Date of Last Drug Administration – Date of First Drug Administration + 1 day 
 


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Where date of first drug administration is the date of first treatment in the previous pivotal study 
for subjects randomized to SB204 in the previous study, and date of first dose in the LTS for 
subjects randomized to vehicle in the previous study. 
Days of exposure will be defined as the total number of days that the subject reported taking study 
medication, and includes the days of exposure to SB204 in the previous study (NI-AC301 or NI-
AC302) if applicable. 
Extent of exposure will be based on the number of areas treated (face, upper back, and/or upper 
chest/shoulders, and any other areas reported) and the number of days with treatment. For subjects 
randomized to SB204 in the previous studies, drug was only applied to the face so for the days of 
exposure from the previous studies, it will be assumed that there is only one area of application, 
i.e. the face. 
Each application is equal to 0.9 g. Extent of exposure is estimated as the sum of application areas 
(face only=1, face and chest=2, etc.) times the number of days of application to those areas times 
0.9g.  For example, a subject who applies 200 applications to the face only will have extent of 
exposure = 180g, while a subject who applies 100 applications to the face and 50 applications to 
the upper back will have extent of exposure = 135 g. The maximum extent of exposure would be: 
[0.9 grams x number of days on treatment in previous study] + [0.9 grams x 4 areas x number of 
LTS days on treatment].  Most subjects will have less exposure than this, so extent of exposure 
will be categorized logically depending on actual distribution of subjects. Initially, quartiles will 
considered. 
4.5 Safety  
  
4.5.1 Adverse Events  
All AEs that occur during the study or continue after enrollment into this study will be recorded 
and classified on the basis of Medical Dictionary for Regulatory Activities (MedDRA) 
terminology version 18.1. Adverse events ongoing at end of the pivotal study will be carried 
forward to this study, will not be considered treatment-emergent for this study, and will be 
summarized separately by SOC, PT, and relatedness.  Treatment-emergent AEs (TEAEs) will be 
defined as AEs reported on or after the first day of enrollment in this long term safety study.   
All information pertaining to an AE noted during the study will be listed by subject, detailing 
verbatim term given by the Investigator or designee, preferred term, system organ class (SOC), 
onset date, resolution date, severity, seriousness, action taken, outcome, and drug relatedness. 
The event onset will also be shown relative (in number of days) to date of first dose in this study.   
Treatment-emergent AEs will be summarized by the number of subjects reporting a TEAE, SOC, 
preferred term, severity, relationship to study drug (causality), and seriousness. When 
summarizing AEs by severity and relationship, each subject will be counted only once, within a 
system organ class or a preferred term, by using the event with the highest severity and greatest 
relationship within each classification.  


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Serious AEs will be summarized by severity, and relationship to study drug, and individual SAEs 
will be listed by subject. In addition, a list of subjects who prematurely discontinue study drug due 
to an AE, had AEs leading to treatment modification, and AEs that resulted in death will be 
provided. 
Adverse events will also be summarized by windows of duration of exposure to study drug to 
determine if there is a safety signal due to duration of exposure. The windows of exposure will 
include but are not limited to: 1) within the first 24 hours (i.e. Day 1 of the LTS study), 2) up to 1 
month (i.e. 2-30 days), 3) up to 3 months (i.e. 31-90 days), 4) up to 6 months (i.e. 91-180 days) 
and 5) up to 12 months (i.e. 181-365 days).  
Adverse event incidence will also be summarized by the extent of exposure categories (in grams) 
as described in section 4.4. 
 
4.5.2 Prior and Concomitant Medications 
Medications will be mapped to their corresponding thesaurus terms (ATC Class and Preferred 
Term) according to the World Health Organization (WHO) Drug Dictionary, Version Mar2016.  
A summary of concomitant medications, sorted by ATC Class 2 and Preferred Term, will be 
provided.  A listing of prior and concomitant medications will be presented, as well a listing of 
any prohibited medications used during the study. 
4.5.3 Physical Examination 
The results of the physical exams will be presented in a listing. Clinically significant changes 
from Baseline will be documented as an AE. 
4.5.4 Vital Signs 
Blood pressure and pulse will be summarized from Baseline through Week 40/ET. Additionally, 
change from Baseline in vital signs will be summarized at Week 4, 12, 24, 36, and 40/ET.  
Clinically significant changes from Baseline will be documented as an AE. 
 
4.5.5 Urine Pregnancy Tests 
Urine pregnancy tests results for WOCBP will be presented in data listings by subject. 
4.6 Tolerability 
Distribution and shift in cutaneous tolerability assessments (erythema, scaling, dryness, pruritus, 
burning/stinging) will be summarized from Baseline to Week 40/ET. 


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4.7 Efficacy Analysis 
The facial area inflammatory and non-inflammatory lesion counts will be summarized at each 
evaluation from Baseline through Week 40/ET. Absolute and percent change in inflammatory and 
non-inflammatory lesion counts will be summarized at Weeks 4, 12, 24, 36 and 40/ET.  The 
absolute and percent change in inflammatory non-inflammatory lesion counts will also be 
summarized by prior treatment (SB204 experienced, SB204 naïve). 
4.8 Deviations from SAP  
Any deviations from the original statistical plan will be described and justified in the final clinical 
study report.  
  


  
 
Protocol: NI-AC303 
 
 
 
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term Safety of SB204 Once 
Daily in the Treatment of Acne Vulgaris. 
 
 
 
Mock Data Displays- Tables 
Version 1.0   
Date: 12Apr2017 
 
 
Prepared for: 
Novan Inc. 
4105 Hopson Road 
Morrisville, NC 27560 
 
Prepared by: 
Chiltern International 
4000 CentreGreen Way, Suite 300, Cary, NC, 27513, United States  
 
 
This document is the confidential information of Novan Inc.  It may not be disclosed 
to parties not associated with the clinical investigation or used for any purpose 
without the prior written consent of Novan Inc. 


  
 
 
   
