A Phase 2a, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Efficacy, Safety, and Duration of Benefit of Increasing Doses of DaxibotulinumtoxinA for Injection (DAXI for Injection) in the Treatment of Moderate or Severe Lateral Canthal Lines
Phase: PHASE2
Conditions: Lateral Canthal Lines
Sponsor: Revance Therapeutics, Inc.

 
 
 
 
 
CLINICAL STUDY PROTOCOL 
Protocol Title:  
A Phase 2a, Multicenter, Open-Label, Dose-Escalation Study to Evaluate 
the Efficacy, Safety, and Duration of Benefit of Increasing Doses of 
DaxibotulinumtoxinA for Injection (DAXI for injection) in the Treatment 
of Moderate or Severe Lateral Canthal Lines 
Protocol Number:  1820205 
Document Type:  
Amended Protocol 
Study Phase:   
Phase 2a 
Short Title:   
Efficacy and Safety of Increasing Doses of DaxibotulinumtoxinA for 
Injection (DAXI for injection) in the Treatment of Moderate or Severe 
Lateral Canthal Lines 
Sponsor:  
 
Revance Therapeutics, Inc. 
7555 Gateway Boulevard 
       
Newark, CA 94560 
Version:  
 
Amendment 2, 14 August 2019 
 
 
The study will be conducted in compliance with the obligations as detailed in this protocol, and 
all applicable regulations and guidelines (e.g., International Conference on Harmonisation [ICH] 
Good Clinical Practices [GCP] guidelines). 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is provided to 
you in confidence as an Investigator, potential investigator, vendor, contractor, or 
consultant for review by you, your staff, and an applicable Institutional Review Board or 
Independent Ethics Committee. The information is only to be used by you in connection 
with authorized clinical studies of the investigational product(s) described in the protocol. 
You will not disclose any of the information to others without written authorization, 
except to the extent necessary to obtain informed consent from those persons to whom 
the investigational product(s) may be administered. 
 

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Investigators Agreement 
I have carefully read the protocol entitled: “A Phase 2a, Multicenter, Open-Label, 
Dose-Escalation Study to Evaluate the Efficacy, Safety, and Duration of Benefit of Increasing 
Doses of DaxibotulinumtoxinA for Injection (DAXI for injection) in the Treatment of 
Moderate or Severe Lateral Canthal Lines” and,  
I will provide copies of the protocol, any subsequent protocol amendments and access to all 
information provided by the Sponsor to the study personnel under my supervision. I will discuss 
this material with them to ensure that they are fully informed about the investigational drug and 
the study protocol. 
I agree to conduct this clinical study according to the attached protocol, in compliance with all 
applicable laws and regulations, and in accordance with the ethical principles stipulated in the 
Declaration of Helsinki.  
 
 
Investigator Signature 
 
Date 
 
 
 
 
Printed Name 
 
 
Institution Name 
 
 
Address 
 
 
City, State, Postal Code, Country 
 
Phone Number 
 
 
 
 

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TABLE OF CONTENTS 
Sponsor Signatories .......................................................................................................................2 
Investigators Agreement ...............................................................................................................3 
List of Abbreviations .....................................................................................................................8 
1. 
Protocol Summary ..........................................................................................................9 
1.1. 
Synopsis ............................................................................................................................9 
1.2. 
Schema ............................................................................................................................19 
1.3. 
Schedule of Assessments (SOA) ....................................................................................20 
2. 
Introduction ...................................................................................................................22 
 
 
 
 
3. 
Objectives and Endpoints ............................................................................................25 
4. 
Study Design ..................................................................................................................28 
4.1. 
Overall Design ................................................................................................................28 
 
 
 
 
4.4. 
Visit Schedule .................................................................................................................29 
5. 
Study Population ...........................................................................................................31 
5.1. 
Inclusion Criteria ............................................................................................................31 
5.2. 
Exclusion Criteria ...........................................................................................................31 
5.3. 
Informed Consent and Authorization to Release Health 
Information .....................................................................................................................33 
5.4. 
Lifestyle Considerations .................................................................................................34 
5.5. 
Protocol Deviations.........................................................................................................34 
5.6. 
Pregnancy........................................................................................................................34 
6. 
Study Intervention ........................................................................................................36 
6.1. 
Study Intervention(s) Administered................................................................................36 
 
 
 
 
 
 
 
 
 
 
 
