Clinical trial NCT03127956
Conditions: Acne Vulgaris
Sponsor: Dermira, Inc.
Start date: 2017-03-21; Completion date: 2018-04-27
Enrollment: 748 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective of this study is to assess the long-term safety of Olumacostat Glasaretil gel, 5.0% in patients with acne vulgaris

Detailed description:

Arms: arm 1: Olumacostat Glasaretil Gel, 5.0%, applied twice daily to the face
Interventions: intervention 1: Olumacostat Glasaretil Gel, 5.0%
Intervention descriptions: intervention 1: Gel containing Olumacostat Glasaretil

Protocol documents:
Prot_000.pdf: 
Dermira, Inc. 
 
Olumacostat Glasaretil Gel 
 
DRM01B-ACN05 
24 April 2017 
Page 1 
Confidential 
 
 
 
AN OPEN-LABEL STUDY ASSESSING LONG-TERM SAFETY OF OLUMACOSTAT 
GLASARETIL GEL IN SUBJECTS WITH ACNE VULGARIS 
 
Protocol Number 
DRM01B-ACN05 
Protocol Final Date 
16 November 2016 
Amendment 1 Date 
24 April 2017 
IND Number 
121136 
Study Drug 
Olumacostat Glasaretil Gel 
Sponsor 
Dermira, Inc. 
 
275 Middlefield Road 
 
Suite 150 
 
Menlo Park, CA 94025 
 
USA 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL INFORMATION 
The information contained herein is confidential and the proprietary property of 
Dermira. Any use or disclosure of such information without the prior written 
authorization of Dermira is expressly prohibited. 


Dermira, Inc. 
 
Olumacostat Glasaretil Gel 
 
DRM01B-ACN05 
24 April 2017 
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AN OPEN-LABEL STUDY ASSESSING LONG TERM SAFETY OF OLUMACOSTAT 
GLASARETIL GEL IN SUBJECTS WITH ACNE VULGARIS 
 
CRO Personnel 
TKL Research 
Name: Lynda McMahon 
Title: Project Director 
Tel: + 201.587.0500, ext 5140 
Mobile: + 508.525.2203 
Email: lmcmahon@tklresearch.com 
SAE/Emergency Contact Information 
Dermira 
Name: Mary Jean Stempien, MD 
Title: Medical Monitor 
Tel: + 415 640 9719 
Fax: +650-365-3410 
Email: Maryjean.stempien-
contractor@dermira.com 
 
Sponsor Personnel  
Dermira 
Name: Beth Zib 
Title: Clinical Lead 
Tel: +650-421-7210 
Mobile: +650-996-7838 
Fax: +650-365-3410 
Email: beth@dermira.com 


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Olumacostat Glasaretil Gel 
 
DRM01B-ACN05 
24 April 2017 
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PROTOCOL AMENDMENT 1 SUMMARY OF CHANGES 
 
 
Change 
Location 
Rationale 
Changed Medical Monitor name 
and contact information 
Page 2  
Change in personnel. 
Clarified permitted and 
prohibited treatments for acne 
vulgaris on the trunk 
Section 7.2 
Since subjects originating in DRM01B-
ACN03 are allowed, if warranted by the 
Investigator, to use study drug on the 
trunk, these subjects are not allowed to 
use any concomitant medication to treat 
acne vulgaris in the DRM01B-ACN05 
study. Subjects originating in DRM01B-
ACN04 are not allowed to use study drug 
on the trunk, and therefore, may use 
approved topical acne treatments on the 
trunk in the DRM01B-ACN05 study. 
 
 
 


Dermira, Inc.
Olumacostat Glasaretil Gel
DRMOlB-ACNOs
SPONSOR SIGNATURE PAGE
AN OPEN-LABEL STUDY ASSESSING LONG-TERM SAFETY OF OLUMACOSTAT
GLASARETIL GEL IN SUBJECTS WITH ACNE VULGARIS
Protocol Number
DRMOlB-ACNOs
Protocol Final Date
Amendment l Date
16 November2016
24 Ãpril20l7
The signature below constitutes approval of this protocol. I certify that I have the authority to
approve this protocol on behalf of the Sponsor, Dermira, Inc. The study will be conducted in
accordance with this protocol and all applicable laws, rules, and regulations and with the
International Conference on Harmonisation Good Clinical Practice (ICH GCP), regulations of
Canada and the United States (US) Food and Drug Administration (FDA) and the ethical
principles that have their origin in the Declaration of Helsinki.
Authorized by:
2óÅrucfut?
Sponsor Signature
Eugene A. Bauer, MD
Chief Medical Officer
Date (DD MMM YYYY)
24 April20l7
Page 4
Confidential


Dermira, Inc. 
 
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DRM01B-ACN05 
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INVESTIGATOR SIGNATURE PAGE 
 
AN OPEN-LABEL STUDY ASSESSING LONG-TERM SAFETY OF OLUMACOSTAT 
GLASARETIL GEL IN SUBJECTS WITH ACNE VULGARIS 
I have read this protocol, including the appendices, and agree that it contains all necessary details 
for carrying out the study as described. I will conduct this protocol as outlined herein, according 
to the ethical principles that have their origin in the Declaration of Helsinki, International 
Conference on Harmonisation (ICH) Guidelines for Good Clinical Practice (GCP) and applicable 
laws, rules and regulatory requirement(s) including those of Canada and the United States (US) 
Food and Drug Administration (FDA). 
I agree to obtain the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
approval of the protocol and informed consent prior to the start of the study. 
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 the Sponsor any 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 the 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. 
I understand that the study may be terminated or enrollment suspended at any time by the Sponsor, 
with or without cause, or by me if it becomes necessary to protect the best interests of the study 
subjects. 
 
 
 
_____________________________________ 
________________________ 
Investigator’s Signature 
Date (DD MMM YYYY) 
 
 
_____________________________________ 
Investigator’s Name (print) 
 
 


Dermira, Inc. 
 
Olumacostat Glasaretil Gel 
 
DRM01B-ACN05 
24 April 2017 
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PROTOCOL SYNOPSIS 
Title: 
An Open-Label Study Assessing Long-Term Safety of Olumacostat 
Glasaretil Gel in Subjects with Acne Vulgaris 
Protocol Number: 
DRM01B-ACN05 
Phase: 
3 
Number of Sites: 
Approximately 100 
Study Population 
Subjects who participated in either the DRM01B-ACN03 or DRM01B-ACN04 
studies 
Sample Size 
Approximately 700 
Study Treatment 
Olumacostat Glasaretil Gel, 5.0%, applied twice daily 
Study Objective: 
To assess the long term safety of Olumacostat Glasaretil Gel, 5.0% in subjects 
with acne vulgaris 
Duration of Subject 
Participation: 
Up to 36 weeks 
Study Visit Schedule 
Day 1 (Week 12 visit of DRM01B-ACN03 or DRM01B-ACN04), Weeks 2 
(phone call only), 4, 8, 12, 16, 20, 24, 28, 32, 36 (Study Exit) 
Study Design/Summary: 
This is an open label, long-term safety study enrolling approximately 700 subjects who participated in 
either the DRM01B-ACN03 or DRM01B-ANC04 studies. All subjects will sign an informed consent 
(adults)/assent (children) prior to continuing in this open label study.  
Eligible subjects will receive open label treatment with Olumacostat Glasaretil Gel, 5.0% and continue 
to dose twice daily for up to 36 weeks. Study drug will be applied twice daily to the face. Subjects, who 
participated in DRM01-ACN03 study with acne on the chest, back or shoulders and applied study drug 
to affected areas will be allowed to continue to apply study drug to the affected areas. Subjects who 
participated in DRM01-ACN04 study will continue to apply study drug to the face only. Subjects will 
return to the clinic at Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 (Study Exit). A follow-up phone call at 
Week 2 will be made to assess safety (adverse events) only.  
At the Week 12 and 24 visits, if the severity of acne has become worse, the subject should be 
withdrawn, at the investigator's discretion. Severity of acne will be assessed by IGA and limited to the 
face only.  
Efficacy will be assessed through investigator global assessment of acne (IGA).  
Safety will be assessed through adverse events, local skin reactions (LSRs), serum chemistry, 
hematology and urinalysis laboratory testing, physical examination, ECGs, pulse and blood pressure. 
Photographs of the face will be taken for all subjects at a subset of study sites in order to visually assess 
the appearance of acne vulgaris during the course of the study.  
During clinic visits, subjects will be asked to complete the Acne Patient Self-Questionnaire.   


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TABLE OF CONTENTS 
Page 
PROTOCOL SYNOPSIS ..............................................................................................................6 
TABLE OF CONTENTS ..............................................................................................................7 
1 
INTRODUCTION ................................................................................................................9 
1.1 
Product Development Rationale .................................................................................9 
1.2 
Summary of Investigational Program .......................................................................10 
1.3 
Study Conduct Statement ..........................................................................................13 
2 
STUDY SUMMARY...........................................................................................................13 
3 
STUDY OBJECTIVES ......................................................................................................14 
4 
STUDY ENDPOINTS.........................................................................................................14 
5 
STUDY DESIGN.................................................................................................................14 
5.1 
Duration of the Study ................................................................................................14 
5.2 
Study Population and Number of Subjects ...............................................................14 
5.3 
Selection of Subjects .................................................................................................15 
5.3.1 Inclusion Criteria ..........................................................................................15 
5.3.2 Exclusion Criteria .........................................................................................15 
6 
STUDY DRUG ....................................................................................................................15 
6.1 
Investigational Medicinal Product ............................................................................15 
6.2 
Packaging, Labeling and Storage ..............................................................................15 
6.3 
Treatment Assignment ..............................................................................................16 
6.4 
Study Blinding ..........................................................................................................16 
6.5 
Study Drug Dispensing and Return ..........................................................................16 
6.6 
Study Drug Application ............................................................................................16 
6.7 
Treatment Compliance ..............................................................................................17 
6.8 
Study Drug Accountability .......................................................................................17 
7 
CONCOMITANT MEDICATIONS AND PROCEDURES ...........................................17 
7.1 
Permitted Treatments and Procedures ......................................................................18 
7.2 
Prohibited Treatments and Procedures .....................................................................18 
8 
STUDY PROCEDURES ....................................................................................................19 
8.1 
Day 1 (Week 12 Visit of DRM01B-ACN03 or DRM01B-ACN04 Study) ..............19 
8.2 
Week 2 Telephone Contact (+/-2 days) ....................................................................20 
8.3 
Weeks 4, 8, 16, 20, 28 and 32 (+/-4 days) ................................................................20 
8.4 
Week 12 and 24 (+/-4 days) ......................................................................................20 
8.5 
Week 36 (+/-4 day) Study Exit or Early Termination Visit .....................................20 
8.6 
Unscheduled Visits ...................................................................................................21 
9 
DETAILS OF ASSESSMENTS .........................................................................................21 
9.1 
Baseline/Day 1 Assessments.....................................................................................21 
9.2 
Acne Patient Self-Questionnaire ...............................................................................22 
9.3 
Assessment of Efficacy .............................................................................................22 
9.3.1 Investigator Global Assessment ....................................................................22 
9.4 
Assessment of Safety ................................................................................................23 
9.4.1 Physical Examination....................................................................................23 


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9.4.2 Pulse and Blood Pressure ..............................................................................23 
9.4.3 ECGs .............................................................................................................23 
9.4.4 Laboratory Evaluations .................................................................................23 
9.4.5 Local Skin Reactions ....................................................................................24 
9.4.6 Adverse Events .............................................................................................25 
9.4.7 Reporting.......................................................................................................26 
9.4.8 Serious Adverse Events ................................................................................26 
9.4.9 Reporting of Serious Adverse Events ...........................................................27 
9.4.10 Dosing Changes Due to AEs.........................................................................28 
9.4.11 Pregnancy ......................................................................................................28 
10 
STUDY DISCONTINUATIONS .......................................................................................29 
10.1 
Discontinuation of the Study ....................................................................................29 
10.2 
Early Study Termination of Study Subjects..............................................................29 
10.3 
Study Drug Discontinuation .....................................................................................30 
11 
STATISTICAL CONSIDERATIONS ..............................................................................30 
11.1 
General Statistical Methodology...............................................................................30 
11.2 
Populations Analyzed ...............................................................................................30 
11.3 
Exposure and Compliance ........................................................................................30 
11.4 
Adverse Events .........................................................................................................31 
11.5 
Local Skin Reactions ................................................................................................31 
11.6 
Other Safety Data ......................................................................................................31 
11.7 
Sample Size Determination.......................................................................................32 
12 
STUDY ADMINISTRATION ...........................................................................................32 
12.1 
Compliance with the Protocol ...................................................................................32 
12.2 
Informed Consent Procedures ...................................................................................32 
12.3 
Study Documentation and the Electronic Case Report Form (eCRF) ......................33 
12.4 
Study Monitoring ......................................................................................................33 
12.5 
Retention of Study Documentation ...........................................................................34 
13 
ACRONYMS AND DEFINITIONS ..................................................................................35 
13.1 
Acronyms ..................................................................................................................35 
14 
REFERENCES....................................................................................................................37 
15 
APPENDIX 1 – SCHEDULE OF VISITS AND PROCEDURES ..................................38 
16 
APPENDIX 2 – ACNE PATIENT Self-QUESTIONNAIRE ..........................................39 
 
LIST OF TABLES  
Table 1: 
Investigator Global Assessment .................................................................................22 
Table 2: 
Subject Assessed Local Skin Reactions .....................................................................25 
Table 3: 
Investigator Assessed Local Skin Reactions ..............................................................25 
 