Contents 
Table 14.1.1.1 Subject Disposition Safety Population.......................................................................................................................................................................... 4 
Table 14.1.1.2 Summary of Protocol Deviations Safety Population .................................................................................................................................................... 5 
Table 14.1.2.1 Demographics  Safety Population ................................................................................................................................................................................. 6 
Table 14.1.2.2 Child Bearing Potential and Contraceptive Use (Females Only)  Safety Population ................................................................................................... 7 
Table 14.1.3 Medical History by System Organ Class and Preferred Term Safety Population ............................................................................................................ 8 
Table 14.1.4 Adverse Events Ongoing at the Start of the Study by System Organ Class, Preferred Term, and Extent of Exposure  Safety Population .................... 9 
Table 14.1.5 Concomitant Medications by WHO Drug Class and WHO Drug Preferred Name  Safety Population ......................................................................... 10 
Table 14.2.1. Summary of Duration and Extent of Drug Exposure Safety Population ...................................................................................................................... 11 
Table 14.2.2.1 Inflammatory Lesion Counts by Study Visit (Face Only) Safety Population ............................................................................................................. 12 
Table 14.2.2.2 Non-Inflammatory Lesion Counts by Study Visit (Face Only) Safety Population ..................................................................................................... 12 
Table 14.2.3.1 Inflammatory Lesion Counts (Face Only) by Prior Treatment and Study Visit  Safety Population ........................................................................... 13 
Table 14.2.3.2 Non-Inflammatory Lesion Counts (Face Only) by Prior Treatment and Study Visit Safety Population .................................................................... 13 
Table 14.3.1.1 Cutaneous Tolerability Evaluation – Erythema - Summarized by Study Visit (Face Only) Safety Population ......................................................... 14 
Table 14.3.1.2 Cutaneous Tolerability Evaluation – Scaling - Summarized by Study Visit Safety Population ................................................................................. 15 
Table 14.3.1.3 Cutaneous Tolerability Evaluation – Dryness - Summarized by Study Visit Safety Population ................................................................................ 15 
Table 14.3.1.4 Cutaneous Tolerability Evaluation – Pruritus - Summarized by Study Visit Safety Population ................................................................................ 15 
Table 14.3.1.5 Cutaneous Tolerability Evaluation – Burning/Stinging - Summarized by Study Visit Safety Population ................................................................. 15 
Table 14.3.2.1 Shift from Baseline in Cutaneous Tolerability Evaluation – Erythema, by Study Visit (Face Only) Safety Population ............................................ 16 
Table 14.3.2.2 Shift from Baseline in Cutaneous Tolerability Evaluation – Scaling - Summarized Continuously by Study Visit Safety Population ...................... 17 
Table 14.3.2.3 Shift from Baseline in Cutaneous Tolerability Evaluation – Dryness - Summarized Continuously by Study Visit Safety Population ..................... 17 
Table 14.3.2.4 Shift from Baseline in Cutaneous Tolerability Evaluation – Pruritus - Summarized Continuously by Study Visit Safety Population ...................... 17 
Table 14.3.2.5 Shift from Baseline in Cutaneous Tolerability Evaluation – Burning/Stinging - Summarized Continuously by Study Visit Safety Population ....... 17 
Table 14.3.3.1  Treatment Emergent Adverse Events (TEAE) Overview Safety Population ............................................................................................................. 18 
Table 14.3.3.2.1 Treatment Emergent Adverse Events (TEAE) by System Organ Class, Preferred Term, and Duration of Exposure  Safety Population ............... 19 
Table 14.3.3.2.2 Treatment Emergent Adverse Events (TEAE) by System Organ Class, Preferred Term, and Extent of Exposure  Safety Population .................. 20 
Table 14.3.3.3.1 Treatment-Related Emergent Adverse Events by System Organ Class, Preferred Term, and Duration of Exposure Safety Population ................ 21 
Table 14.3.3.3.2 Treatment-Related Emergent Adverse Events by System Organ Class, Preferred Term, and Extent of Exposure Safety Population .................... 21 
Table 14.3.3.4.1 Treatment Emergent Adverse Events Leading to Treatment Modification by Duration of Exposure Safety Population ........................................ 21 
Table 14.3.3.4.2 Treatment Emergent Adverse Events Leading to Treatment Modification by Extent of Exposure Safety Population ........................................... 21 
Table 14.3.3.5.1 Treatment-Related Treatment Emergent Adverse Events Leading to Treatment Modification by Duration of Exposure Safety Population ......... 21 
Table 14.3.3.5.2 Treatment-Related Treatment Emergent Adverse Events Leading to Treatment Modification by Extent of Exposure Safety Population ............. 21 
Table 14.3.3.6.1 Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Duration of Exposure Safety Population ............................. 21 
Table 14.3.3.6.2 Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Extent of Exposure Safety Population ................................ 21 
Table 14.3.3.7.1 Treatment-Related Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Duration of Exposure Safety Population
 ............................................................................................................................................................................................................................................................ 21 
Table 14.3.3.7.2 Treatment-Related Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Extent of Exposure Safety Population .. 22 


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Table 14.3.3.8.1 Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Duration of Exposure Safety Population ................. 22 
Table 14.3.3.8.2 Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Extent of Exposure Safety Population .................... 22 
Table 14.3.3.9.1 Treatment-Related Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Duration of Exposure Safety 
Population ........................................................................................................................................................................................................................................... 22 
Table 14.3.3.9.2 Treatment-Related Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Extent of Exposure Safety 
Population ........................................................................................................................................................................................................................................... 22 
Table 14.3.3.10.1 Treatment Emergent Adverse Events Leading to Death by Duration of Exposure Safety Population .................................................................. 22 
Table 14.3.3.10.2 Treatment Emergent Adverse Events Leading to Death by Extent of Exposure Safety Population ...................................................................... 22 
Table 14.3.3.11.1 Treatment-Related Treatment Emergent Adverse Events Leading to Death by Duration of Exposure Safety Population ................................... 22 
Table 14.3.3.11.2 Treatment-Related Treatment Emergent Adverse Events Leading to Death by Extent of Exposure Safety Population ....................................... 22 
Table 14.3.3.13  Summary of Treatment Emergent Adverse Events (TEAE) by Highest Severity, System Organ Class and Preferred Term Safety Population .... 23 
Table 14.3.3.14 Summary of Treatment-Related Emergent Adverse Events (TEAE) by Severity, System Organ Class and Preferred Term Safety Population ..... 24 
Table 14.3.4  Summary of Vital Signs  Safety Population ................................................................................................................................................................. 25 
 
 
 


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Table 14.1.1.1 
Subject Disposition 
Safety Population 
Notes: Safety (SAF) Population includes all subjects that have been dispensed study drug and received at least one 
dose of SB204. 
Unless stated otherwise, denominator is the number of subjects in safety population. 
[a]Denominator is the number of subjects who were randomized. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
 
 
   SB204  
  (N=XXX) 
 
 
SAF Population  
  xx (xx.x) 
 
Treatment-naïve at enrollment 
  xx (xx.x) 
 
Previously on SB204 at enrollment 
  xx (xx.x) 
 
 
Completed Study 
  xx (xx.x) 
 
SB204 Experienced 
  xx (xx.x) 
 
SB204 Naїve 
  xx (xx.x) 
 
 
Discontinued Early 
  xx (xx.x) 
 
 
Primary Reason for Study Discontinuation [a] 
 
Adverse Events 
  xx (xx.x) 
Lack of Efficacy as Determined by Investigator 
  xx (xx.x) 
Withdrawal by Subject 
  xx (xx.x) 
Physician Decision 
  xx (xx.x) 
Protocol Violation 
  xx (xx.x) 
Lost to Follow-up 
  xx (xx.x) 
Pregnancy 
  xx (xx.x) 
Worsening of Condition 
  xx (xx.x) 
Other 
  xx (xx.x) 
 
 


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Protocol Number: NI-AC303                                                             
 
Table 14.1.1.2 
Summary of Protocol Deviations 
Safety Population 
 
Protocol Deviations 
   SB204 
  (N=XXX) 
 
 
Subjects with Any Protocol Deviation 
  xxx (xx.x) 
 
 
   Deviation A 
  xxx (xx.x) 
   … 
 
   Deviation B 
  xxx (xx.x) 
   … 
 
   Deviation C 
  xxx (xx.x) 
 
 
   Etc. 
 
 
 
 
 
      
 
Note (s): Percentages are based on the number of subjects in safety population. 
Reference: Listing 16.2.x 
 
 


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Table 14.1.2.1 
Demographics  
Safety Population 
 
 
SB204 Experienced 
(N=XXX) 
SB204 Naïve  
(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 
 Min, Max 
x.x, xx.x 
x.x, xx.x 
x.x, xx.x 
 
 
 
 
Age Group 
 
 
 
 Juvenile (Age <18 years) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Adult (Age 18+ years) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Race 
 
 
 
   White 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Black or African American 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   American Indian or Alaska Native 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Native Hawaiian or Other Pacific  
   Islander 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Asian 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Ethnicity 
 
 
 
   Hispanic or Latino 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Not Hispanic or Latino 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Sex  
 
 
 
   Male 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Female 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Previously in Study 
 
 
 
   NI-AC301 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   NI-AC302 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Note(s): Percentages are based on the number of subjects in safety population. Age is based on the date of informed 
consent from the previous study (NI-AC301 or NI-AC302); LTS = Long Term Safety Study. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.1.2.2 
Child Bearing Potential and Contraceptive Use (Females Only)  
Safety Population 
 
 
SB204 
(N=XXX) 
 
 
If Female, of Childbearing Potential? 
 