 
6.3. 
Concomitant Medications/Therapies ..............................................................................38 
 
 
6.5. 
Dose Modification ..........................................................................................................40 
7. 
Discontinuation of Study Intervention and Subject 
Discontinuation/Withdrawal........................................................................................41 
7.1. 
Subject Discontinuation/Withdrawal from the Study .....................................................41 
7.2. 
Lost to Follow-up............................................................................................................41 
8. 
Study Assessments and Procedures.............................................................................42 

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8.1. 
Subject Entry Procedures ................................................................................................42 
8.2. 
Schedule of Visits and Procedures..................................................................................42 
8.2.1. 
Screening Visit ................................................................................................................42 
8.2.2. 
Treatment Visit (Baseline/Day 1) ...................................................................................43 
8.2.3. 
Week 1 Follow-up Phone Call ........................................................................................45 
8.2.4. 
Follow-up Visits..............................................................................................................46 
8.2.5. 
Final Evaluation Visit (Week 36) or Early Discontinuation ...........................................47 
8.2.6. 
Variation from Scheduled Visit Days .............................................................................48 
8.3. 
Efficacy Assessments .....................................................................................................48 
8.3.1. 
Investigator Global Assessment of Lateral Canthal Wrinkle 
Severity ...........................................................................................................................48 
8.3.2. 
Patient Lateral Canthal Wrinkle Severity Scale..............................................................49 
8.3.3. 
Global Aesthetic Improvement Scale (GAIS) ................................................................49 
8.3.4. 
Facial Age Self Evaluation (FASE) ................................................................................50 
8.3.5. 
FACE-QTM Appraisal of Lines: Crow’s Feet Lines ........................................................50 
 
 
8.4. 
Safety Assessments .........................................................................................................51 
8.4.1. 
Physical Examination......................................................................................................51 
8.4.2. 
Vital Signs .......................................................................................................................51 
8.4.3. 
Pregnancy Testing ...........................................................................................................52 
8.4.4. 
Injection Site Evaluation .................................................................................................52 
8.4.5. 
Clinical Safety Laboratory Assessments ........................................................................52 
 
 
8.4.7. 
Regional House-Brackmann Facial Nerve Grading System ...........................................54 
8.5. 
Adverse Events and Serious Adverse Events .................................................................56 
8.5.1. 
Evaluation of Adverse Events and Serious Adverse Events ...........................................56 
8.5.2. 
Assessment and Reporting Requirements .......................................................................57 
8.5.3. 
Serious Adverse Events ..................................................................................................57 
 
 
8.5.5. 
Follow-up of Non-Serious Adverse Events ....................................................................59 
8.5.6. 
Follow-up of Post-Study Serious Adverse Events ..........................................................59 
8.5.7. 
Investigational Product Causality and Severity ..............................................................60 
9. 
Statistical Considerations .............................................................................................61 
9.1. 
Statistical Hypotheses .....................................................................................................61 
9.2. 
Sample Size Determination ............................................................................................61 
9.3. 
Populations for Analyses ................................................................................................61 
9.4. 
Statistical Analyses .........................................................................................................61 
9.4.1. 
Efficacy Analyses ...........................................................................................................62 
9.4.2. 
Safety Analyses ...............................................................................................................62 
9.5. 
Interim Analyses .............................................................................................................62 
9.5.1. 
Data Review Committee (DRC) .....................................................................................63 
10. 
Records Management ...................................................................................................64 
10.1. 
Data Collection ...............................................................................................................64 
10.2. 
File Management at the Study Center.............................................................................65 
10.3. 
Records Retention at the Study Center ...........................................................................65 

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11. 
Monitoring and Compliance ........................................................................................67 
 
 
12. 
Ethics and Responsibility .............................................................................................68 
 
 
 
 
 
 
 
 
List of In-Text Tables and Figures 
 
 
 
Table 3: Allowed Variation from Scheduled Visit Days...........................................................48 
Table 4: Investigator Global Assessment Lateral Canthal Wrinkle 
Severity ..........................................................................................................................48 
Table 5: Patient Lateral Canthal Wrinkle Severity ..................................................................49 
Table 6: Global Aesthetic Improvement Scale ..........................................................................50 
Table 7: Injection Site Evaluation ..............................................................................................52 
Table 8: Clinical Laboratory Tests ............................................................................................53 
 
 
List of Appendices 
 
 
 
 
 
 
 
 
 
 
 