 
 


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1 
INTRODUCTION 
1.1 
Product Development Rationale 
Acne arises from a combination of physiological changes in the skin including altered sebaceous 
gland cell differentiation, heightened sebum production, localized bacterial colonization and 
inflammation. Although acne is generally viewed as a benign dermatological disease of 
adolescence, more severe forms may lead to permanent scar formation, with some of these 
patients suffering from psychological injury and significant loss of self-worth. Recent scientific 
advances in the understanding of the complex multi-factorial nature of this common disease offer 
great opportunity for scientific innovation through selective targeting of key elements of the 
disease process. 
Sebum is a waxy/oily substance comprised of cholesterol, fatty acids, fatty alcohols, triglycerides 
(TGs), wax esters, sterol esters and squalene produced by sebaceous gland cells [1]. Sebaceous 
glands are associated with hair follicles. The basal layer of sebocytes just inside the basement 
membrane consists of small, nucleated cells devoid of lipid droplets. This layer contains the 
dividing cells that replenish the gland as cells are lost in the process of holocrine rupture. As 
cells move from the basal layer towards the center of the gland, they differentiate and produce 
lipids that accumulate in droplets. Eventually the cells become distended with lipid droplets and 
the nuclei and other sub-cellular structures disappear. As the cells approach the sebaceous duct, 
they disintegrate and release their contents through holocrine secretion. In acne, diglycerides and 
free fatty acid levels may be increased by bacterial degradation of diglycerides and triglycerides 
present within sebum. Free fatty acids may promote inflammatory response in acne by activating 
local immune cells and their subsequent release of pro-inflammatory factors. 
A direct correlation between the degree of acne improvement and the extent of sebum reduction 
produced by different oral anti-acne medications has been established [2]. The oral retinoid 
13-cis-retinoic acid (13-cis-RA, Accutane) is particularly effective at reducing sebum 
output although its mode-of-action is not likely related to a direct effect on sebum synthesis 
pathways [3]. 
Topical agents routinely prescribed for acne, including antibiotics, retinoids and combinations 
thereof, often produce only modest therapeutic benefits and do not affect sebum production. A 
locally-delivered medication that selectively inhibited sebum formation would represent a 
breakthrough advance in reducing the pathogenic influences of sebum overproduction in acne. 
Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in humans 
and most other living organisms [4]. ACC catalyzes the carboxylation of acetyl-CoA to form 
malonyl-CoA. This is the first committed step in fatty acid biosynthesis and is the rate limiting 
reaction for the pathway [5, 6, 7]. These fatty acids then can be stored or converted to 
triglycerides (TGs) and phospholipids. In addition to its role as a substrate in fatty acid 
biosynthesis, malonyl-CoA, also plays an important regulatory role in controlling mitochondrial 
fatty acid uptake through allosteric inhibition of carnitine palmitoyltransferase I (CPT-I), the 
enzyme catalyzing the first committed step in mitochondrial fatty acid oxidation [8]. Malonyl-
CoA, therefore, is a key metabolic signal for the control of fatty acid production and utilization 
in response to dietary changes and altered nutritional requirements in animals [6]. As a result of 


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its unique position in intermediary metabolism, inhibition of ACC offers the ability to inhibit 
de novo fatty acid production in lipogenic tissues, such as liver, adipose tissue, and sebaceous 
glands. 
A variety of structurally diverse ACC inhibitors has recently been described in the scientific and 
patent literature for potential use in metabolic syndrome. One class of ACC inhibitors, including 
TOFA (5-(tetradecyloxy)-2-furancarboxylic acid), consists of lipophilic fatty acid mimetics that 
compete with acetyl-CoA in the ACC-mediated formation of malonyl-CoA. Investigators have 
demonstrated that TOFA reduced fatty acid synthesis and TG secretion both in cultured hepatic 
cells [8, 10] and in experimental animals [11, 12], reduced plasma cholesterol and TGs in 
experimental animals including rhesus monkeys [10, 11], and reduced body weight [13]. 
The ability to deliver TOFA topically could offer a means to inhibit de novo fatty acid 
production in sebaceous glands, introducing a new treatment paradigm for acne vulgaris.  
1.2 
Summary of Investigational Program 
Dermira, Inc. is pursuing the development of olumacostat glasaretil, previously referred to as 
DRM01B, a pro-drug of TOFA, sarcosine ester, a topical treatment for acne vulgaris. 
Olumacostat glasaretil is hydrolyzed by esterases in vivo to form the pharmacologically active 
moiety, TOFA. TOFA is converted to Tofyl-CoA intracellularly, which competes with acetyl-
CoA in the ACC-mediated formation of malonyl-CoA. As a result, inhibition of malonyl-CoA 
synthesis offers a means to inhibit de novo fatty acid production in the sebaceous glands in 
subjects with acne vulgaris. Olumacostat glasaretil is a new chemical entity and has been 
formulated for clinical development as Olumacostat Glasaretil Gel, 5.0%. 
A summary of clinical and nonclinical pharmacology, toxicology and metabolism data is 
presented below. Detailed information is provided in the current Investigator’s Brochure. 
Safety pharmacology studies were conducted with olumacostat glasaretil administered 
intravenously (IV) which included neurobehavioral and pulmonary function studies in rats and a 
cardiovascular study in telemetered minipigs. These studies revealed no adverse findings 
attributable to olumacostat glasaretil. In vitro studies assessing the effects of olumacostat 
glasaretil and TOFA upon human ether-à-go-go-related gene (hERG) ionic conductance in 
human embryonic kidney (HEK) cells also revealed no significant inhibition at the maximum 
concentrations tested. Overall, the results from the safety pharmacology showed no adverse 
effects at exposures to parent drug and/or TOFA several orders of magnitude beyond that 
anticipated to be seen following topical application in humans. 
Following IV administration in rats and minipigs, olumacostat glasaretil was quickly 
metabolized to TOFA; no evidence of any gender-specific differences or accumulation upon 
repeated dosing of either olumacostat glasaretil or TOFA was observed. With oral administration 
in rats, low ng/mL levels of olumacostat glasaretil were noted while exposure to TOFA reached 
levels exceeding 1 µg/mL. In vitro metabolism and plasma protein binding experiments indicated 
that olumacostat glasaretil was metabolized and bound to plasma protein in a similar manner 
between humans and the species utilized for toxicology and safety pharmacology assessments 
(rat and minipig).  


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Toxicokinetic assessments conducted following the topical dermal application of Olumacostat 
Glasaretil Gel to minipigs indicated that olumacostat glasaretil and TOFA were poorly absorbed; 
peak plasma levels recorded in these studies were below the detectable limit for olumacostat 
glasaretil and while TOFA was detectable following application of the highest strength of 
Olumacostat Glasaretil Gel (7.5% w/w), mean values did not exceed 6 ng/mL for TOFA. The 
test article used in this study is the same formulation and concentration that was used in the 
clinical proof of concept study (DR01B-ACN01) and the same formulation that was included in 
the clinical dose ranging trial DR01B-ACN02).  
Toxicology studies conducted with olumacostat glasaretil included dermal studies in minipigs of 
up to 13 weeks in duration, IV studies in rats and minipigs of up to 4 weeks in duration, and oral 
studies in rats of up to 90 days in duration. Based upon the nonclinical studies conducted to date, 
olumacostat glasaretil has exhibited an acceptable safety profile. No test article-related effects 
were noted in any nonclinical study, aside from histological findings associated with the non-
glandular stomach (fore-stomach) in the 13-week rat oral study. This finding was considered a 
direct local effect (not due to systemic absorption), reversible and non-adverse, and is of doubtful 
clinical relevance given the absence of this structure in humans. In the other toxicology studies, 
there were no remarkable olumacostat glasaretil-related findings and olumacostat glasaretil was 
well tolerated. No adverse systemic effects were associated with mean peak plasma exposures to 
olumacostat glasaretil and TOFA up to 9955 and 3630 ng/mL, respectively, which are 
concentrations exceeding 4000-fold that seen following the dermal application of maximum 
feasible doses (10 mg/kg) to minipigs. In vivo and in vitro studies conducted to assess dermal 
sensitization, ocular irritation, and phototoxicity did not reveal any remarkable effects following 
the exposure of cells/tissues to olumacostat glasaretil. Genetic toxicology results indicated that 
olumacostat glasaretil was neither mutagenic nor clastogenic. Predictive software assessments 
indicated there were no potential theoretical manufacturing impurities or metabolic products that 
were of mutagenic concern. Overall, the results of the nonclinical toxicology and safety 
pharmacology studies suggest the safety risks posed by olumacostat glasaretil are low. 
Two clinical studies, DRM01B-ACN01 and DRM01B-ACN02, have been completed as part of 
the Phase 2 development program. DRM01B-ACN01 was a proof of concept study which 
assessed the safety and efficacy of one strength of Olumacostat Glasaretil Gel compared to 
vehicle gel in adult subjects with acne vulgaris. DRM01B-ACN02 was a dose-ranging study 
which assessed the safety and efficacy of multiple strengths and regimens of Olumacostat 
Glasaretil Gel and vehicle gel in adult subjects with acne vulgaris. In both studies, Olumacostat 
Glasaretil Gel was shown to be well-tolerated and demonstrated statistically significant 
improvements in acne lesions counts and severity. Additional information on these studies is 
provided below.  
Study DRM01B-ACN01 
DRM01B-ACN01 was randomized, vehicle controlled, parallel group study designed to assess 
the safety and tolerability of Olumacostat Glasaretil Gel, 7.5% in healthy volunteers (Phase 1) 
before assessing the safety, tolerability and preliminary efficacy of the drug in subjects with acne 
vulgaris (Phase 2a). In the Phase 1 portion of the study, 6 healthy volunteers applied study 
Olumacostat Glasaretil Gel twice daily, to the face, for one week. Review of the data from Phase 


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1 showed that Olumacostat Glasaretil Gel was well tolerated with no safety concerns. As such, 
the Phase 2a portion of the study was conducted. 
In the Phase 2a portion of the study, Olumacostat Glasaretil Gel was applied, twice daily, to the 
face in 108 adult subjects with acne vulgaris for a 12–week treatment period. Similar to Phase 1, 
Olumacostat Glasaretil Gel was well tolerated with most AEs reported to be mild to moderate 
severity. Subjects treated with Olumacostat Glasaretil Gel had significantly greater reductions in 
inflammatory and noninflammatory lesion counts from Baseline to Week 12 compared with 
subjects treated with vehicle gel. In addition, a significantly greater proportion of subjects treated 
with Olumacostat Glasaretil Gel had a successful improvement in IGA score (corresponding to 
less severe acne) than subjects treated with vehicle gel.  
Study DRM01B-ACN02 
Study DRM01B-ACN02 was a Phase 2 dose-ranging study in adult subjects with acne vulgaris 
on the face. The study was a randomized, vehicle controlled, parallel group study designed to 
assess the efficacy and safety of Olumacostat Glasaretil Gel at a doses of 7.5% BID, 7.5% QD, 
and 4.0% QD, compared to vehicle BID or QD in subjects with moderate to severe facial acne.  
A total of 420 adult subjects were randomized to active and vehicle in a 2:2:2:1:1 fashion. Study 
treatments continued for 12 weeks. Subjects returned to the study clinic at Weeks 1, 2 (phone 
call only), 4, 8 and 12 (study exit).  
The results of the study showed that all three Olumacostat Glasaretil Gel treatment groups 
showed statistically significantly greater reductions in the absolute change in inflammatory 
lesion counts from baseline to Week 12 than the combined vehicle group. The LS mean changes 
in inflammatory lesion counts were −14.6 and −14.5, and −15.0 for the Olumacostat 
Glasaretil Gel, 4.0% QD, 7.5% QD, and 7.5% BID groups, respectively, compared with −10.7 
for the combined vehicle group (P = 0.011, P = 0.014, and P = 0.011, respectively).  
All 3 Olumacostat Glasaretil Gel treatment groups showed statistically significantly greater 
reductions in the absolute change in noninflammatory lesion counts from baseline to Week 12 
than the combined vehicle group. The LS mean changes in noninflammatory lesion counts at 
Week 12 were −15.3, −13.4, and −17.5 for the Olumacostat Glasaretil Gel 4.0% QD, 7.5% QD, 
and 7.5% BID groups, respectively, compared with −9.3 for the combined vehicle group 
(P = 0.004, P = 0.050, and P < 0.011, respectively).  
The Olumacostat Glasaretil Gel 4.0% QD and 7.5% BID groups each had a statistically 
significantly greater proportion of subjects achieve a minimum 2-grade improvement (reduction) 
in IGA score from baseline at Week 12 compared with the combined vehicle group. The percent 
of subjects achieving this endpoint was 21.6% in the Olumacostat Glasaretil Gel 4.0% QD and 
25.9% of subjects in the Olumacostat Glasaretil Gel 7.5% BID group compared with 9.8% in the 
combined vehicle QD group (P = 0.024 and P = 0.004, respectively). 
A comparison of subjects with a 2-grade improvement in IGA score with or without a concurrent 
IGA score of clear or almost clear at Weeks 4, 8, and 12 showed that in each treatment group at 
each IGA assessment time point, most subjects who achieved a 2-grade improvement in IGA 
score also had an IGA score of clear or almost clear.  