   Yes 
xx (xx.x) 
   No 
xx (xx.x) 
 
 
If No to Childbearing Potential, Why 
 
   Post-Menopausal 
xx (xx.x) 
   Hysterectomy or Bilateral Oophorectomy 
xx (xx.x) 
 Surgically Sterilized 
xx (xx.x) 
 
 
If Yes to Childbearing Potential, Primary Method of Birth Control 
 
   Oral Contraceptive 
xx (xx.x) 
 Intra-Uterine Device 
xx (xx.x) 
 Condom with Spermicide 
xx (xx.x) 
 Diaphragm with Spermicide 
xx (xx.x) 
   Implant 
xx (xx.x) 
 Nuvaring 
xx (xx.x) 
 Medroxyprogesterone Injection 
xx (xx.x) 
Transdermal Patch 
xx (xx.x) 
   Abstinence 
xx (xx.x) 
   Other 
xx (xx.x) 
 
 
 
 
Note(s): Percentages are based on the number of female subjects in Safety population. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
  
Table 14.1.3 
Medical History by System Organ Class and Preferred Term 
Safety Population  
 
Body System Class 
  Preferred Term 
SB204 
(N=XXX) 
 
 
Subject with Any Medical History 
xx (xx.x) 
 
 
System Organ Class 1 
xx (xx.x) 
 
Preferred Term 1 
xx (xx.x) 
 
Preferred Term 2 
xx (xx.x) 
        …… 
 
 
Preferred Term n 
xx (xx.x) 
 
 
…… 
 
 
 
System Organ Class n 
xx (xx.x) 
 
Preferred Term 1 
xx (xx.x) 
 
Preferred Term 2 
xx (xx.x) 
        …… 
 
 
Preferred Term n 
xx (xx.x) 
 
 
 
 
 
xx (xx.x) 
System Organ Class q 
xx (xx.x) 
 
Preferred Term 1 
xx (xx.x) 
 
Preferred Term 2 
xx (xx.x) 
     …… 
 
 
 
 
 
 
 
Note(s): All investigator terms were coded using MedDRA dictionary version 18.1. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.1.4 
Adverse Events Ongoing at the Start of the Study by System Organ Class, Preferred Term, and Extent of Exposure  
Safety Population 
 
System Organ Class 
  Preferred Term 
SB204 Experienced 
(N=XXX) 
SB204 Naïve  
(N=XXX) 
Overall 
(N=XXX) 
 
 
 
 
Number of Subjects with at Least One Event 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Events 
xx 
xx 
xx 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Note(s): Adverse event terms were coded using MedDRA dictionary version 18.1. Subjects are counted once within each 
level of summary. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
Programmer Note: Order SOC by decreasing frequency and preferred term by decreasing frequency within SOC based on 
overall incidence. 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.1.5 
Concomitant Medications by WHO Drug Class and WHO Drug Preferred Name  
Safety Population 
 
Drug Class 
  Preferred Name 
SB204 
(N=XXX) 
 
 
Subjects Who Took at Least One Concomitant Medication 
xx (xx.x) 
 
 
Drug Class 1 
xx (xx.x) 
  Preferred Name 1 
xx (xx.x) 
  Preferred Name 2 
xx (xx.x) 
  Preferred Name 3 
xx (xx.x) 
  etc. 
xx (xx.x) 
 
 
Drug Class 2 
xx (xx.x) 
  Preferred Name 1 
xx (xx.x) 
  Preferred Name 2 
xx (xx.x) 
  Preferred Name 3 
xx (xx.x) 
  etc. 
xx (xx.x) 
 
 
Drug Class 3 
xx (xx.x) 
  Preferred Name 1 
xx (xx.x) 
  Preferred Name 2 
xx (xx.x) 
…… 
xx (xx.x) 
 
 
 
Note(s): Subjects are counted only once at each level of summarization. 
Concomitant medications are all medications taken during the study period, including those started before but ongoing 
at first dose. All medications were coded using WHO Drug dictionary version March 2016. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
Programmer’s Note(s): Continue with all drug classes and preferred names which appear in the data. Sort drug classes 
and within drug classes, preferred terms by decreasing overall frequency. 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.2.1. 
Summary of Duration and Extent of Drug Exposure 
Safety Population 
 
 
SB204 Experienced 
(N=XXX) 
SB204 Naïve  
(N=XXX) 
Overall 
(N=XXX) 
 
 
 
 
Overall Duration of Exposure (Days) 
 
 
 
Number of Subjects with Exposure 
xx 
xx 
xx 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
Min, Max 
x.x, xx.x 
x.x, xx.x 
x.x, xx.x 
Unknown 
 
 
 
Days of Exposure 
 
 
 
n 
xx 
xx 
xx 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
x.x, xx.x 
x.x, xx.x 
x.x, xx.x 
   Unknown 
 
 
 
Areas of Application 
 
 
 
  Face 
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
  Upper Back 
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
  Upper Chest 
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
  Shoulders 
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x)
xx (xx.x) 
xx (xx.x) 
Extent of Exposure (grams) 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
Min, Max 
x.x, xx.x 
x.x, xx.x 
x.x, xx.x 
Unknown 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
   1-100 grams 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >100-330 grams  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >330-675 grams 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >675 grams 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Notes: All exposure endpoints includes exposure to SB204 from the previous study (NI-AC301 or NI-AC302), if applicable. 
Duration of Exposure = Date of Last Drug Administration – Date of First Drug Administration + 1 day.  
Days of exposure will be defined as the total number of days that the subject reported taking study medication.  
Areas of application indicate if the subject ever applied drug to that area.  Each subject is counted only once per 
area.  
Extent of exposure is determined as: 0.9 grams times the number of application areas times the number of days applied.  
Application to neck and jawline are considered part of application to the face when determining extent of exposure. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
 
Table 14.2.2.1 
Inflammatory Lesion Counts by Study Visit (Face Only) 
Safety Population 
 
Visit 
Statistic 
SB204 
(N=XXX) 
    Count 
Absolute Change  
from Baseline 
Percent Change  
from Baseline 
 
 
 
 
 
Baseline 
N 
XX 
 
 
 
Mean 
XX.X 
 
 
 
SD 
XX,XX 
 
 
 
Median 
XX 
 
 
 
Min. to Max. 
XX to XX 
 
 
 
 
 
 
 
Week 4 
N 
XX 
XX
XX
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX,XX 
XX,XX 
XX,XX 
 
Median 
XX 
XX,X 
XX,X 
 
Min. to Max. 
XX to XX 
XX to XX 
XX to XX 
 
 
 
 
 
Week 12 
N 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX,XX 
XX,XX 
XX,XX 
 
Median 
XX 
XX,X 
XX,X 
 
Min. to Max. 
XX to XX 
XX to XX 
XX to XX 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
 
 
Programming Note:  Repeat table for Non-Inflammatory Lesions: 
 
Table 14.2.2.2 Non-Inflammatory Lesion Counts by Study Visit (Face Only) Safety Population 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.2.3.1 
Inflammatory Lesion Counts (Face Only) by Prior Treatment and Study Visit  
Safety Population 
 
Visit 
Statistic 
SB204 Experienced 
(N=XXX) 
SB204 Naїve 
(N=XXX) 
    Count 
Absolute 
Change  
from 
Baseline 
Percent 
Change  
from 
Baseline 
    Count 
Absolute 
Change  
from 
Baseline 
Percent Change 
from Baseline 
 
 
 
 
 
 
 
 
Baseline N 
XX 
 
 
XX 
 
 
 
Mean 
XX.X 
 
XX.X 
 
 
 
SD 
XX,XX 
 
XX,XX 
 
 
 
Median 
XX 
 
XX 
 
 
 
Min. to Max. 
XX to XX 
 
XX to XX 
 
 
 
 
 
 
 
 
 
 
Week 4 
N 
XX 
XX
XX
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX,XX 
XX,XX 
XX,XX 
XX,XX 
XX,XX 
XX,XX 
 
Median 
XX 
XX,X 
XX,X 
XX 
XX,X 
XX,X 
 
Min. to Max. 
XX to XX 
XX to XX 
XX to XX 
XX to XX 
XX to XX 
XX to XX 
 
 
 
 
 
 
 
 
Week 12 
N 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX,XX 
XX,XX 
XX,XX 
XX,XX 
XX,XX 
XX,XX 
 