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Pharmacokinetic (PK) results, assessed in a subset of subjects, showed that plasma 
concentrations of olumacostat glasaretil on Day 1 were undetectable for all but one subject, who 
had a plasma concentration of 0.304 ng/mL at one time point (2 hours post-dosing). Plasma 
concentrations of olumacostat glasaretil at Week 8 were undetectable for all tested subjects. 
Plasma concentrations of TOFA on Day 1 were undetectable in most subjects, but detectable in a 
few subjects in each dose group, with values ranging from 0.101 to 1.02 ng/mL. Plasma 
concentration of TOFA at Week 8 were undetectable for most subjects in the Olumacostat 
Glasaretil Gel QD dose groups, but detectable in a few subjects, with values ranging from 
0.100 to 0.299 ng/mL. In the Olumacostat Glasaretil Gel, 7.5% BID group, approximately half of 
the tested subjects had detectable TOFA levels at each time point, with mean values ranging 
from 0.156 to 0.340 ng/mL. 
The most common AEs reported during the study were nasopharyngitis, upper respiratory tract 
infection, and application site pruritus. Most AEs were mild or moderate in severity. Erythema 
was the most common LSR. Laboratory values, vital signs, and ECGs measured at the end of the 
study were generally consistent with baseline values, with no clinically significant trends. 
Study Rationale 
Data from the completed Phase 2 dose ranging study, DRM01B-ACN02, and data from study 
DRM01B-ACN01 have shown that Olumacostat Glasaretil Gel was well tolerated at multiple 
concentrations. Olumacostat Glasaretil Gel at a strength of 5.0% has been selected as the 
concentration to take forward in Phase 3 development. Two Phase 3 pivotal trials, DRM01B-
ACN03 and DRM01B-ACN04, are planned as part of the Phase 3 development program and will 
include adults and children (ages 9 years and older) in order to assess the safety and efficacy of 
Olumacostat Glasaretil Gel for the treatment of acne vulgaris.  
The DRM01B-ACN05 study described herein is an open-label study to assess the long term 
safety of continuous treatment with Olumacostat Glasaretil Gel, 5% for up to an additional 
36-weeks in subjects who have completed either of the DRM01-ACN03 or DRM01-ACN04 
studies.  
1.3 
Study Conduct Statement 
This study will be conducted in compliance with the protocol, according to current United States 
federal regulations (Title 21, Code of Federal Regulations [CFR] Parts 11, 50, 54, 56, 312, and 
314 as appropriate) and the principles of the International Conference on Harmonisation (ICH) 
(ICH E6 1997) Good Clinical Practice (GCP), Food and Drug Administration (FDA) guidelines, 
Canadian guidelines and the Declaration of Helsinki, 1964 (as amended in Edinburgh [2000]). 
2 
STUDY SUMMARY 
This study is an open-label, long-term safety study enrolling approximately 700 subjects who 
participated in either DRM01B-ACN03 or DRM01B-ACN04 studies. All subjects will sign an 
informed consent / assent prior to continuing in this open label study.  


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Eligible subjects will receive open label treatment with Olumacostat Glasaretil Gel, 5.0% and 
continue to dose twice daily for 36 weeks. Subjects, who participated in DRM01-ACN03 study 
with acne on the chest, back or shoulders and applied study drug to affected areas will be 
allowed to continue to apply study drug to the affected areas. Subjects who participated in 
DRM01-ACN04 study will continue to apply study drug to the face only. Subjects will receive a 
phone call at Week 2 to assess safety, and will return to the clinic at Weeks 4, 8, 12, 16, 20, 24, 
28, 32, and 36 (End of Study). 
Efficacy will be assessed via a static evaluation of qualitative overall acne severity, the 
investigator’s global assessment of acne (IGA).  
At the Week 12 and 24 visit, if the severity of acne has become worse, as determined by the 
IGA, the subject should be withdrawn, at the investigator’s discretion. Severity of acne will be 
assessed on the face only.  
Safety will be assessed through adverse events, local skin reactions (LSRs), serum chemistry, 
hematology and urinalysis laboratory testing, ECGs, physical examination, pulse and blood 
pressure. 
Photographs of the face will be taken for all subjects in a subset of study sites in order to assess 
visually, the appearance of acne vulgaris during the course of the study.  
During the clinic visit, subjects will be asked to complete the Acne Patient Self-Questionnaire. 
3 
STUDY OBJECTIVES 
The objective of this study is to assess the long-term safety of Olumacostat Glasaretil Gel, 5.0%, 
in subjects with acne vulgaris.  
This study may be stopped once at least 100 subjects have been treated for 36 weeks. 
4 
STUDY ENDPOINTS 
No inferential statistics are planned for this study. 
5 
STUDY DESIGN 
5.1 
Duration of the Study 
Each subject will participate in this study for up to 36 weeks.  
5.2 
Study Population and Number of Subjects 
Approximately 700 subjects who participated in either of the DRM01B-ACN03 or DRM01B-
ACN04 studies may enroll in this trial. 


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5.3 
Selection of Subjects 
Subject selection criteria are outlined below. Any questions on the eligibility of a subject for this 
study must be referred to the Sponsor or its designee, prior to enrollment. No exceptions to 
inclusion or exclusion criteria will be made. 
5.3.1 
Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for study participation: 
1. 
Signed informed consent or assent (for subjects under legal adult age) 
2. 
Completed Week 12 visit of either DRM01B-ACN03 or DRM01B-ACN04 studies.  
3. 
Willing to comply with the protocol. Subjects under legal adult age will be assessed by 
the investigator as to their ability to comply with the protocol  
4. 
Willing to refrain from using any treatments on the face for acne vulgaris, other than the 
investigational product, including topical or systemic antibiotics.  
5.3.2 
Exclusion Criteria 
Subjects meeting any of the following criteria are not eligible for study participation: 
1. 
Abnormal clinically significant findings on physical exam, vital signs or ECG at Week 12 
visit of either the DRM01-ACN03 or DMR01-ACN04 studies that would make further 
treatment with Olumacostat Glasaretil Gel contraindicated, as determined by the 
Investigator 
2. 
Any other condition which, in the judgment of the investigator, would put the subject at 
unacceptable risk for participation in the study 
6 
STUDY DRUG 
6.1 
Investigational Medicinal Product 
The study medication is Olumacostat Glasaretil Gel, 5.0%.  
Olumacostat Glasaretil Gel is formulated as an alcohol based gel for topical application 
Olumacostat Glasaretil Gel, 5.0% contains 50 mg of Olumacostat Glasaretil per gram of gel, 
ethanol, isopropanol, polyethylene glycol 400, dimethyl isosorbide and hydroxypropy-cellulose 
and appears as a translucent, colorless to faintly yellow gel.  
6.2 
Packaging, Labeling and Storage 
Olumacostat Glasaretil Gel, 5.0% will be packaged in 45g aluminum tubes. Each tube contains 
approximately 40g of gel.  
Study drug tubes will be labeled with the study number, a unique tube number, contents, storage 
conditions, manufacturer and Sponsor information, precautionary statements and expiry date if 
applicable.  


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Study drug tubes are to be stored at room temperature (25°C with allowable excursion to 15-
30°C) in a secure, locked facility accessible only to authorized study personnel. Study drug must 
not be placed in refrigerator or frozen, exposed to heat or stored at high temperatures. This 
product is flammable. Avoid fire, flame, or smoking during and immediately following 
application. 
6.3 
Treatment Assignment 
Subjects will maintain the unique subject number assigned at randomization into their study of 
origin (either DRM01B-ACN03 or DRM01B-ACN04). All subjects will receive Olumacostat 
Glasaretil Gel, 5.0%, BID. 
6.4 
Study Blinding 
This is an open-label study. Subjects will not be unblinded to their treatment assignment prior to 
enrollment into this study (DRM01B-ACN05). Once enrolled, each subject will receive 
Olumacostat Glasaretil Gel, 5.0%. 
6.5 
Study Drug Dispensing and Return 
It is the responsibility of the Investigator to ensure that study drug is only used on study subjects 
enrolled in this study. The study drug must only be dispensed from official study sites by 
authorized personnel according to the protocol and local regulations.  
Study drug will be dispensed by the study site to the subject at each study visit. Two tubes 
contain enough study drug for 1 month of application. At each visit, the subject will be dispensed 
enough tubes to allow dosing until the next visit. Partially used tubes may be re-dispensed at the 
site’s discretion. 
Subjects are to return all study medication tubes (used and unused) to the study site. Study tubes 
will be weighed prior to dispensing and upon return, and if required, prior to re-dispensing. 
Weights will be recorded in the source documents and eCRF.  
Each subject is to be instructed on the importance of returning study drug at the next study visit. 
If a subject does not return study drug, they will be instructed to return it as soon as possible. The 
site staff will visually inspect the tube to ensure product usage is consistent with the subject’s 
dosing diary.  
6.6 
Study Drug Application 
Subjects will apply the study drug twice daily (morning and evening) to a clean, dry face. 
Subjects will be re-instructed on the application of the study drug, if needed. 
Study drug is to be applied topically, to the entire face (forehead, nose, cheeks, and chin) by 
squeezing approximately ½ inch or 1.3 centimeter long line of gel onto a finger and spreading 
the gel over the face, avoiding the skin around the eyes, eyelids and mouth, until the face is 
completely covered.  


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For subjects originating in the DRM01B-ACN03 study, subjects may continue to apply study 
drug may all affected areas on the trunk (i.e., chest, shoulders and back) by spreading a thin layer 
of gel over the entire affected areas.  
Subjects originating in DRM01B-ACN04 should continue to apply study drug to the face only.  
Subjects will be instructed to wash their hands prior to and immediately following study drug 
application. 
Subjects should avoid washing the face or swimming within 2 hours of applying study 
medication. Missed doses should be applied, provided there is an 8-hour window until the next 
scheduled dose.  
6.7 
Treatment Compliance 
Treatment compliance will be assessed at each visit using a subject-completed diary and visual 
inspection of the tubes. Subjects will be given a paper diary at each visit in conjunction with 
study medication. The subject-completed diary will collect application information for the face, 
chest, back and shoulders.  Subjects will be instructed to bring all study medication and diaries to 
the clinic at the next study visit. 
A subject deviating significantly from the assigned dosing regimen on the face, will be 
counseled. All diaries will be maintained as source documentation.  
The first and last dates of study product usage, location and any missed applications will be 
recorded in the eCRF. 
6.8 
Study Drug Accountability 
The Investigator or designee will be responsible for study drug accountability and records at the 
site. Study drug accountability records will document the receipt, dispensing and return of study 
drug and provide a complete account of all used and unused drug product. Study drug 
accountability records will be reviewed regularly throughout the study by the Sponsor/designee. 
Study drug will be returned to the Sponsor, or designee, at the end of the study, following final 
study drug accountability.  
7 
CONCOMITANT MEDICATIONS AND PROCEDURES 
All medications (including over-the-counter drugs, vitamins, antacids and skin care products) 
taken throughout the study will be recorded on the eCRF.  
Medication entries should be specific to the generic name (if a combination drug, then marketed 
product name) and will include the dose, unit, frequency, route of administration, start date, 
discontinuation date, and indication. When listing medications indicated for acne, the area 
treated will be collected.  


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The Investigator should examine the acceptability of all concomitant procedures, medications, 
topical preparations and dietary supplements not explicitly prohibited in this study. In order to 
ensure that appropriate concomitant therapy is administered, subjects will be instructed to 
consult with the Investigator prior to taking any medication (either self-administered non-
prescription drugs or prescription therapy prescribed by another physician). 
7.1 
Permitted Treatments and Procedures 
The use of concomitant medications for medical conditions (e.g., hypertension, diabetes, acute 
infections) or treatment of an adverse event is permitted during this study as long as medications 
are not explicitly prohibited by the protocol.  
Non-medicated moisturizers and make-up may be used during study participation, provided 
application occurs after study medication is applied. On study visit days, non-medicated 
moisturizers and make-up must be removed prior to each study visit as instructed by the 
Investigator. Subjects’ skin care regimen should remain stable/unchanged during study 
participation.  
Non-medicated moisturizers, soaps, and make-up do not need to be recorded as concomitant 
medications. 
7.2 
Prohibited Treatments and Procedures 
Subjects should not undergo any elective medical procedure without prior consultation with the 
Investigator. Elective out-patient procedures (e.g., minor outpatient surgery) that might require 
hospitalization or anesthesia should be deferred until after the study, whenever clinically 
appropriate. However, subjects may continue in the study if not contraindicated by the procedure 
or if continuation is not deemed in the subject’s best interest. 
The following medications and treatments are prohibited during the study:  
 Over-the-counter topical medications for acne vulgaris including benzoyl peroxide, 
topical anti-inflammatory medications, corticosteroids, α-hydroxy/glycolic acid  
 With the following exception: Subjects originating in DRM01B-ACN04 may apply 
non-systemically-absorbing over-the-counter topical medications for acne vulgaris on 
truncal acne if warrented by the Investigator 
 Systemically absorbed anti-acne drugs 
 Systemic corticosteroids (use of intranasal and inhaled corticosteroids allowed for 
seasonal allergies and asthma) 
 Systemic antibiotics (except in the case of acute medical need to treat infections) 
 Prescription topical retinoid use (e.g., tretinoin, tazarotene, adapalene) 
 New hormonal therapy or dose change to existing hormonal therapy. Hormonal therapies 
include, but are not limited to, estrogenic and progestational agents such as birth control 
pills.  


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 Use of androgen receptor blockers (such as spironolactone or flutamide) 
 Oral retinoid use (e.g., isotretinoin) or vitamin A supplements greater than 
10,000 units/day  
 Facial procedures (chemical or laser peel, microdermabrasion, etc.) 
 Sun exposure which in the opinion of the investigator could affect the course of acne or 
any tanning booth use 
8 
STUDY PROCEDURES 
The procedures required for subject evaluation at each study visit are outlined below and in the 
study Schedule of Visits and Procedures (see Appendix 1). The timing of each study day is 
relative to the day of initial dosing (Baseline/Day 1). Visit windows are provided to allow study 
sites some flexibility in maintaining the study visit schedule for participating subjects. Out of 
window visits may be unavoidable in certain circumstances. Out of window visits are not 
considered deviations to the protocol. 
8.1 
Day 1 (Week 12 Visit of DRM01B-ACN03 or DRM01B-ACN04 Study) 
 Obtain written informed consent/assent. For subjects under legal adult age, both parents 
or legal representatives may be required to sign informed consent as applicable. 
 Assess Inclusion/Exclusion criteria 
 Dispense study drug and diary 
 Schedule next visit 
The following Week 12 data collected as part of the DRM01-ACN03 or DRM01-ACN04 study 
will be used for the Day 1 visit: 
 Query subject for concomitant medication use 
 Perform a complete physical examination 
 Record weight 
 Measure pulse and blood pressure 
 Collect a 12-lead ECG 
 Conduct Investigator Global Assessment 
 Collect Acne Patient Self-Questionnaire 
 Draw blood samples for laboratory tests and urine for urinalysis. Include serum 
pregnancy test for women of childbearing potential 
 Assess Local Skin Reactions (LSR) 
 Review and record AEs 
 Collect photographs (selected sites) 


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8.2 
Week 2 Telephone Contact (+/-2 days) 
 Call subject to review AEs and concomitant medications 
 Schedule next visit 
8.3 
Weeks 4, 8, 16, 20, 28 and 32 (+/-4 days) 
 Collect concomitant medication information 
 Collect urine pregnancy for women of childbearing potential 
 Measure pulse and blood pressure 
 Review and record AEs 
 Assess LSRs 
 Perform symptom-directed physical exam 
 Review compliance/Weigh tubes and dispense drug and diary 
 Schedule next visit 
8.4 
Week 12 and 24 (+/-4 days) 
 Collect concomitant medication information 
 Collect urine pregnancy for women of childbearing potential 
 Measure pulse and blood pressure 
 Review and record AEs 
 Assess LSRs 
 Conduct Investigator’s Global Assessment and assess subject’s eligibility to continue 
treatment. 
 Collect Acne Patient Self-Questionnaire 
 Collect photographs at Week 12 only (selected sites) 
 Perform symptom-directed physical exam 
 Review compliance/Weigh tubes and dispense drug and diary 
 Schedule next visit 
8.5 
Week 36 (+/-4 day) Study Exit or Early Termination Visit 
 Collect concomitant medication information 
 Measure pulse and blood pressure 
 Review and record AEs 
 Conduct a complete physical exam 


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 Measure weight and height 
 Collect a 12 lead ECG 
 Draw blood samples for laboratory tests. Include serum pregnancy test for women of 
childbearing potential. Include urinalysis if clinically indicated  
 Assess LSRs 
 Conduct Investigator Global Assessment 
 Collect Acne Patient Self-Questionnaire 
 Collect photographs (selected sites) 
 Review compliance/Weigh tubes and collect all study medication and diary 
8.6 
Unscheduled Visits 
Additional visits may be scheduled as necessary to ensure the safety and well-being of subjects 
who experience AEs. Laboratory evaluations, if necessary, will be collected and analyzed using 
the central laboratory for this study. Data will be recorded in the eCRF. If an immediate result is 
required to adequately care for a subject, a duplicate sample may be submitted to a local lab. 
9 
DETAILS OF ASSESSMENTS 
Parental assistance for study drug application and study conduct procedures may be needed for 
younger subjects qualifying for study participation. 
9.1 
Baseline/Day 1 Assessments 
The Baseline/Day 1 visit for this study occurs on the same day as the Week 12/study exit visit of 
the DRM01B-ACN03 or DRM01B-ACN04 visit. Therefore, if subjects choose to enroll in this 
study, study procedures will not be repeated; study sites will carry over the information from the 
DRM01B-ACN03 or DRM01B-ACN04 study to the Baseline/Day 1 visit for this study.  
The study procedures that are to be carried over are: 
 Demographic information: age, gender, race, ethnicity and Fitzpatrick Skin Type 
 Medical history 
 Adverse events 
 Local skin reactions 
 Concomitant medications 
 Laboratory evaluations: hematology, serum chemistries and urinalysis 
 Pregnancy testing 
 12-lead ECG 
 Investigator Global Assessment of acne 


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 Photography (at selected sites) 
 Vital signs and weight 
 Acne Patient Self-Questionnaire 
9.2 
Acne Patient Self-Questionnaire 
Subjects will be asked to complete Acne Patient Self-Questionnaire. The questionnaire is paper-
based and will be completed by subjects during clinic visits (see Appendix 2). Subject responses 
will be entered in the eCRF by the study site and the completed questionnaires kept as part of the 
subject’s source document. Study site staff must review all forms to ensure complete responses 
prior to a subject leaving the study site.  
9.3 
Assessment of Efficacy 
9.3.1 
Investigator Global Assessment 
An Investigator Global Assessment (IGA) of acne severity on the face only will be conducted for 
each subject every 12 weeks (Table 1). 
Where possible, the same efficacy assessor should assess acne severity on the same subject at 
all visits. At the Week 12 and 24 visit, if the severity of acne has become worse, as determined 
by the IGA, the investigator should assess whether or not the subject should be withdrawn from 
the study. If the decision is made to withdraw the subject, all Early Termination Visit procedures 
should be completed. For additional details regarding subject withdrawal, please refer to 
Section 10.2 Early Study Termination of Study Subjects.  
Individuals performing the IGA will be trained and certified prior to study start. IGA grades will 
be entered into the eCRF. 
Table 1: 
Investigator Global Assessment 
Investigator Global Assessment 
Grade 
Description 
0 
Clear; normal, clear skin with no evidence of acne vulgaris 
1 
Almost clear; Rare non-inflammatory lesions present, with rare non-inflamed papules (papules 
must be resolving and may be hyperpigmented, though not pink-red) 
2 
Mild; some non-inflammatory lesions are present, with few inflammatory lesions 
(papules/pustules only; no nodulocystic lesions) 
3 
Moderate; non-inflammatory lesions predominate, with multiple inflammatory lesions evident: 
several to many comedones and papules/pustules, and there may or may not be one small 
nodulocystic lesions 
4 
Severe; Inflammatory lesions are more apparent, many comedones and papules/pustules, there 
may or may not be a few nodulocystic lesions 


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9.4 
Assessment of Safety 
9.4.1 
Physical Examination 
A complete physical examination will be conducted at Day 1 and Week 36 (End of Treatment) 
visit and cover general appearance, dermatological, head, ears, eyes, nose, throat, respiratory, 
cardiovascular, abdominal, neurological, musculoskeletal, and lymphatic body systems. A 
symptom directed physical exam may be performed at other clinic visits, if needed, to assess the 
subject. Weight will be recorded with the end of study physical exam. Findings will be recorded 
in the source document and eCRF. 
9.4.2 
Pulse and Blood Pressure 
Pulse (beats per minute), and blood pressure (mmHg), will be obtained with the subject in the 
seated position, after sitting for at least 5 minutes. Any abnormal findings which are new or 
worsened in severity and clinically significant, in the opinion of the Investigator, will be 
recorded as an AE.  
Pulse and blood pressure measurements will be recorded in the source document and eCRF. 
9.4.3 
ECGs 
12-lead ECG measurements will be obtained for all subjects at the Day 1 and Week 36 Study 
Exit or Early Termination visits. The subject should rest quietly for at least 5 minutes in a supine 
position prior to ECG collection. The ECG should be obtained either prior to the time of blood 
collection, or at least 15 minutes afterwards.  
All study sites will be supplied with standardized, validated digital 12-lead ECG (12 lead at 
25 mm/sec reporting rhythm, ventricular rate, the RR interval, the PR interval, QRS duration, QT 
and QTcF intervals) equipment capable of recording, storing, and printing producing high 
resolution 12-lead ECG data by the central laboratory. Study sites will be trained on the use of 
the equipment prior to study start.  
Machine-read ECG recordings will be collected and analyzed centrally. Data will be transferred 
electronically to the database. 
9.4.4 
Laboratory Evaluations  
Laboratory tests will be collected to evaluate safety in all study subjects and analyzed using a 
central laboratory. Labs will be collected per the Schedule of Visits and Procedures (see 
Appendix 1) or more frequently as clinically indicated. Laboratory samples are to be shipped on 
the same day as collected. No more than 4 mL/kg total will be collected over an 8-week period in 
subjects under legal adult age. Laboratory tests are described below.  
Hematology: hematocrit, hemoglobin, red blood cell (RBC) count, white blood cell count and 
differential (%), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin 
concentration (MCHC), mean corpuscular volume, RBC morphology, platelet count, absolute 


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neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute 
basophils. 
Chemistry: sodium, potassium, chloride, calcium, phosphorus, bicarbonate, uric acid, blood urea 
nitrogen (BUN), creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), alkaline phosphatase, bilirubin (total and direct), and glucose (fasting or 
non-fasting). 
Serum pregnancy testing will be performed at Baseline/Day 1and Week 36 Study Exit or Early 
Termination visits. Urine pregnancy testing (beta human chorionic gonadotropin [β-hCG]) will 
be performed at Weeks 4 – 36 visits for all females unless post-menopausal/sterile.  
Urinalysis: pH, specific gravity, protein, glucose, ketones, bilirubin, blood, nitrite, urobilinogen, 
leukocyte esterase. A microscopic examination of urine will be performed if clinically indicated 
(e.g. a positive dipstick for protein, blood, leucocyte esterase) in the opinion of the Investigator 
based on the findings of the urinalysis or clinical signs and symptoms. Any new or worsened 
clinically significant laboratory result is to be recorded as an AE after study drug dosing. 
The central laboratory should be used for any laboratory testing required for a subject during 
study participation, including laboratory testing needed for unscheduled visits. If an immediate 
result is required to adequately care for a subject, a duplicate sample may be submitted to a local 
lab. Clinically significant laboratory results must be recorded as an AE, preferably as a diagnosis 
rather than individual test results. Any subject who has a clinically significant laboratory test 
result will be evaluated by the Investigator, and will be treated and/or followed up until the value 
returns to clinically acceptable levels, in the opinion of the investigator. 
9.4.5 
Local Skin Reactions 
All subjects will be assessed for LSRs, on the face, at each visit. LSRs include burning/stinging, 
pruritus, erythema, dryness and peeling. Each LSR will be scored as 0 (None), 1 (Mild), 
2 (Moderate) or 3 (Severe) (Table 2). LSRs observed on a visit day will not be recorded as 
adverse events unless scored as 3 (Severe). Local skin reactions experienced by the subject in 
between study visits are to be recorded as an AE.  
Burning/stinging and pruritus will be assessed by the subject and erythema, dryness and scaling 
will be assessed by the Investigator/designee (Table 3). Subjects will be read the definition of 
each subject-assessed LSR and asked to select the appropriate definition. The corresponding 
grade will be assigned by the site and entered in the eCRF. 


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Table 2: 
Subject Assessed Local Skin Reactions 
Score 
Grade 
Burning/Stinging 
Pruritus 
0 
None 
No stinging/burning 
No pruritus 
1 
Mild 
Slightly warm, tingling sensation; not 
really bothersome 
Occasional, slight itching/scratching 
2 
Moderate 
Definite warm; tingling/stinging sensation 
that is somewhat bothersome 
Intermittent itching/scratching which does 
not disturb sleep 
3 
Severe 
Hot, tingling/stinging sensation that has 
caused definite discomfort 
Bothersome itching/scratching which 
disturbs sleep 
Table 3: 
Investigator Assessed Local Skin Reactions 
Score 
Grade 
Erythema 
Dryness 
Peeling 
0 
None 
None 
None 
None 
1 
Mild 
Slight erythema: very light-
pink 
Perceptible dryness with no 
flakes or fissure formation 
Mild diffuse peeling 
2 
Moderate 
Dull red, clearly 
distinguishable 
Easily noted dryness and 
flakes but no fissure 
formation 
Moderate diffuse peeling 
3 
Severe 
Deep/dark red 
Easily noted dryness with 
flakes and fissure 
formation 
Moderate to prominent, 
dense peeling 
9.4.6 
Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of 
a study drug in humans, whether or not considered drug related. An AE can, therefore, be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease 
temporally associated with the use of the study drug, whether or not related to the investigational 
product.  
AEs will be monitored throughout the study. Subjects will be instructed to inform the 
Investigator and/or study staff of any AEs. At each visit, subjects will be asked about AEs in a 
non-specific manner using open-ended questions so as not to bias the response (e.g., How have 
you been since the last visit?). Specific inquiry regarding reported AEs will be conducted when 
applicable. All AEs will be documented and recorded in the subject’s eCRF. 
Any subject who has an AE (serious or non-serious) or clinically significant abnormal laboratory 
test value will be evaluated by the Investigator, and will be treated and/or followed up until the 
symptoms or values return to normal or to clinically acceptable levels, as judged by the 
Investigator. A physician, either at clinical site, or at a nearby hospital emergency room, will 
administer treatment for any serious adverse events (SAEs), if necessary. When appropriate, 
medical tests and examinations will be performed to document resolution of event(s). 