Median 
XX 
XX,X 
XX,X 
XX 
XX,X 
XX,X 
 
Min. to Max. 
XX to XX 
XX to XX 
XX to XX 
XX to XX 
XX to XX 
XX to XX 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
 
 
Programming Note:  Repeat table for Non-Inflammatory Lesions: 
 
Table 14.2.3.2 Non-Inflammatory Lesion Counts (Face Only) by Prior Treatment and Study Visit Safety Population 
 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.3.1.1 
Cutaneous Tolerability Evaluation – Erythema - Summarized by Study Visit (Face Only) 
Safety Population 
 
Study Visit 
   SB204 
(N=XXX) 
Baseline 
 
   0 – None 
xx (xx.x) 
   1 – Mild 
xx (xx.x) 
   2 – Moderate 
xx (xx.x) 
   3 - Severe 
xx (xx.x) 
   Missing 
xx (xx.x) 
Week 4 
 
   0 – None 
xx (xx.x) 
   1 – Mild 
xx (xx.x) 
   2 – Moderate 
xx (xx.x) 
   3 - Severe 
xx (xx.x) 
       Missing 
xx (xx.x) 
Week 12 
 
   0 – None 
xx (xx.x) 
   1 – Mild 
xx (xx.x) 
   2 – Moderate 
xx (xx.x) 
   3 - Severe 
xx (xx.x) 
   Missing 
xx (xx.x) 
Week 24 
 
   0 – None 
xx (xx.x) 
   1 – Mild 
xx (xx.x) 
   2 – Moderate 
xx (xx.x) 
   3 - Severe 
xx (xx.x) 
   Missing 
xx (xx.x) 
Week 36 
 
   0 – None 
xx (xx.x) 
   1 – Mild 
xx (xx.x) 
   2 – Moderate 
xx (xx.x) 
   3 - Severe 
xx (xx.x) 
   Missing 
xx (xx.x) 
Week 40\ET 
 
   0 – None 
xx (xx.x) 
   1 – Mild 
xx (xx.x) 
   2 – Moderate 
xx (xx.x) 
   3 - Severe 
xx (xx.x) 
   Missing 
xx (xx.x) 
 
 
Note: Baseline is the Week 12 assessment from the previous study (NI-AC301 or NI-AC302). 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
 
 
Using shell 14.3.1.1, repeat table for the following: 
Table 14.3.1.2 Cutaneous Tolerability Evaluation – Scaling - Summarized by Study Visit Safety Population 
Table 14.3.1.3 Cutaneous Tolerability Evaluation – Dryness - Summarized by Study Visit Safety Population 
Table 14.3.1.4 Cutaneous Tolerability Evaluation – Pruritus - Summarized by Study Visit Safety Population 
Table 14.3.1.5 Cutaneous Tolerability Evaluation – Burning/Stinging - Summarized by Study Visit Safety Population 
 
 
 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.3.2.1 
Shift from Baseline in Cutaneous Tolerability Evaluation – Erythema, by Study Visit (Face Only) 
Safety Population 
 
Study Visit / 
Cutaneous Tolerability 
Score 
Cutaneous Tolerability Score at Baseline 
0 - None 
1 - Mild 
2 - Moderate 
3 - Severe 
Missing 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
0 – None 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 – Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 - Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3 – Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
0 – None 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 – Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 - Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3 – Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Week 24 
 
 
 
 
 
 
0 – None 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 – Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 - Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3 – Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 
0 – None 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 – Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 - Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3 – Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Week 40 
 
 
 
 
 
        0 – None 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        1 – Mild 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        2 - Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        3 – Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
Note: Baseline is the Week 12 assessment from the previous study (NI-AC301 or NI-AC302). 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Using shell 14.3.2.1, Repeat table for the following: 
 
Table 14.3.2.2 Shift from Baseline in Cutaneous Tolerability Evaluation – Scaling - Summarized Continuously by Study 
Visit Safety Population 
Table 14.3.2.3 Shift from Baseline in Cutaneous Tolerability Evaluation – Dryness - Summarized Continuously by Study 
Visit Safety Population 
Table 14.3.2.4 Shift from Baseline in Cutaneous Tolerability Evaluation – Pruritus - Summarized Continuously by Study 
Visit Safety Population 
Table 14.3.2.5 Shift from Baseline in Cutaneous Tolerability Evaluation – Burning/Stinging - Summarized Continuously by 
Study Visit Safety Population 
 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
 
Table 14.3.3.1  
Treatment Emergent Adverse Events (TEAE) Overview 
Safety Population 
 
Number of Subjects with 
SB204 Experienced 
(N=XXX) 
SB204 Naïve 
(N=XXX) 
Overall 
(N=XXX) 
 
 
 
 
Any TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of TEAEs 
xx 
xx 
xx 
 
 
 
 
Treatment-Related TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Treatment-Related TEAEs 
xx 
xx 
xx 
 
 
 
 
TEAE Leading to Treatment Modification 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of TEAE Leading to Treatment Modification 
xx 
xx 
xx 
 
 
 
 
Treatment-Related TEAE Leading to Treatment Modification 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of TRTEAE Leading to Treatment Modification 
xx 
xx 
xx 
 
 
 
 
TEAE Leading to Treatment Discontinuation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of TEAE Leading to Treatment Discontinuation  
xx 
xx 
xx 
 
 
 
 
Treatment-Related TEAE Leading to Treatment Discontinuation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of TRTEAE Leading to Treatment Discontinuation  
xx 
xx 
xx 
 
 
 
 
Serious TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Serious TEAEs 
xx 
xx 
xx 
 
 
 
 
Treatment-Related Serious TEAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Treatment-Related Serious TEAEs 
xx 
xx 
xx 
 
 
 
 
TEAE Leading to Death 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of TEAE Leading to Death 
xx 
xx 
xx 
 
 
 
 
Treatment-Related TEAE Leading to Death 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Treatment-Related TEAE Leading to Death 
xx 
xx 
xx 
 
 
 
 
Note: TEAE onset is based on the start of treatment in the LTS. Adverse events were coded using MedDRA 18.1. 
TR=Treatment-Related. 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.3.3.2.1 
Treatment Emergent Adverse Events (TEAE) by System Organ Class, Preferred Term, and Duration of Exposure  
Safety Population 
 
System Organ Class 
  Preferred Term 
Within 24 
hours 
(N=XXX) 
Within 
2-30 days 
(N=XXX) 
Within 
31-90 
Days 
(N=XXX) 
Within 
91-180 
Days 
(N=XXX) 
Within 
181-365 
Days 
(N=XXX) 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
Number of Subjects with at Least One TEAE 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
Number of Events 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
 Preferred Term 1 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
 Preferred Term 2 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
 Preferred Term 1 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
 Preferred Term 2 
xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse event terms were coded using MedDRA dictionary version 18.1. Subjects are counted once within each 
level of summary. Duration of exposure is based on date of first dose of SB204, which could be in the previous study 
(NI-AC301 or NI-AC302). 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
Programmer Note: Order SOC by decreasing frequency and preferred term by decreasing frequency within SOC based on 
overall incidence. 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.3.3.2.2 
Treatment Emergent Adverse Events (TEAE) by System Organ Class, Preferred Term, and Extent of Exposure  
Safety Population 
 
System Organ Class 
  Preferred Term 
1-100 
grams 
(N=XXX) 
>100-330 
grams 
(N=XXX) 
>330-675 
grams 
(N=XXX) 
>675 
Grams 
(N=XXX) 
Overall 
(N=XXX) 
 
 
 
 
 
 
Number of Subjects with at Least One Event 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Events 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse event terms were coded using MedDRA dictionary version 18.1. Subjects are counted once within each 
level of summary. TEAE onset is based on the start of treatment in the LTS. Extent of exposure is based on first 
exposure to SB204 – which could be in the previous study (NI-AC301 or NI-AC302). 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
Programmer Note: Order SOC by decreasing frequency and preferred term by decreasing frequency within SOC based on 
overall incidence. 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
 