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9.4.7 
Reporting 
Only AEs that occur during or following study treatment with the drug will be reported in the AE 
section of the eCRF. Events recorded prior to treatment with the study drug will be reported in 
the Medical History section of the eCRF as appropriate. All AEs occurring during the course of 
the study will be individually recorded in the eCRF. A condition that is present prior to 
administration of study drug and that worsens after administration of study drug should be 
reported as an AE. Information regarding the onset, duration, severity, action taken, outcome, 
and relationship to study drug will be recorded.  
New or worsening abnormal laboratory values and/or pulse and blood pressure are to be recorded 
as AEs if they are considered to be of clinical significance by the Investigator or meet the criteria 
of an SAE as described in Section 9.4.8. 
Unless a diagnosis is available, signs and symptoms must be reported as individual AEs in the 
eCRF; a diagnosis is preferred. 
The severity of an AE will be designated as mild, moderate or severe. The term “severe” is used 
to describe the intensity of an adverse event; the event itself, however, may be of relatively 
minor clinical significance (e.g., ‘severe’ upper respiratory infection). Severity is not the same as 
“serious”. Seriousness of AEs is based on the outcome/action of an AE.  
The relationship of the AE to the study treatment should be determined by the Investigator and 
will be based on the following two definitions: 
Not related: An AE is defined as “not related” if the AE is not judged to be associated with the 
study drug and is attributable to another cause 
Related: An AE is defined as “related” where a causal relationship between the event and the 
study drug is a reasonable possibility (possibly or probably related). A reasonable causal 
relationship is meant to convey that there are facts (e.g., evidence such as dechallenge/ 
rechallenge) or other clinical arguments to suggest a causal relationship between the AE and 
study treatment.  
9.4.8 
Serious Adverse Events 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose, 
 Results in death; 
 Is immediately life-threatening (i.e., in the opinion of the Investigator, the AE places the 
subject at immediate risk of death; it does not include a reaction that, had it occurred in a 
more severe form, might have caused death); 
 Requires inpatient hospitalization or results in prolongation of an existing hospitalization; 
 Results in persistent or significant disability or incapacity; 
 Is a congenital anomaly or birth defect; 


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 Is an important medical event that may not be immediately life-threatening, result in 
death, or require hospitalization, but may be considered an SAE when, based upon 
appropriate medical judgment, it jeopardizes the subject or may require medical or 
surgical intervention to prevent one of the outcomes listed above. 
As soon as the Investigator becomes aware of an AE that meets the criteria for an SAE, the SAE 
should be documented to the extent that information is available. A report must be submitted by 
the study site to the Sponsor or designee within 24 hours. 
Any SAE, regardless of causal relationship, must be reported to the Sponsor immediately (within 
24 hours of the Investigator’s knowledge of the event).  
SAEs will be recorded from the time of informed consent/assent, through to end of the study. If, 
in the opinion of the Investigator, an SAE occurring outside the specified time window, (i.e., 
following subject completion or terminations of the study) is deemed to be drug-related, then the 
event should be reported with 24 hours as outlined above. 
The Investigator should institute any clinically necessary supplementary investigation of SAE 
information. In the case of subject death, any post-mortem findings/reports will be requested. 
9.4.9 
Reporting of Serious Adverse Events 
All SAEs, as defined by the criteria above, must be reported to the Sponsor or designee using the 
SAE form provided, within 24 hours of the Investigator becoming aware of the event. 
Serious adverse events must be recorded on an SAE form. The minimum information required 
for SAE reporting includes the identity of the PI, site number, subject number, event description, 
SAE term(s), reason why the event is considered to be serious (i.e., the seriousness criteria), and 
PI’s assessment of the relationship of the event to study drug. Additional SAE information 
including medications or other therapeutic measures used to treat the event, and the 
outcome/resolution of the event should also be recorded on the SAE form. 
In all cases, the Investigator should continue to monitor the clinical situation and report all 
material facts relating to the progression or outcome of the SAE. The Investigator may be 
required to provide supplementary information as requested by the Sponsor or its designee. 
When reporting SAEs, the following additional points should be considered: 
 When the diagnosis of an SAE is known or suspected, the Investigator should report the 
diagnosis or syndrome as the primary SAE term, rather than as signs or symptoms; signs, 
symptoms and tests that support the diagnosis should be provided  
 Death should not be reported as an SAE, but as an outcome of a specific SAE, unless the 
event preceding the death is unknown. If an autopsy was performed, the autopsy report 
should be provided; 
While most hospitalizations necessitate reporting of an SAE, some hospitalizations do not 
require SAE reporting, as follows:  


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 Hospitalization for elective or previously scheduled surgery or procedure for a pre-
existing condition that has not worsened after administration of study drug (e.g., a 
previously scheduled ventral hernia repair). SAEs must, however, be reported for any 
surgical or procedural complication resulting in prolongation of the hospitalization; 
 Events that result in hospital stays for observation only of fewer than 24 hours and that do 
not require admission or therapeutic intervention/treatment (e.g., an emergency room 
visit for hematuria that results in a diagnosis of cystitis and discharge to home on oral 
antibiotics). 
The Sponsor will process and evaluate all SAEs as soon as the reports are received. For each 
SAE received, the Sponsor will make a determination as to whether the criteria for expedited 
reporting to relevant regulatory authorities have been met.  
The Sponsor will assess the expectedness of each SAE to the study treatment. The current 
Investigator’s Brochure will be used as the reference document to assessed expectedness of the 
event to study drug. 
9.4.10 
Dosing Changes Due to AEs 
Dose interruptions are allowed should a subject experience intolerable treatment-related adverse 
events (e.g., pruritis) on study. In cases where the Investigator feels a dose interruption is 
warranted, the subject should be instructed to interrupt study drug application to allow symptoms 
to resolve. Subjects should be instructed to return to the twice daily application regimen within 
2 days of dose interruption.  
Dosing interruptions are to be recorded in the subject diary as a missed dose. 
Study drug must be discontinued if an adverse event is deemed persistent and if continuation of 
study drug would not be in the best interest of the subject.  
Refer to Section 10.3 for further information regarding discontinuation of study drug or early 
withdrawal. 
9.4.11 
Pregnancy 
Should a subject become pregnant during study participation, study drug dosing will be 
discontinued and the subject will be withdrawn from study. The Investigator must perform 
medical assessments as clinically indicated and continue to follow the subject for at least 
4 weeks after delivery. Details for both the mother and baby must be obtained. Pregnancy is not 
itself an AE or SAE; however, maternal/fetal complications or abnormalities will be recorded as 
AEs or SAEs, as appropriate. The Investigator must complete a study-specific pregnancy form 
upon confirmation of a pregnancy. Pregnancy reporting forms will be provided to the study site. 


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10 
STUDY DISCONTINUATIONS 
10.1 
Discontinuation of the Study 
The Sponsor has the right to terminate or to stop the study at any time. Should this be necessary, 
both the Sponsor and the Investigator will ensure that proper study discontinuation procedures 
are completed. The entire study will be stopped if: 
 Evidence has emerged that, in the collective opinion of the Investigators at each site with 
the concurrence of the Sponsor or the sole opinion of the Sponsor, makes the 
continuation of the study unnecessary or unethical 
 The stated objectives of the study are achieved 
 The Sponsor discontinues the development of the study drug 
Regardless of the reason for withdrawal, all data available for the subject at the time of 
discontinuation of follow-up must be recorded in the eCRF. All reasons for discontinuation of 
treatment must be documented. 
10.2 
Early Study Termination of Study Subjects 
The Investigator will make every reasonable effort to keep each subject in the study; however, 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 schedule an Early 
Termination visit as soon as possible, determine the reason for discontinuation, and record the 
reason in the subject’s study records and in the eCRF.  
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 eCRF regarding the 
reason for discontinuation must be completed. 
All subjects who fail to return to the study site for the required follow-up visits will be contacted 
by phone to determine the cause(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 registered letter will be sent 
requesting that subject contact the site regarding study follow-up.  
Subjects will be discontinued early from the study if any of the following occur: 
 Withdrawal of informed consent (subject’s decision to withdraw for any reason) 
 Any clinical adverse event, laboratory abnormality, or inter-current illness which, in the 
opinion of the Investigator, indicates that continued treatment and/or participation in the 
study is not in the best interest of the subject 
 Death 


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 Serious protocol violation, including persistent noncompliance or subject requiring 
medication or procedures prohibited by the protocol, to allow subjects to receive the 
appropriate medical attention.  
 Discontinuation of the study by the Sponsor 
10.3 
Study Drug Discontinuation 
For subjects who decide to prematurely discontinue study drug treatment, all reasonable efforts 
should be made to obtain all protocol-specified safety assessments and end of study procedures.  
The Investigator should stop study drug treatment in the following instances: 
 Inter-current illness that would, in the judgment of the Investigator, affect assessments of 
clinical status to a significant degree. In such cases, the Investigator must contact the 
Sponsor or designee, as the need to withdraw the subject will assessed by the Sponsor 
 Unacceptable toxicity 
11 
STATISTICAL CONSIDERATIONS 
11.1 
General Statistical Methodology 
All statistical processing will be performed using SAS® unless otherwise stated. Data will be 
summarized using descriptive statistics. No inferential testing or imputations for missing data 
will be performed.  
Subject demographic and baseline characteristics will be summarized for the Safety Population. 
Categorial variables will be tabulated with frequencies and percentages. Continuous variables 
will be tabulated with mean, median, SD, and range (minimum and maximum). 
A statistical analysis plan (SAP), describing all statistical analyses will be provided as a separate 
document. 
11.2 
Populations Analyzed 
All analyses will be performed using the Safety Population. All subjects who receive at least one 
confirmed dose of Olumacostat Glasaretil Gel and have at least one post-baseline (where 
baseline is the day that the subject received their first study drug) assessment will be included in 
the Safety Population. 
The number of subjects included in the Safety Population will be summarized.  
11.3 
Exposure and Compliance 
The extent of exposure to study drug in each treatment group will be summarized by total 
number of days of exposure, total number of applications, number of missed applications and 
number and percentage of subjects who are compliant. A subject will be considered compliant 


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with the dosing regimen if the subject applied 80% to 120% of the expected number of 
applications while enrolled in the study.  
11.4 
Adverse Events 
All AEs that occur during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities (MedDRA) terminology. Treatment-emergent AEs 
(TEAEs) are defined as AEs with an onset on or after the date of the first study drug application. 
Adverse events noted prior to the first study drug administration that worsen after baseline will 
also be reported as AEs and included in the summaries.  
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 application.  
Treatment-emergent AEs will be summarized by treatment group, 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 
once within a system organ class or a preferred term by using the event with the highest severity 
and greatest relationship within each classification. 
Serious AEs will be summarized by treatment group, 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. 
11.5 
Local Skin Reactions 
Local Skin Responses (LSRs) include erythema, peeling, dryness, burning/stinging and pruritus. 
These will be scored as 0 (None), 1 (Mild), 2 (Moderate) or 3 (Severe). LSRs will be 
summarized by treatment group and visit using descriptive statistics. A by-subject listing of 
subjects with any LSR 3 or higher will be presented. 
11.6 
Other Safety Data 
Laboratory data will be presented in a by-subject listing. Any clinically significant laboratory 
abnormalities will be captured as adverse events. Changes from Baseline in safety laboratory 
values will be summarized at the final follow up evaluation during the treatment period using 
descriptive statistics or frequency tables as appropriate.  
Additionally, changes from Baseline in safety laboratory values will be summarized using shift 
tables according to normal ranges.  
Pulse and blood pressure will be presented as absolute values and changes from baseline using 
descriptive statistics. 
Concomitant medications will be coded using the WHO-Drug dictionary. Concomitant 
medications will be summarized by treatment, drug class, and preferred term.  


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Physical examination data will be presented in a by-subject listing.  
11.7 
Sample Size Determination 
The sample size for this study was based on the minimum requirement for a long-term safety 
study. 
12 
STUDY ADMINISTRATION 
12.1 
Compliance with the Protocol  
The study shall be conducted as described in this protocol. All revisions to the protocol must be 
prepared by the Sponsor. The Investigator will not implement any deviation or change to the 
protocol without prior review and documented approval/favorable opinion from the IRB/EC of 
an Amendment, except where necessary to eliminate an immediate hazard(s) to study subjects. 
Any significant deviation must be documented and submitted to the: IRB/EC; the Sponsor or 
designee; and, if required, Regulatory Authority (ies). 
Documentation of approval signed by the chairperson or designee of the IRB(s)/EC(s) must be 
sent to the Sponsor and/or designee. 
12.2 
Informed Consent Procedures 
The Informed Consent Form (ICF) and Assent Forms for subjects under legal adult age must 
include all elements required by ICH/GCP and applicable regulatory requirements, and must 
adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki. 
For subjects under legal adult age, both parents or legal representative may be required to sign 
informed consent as applicable. Assent to participate in a clinical trial applies to all subjects who 
are not legal adult subjects (in the state or location in which they are participating) and is defined 
as a child’s affirmative agreement to participate in research. Permission of the minor subject’s 
parent or legal guardian must also be obtained in compliance with part 50, subpart B of the Code 
of Federal Regulations and must include the elements of informed consent as described in 
Section 50.21 and according to the regulations where the study is being conducted. Appropriate 
ICFs and assent forms will be provided according to local law/regulations. If a subject reaches 
legal adult age during the course of the trial, an adult ICF will be signed.  
The ICF and Assent Forms must also include a statement that the Sponsor and regulatory 
authorities have direct access to subject records. Prior to the beginning of the study, the 
Investigator must have the IRB/EC’s written approval/favorable opinion of the written ICF, 
Assent Forms and any other information to be provided to the subjects. 
The Investigator must provide the subject or legally acceptable representative with a copy of the 
consent form and written information about the study in the language in which the subject is 
most proficient. The language must be nontechnical and easily understood. The Investigator 
should allow time necessary for subject or subject’s legally acceptable representative to inquire 
about the details of the study, then the ICF must be signed and personally dated by the subject or 
the subject’s legally acceptable representative, by the Investigator and by the person who 


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conducted the informed consent discussion as required by local law. The subject or legally 
acceptable representative should receive a copy of the signed ICF and any other written 
information provided to study subjects prior to subject’s participation in the study. This also 
applies to Assent Forms. All subjects and/or the legally acceptable representative (i.e. parents or 
guardian) will be provided with a contact address where they may obtain further information 
regarding the study. 
The ICF, Assent Forms and any other information provided to the subjects or the subject’s 
legally acceptable representative, should be revised whenever important new information 
becomes available that is relevant to the subject’s consent, and should receive IRB/EC approval/ 
favorable opinion prior to use. The Investigator or designee should fully inform the subject or the 
subject’s legally acceptable representative of all pertinent aspects of the study and of any new 
information relevant to the subject’s willingness to continue participation in the study. This 
communication to the subject should be documented in the source documents.  
During a subject’s participation in the study, any updates to the consent or assent forms and any 
updates to the written information will be provided to the subject 
12.3 
Study Documentation and the Electronic Case Report Form (eCRF) 
The Investigator is responsible for ensuring that data are properly recorded in the eCRFs and on 
related documents. All entries must be supported by the subject’s medical records or source 
documents. The Investigator to ensure that the observations and findings are recorded correctly 
and completely. 
All Investigator observations/assessments must be reported in the eCRF. The original reports and 
any traces and films must be reviewed, signed and dated and retained by the Investigator for 
future reference. 
The Investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the investigation on each 
individual treated with the investigational product or entered as a control in the investigation. 
Data reported in the eCRFs that are derived from source documents must be consistent with the 
source documents or the discrepancies must be explained. 
The Investigator must certify that the data are complete and accurate at the time the subject ends 
the study or as instructed by the Sponsor or designee by applying an electronic signature to the 
eCRF study completion page. 
12.4 
Study Monitoring 
The Sponsor or designee will be responsible for the monitoring of the study. Study monitors will 
contact and visit the Investigators at regular intervals throughout the study. The study monitor 
will verify adherence to the protocol and completeness, consistency and accuracy of the data by 
comparing subjects’ medical records with entries in the eCRF. The study monitor must be 
allowed access to laboratory test reports and other subject records that are needed to verify the 
entries on the eCRF. The Investigators will allow the study monitor to inspect the various records 
of the study (eCRFs and other pertinent data), provided that subject confidentiality is maintained 


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in accordance with local requirements. These records, and other relevant data, may also be 
reviewed by appropriate qualified personnel independent from the Sponsor or designee, who is 
appointed to audit the study. Subject confidentiality will be maintained at all times. 
The Investigators agree to co-operate with the study monitor to ensure that any problems 
detected in the course of the monitoring visits are resolved. 
12.5 
Retention of Study Documentation 
The Investigator must retain study drug disposition records, copies of eCRFs and all study-
related source documents for the maximum period required by applicable regulations and 
guidelines, or Institution procedures, or for the period specified by the Sponsor, whichever is 
longer. The Investigator must contact the Sponsor prior to destroying any records associated with 
the study. 
If the Investigator withdraws from the study (e.g., relocation, retirement), the records will be 
transferred to a mutually agreed upon designee (e.g., another Investigator, IRB/Ethics 
Committee). Notice of such transfer will be given in writing to the Sponsor or designee. 
If the Investigator cannot guarantee this archiving requirement for any or all the documents at the 
investigational site, arrangements must be made between the Investigator and the Sponsor, to 
store these in a secure archive facility outside the site; they can therefore be returned to the 
Investigator in case of a regulatory audit. Where source documents are required for the continued 
care of the subject, appropriate copies should be made for storing outside the site. 
Following the study close-out visit data will be provided to the Investigator to store with the 
Investigator’s study file for archiving purposes. 


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13 
ACRONYMS AND DEFINITIONS 
13.1 
Acronyms 
The acronyms listed below are a non-exhaustive list of those commonly used in Dermira study 
documents. Not all acronyms listed below are used within this document. 
Abbreviation 
Definition 
ACC 
acetyl-coenzyme A carboxylases 
AE 
adverse event(s) 
ALT 
alanine amino-transferase 
ANCOVA 
analysis of covariance 
AR 
adverse reaction(s) 
AST 
aspartate amino-transferase 
BID 
twice daily 
BUN 
blood urea nitrogen 
CFR 
code of federal regulations 
CMH 
Cochran-Mantel-HAEnszel 
CRO 
clinical research organization 
eCRF 
electronic case report form 
ET 
early termination 
F 
Fahrenheit 
FDA 
US Food and Drug Administration 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
HCT 
hematocrit 
HEENT 
head, ears, eyes, nose, throat 
HGB 
hemoglobin 
ICF 
informed consent form 
ICH 
International Conference on Harmonization  
IEC 
independent ethics committee 
IGA 
Investigator’s global assessment 
IRB 
institutional review board 
ITT 
intent-to-treat 
IV 
intravenous 
LDH 
lactate dehydrogenase 
LOCF 
last observation carried forward 
LSR 
local skin reactions 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 


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Abbreviation 
Definition 
MedDRA 
medical dictionary for regulatory activities 
NSAID 
non-steroidal anti-inflammatory drug 
PP 
per protocol 
QD 
once daily 
RBC 
red blood cells 
SAS 
statistical analysis software 
SSAR 
serious suspected adverse reaction(s) 
TG 
triglycerides 
TK 
toxicokinetic  
UPT 
urine pregnancy test 
US 
united states 
WBC 
white blood cells 
WOCBP 
women of childbearing potential 
β-hCG 
beta-human chorionic gonadotropin 


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14 
REFERENCES 
1. 
Thiboutot D. Regulation of human sebaceous glands. J Invest Dermatol. 2004;123:1–12. 
2. 
Janiczek-Dolphin N, Cook J, Thiboutot D, Harness J, Clucas A. Can sebum reduction 
predict acne outcome? Br J Dermatol. 2010;163:683–688. 
3. 
Nelson AM, Zhao W, Gilliland KL, ZAEnglein AL, Liu W, Thiboutot DM. Neutrophil 
gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human 
sebaceous gland cells. J Clin Invest. 2008;118:1468–1478. 
4. 
Tong L, Harwood HJ Jr. Acetyl-coenzyme A carboxylases: versatile targets for drug 
discovery. J Cell Biochem. 2006;99(6):1476–1488. 
5. 
Kim KH. Regulation of mammalian acetyl-coenzyme A carboxylase. Annu Rev Nutr. 
1997;17:77–99. 
6. 
Harwood HJ Jr. Treating the metabolic syndrome: acetyl-CoA carboxylase inhibition. 
Expert Opin Ther Targets. 2005;9(2):267–281. 
7. 
Tong L. Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target 
for drug discovery. Cell Mol Life Sci. 2005;62(16):1784–1803. 
8. 
McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From 
concept to molecular analysis. Eur J Biochem. 1997;244(1):1–14. 
9. 
McCune SA, Harris RA. Mechanism responsible for 5-(tetradecyloxy)-2-furoic acid 
inhibition of hepatic lipogenesis. J Biol Chem. 1979;254:10095–10101. 
10. Arbeeny CM, Meyers DS, Bergquist KE, Gregg RE. Inhibition of fatty acid synthesis 
decreases very low density lipoprotein secretion in the hamster. J Lipid Res. 
1992;33(6):843–851. 
11. Parker RA, Kariya T, Grisar JM, Petrow V. 5-(Tetradecyloxy)-2-furancarboxylic acid and 
related hypolipidemic fatty acid-like alkyloxyarylcarboxylic acids. J Med Chem. 
1977;20:781–91. 
12. Fukuda N, Ontko JA. Interactions between fatty acid synthesis, oxidation, and esterification 
in the production of triglyceride-rich lipoproteins by the liver. J Lipid Res. 
1984;25(8):831–842. 
13. Triscari J, Sullivan AC. Anti-obesity activity of a novel lipid synthesis inhibitor. Int J Obes. 
1984;8 Suppl 1:227–239. 
 


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15 
APPENDIX 1 – SCHEDULE OF VISITS AND PROCEDURES 
Visit 
Day 1 
Week 2 
(phone call) 
(+/- 2 days) 
Week 4, 8, 
16, 20, 28, 
32  
(+/- 4 days) 
Weeks 12, 
24 
(+/- 4 days 
Week 36 
Study Exit/ 
Early 
Term. 
(+/- 4 days) 
Informed Consent/Assent 
X 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
Complete Physical Exam, Weight, 
Height 
Xb 
 
 
 
X 
Symptom-directed Physical Exam 
 
 
X 
X 
 
Pulse and Blood Pressure 
X 
 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
Local Skin Reactions 
Xb 
 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
Safety labs: Serum Chemistry, 
Hematology, Serum Pregnancy, 
Urinalysis 
Xb 
 
 
 
X  
Urine Pregnancy Test  
 
 
X 
X 
 
Photographsa 
Xb 
 
 
Xc 
X 
12-Lead ECGs 
Xb 
 
 
 
X 
Dispense Study Medication/Diary 
X 
 
X 
X 
 
Investigator Global Assessment 
Xb 
 
 
X 
X 
Acne Patient Self-Questionnaire 
Xb 
 
 
X 
X 
Study Medication Compliance 
 
 
X 
X 
X 
a Selected sites only 
b  Week 12 data collected as part of the DRM01-ACN03 or DRM01-ACN04 study will be used for the Day 1 visit 
c Week 12 only 


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16 
APPENDIX 2 – ACNE PATIENT SELF-QUESTIONNAIRE 
1. Over the past 7 days, rate how oily your face looked: 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
Not at all oily
 
Slightly oily
 
Moderately oily
 
Very oily
 
Extremely oily
 
 
2. Over the past 7 days, rate how your face looked overall as the result of your acne: 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
 
 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
            Bad 
 
 
 
 
 
 
 
 
          Excellent 
 
3. Overall, how would you rate your acne now as compared to before starting the study 
treatment? 
 Only asked at wk 4, 8, 12, and OLE 12, 24, 36 
Very much improved
 
Moderately improved
 
No difference
 
Moderately worse
 
Very much worse
 
 
4. Over the past 7 days, how self-conscious did you feel about the way your face looks 
because of your facial acne? 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
1. Not at all self-conscious 
2. Slightly self-conscious 
3. Moderately self-conscious 
4. Very self-conscious 
5. Extremely self-conscious 
 


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5. Over the past 7 days, how insecure did you feel about the way your face looks 
because of your facial acne? 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
1. Not at all insecure 
2. Slightly insecure 
3. Moderately insecure 
4. Very insecure 
5. Extremely insecure 
 
6. Over the past 7 days, how often did you avoid interactions with other people because 
of your facial acne? 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
1. Never 
2. Rarely 
3. Some of the time 
4. Most of the time 
5. All of the time 
 
7. Over the past 7 days, how embarrassed were you by the way your face looked 
because of your facial acne? 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
1. Not at all embarrassed 
2. Slightly embarrassed 
3. Moderately embarrassed 
4. Very embarrassed 
5. Extremely embarrassed 
 
8. Over the past 7 days, how sad were you by the way your face looked because of you 
facial acne? 
 Asked at BL, wk 4, 8, 12, and OLE 12, 24, 36 
1. Not at all sad 
2. Slightly sad 
3. Moderately sad 
4. Very sad 
5. Extremely sad 


Der mira, I nc. 
 