Using shells 14.3.3.2.1 and 14.3.3.2.2, repeat for the following: 
Table 14.3.3.3.1 Treatment-Related Emergent Adverse Events by System Organ Class, Preferred Term, and Duration of 
Exposure Safety Population 
Table 14.3.3.3.2 Treatment-Related Emergent Adverse Events by System Organ Class, Preferred Term, and Extent of 
Exposure Safety Population 
 
Programmer’s Note: subset on TEAEs related to study treatment.  
Table 14.3.3.4.1 Treatment Emergent Adverse Events Leading to Treatment Modification by Duration of Exposure Safety 
Population 
Table 14.3.3.4.2 Treatment Emergent Adverse Events Leading to Treatment Modification by Extent of Exposure Safety 
Population 
 
Programmer’s Note: subset on TEAEs leading to treatment modification. Add the following footnote: 
 
Note: Treatment modification includes reduction, interruption, or discontinuation of Study Drug  
 
Table 14.3.3.5.1 Treatment-Related Treatment Emergent Adverse Events Leading to Treatment Modification by Duration of 
Exposure Safety Population 
 
Table 14.3.3.5.2 Treatment-Related Treatment Emergent Adverse Events Leading to Treatment Modification by Extent of 
Exposure Safety Population 
 
Programmer’s Note: subset on Treatment-Related TEAEs leading to treatment modification. Add the following footnote: 
 
Note: Treatment modification includes reduction, interruption, or discontinuation of Study Drug. 
 
Table 14.3.3.6.1 Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Duration of Exposure 
Safety Population 
 
Table 14.3.3.6.2 Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Extent of Exposure 
Safety Population 
 
Programmer’s Note: subset on TEAEs leading to discontinuation of Study Drug. 
 
Table 14.3.3.7.1 Treatment-Related Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by 
Duration of Exposure Safety Population 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.3.3.7.2 Treatment-Related Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by Extent 
of Exposure Safety Population 
 
Programmer’s Note: subset on Treatment-Related TEAEs leading to discontinuation of Study Drug. 
 
Table 14.3.3.8.1 Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Duration of 
Exposure Safety Population 
 
Table 14.3.3.8.2 Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Extent of 
Exposure Safety Population 
 
Programmer’s Note: subset on Serious TEAEs. 
 
Table 14.3.3.9.1 Treatment-Related Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and 
Duration of Exposure Safety Population 
 
Table 14.3.3.9.2 Treatment-Related Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and 
Extent of Exposure Safety Population 
 
Programmer’s Note: subset on Treatment-Related Serious TEAEs. 
 
Table 14.3.3.10.1 Treatment Emergent Adverse Events Leading to Death by Duration of Exposure Safety Population 
Table 14.3.3.10.2 Treatment Emergent Adverse Events Leading to Death by Extent of Exposure Safety Population 
 
Programmer’s Note: subset on TEAEs with fatal outcome.  
 
Table 14.3.3.11.1 Treatment-Related Treatment Emergent Adverse Events Leading to Death by Duration of Exposure Safety 
Population 
 
Table 14.3.3.11.2 Treatment-Related Treatment Emergent Adverse Events Leading to Death by Extent of Exposure Safety 
Population 
 
Programmer’s Note: subset on treatment related TEAEs with fatal outcome.  
.  
 
 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
Table 14.3.3.13  
Summary of Treatment Emergent Adverse Events (TEAE) by Highest Severity, System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
  Preferred Term 
Severity 
SB204 
(N=XXX) 
 
 
 
Subjects with at least one event 
Mild 
xx (xx.x) 
    
Moderate 
xx (xx.x) 
 
Severe 
xx (xx.x) 
 
 
 
Number of events 
Mild 
   xx 
 
Moderate 
   xx 
 
Severe 
   xx 
 
 
 
System Organ Class 1  
Mild 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
 
Severe 
xx (xx.x) 
   
 
 
  Preferred Term 1  
Mild 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
 
Severe 
xx (xx.x) 
 
 
 
Note(s): TEAE onset is based on the start of treatment in the LTS. Adverse event terms were coded using MedDRA 
dictionary version 18.1. Subjects are counted once within each level of summary. If a subject has multiple events, 
the event with highest severity will be considered.  
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
Programmer Note: Order SOC by decreasing frequency and preferred term by decreasing frequency within SOC based on 
overall incidence. 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
 
 
Using shell 14.3.3.13, repeat table for the following: 
 
Table 14.3.3.14 Summary of Treatment-Related Emergent Adverse Events (TEAE) by Severity, System Organ Class and 
Preferred Term Safety Population 
 
Programmer’s Note: subset on related TEAEs  
 
 
 


Novan Inc.                                                                                 Page x of y             
Protocol Number: NI-AC303                                                             
 
 
Table 14.3.4  
Summary of Vital Signs  
Safety Population 
<Parameter> (<units>) 
Timepoint 
SB204 
(N=XXX) 
Actual 
Change from Baseline 
 
 
 
Baseline 
 
 
   n 
xx 
 
   Mean (SD) 
xx.x (xx.xx) 
 
   Median 
xx.x 
 
   Min, Max 
xx, xx 
 
   Missing 
xx 
 
 
 
 
Week 4 
 
 
   N 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
   Missing 
xx 
xx 
 
 
 
Week 12 
 
 
   n 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
.... 
 
xx 
 
 
 
 
 
 
Note(s): Baseline is defined as the Week 12 assessment from the previous study (NI-AC301 or NI-AC302). 
Source: Listing xx.x.x.x.x, Program: xxxxx.sas, Output: T_xx.x_x_x_xxxx.rtf, Generated on: DDMMMYYYY HH:MM  
 
Programmer Note: Include all vital signs parameters (e.g. SBP, DBP, Pulse) and all available post-baseline visits. 
Missing not presented if no missing values. 
 


Protocol: NI-AC303 
 
 
 
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term Safety of SB204 Once Daily in the Treatment of Acne 
Vulgaris. 
 
 
Mock Data Displays - Figures 
Version 1.0   
Date: 12Apr2017 
 
 
Prepared for: 
Novan Inc. 
4105 Hopson Road 
Morrisville, NC 27560 
 
Prepared by: 
Chiltern International 
4000 CentreGreen Way, Suite 300, Cary, NC, 27513, United States  
 
 
This document is the confidential information of Novan Inc.  It may not be disclosed to parties not associated with the clinical 
investigation or used for any purpose without the prior written consent of Novan Inc. 
 
Contents 


Figure 14.1.1 Distribution of Erythema Scores by Treatment and Visit  Safety Population ............................................................. 3 
Figure 14.1.2 Distribution of Dryness Scores by Treatment and Visit, Safety Population ................................................................ 4 
Figure 14.1.3 Distribution of Scaling Scores by Treatment and Visit, Safety Population ................................................................. 4 
Figure 14.1.4 Distribution of Pruritus Scores by Treatment and Visit, Safety Population ............................................................... 4 
Figure 14.1.5 Distribution of Burning/stinging Scores by Treatment and Visit, Safety Population ................................................. 4 
Figure 14.2.1 Average Change from Baseline in Inflammatory Lesion Count Over Time Safety Population ................................ 5 
Figure 14.2.2 Average Percent Change from Baseline in Inflammatory Lesion Count Over Time Safety Population .................. 6 
Figure 14.3.1 Average Change from Baseline in Non-Inflammatory Lesion Count Over Time, Safety Population....................... 7 
Figure 14.3.2 Average Percent Change from Baseline in Non-Inflammatory Lesion Count Over Time, Safety Population ........ 7 
 
 
 


Figure 14.1.1 Distribution of Erythema Scores by Treatment and Visit  
Safety Population 
 
 
 
Erythema Score


 
 
Using shell for Figure 14.1.1, repeat for the following: 
 
Figure 14.1.2 Distribution of Dryness Scores by Treatment and Visit, Safety Population 
 
Figure 14.1.3 Distribution of Scaling Scores by Treatment and Visit, Safety Population 
 
Figure 14.1.4 Distribution of Pruritus Scores by Treatment and Visit, Safety Population 
 