Ol u mac ostat Glasaretil Gel  
 
D R M 0 1 B- A C N 0 5 
2 4 A pril 2 0 1 7 
P a ge 4 1  
C o nfi de ntial 
O n a scale of 1 t o 5 ( 1 = Very u ns atisfie d, 5 = Ver y s atisfie d ), h o w satisfie d were y o u 
wit h eac h of t he f oll o wi n g? 
 T o be aske d j ust at wk 1 2 
 
1 –  V er y 
U ns atisfi e d  
2 –  
U ns atisfi e d  
3 –   
N e utr al  
4 –  
S atisfi e d  
5 –  V er y 
S atisfi e d  
9.  E as e of pr o d uct a p plic ati o n  
 
 
 
 
 
1 0.  H o w t h e pr o d uct l o o ks o n m y 
ski n at ti m e of a p plic ati o n 
 
 
 
 
 
1 1.  H o w t h e pr o d uct f e els o n m y 
ski n w hil e a p pl yi n g 
 
 
 
 
 
1 2.  H o w w ell t h e pr o d uct fits 
i nt o m y d ail y s ki n c ar e 
r o uti n e 
 
 
 
 
 
 

SAP_001.pdf: 
CONFIDENTIAL 
Statistical Analysis Plan for Dermira, Inc. 
Page 1 
Protocol Number: DRM01B-ACN05 
10 April 2018 
STATISTICAL ANALYSIS PLAN 
Protocol Number: 
DRM01B-ACN05 
Study Title: 
An Open-Label Study Assessing Long-
Term Safety of Olumacostat Glasaretil 
Gel in Subjects with Acne Vulgaris 
Development Phase of Study: 
3 
Sponsor: 
Dermira, Inc. 
Sponsor Contact: 
Beth Zib 
Statistical Analysis Plan based on Protocol Version: Amendment 1, 24 April 2017 
Statistical Analysis Plan Date: 
10 April 2018 
Statistical Analysis Plan Version: 
v1 




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Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
10 April 2018 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................5 
2. 
INTRODUCTION .................................................................................................................5 
3. 
STUDY OBJECTIVES .........................................................................................................6 
4. 
STUDY DESIGN ...................................................................................................................6 
4.1 Overall Study Design ......................................................................................................6 
4.1.1 
Schedule of Visits and Assessments .................................................................7 
4.1.2 
Method of Assigning Subjects to Treatment Groups ........................................7 
4.1.3 
Blinding .............................................................................................................7 
5. 
EFFICACY AND SAFETY ENDPOINTS .........................................................................7 
5.1 Efficacy Endpoint ...........................................................................................................7 
5.2 Safety Endpoints .............................................................................................................7 
6. 
STATISTICAL AND ANALYTICAL PLANS ..................................................................7 
6.1 General Methodology .....................................................................................................7 
6.1.1 
Statistical Analysis ............................................................................................8 
6.1.2 
Baseline Definition ............................................................................................8 
6.1.3 
Visit Windowing ...............................................................................................9 
6.1.4 
Adjustments for Covariates .............................................................................11 
6.1.5 
Handling of Dropouts or Missing Data ...........................................................11 
6.1.6 
Multicenter Studies ..........................................................................................11 
6.1.7 
Examination of Subgroups ..............................................................................11 
6.2 Disposition of Subjects .................................................................................................11 
6.3 Protocol Deviations .......................................................................................................11 
6.4 Data Sets Analyzed .......................................................................................................11 
6.4.1 
Safety Population ............................................................................................11 
6.5 Demographic and Other Baseline Characteristics ........................................................11 
6.6 Prior and Concomitant Medications .............................................................................12 
6.7 Analysis of Efficacy ......................................................................................................12 
6.7.1 
Primary Efficacy Analysis ...............................................................................12 
6.7.2 
Other Supportive Efficacy Analyses ...............................................................12 
6.8 Safety Evaluation ..........................................................................................................13 
6.8.1 
Extent of Exposure ..........................................................................................13 
6.8.2 
Adverse Events ................................................................................................14 
6.8.3 
Clinical Laboratory Evaluation .......................................................................15 
6.8.4 
Other Observations Related to Safety .............................................................15 


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Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
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6.8.4.1 
ECG Measurements .....................................................................15 
6.8.4.2 
Vital Signs ....................................................................................16 
6.8.4.3 
Physical Examination...................................................................16 
6.8.4.4 
Local Skin Reactions (LSRs) .......................................................16 
7. 
DETERMINATION OF SAMPLE SIZE .........................................................................16 
8. 
CHANGES IN THE PLANNED ANALYSES..................................................................16 
 
 


CONFIDENTIAL 
 
 
 
Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
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1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE(s) 
adverse event(s) 
BID 
twice daily 
DRM01B-ACN03 
ACN03 
DRM01B-ACN04 
ACN04 
DRM01B-ACN05 
ACN05 
ECG 
electrocardiogram 
eCRF(s) 
electronic case report form(s) 
ET 
early termination 
ICF 
informed consent form 
IGA 
Investigator’s global assessment 
ITT 
intent-to-treat 
LSR(s) 
local skin reaction(s) 
MedDRA 
Medical Dictionary for Regulatory Activities 
PI 
Principal Investigator 
QD 
once daily 
SAS® 
Statistical Analysis System (SAS® Institute Inc., Cary, NC) 
SOC 
system organ class 
TEAE(s) 
treatment-emergent adverse event(s) 
2. INTRODUCTION 
Acne arises from a combination of physiological changes in the skin including altered sebaceous 
gland cell differentiation, heightened sebum production, localized bacterial colonization and 
inflammation. Although acne is generally viewed as a benign dermatological disease of 
adolescence, more severe forms may lead to permanent scar formation, with some of these 
patients suffering from psychological injury and significant loss of self-worth. Recent scientific 
advances in the understanding of the complex multi-factorial nature of this common disease offer 
great opportunity for scientific innovation through selective targeting of key elements of the 
disease process. 
Topical agents routinely prescribed for acne, including antibiotics, retinoids and combinations 
thereof, often produce only modest therapeutic benefits and do not affect sebum production. A 
locally-delivered medication that selectively inhibited sebum formation would represent a 
breakthrough advance in reducing the pathogenic influences of sebum overproduction in acne. 
Dermira, Inc. is pursuing the development of olumacostat glasaretil, previously referred to as 
DRM01B, a pro-drug of TOFA (5-(tetradecyloxy)-2-furancarboxylic acid), sarcosine ester, as a 
topically applied sebum inhibitor for the treatment of acne vulgaris. Olumacostat glasaretil is a 


CONFIDENTIAL 
 
 
 
Statistical Analysis Plan for Dermira, Inc. 
Page 6 
Protocol Number: DRM01B-ACN05 
10 April 2018 
new chemical entity and has been formulated for clinical development as Olumacostat Glasaretil 
Gel, 5.0%. 
The DRM01B-ACN05 (ACN05) study described herein is an open-label study to assess the 
long-term safety of continuous treatment with Olumacostat Glasaretil Gel, 5% for up to an 
additional 36-weeks in subjects who have completed either of the DRM01B-ACN03 (ACN03) or 
DRM01B-ACN04 (ACN04) studies. 
3. STUDY OBJECTIVES 
The objective of this study is to assess the long-term safety of Olumacostat Glasaretil Gel, 5.0%, 
in subjects with acne vulgaris. 
This study may be stopped once at least 100 subjects have been treated for 36 weeks. 
4. STUDY DESIGN 
4.1 
Overall Study Design 
This study is an open-label, long-term safety study enrolling up to 700 subjects who participated 
in either ACN03 or ACN04 studies. All subjects will sign an informed consent / assent prior to 
continuing in this open label study. 
Eligible subjects will receive open-label treatment with Olumacostat Glasaretil Gel, 5.0% and 
continue to dose twice daily for 36 weeks. Subjects, who participated in ACN03 study with acne 
on the chest, back or shoulders and applied study drug to affected areas will be allowed to 
continue to apply study drug to the affected areas. Subjects who participated in ACN04 study 
will continue to apply study drug to the face only. Subjects will receive a phone call at Week 2 to 
assess safety, and will return to the clinic at Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36 (End of 
Study). 
Efficacy will be assessed via a static evaluation of qualitative overall acne severity, the 
investigator’s global assessment of acne (IGA). 
At the Week 12 and 24 visits, if the severity of acne has become worse, as determined by the 
IGA, the subject should be withdrawn, at the investigator’s discretion. Severity of acne will be 
assessed on the face only. 
Safety will be assessed through adverse events, local skin reactions (LSRs), serum chemistry, 
hematology and urinalysis laboratory testing, ECGs, physical examination, pulse and blood 
pressure. 
Photographs of the face will be taken for all subjects in a subset of study sites in order to assess 
visually, the appearance of acne vulgaris during the course of the study. 
During the clinic visit, subjects will be asked to complete the Acne Patient Self-Questionnaire. 


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Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
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4.1.1 
Schedule of Visits and Assessments 
The schedule of assessments can be found in Section 8 and Appendix 1 of the protocol. 
4.1.2 
Method of Assigning Subjects to Treatment Groups 
Subjects will maintain the unique subject number assigned at randomization into their study of 
origin (either ACN03 or ACN04). All subjects will receive Olumacostat Glasaretil Gel, 5.0%, 
BID. 
4.1.3 
Blinding 
This is an open-label study. Subjects will not be unblinded to their treatment assignment prior to 
enrollment into this study (ACN05). Once enrolled, each subject will receive Olumacostat 
Glasaretil Gel, 5.0%. 
5. EFFICACY AND SAFETY ENDPOINTS 
5.1 
Efficacy Endpoint 
The IGA of acne severity on the face only will be conducted for each subject every 12 weeks. 
5.2 
Safety Endpoints 
Safety will be assessed through adverse events (AEs), local skin reactions (LSRs), serum 
chemistry, hematology and urinalysis laboratory testing, ECG testing, physical examination and 
vital signs. 
6. STATISTICAL AND ANALYTICAL PLANS 
6.1 
General Methodology 
All statistical processing will be performed using SAS® unless otherwise stated. Data will be 
summarized using descriptive statistics. No inferential testing or imputations for missing data 
will be performed. 
Categorical variables will be tabulated with frequencies and percentages. Continuous variables 
will be tabulated with mean, median, SD, and range (minimum and maximum). 
Reported AEs and prior and concomitant procedures and therapies will be classified on the basis 
of Medical Dictionary for Regulatory Activities (MedDRA) terminology.  Concomitant 
medications will be classified on the basis of World Health Organization Drug Dictionary 
(WHO-DDE) terminology. 
 
 


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Statistical Analysis Plan for Dermira, Inc. 
Page 8 
Protocol Number: DRM01B-ACN05 
10 April 2018 
The following data will be imported from ACN03/ACN04 (Baseline defined in section 6.1.2): 
Subjects receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04: 
• 
Demographic information: age, gender, race and ethnicity 
• 
Prior and Concomitant medications 
• 
Adverse events 
• 
Local skin reactions (Baseline and Weeks 4, 8, 12) 
• Vital signs and weight (Baseline and Weeks 4, 8, 12) 
• Investigator Global Assessment of acne (Baseline and Week 12) 
• Acne Patient Self-Questionnaire (Baseline and Week 12) 
• 
Laboratory evaluations: hematology, serum chemistries and urinalysis (Baseline) 
• 
12-lead ECG (Baseline) 
 
Subjects receiving Olumacostat Glasaretil Gel, Vehicle in ACN03/ACN04: 
• 
Demographic information: age, gender, race, and ethnicity 
• 
Prior and Concomitant medications 
• 
Adverse events 
• 
Local skin reactions (Baseline) 
• Vital signs and weight (Baseline) 
• Investigator Global Assessment of acne (Baseline) 
• Acne Patient Self-Questionnaire (Baseline) 
• 
Laboratory evaluations: hematology, serum chemistries and urinalysis (Baseline) 
• 
12-lead ECG (Baseline) 
6.1.1 
Statistical Analysis 
All analyses will be performed by QST using SAS® Version 9.3 or later.  All summary tables 
and data listings will be prepared utilizing SAS® software. 
The standard operating procedures (SOPs) of QST will be followed in the creation and quality 
control of all data displays and analyses. 
6.1.2 
Baseline Definition 
The baseline value for each parameter will be defined as the last observation prior to first dose of 
Olumacostat Glasaretil Gel, 5.0%. For subjects receiving Olumacostat Glasaretil Gel, 5.0% in 
ACN03/ACN04, the baseline values from ACN03/ACN04 will be considered the baseline values 
for calculations in ACN05. For subjects receiving Olumacostat Glasaretil Gel, Vehicle in 
ACN03/ACN04, baseline values will most commonly be from the Week 12/study exit visit of 
ACN03/ACN04. If subjects choose to enroll in this study, study procedures will not be repeated; 
study sites will carry over the information from the ACN03/ACN04 study to the Day 1 visit for 
this study.   


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Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
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6.1.3 
Visit Windowing 
For subjects receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, data from 
ACN03/ACN04 will be included in summaries of ACN05. For subjects receiving Olumacostat 
Glasaretil Gel, Vehicle in ACN03/ACN04, baseline values will be sourced from ACN03/ACN04 
and data from follow-up visits of ACN05 will be used in summaries. The table below details the 
analysis visits to be summarized and the associated visits from ACN03/ACN04 or ACN05 which 
will be sourced for each type of subject. 
Analysis Visits for Efficacy and Safety Assessments 
Analysis Visit 
Subjects Receiving 
Olumacostat Glasaretil Gel, 
5.0% in ACN03/ACN04 
Subjects Receiving 
Olumacostat Glasaretil Gel, 
Vehicle in ACN03/ACN04 
Week 4 
ACN03/ACN04 - Week 4 
ACN05 - Week 4 
Week 8 
ACN03/ACN04 - Week 8 
ACN05 - Week 8 
Week 12 
ACN03/ACN04 - Week 12 
ACN05 - Week 12 
Week 16 
ACN05 - Week 4 
ACN05 - Week 16 
Week 20 
ACN05 - Week 8 
ACN05 - Week 20 
Week 24 
ACN05 - Week 12 
ACN05 - Week 24 
Week 28 
ACN05 - Week 16 
ACN05 - Week 28 
Week 32 
ACN05 - Week 20 
ACN05 - Week 32 
Week 36 
ACN05 - Week 24 
ACN05 - Week 36 
Week 40 
ACN05 - Week 28 
Not available 
Week 44 
ACN05 - Week 32 
Not available 
Week 48 
ACN05 - Week 36 
Not available 
Note: analysis visits from ACN03/ACN04 will be utilized. 
 