Figure 14.1.5 Distribution of Burning/stinging Scores by Treatment and Visit, Safety Population 
 
 
 


Figure 14.2.1 Average Change from Baseline in Inflammatory Lesion Count (Face only) Over Time 
Safety Population 
 
Average Change from Baseline
-10
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
Figure 14.2.1
Average Change from Baseline in Inflammatory Lesion Count Over Time
Safety Population
Treatment Group:
SB204
Week 4
Week 12
Week 24
Week 36
Week 40/ET
Visit


Figure 14.2.2 Average Percent Change from Baseline in Inflammatory Lesion Count (Face only) Over Time 
Safety Population 
 
 
Average Percent Change from Baseline


Using shell for Figure 14.2.1, repeat for the following: 
 
Figure 14.3.1 Average Change from Baseline in Non-Inflammatory Lesion Count (Face only) Over Time, Safety Population 
 
Using shell for Figure 14.2.2 repeat for the following: 
 
 
Figure 14.3.2 Average Percent Change from Baseline in Non-Inflammatory Lesion Count (Face only) Over Time, Safety 
Population 
 


 
1 
 
Protocol: NI-AC303 
 
 
 
A Phase 3 Multi-Center, Open Label Study Evaluating the Long Term Safety 
of SB204 Once Daily in the Treatment of Acne Vulgaris. 
 
 
Mock Data Displays- Listings 
Version 1.0 
Date: 12Apr2017  
 
 
Prepared for: 
Novan Inc. 
4105 Hopson Road 
Morrisville, NC 27560 
 
Prepared by: 
Chiltern International 
4000 CentreGreen Way, Suite 300, Cary, NC, 27513, United States 
 
 
This document is the confidential information of Novan Inc.  It may not be 
disclosed to parties not associated with the clinical investigation or used for any 
purpose without the prior written consent of Novan Inc. 
 


 
 
 
Novan Inc                                                                             
Protocol Number: NI-AC303                                                          
2 
 
 
Table of Contents 
 
Listing 16.2.1.1 Subject Disposition Safety Population ............................................................................................................................. 3 
Listing 16.2.2 Protocol Violations/Deviations Safety Population .............................................................................................................. 4 
Listing 16.2.3 Inclusion/Exclusion Criteria not Met Safety Population ..................................................................................................... 5 
Listing 16.2.4.1 Demographics Safety Population ..................................................................................................................................... 6 
Listing 16.2.4.2 Medical History Safety Population ................................................................................................................................... 7 
Listing 16.2.4.3 Child Bearing Potential and Pregnancy Test Results Safety Population (Females only) ................................................ 8 
Listing 16.2.4.4 Physical Exam Safety Population ..................................................................................................................................... 9 
Listing 16.2.5 Study Drug Management Safety Population ..................................................................................................................... 10 
Listing 16.2.6 Extent and Duration of Exposure Safety Population ......................................................................................................... 11 
Listing 16.2.7.1.1 Lesion Counts : Total Inflammatory and Non-Inflammatory Lesions  Safety Population ......................................... 12 
Listing 16.2.7.1.2 Lesion Counts: Papules, Pustules, Nodules, and Cysts Safety Population .................................................................. 13 
Listing 16.2.7.3 Cutaneous Tolerability Safety Population ...................................................................................................................... 14 
Listing 16.2.7.4 Vital Signs Safety Population ......................................................................................................................................... 15 
Listing 16.2.7.5 Concomitant Medications Safety Population ................................................................................................................. 16 
Listing 16.2.8.1 Adverse Events Safety Population ................................................................................................................................. 17 
Listing 16.2.8.2 Treatment-Emergent Adverse Events Leading to Discontinuation of Study Drug Safety Population .......................... 18 
Listing 16.2.8.3 Treatment-Emergent Adverse Events Leading to Treatment Modification Safety Population ...................................... 18 
Listing 16.2.8.4 Treatment-Emergent Serious Adverse Events Safety Population .................................................................................. 18 
Listing 16.2.8.5 Treatment-Emergent Adverse Events Leading to Death Safety Population .................................................................. 18 
Listing 16.2.9 Concomitant Medical and Surgical Procedures  Safety Population .................................................................................. 19 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
3 
 
Listing 16.2.1.1 
Subject Disposition 
Safety Population 
 
 
 
 
Previous 
Study  
Previous 
Treatment 
Group 
 
 
Subject 
ID  
Met All 
Inc/Exc 
Criteria 
Date of:  
Informed 
Consent 
Date of 
Completion or 
Discontinuation  
Reason for Discontinuation 
 
 
 
 
 
  
 
xxxxxxx 
xxxxxxx 
xxxxxxx 
Yes 
DDMMMYYYY 
DDMMMYYYY  
Completed 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxx 
xxxxxxxx Yes 
DDMMMYYYY 
DDMMMYYYY  
Withdrawal by Subject 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
s<nnn>xxxx yyyymmddthh:mm 
 
Programmer’s Note(s): This listing will be sorted by previous study number and then by Subject ID.  
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
4 
 
Listing 16.2.2 
Protocol Violations/Deviations 
Safety Population 
 
 
 
Subject ID  
Date of 
Violation/ 
Deviation  
/Day 
Type of Violation 
Details of Violation/Deviation 
 
 
 
 
xxxxxxx 
DDMMMYYYY/xx 
ICF Issue 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
xxxxxxxx 
DDMMMYYYY/xx 
Assessment not 
Performed per Protocol 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
xxxxxxxx 
DDMMMYYYY/xx 
Non-compliance with IP 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Day = Day relative to the date of first dose of study medication. 
s<nnn>xxxx yyyymmddthh:mm 
 
Programmer’s Note(s): This and subsequent listings will be sorted by Subject ID.  
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
5 
 
Listing 16.2.3 
Inclusion/Exclusion Criteria not Met 
Safety Population  
 
 
 
Subject ID  
Criteria Not Met 
Description of Criteria 
 
 
 
 
 
 
xxxxxxx 
INCXX 
XXXXXXXXXXXXXXXXXXXXXX 
 
 
 
xxxxxxxx 
EXCLXX 
XXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 s<nnn>xxxx yyyymmddthh:mm 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
6 
 
Listing 16.2.4.1 
Demographics 
Safety Population 
 
 
Subject ID 
Study 
Center 
 
Date of 
Birth  
Age 
(years) Gender  
Ethnicity  
Race 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
DDMMMYYYY 
xx.x 
Male 
Not Hispanic or 
Latino  
xxxxxx 
xxxxxxxx 
xxxxxxx 
DDMMMYYYY 
xx.x 
Female 
Not Hispanic or 
Latino  
xxxxx  
xxxxxxxx 
xxxxxxx 
DDMMMYYYY 
xx.x 
Female 
Not Hispanic or 
Latino  
Other: xxxxxx  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Age is calculated as the interval between date of birth and date of baseline visit from the previous study 
(NI-AC301 or NI-AC302). 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
7 
 
Listing 16.2.4.2 
Medical History 
Safety Population 
 
 
 
Subject ID  
 
SOC / 
  Preferred Term /  
     Verbatim Term 
Onset / End  
 
 
 
 
 
 
xxxxxxx 
Xxxxxxxx / 
  Xxxxxxxx / 
     xxxxxxxx 
DDMMYYYY / DDMMYYYY 
 
 
 
xxxxxxxx 
Xxxxxxxx / 
  Xxxxxxxx / 
     xxxxxxxx 
DDMMYYYY / Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
8 
 
Listing 16.2.4.3 
Child Bearing Potential and Pregnancy Test Results 
Safety Population (Females only) 
 
Subject ID 
 
Of Child-
Bearing 
Potential? 
If no, why? 
If Yes, Method 
of Birth Control 
Visit 
Collection Date 
/ Day  
Pregnancy Test 
Result or 
Reason Not Done 
 
 
 
 
 
 
 
XXXXXXX 
Yes 
 
XXXXXXXXXX 
Baseline 
DDMMMYYYY /XX 
Negative 
XXXXXXX 
No 
XXXXXXXXXXXX 
 
Baseline 
DDMMMYYYY /XX 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Day = Day relative to the date of first day of LTS. 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
9 
 
Listing 16.2.4.4 
Physical Exam 
Safety Population 
 
 
 
Subject ID 
Visit 
Date 
Body System 
Evaluation 
 
Abnormality 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXX 
Baseline 
DDMMMYYYY 
General Appearance 
Normal 
 
 
 
 
Respiratory 
Normal 
 
 
 
 
Cardiovascular 
Normal 
 
 
 
 
Other: XXXXXXXx 
ANCS 
XXXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
Week 40\ET 
DDMMMYYYY
General Appearance
ACS 
XXXXXXXXXXXXXXXXXXX 
 
 
 
Respiratory
Normal 
 
 
 
 
Cardiovascular
Normal 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
XXXXXXX 
Baseline 
DDMMMYYYY
General Appearance
Normal
 
 
 
 
Respiratory
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s):ANCS = Abnormal, Not clinically significant; ACS = Abnormal, Clinically Significant. If a finding was 
determined to be clinically significant, it is also reported as an adverse event, or, if it occurred prior to study 
start, it is reported in medical history. 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
10 
 
Listing 16.2.5 
Study Drug Management 
Safety Population 
 
 
Subject 
ID 
Visit 
Date/ Day 
Was Pump 
dispensed? 
If yes, Pump number(s) 
Was previous 
pump returned? 
If no. Reason why: 
 
 
 
 
 
 
 
xxxxxxx 
Baseline 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 4 
DDMMMYYYY/xx 
No 
 
No 
XXXXXXXXXX 
 
Week 12 
DDMMMYYYY/xx 
Yes 
XXXXXX, XXXXX 
 
 
 
Week 24 
DDMMMYYYY/xx 
Yes 
XXXXXX, XXXXX, XXXXX 
 
 
 
Week 36 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 40 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
 
 
 
 
 
 
Xxxxxxx 
Baseline 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 4 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 12 
DDMMMYYYY/xx 
Yes 
XXXXXX 
Yes 
 
 
Week 24 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 36 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 40 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
 
 
 
 
 
 
xxxxxxx 
Baseline 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 4 
DDMMMYYYY/xx 
Yes 
XXXXXX 
Yes 
 
 
Week 12 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 24 
DDMMMYYYY/xx 
No 
 
 
 
 
Week 36 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
Week 40 
DDMMMYYYY/xx 
Yes 
XXXXXX 
 
 
 
 
 
 
 
 
 
Note(s): Day = Day relative to the date of first day of LTS. 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
11 
 
 
 
Listing 16.2.6 
Extent and Duration of Exposure 
Safety Population 
 
Subject 
ID 
Visit 
Date 
Duration 
of 
Exposure 
(days) 
Number of 
Doses 
Reported 
Missed 
Days of 
Exposure 
Extent 
of 
Exposure 
(grams) 
Areas of Application 
Face 
Upper 
Back 
Upper 
Chest 
Shoulders 
Other:  
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
Week 4 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
x 
X 
 
 
 
 
Week 12 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
x 
 
X 
 
 
Week 24 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
x 
X 
 
 
Week 36 
DDMMMYYYY 
UNK 
UNK 
UNK 
UNK 
 
 
 
x 
Neck and Jawline 
 
Week 40  DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Overall 
 
XXX 
UNK 
UNK 
UNK 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
XXXXXXXXX 
Xxxxxxx 
Week 4 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Week 12 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Week 24 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Week 36 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Week 40 
DDMMMYYYY 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Overall 
 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s):  
Duration of Exposure = (Date of next drug dispensation or if last dispensataion, date of last dose) – Date of Drug 
Dispensation + 1 day. Overall is based on the date of first dose of study drug, which could be from the previous study 
(NI-AC301 or NI-AC302). 
Days of Exposure = Duration of exposure minus the number of days that the subject reported not taking study medication. 
Extent of Exposure: Each application is equal to 0.9 g. Extent of exposure is estimated as the sum of application areas 
(face only=1, face and chest=2, etc) times the number of days of application to those areas times 0.9g.  If the other 
specification is jaw or neckline, it is assumed that the same pump stroke used to apply drug to face is being used for 
the jaw and/or neckline application. For subjects randomized to SB204 in the previous studies, drug was only applied to 
the face so for the days of exposure from the previous studies, it will be assumed that there is only one area of 
application, i.e. the face. 
UNK = Unknown: For subjects who are lost-to-follow-up or who did not return diaries but reported an unknown number of 
missed doses, duration of exposure and days of exposure for that visit interval are defined as unknown. Overall 
duration will be defined as above; days of exposure will remain unknown. 
s<nnn>xxxx yyyymmddthh:mm 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
12 
 
 
 
 
 
 
Listing 16.2.7.1.1 
Lesion Counts (Face Only): Total Inflammatory and Non-Inflammatory Lesions  
Safety Population 
 
 
 
 
 
 
Inflammatory Lesions 
Non-Inflammatory Lesions 
 
 
Previous 
Study  
 
 
Subject 
ID 
Visit 
Date 
Counter’s 
Initials 
Count 
Absolute 
Change 
from 
Baseline 
Percent 
Change 
from 
Baseline 
Count  
Absolute 
Change 
from 
Baseline 
Percent 
Change 
from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
Baseline 
DDMMMYYYY 
XXXX 
XX 
 
 
XX 
 
 
 
 
Week 4 
DDMMMYYYY 
XXXX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
Week 12 
DDMMMYYYY 
XXXX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
Week 24 
DDMMMYYYY 
XXXX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
Week 36 
DDMMMYYYY 
XXXX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
Week 40 
DDMMMYYYY
XXXX
XX
XX 
XX
XX
XX
XX
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
Baseline 
DDMMMYYYY
XXXX
XX
 
 
XX
 
 
 
 
Week 4 
DDMMMYYYY
XXXX
XX
XX 
XX
XX
XX
XX
 
 
Week 12 
DDMMMYYYY
XXXX
XX
XX 
XX
XX
XX
XX
 
 
Week 24 
DDMMMYYYY
XXXX
XX
XX 
XX
XX
XX
XX
 
 
Week 36 
DDMMMYYYY
XXXX
XX
XX 
XX
XX
XX
XX
 
 
Week 40 
DDMMMYYYY
XXXX
XX
XX 
XX
XX
XX
XX
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  Inflammatory Lesions includes: papules/pustules + nodules/cysts. 
s<nnn>xxxx yyyymmddthh:mm 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
13 
 
Listing 16.2.7.1.2 
Lesion Counts (Face Only): Papules, Pustules, Nodules, and Cysts 
Safety Population 
 
 
 
Previous Study  
 
 
Subject ID 
Visit 
Date 
Counter’s 
Initials 
Papules/Pustules 
Nodules/Cysts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
Baseline 
DDMMMYYYY 
XXXX 
XXX 
XXX 
 
 
Week 4 
DDMMMYYYY 
XXXX 
XXX 
XXX 
 
 
Week 12 
DDMMMYYYY 
XXXX 
XXX 
XXX 
 
 
Week 24 
DDMMMYYYY 
XXXX 
XXX 
XXX 
 
 
Week 36 
DDMMMYYYY 
XXXX 
XXX 
XXX 
 
 
Week 40
DDMMMYYYY
XXXX
XXX
XXX
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
Baseline
DDMMMYYYY
XXXX
XXX
XXX
 
 
Week 4
DDMMMYYYY
XXXX
XXX
XXX
 
 
Week 12
DDMMMYYYY
XXXX
XXX
XXX
 
 
Week 24
DDMMMYYYY
XXXX
XXX
XXX
 
 
Week 36
DDMMMYYYY
XXXX
XXX
XXX
 
 
Week 40
DDMMMYYYY
XXXX
XXX
XXX
 
 
 
 
 
 
 
 
 
 
 
 
 
 
s<nnn>xxxx yyyymmddthh:mm 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
14 
 
 
 