 
 


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Statistical Analysis Plan for Dermira, Inc. 
Page 10 
Protocol Number: DRM01B-ACN05 
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Data from ACN05 will be mapped to the appropriate analysis visit described above based on 
nominal visit indications. The nominal visit for vital sign and LSR data from early termination 
(ET) and unscheduled visits will be determined using nominal visit windows. The nominal visit 
windows for ET and unscheduled visits are presented in the following table.  
 
ACN05 Nominal Visit Windows for Efficacy and Safety Assessments 
Nominal Visit 
Target Study Day 
Window (Days) 
Week 4 
29 
22 to 42 
Week 8 
57 
43 to 70 
Week 12 
85 
71 to 98 
Week 16 
113 
99 to 126 
Week 20 
141 
127 to 154 
Week 24 
169 
155 to 182 
Week 28 
197 
183 to 210 
Week 32 
225 
211 to 238 
Week 36 
253 
239 to 266 
 
Data collected at ET and unscheduled visits prior to study day 22 will not be analyzed.  Data 
collected at ET and unscheduled visits after study day 266 will not be included in analyses.   
The definition for the study day included in each study window is defined as below: 
 
Study Day prior to Day 1 = Visit Date – Day 1 Date 
 
Study Day on or after Day 1 = Visit Date – Day 1 Date + 1 
If an assessment’s mapped nominal visit is a visit at which the subject has data from a scheduled 
visit present, or if no analyses are planned for the assessment at the mapped nominal visit, the 
data collected at the ET or unscheduled visit will not be included in analyses.   
In the event of multiple values from unscheduled or ET assessments within a nominal visit 
window, the value closest to the scheduled visit target study day will be used for analyses.  If two 
values tie as closest to the time point (for example, one value is before and the other value is 
after the time point), then the later value will be selected.  
Other data summaries will include information collected at ET visits as Week 36/ET. 
Data collected at all visits will be included in the data listings with the ACN05 analysis visit 
presented. 


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Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
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6.1.4 
Adjustments for Covariates 
Not applicable to this study. 
6.1.5 
Handling of Dropouts or Missing Data 
No imputations for missing data will be performed. 
6.1.6 
Multicenter Studies 
The clinical study will be conducted under a common protocol for each investigational site with 
the intention of pooling all the data for analysis. Every effort will be made to promote 
consistency in study execution at each study site. 
6.1.7 
Examination of Subgroups 
As applicable, data will be summarized in total and by treatment received in ACN03/ACN04. 
6.2 
Disposition of Subjects 
The number of subjects included in the safety population will be summarized for all subjects, for 
subjects that received Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, and for subjects that 
received Olumacostat Glasaretil Gel, Vehicle in ACN03/ACN04. The number of subjects 
enrolled, completed, and discontinued (including the reasons for discontinuation) will be 
summarized similarly. 
Subjects who are excluded from the safety population will be summarized by the reasons for 
exclusion. 
6.3 
Protocol Deviations 
Protocol deviations will not be entered into the database.  Deviations will not be programmed or 
summarized.   
6.4 
Data Sets Analyzed 
6.4.1 
Safety Population 
All subjects who receive at least one confirmed dose of Olumacostat Glasaretil Gel, 5.0% and 
have at least one post-baseline (where baseline is the day that the subject received their first 
study drug) assessment will be included in the Safety Population. All analyses (efficacy and 
safety) will be performed using the Safety Population. 
6.5 
Demographic and Other Baseline Characteristics 
All baseline summaries will be done on the safety population. 


CONFIDENTIAL 
 
 
 
Statistical Analysis Plan for Dermira, Inc. 
Page 12 
Protocol Number: DRM01B-ACN05 
10 April 2018 
Sex, race, and ethnicity will be summarized by counts and percentages.  Age will be summarized 
with descriptive statistics.   
Age will be carried over from ACN03/ACN04 for those subjects who have the complete date of 
birth entered into the eCRF. 
6.6 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded to preferred name and anatomical therapeutic 
chemical (ATC) classification of ingredients using the WHO-DDE. 
Counts and percentages will be provided to summarize the use of prior and concomitant 
medications other than the study drug reported throughout the study. The number and percent of 
subjects reporting medications will be summarized by ATC level 2 term and preferred name. 
Ongoing medications and medications ending after the date of first application of Olumacostat 
Glasaretil Gel, 5.0% (from ACN03/ACN04 or ACN05) will be considered concomitant 
medications. Incomplete start and end dates which could be prior to first dose or after first dose 
will be considered prior to first dose. 
A by-subject listing of all concomitant medications will be presented.  
6.7 
Analysis of Efficacy 
6.7.1 
Primary Efficacy Analysis 
IGA will be summarized with frequency and percent distributions at baseline and final visit 
(Week 36/ET). The change in IGA level from Baseline to Week 36 will be summarized for the 
safety population in total, as well as by treatment received in ACN03/ACN04. 
A by-subject listing of all IGA results will be presented. 
6.7.2 
Other Supportive Efficacy Analyses 
IGA Scores and Acne Patient Self-Questionnaire assessments will be summarized by visit. 
Summaries of the frequency and percent distributions of the IGA Scores will be presented and 
descriptive statistics will be used to summarize the Acne Patient Self-Questionnaire. Satisfaction 
questions will be summarized with frequency and percent distributions. IGA Scores will be 
summarized by visit for all subjects as well as by treatment received in ACN03/ACN04. 
For subjects receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, summary visits will 
include Baseline and Weeks 12, 24, 36 and 48. For subjects receiving Olumacostat Glasaretil 
Gel, Vehicle in ACN03/ACN04, summary visits will include Baseline and Weeks 12, 24, and 36. 


CONFIDENTIAL 
 
 
 
Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
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6.8 
Safety Evaluation 
6.8.1 
Extent of Exposure 
The extent of exposure to study drug in each treatment group will be summarized by total 
number of days of exposure, total number of applications, number of missed applications, 
amount of study drug used, amount of study drug per day, percent compliance and number and 
percentage of subjects who are compliant. A subject will be considered compliant with the 
dosing regimen if the subject applied 80-120% of the expected number of applications while 
enrolled in the study. 
For subjects receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, the date of first 
application will be from ACN03/ACN04. For subjects receiving Olumacostat Glasaretil Gel, 
Vehicle in ACN03/ACN04, the date of first application will be from ACN05.  
Total number of days of exposure will be computed as follows: 
Total Exposure = Date of Last Application – Date of First Application + 1. 
Dosing deviations reported for areas other than the face will not be considered in calculations. 
On the date of first application and the date of last application, some subjects were to apply one 
dose and others were to apply two doses, depending on the time of the study visit. After the date 
of first application and before the date of last application subjects were expected to apply two 
doses. Missed applications will be calculated from dosing deviations which report zero or one 
application on a given date. Extra doses will be calculated from dosing deviations which report 
more than the expected number of applications on a given date.  
For subjects receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, the total number of 
applications will be the sum of the applications from ACN03/ACN04 and ACN05, as dosing 
deviations are specific to the dates of first and last application within each study. The 
methodology below will be applied to ACN03/ACN04 and ACN05 data separately, then 
summed. 
The total number of applications will be calculated as follows: 
If the Date of First Application is not equal to Date of Last Application, then 
Total Applications = 2*(Date of Last Application – Date of First Application – 1) 
+ Expected Applications on Date of First Application 
+ Expected Applications on Date of Last Application 
– Missed Applications + Extra Applications. 
If the Date of First Application = Date of Last Application, then 


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Statistical Analysis Plan for Dermira, Inc. 
Page 14 
Protocol Number: DRM01B-ACN05 
10 April 2018 
Total Applications = Expected Applications on Date of First Application 
– Missed Applications + Extra Applications. 
Treatment compliance will be based on the expected number of doses given the treatment period 
duration. Treatment period duration will be computed from the date of first application of 
Olumacostat Glasaretil Gel, 5.0% (from ACN03/ACN04 or ACN05) and the date of last 
application.  
Then treatment period duration may be calculated as: 
 
Treatment Period Duration = Date of Last Application – Date of First Application + 1. 
Missed applications due to treatment-related AEs will be considered when determining the 
expected number of doses for each subject. If a treatment-related AE (regardless of location) 
requires interruption of study drug during the treatment period, missed applications during the 
AE (onset date to resolution date) will be deducted from the expected number of doses. 
Therefore, the expected number of applications will be calculated as:  
Expected Applications = 2*(Treatment Period Duration – 2) 
 
 + Expected Applications on Date of First Application  
 
 + Expected Applications on Date of Last Application  
 
 – Applications Missed Due to a Treatment-Related AE. 
Percent compliance will be calculated from total number of applications and total number of 
expected applications as follows: 
Percent Compliance = 100*(Total Applications/Expected Applications). 
Percent compliance will not be calculated for subjects who are lost to follow-up. 
6.8.2 
Adverse Events 
AEs from ACN03/ACN04 will be included in the analysis for study ACN05. All AEs will be 
classified on the basis of Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
Treatment-emergent AEs (TEAEs) are defined as AEs with an onset on or after the date of the 
first application of Olumacostat Glasaretil Gel, 5.0% (from ACN03/ACN04 or ACN05). If 
treatment-emergent status cannot be determined (e.g., unknown date of first application), the AE 
will be considered treatment-emergent. AEs noted prior to the first study drug administration that 
worsen after baseline will also be reported as AEs and included in the summaries.  
TEAEs will be summarized in total as well as by 12-week periods based on time of onset in 
relation to date of first application of Olumacostat Glasaretil Gel, 5.0%, based on the definitions 
below. 


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Statistical Analysis Plan for Dermira, Inc. 
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Protocol Number: DRM01B-ACN05 
10 April 2018 
• 0-12 Weeks 
 
0 <= onset day <= 85 
• >12-24 Weeks  
86 <= onset day <= 169 
• >24-36 Weeks  
170 <= onset day <= 253 
• >36 Weeks 
 
onset day >= 254 
Summaries will present the number of subjects reporting a TEAE by system organ class (SOC), 
preferred term, severity, relationship to study drug (causality), and seriousness. When 
summarizing TEAEs by severity and relationship, each subject will be counted once within a 
SOC or a preferred term by using the event with the greatest relationship or highest severity 
within each classification.  
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, 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 application.  
Serious AEs (SAEs) will be summarized and listed using the same methodology as noted above. 
In addition, a listing of subjects who prematurely discontinue from the study due to an AE will 
be provided. 
6.8.3 
Clinical Laboratory Evaluation 
Laboratory data will be presented in a by-subject listing. Any clinically significant laboratory 
abnormalities will be captured as adverse events. Changes from Baseline in safety laboratory 
values will be summarized at the final follow-up evaluation using descriptive statistics for the 
safety population in total, as well as by treatment received in ACN03/ACN04. For subjects 
receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, the final follow-up analysis visit 
will be Week 48/ET. For subjects receiving Olumacostat Glasaretil Gel, Vehicle in 
ACN03/ACN04, the final follow-up analysis visit will be Week 36/ET. 
Additionally, changes from Baseline in safety laboratory values will be summarized using shift 
tables according to normal ranges.  
If repeat laboratory testing was performed to follow-up on original results, summaries will be 
based on original results for each visit.  If repeat laboratory testing was performed due to 
unavailable original test results (e.g., poor sample quality, insufficient amounts, etc.) summaries 
will be based on repeat results for each visit. 
6.8.4 
Other Observations Related to Safety 
6.8.4.1 
ECG Measurements 
ECG data will be summarized at the final follow-up evaluation using descriptive statistics for the 
safety population in total, as well as by treatment received in ACN03/ACN04. Descriptive 
statistics will be provided for the following ECG parameters, for observed values and changes 


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Protocol Number: DRM01B-ACN05 
10 April 2018 
from Baseline: heart rate (HR), RR duration, QRS duration, PR duration, QT duration and QTc 
duration. Change from Baseline in ECG abnormalities will also be summarized using shift tables 
at the final evaluation visit.  
Shift tables will be based on the following categories: 
• PR Interval: < 100 msec, 100 – 220 msec and > 220 msec; 
• QRS Interval: < 50 msec, 50 – 110 msec and > 110 msec; 
• QTcF Interval: < 450 msec, 450 – 500 msec and > 500 msec. 
For subjects receiving Olumacostat Glasaretil Gel, 5.0% in ACN03/ACN04, the final follow-up 
analysis visit will be Week 48/ET. For subjects receiving Olumacostat Glasaretil Gel, Vehicle in 
ACN03/ACN04, the final follow-up analysis visit will be Week 36/ET.  
6.8.4.2 
Vital Signs 
Vital signs will be presented by analysis visit as observed values and changes from Baseline 
using descriptive statistics. Specifically, analysis visits to be summarized include Baseline and 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48. 
6.8.4.3 
Physical Examination 
Physical examination data will be presented in a by-subject listing.  
6.8.4.4 
Local Skin Reactions (LSRs) 
Local Skin Responses (LSRs) include erythema, peeling, dryness, burning/stinging and pruritus. 
These will be scored as 0 (None), 1 (Mild), 2 (Moderate) or 3 (Severe). LSRs will be 
summarized by analysis visit using descriptive statistics. Specifically, analysis visits to be 
summarized include Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48. Each 
subject’s worst post-baseline grade for each LSR will also be summarized.  Additionally, the 
number of subjects who experience mild, moderate or severe LSRs post-baseline will be 
presented.  By-subject listings of all LSRs, as well as subjects with any severe LSRs will be 
included. 
7. DETERMINATION OF SAMPLE SIZE 
The sample size for this study was based on the minimum requirement for a long-term safety 
study. 
8. CHANGES IN THE PLANNED ANALYSES 
No changes to planned analyses.