 
Listing 16.2.7.3 
Cutaneous Tolerability 
Safety Population 
 
 
 
Previous 
Study 
 
 
Subject 
ID 
Visit 
Date 
Erythema 
Scaling 
Dryness 
Pruritus 
Burning/ 
Stinging 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
Baseline 
DDMMMYYYY 
Mild 
Mild 
Moderate 
None 
None 
 
 
Week 4 
DDMMMYYYY 
Mild 
Mild 
Moderate 
None 
None 
 
 
Week 12 
DDMMMYYYY 
Mild 
Mild 
Moderate 
None 
None 
 
 
Week 24 
DDMMMYYYY 
Mild 
Mild 
Moderate 
None 
None 
 
 
Week 36 
DDMMMYYYY 
Mild 
Mild 
Moderate 
None 
None 
 
 
Week 40 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
Baseline 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
Week 4 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
Week 12 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
Week 24 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
Week 36 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
Week 40 
DDMMMYYYY
Mild
Mild
Moderate
None
None
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): 0 = None, 1 = Mild, 2=Moderate, 3 = Severe. 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
15 
 
  
Listing 16.2.7.4 
Vital Signs 
Safety Population 
 
 
 
Previous 
Study 
 
 
Subject ID 
Visit 
Date/ Day 
Systolic 
BP (mmHg) 
Diastolic 
BP (mmHg) 
Pulse 
(bpm) 
Evaluation 
If Abnormal and 
Clinically 
Significant, provide 
MH or AE term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
Baseline 
DDMMMYYYY/xx 
xxx 
xxx 
xxx 
Normal 
 
 
 
Week 4 
DDMMMYYYY/xx 
xxx 
xxx 
xxx 
Abnormal, NCS 
 
 
 
Week 12 
DDMMMYYYY/xx 
xxx 
xxx 
xxx 
Normal 
 
 
 
Week 24 
DDMMMYYYY/xx 
xxx 
xxx 
xxx 
Normal 
 
 
 
Week 36 
DDMMMYYYY/xx 
xxx 
xxx 
xxx 
Normal 
 
 
 
Week 40 
DDMMMYYYY/xx
xxx 
xxx 
xxx 
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
Baseline 
DDMMMYYYY/xx 
xxx 
xxx 
xxx 
Abnormal, CS 
XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Day = Day relative to the first day of LTS. NCS = Not clinically significant;  
CS = Clinically Significant. If a post-baseline finding was determined to be clinically significant, it is also 
reported as an adverse event. 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
16 
 
Listing 16.2.7.5 
Concomitant Medications 
Safety Population 
 
 
 
Previous 
Study 
 
 
Subject ID  
Drug Class/ 
   Preferred Name/ 
       Reported Term 
Indication 
Start Date (Day)/ 
End Date (Day) 
Dose (Unit) / 
Frequency / 
Route 
If for AE or 
MH, Primary 
Term 
 
 
Ongoing from 
Previous 
Study? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
XXXXXXXXXXXXXX/  
 XXXXXXXXXXXXXXX/    
    XXXXXXXXXXXXXXX 
Adverse Event 
DDMMMYYYY (XX)/ 
Ongoing 
 
 
 
xxxxxxxx 
xxxxxxxx 
XXXXXXXXXXXXXX/  
 XXXXXXXXXXXXXXX/   
    XXXXXXXXXXXXXXX 
Medical History 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
XXX.X (XXXXX) / 
XXX / 
XXXXXXXXXX 
XXXXXXXXX 
Yes 
xxxxxxx 
xxxxxxx 
XXXXXXXXXXXXXX/  
 XXXXXXXXXXXXXXX/    
    XXXXXXXXXXXXXXX 
Prophylaxis 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
XXX.X (XXXXX) / 
XXX / 
XXXXXXXXXX 
 
 
xxxxxxxx 
xxxxxxxx 
XXXXXXXXXXXXXX/  
 XXXXXXXXXXXXXXX/   
    XXXXXXXXXXXXXXX 
Dietary Supplement 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
XXX.X (XXXXX) / 
XXX / 
XXXXXXXXXX 
XXXXXXXXX 
No 
xxxxxxxx 
xxxxxxxx 
XXXXXXXXXXXXXX/  
 XXXXXXXXXXXXXXX/   
    XXXXXXXXXXXXXXX 
Contraception 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
XXX.X (XXXXX) / 
XXX / 
XXXXXXXXXX 
 
 
xxxxxxxx 
xxxxxxxx 
XXXXXXXXXXXXXX/  
 XXXXXXXXXXXXXXX/   
    XXXXXXXXXXXXXXX 
Other: XXXXXXXXXXX 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
XXX.X (XXXXX) / 
XXX / 
XXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Day = Day relative to the first day of LTS. Coding will be done using the WHO March 2016 dictionary.  Drug 
Class corresponds to ACT level 2. 
s<nnn>xxxx yyyymmddthh:mm 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
17 
 
 
Listing 16.2.8.1 
Adverse Events 
Safety Population 
 
 
 
Subject ID  
 
Duration 
of 
Exposure 
(days)  
Extent 
of 
Exposure 
(grams) 
System Organ Class/
  Preferred Term/ 
      Reported Term 
T
E
A
E
 
First Dose 
Date/ 
Start Date/ 
End Date / 
(Days) 
Cause 
Study 
Discon-
tinuation? 
Severity / 
Relationship 
Action / 
Treatment / 
Final 
Outcome 
SAE? 
SAE 
Criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
XX 
XX.X 
XXXXXXXXXXXXXXX / 
    XXXXXXXXXXXXXX / 
     XXXXXXXXXXXXXXX 
Y
DDMMMYYY / 
DDMMMYYY / 
DDMMMYYYY / 
XX 
No 
Mild / 
Unlikely 
Dose Not 
Changed / 
XXXXXXXX / 
XXXXXXXXXXX
XX 
No 
 
xxxxxxx 
XX 
XX.X 
XXXXXXXXXXXXXXX / 
   XXXXXXXXXXXXXX / 
    XXXXXXXXXXXXXXXX 
Y
DDMMMYYY / 
DDMMMYYY / 
DDMMMYYYY / 
XX 
Yes 
XXXXXXX / 
XXXXXXX 
XXXXXXXX / 
XXXXXXXX / 
XXXXXXXXXXX
XX 
Yes 
XXXXXXXXXX
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): TEAE=Treatment-emergent Adverse Event. TEAE onset is based on the start of treatment in the LTS. Days = 
(Adverse event end date – event start date)+1. Adverse events were coded using MedDRA 18.1. Duration and extent of 
exposure are based on the date of first dose of study drug, which could from the previous study (NI-AC301 or NI-AC302). 
s<nnn>xxxx yyyymmddthh:mm 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
18 
 
 
 
Repeat Listing 16.2.8.1 for: 
 
Listing 16.2.8.2 Treatment-Emergent Adverse Events Leading to Discontinuation of Study Drug Safety Population 
Listing 16.2.8.3 Treatment-Emergent Adverse Events Leading to Treatment Modification Safety Population 
Listing 16.2.8.4 Treatment-Emergent Serious Adverse Events Safety Population 
Listing 16.2.8.5 Treatment-Emergent Adverse Events Leading to Death Safety Population 
 
 
 


 
 
 
Novan Inc                                                                                      Page x of y  
Protocol Number: NI-AC303                                                       
19 
 
 
Listing 16.2.9 
Concomitant Medical and Surgical Procedures  
Safety Population 
 
 
 
Previous 
Study  
 
 
Subject ID  
Verbatim Term 
Start Date (Day) /  
End Date (Day) 
Was it for an AE/SAE? 
Ongoing from 
Previous 
Study? 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxx 
XXXXXXXXXXXXXXXXXXXXX 
DDMMYYYY (XX) / 
DDMMYYYY (XX) 
No 
Yes 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
XXXXXXXXXXXXXXXXXXXXX 
DDMMYYYY (XX) / 
Ongoing 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
s<nnn>xxxx yyyymmddthh:mm