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List of Abbreviations 
 
 
AE 
Adverse event 
CI 
Confidence interval 
DAXI 
DaxibotulinumtoxinA 
DRC 
Data Review Committee 
eCRF 
Electronic case report form 
FASE 
Facial Age Self Evaluation 
FWS 
Facial Wrinkle Severity 
GAIS 
Global Aesthetic Improvement Scale 
GCP 
Good Clinical Practice 
GL 
Glabellar lines 
ICF 
Informed consent form 
IEC 
Independent Ethics Committee 
IGA-LCWS 
Investigator Global Assessment Lateral Canthal Wrinkle Severity 
IM 
Intramuscular 
IRB 
Institutional Review Board 
kDa 
Kilodalton 
KM 
Kaplan-Meier 
LCL 
Lateral canthal lines 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
 
 
NSAID 
Nonsteroidal anti-inflammatory drug 
PLCWS 
Patient Lateral Canthal Wrinkle Severity 
PHI 
Protected health information 
PI 
Principal Investigator 
SAE 
Serious adverse event 
SNAP-25 
25 kDa synaptosome associated protein 
SOA 
Schedule of Assessments 
TEAE 
Treatment-emergent adverse event 
UPT 
Urine pregnancy test 
WOCBP 
Women of childbearing potential 
 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
 
Name of Sponsor/Company: 
Revance Therapeutics, Inc. 
Name of Finished Product: 
DaxibotulinumtoxinA for injection (DAXI for injection) 
Name of Active Ingredient: 
DaxibotulinumtoxinA 
Protocol Title: 
A Phase 2a, Multicenter, Open-Label, Dose-Escalation 
Study to Evaluate the Efficacy, Safety, and Duration of 
Benefit of Increasing Doses of DaxibotulinumtoxinA 
(DAXI for injection) in the Treatment of Moderate or 
Severe Lateral Canthal Lines 
Short Title: 
Efficacy, Safety, and Duration of Benefit of Increasing 
Doses of DAXI for injection in the Treatment of Moderate 
or Severe Lateral Canthal Lines 
Rationale:  
 
This phase 2a, multicenter, open-label, dose-escalation 
study will evaluate treatment of moderate to severe lateral 
canthal lines (LCL). The proposed dosing regimen for LCL 
treatment in this study is 1 of 4 dose cohorts (approximately 
16 subjects per cohort) 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 

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Objectives 
Endpoints 
Primary 
 
• To evaluate the efficacy 
and safety of DAXI for 
injection in the 
treatment of dynamic 
LCL 
• Proportion of subjects achieving a score or 0 or 1 
(none or mild) in LCL severity at maximum smile at 
Week 4 after LCL treatment on the Investigator 
Global Assessment Lateral Canthal Wrinkle 
Severity (IGA-LCWS) scale 
• Incidence, severity, and relationship to study drug of 
treatment-emergent adverse events (TEAEs) and 
serious adverse events (SAEs) during the overall 
study duration. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Population: 
Approximately 64 male and female subjects, 18-65 years old, will be enrolled into the study. 
Subjects must meet all the inclusion criteria and none of the exclusion criteria to be eligible for 
this study. 
Inclusion Criteria: 
To be eligible for participation, subjects must: 
1. Provide written informed consent consistent with International Conference on 
Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines and local laws, 
including authorization to release health information, signed prior to any study 
procedures being performed 
2. Be outpatient, male or female subjects, in good general health, 18-65 years old 
3. Have a score of moderate (2) or severe (3) LCL at maximum smile effort as assessed 
by the IGA-LCWS (scores must be consistent bilaterally) 
4. Have a score of moderate (2) or severe (3) LCL at maximum smile effort as assessed 
by the PLCWS (scores must be consistent bilaterally) 
5. Have sufficient visual acuity without the use of eyeglasses (contact lens use is 
acceptable) to accurately assess their facial wrinkles 
6. Be willing to refrain from receiving facial fillers, laser treatments, use of any product 
that affects skin remodeling, or a product that may cause an active dermal response in 

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the treatment areas (e.g., above the oral commissures) from screening through the end 
of the study 
7. All women of childbearing potential (WOCBP) must have a negative urine pregnancy 
test (UPT) result at the Screening Visit and must practice an effective method of 
contraception throughout the study (e.g., oral contraceptive pill, injection, implant, 
patch, vaginal ring, intrauterine coil, intrauterine device, tubal ligation, barrier method) 
used WITH an additional form of contraception (e.g., sponge, spermicide or condom); 
abstinence; no heterosexual intercourse; or has a vasectomized partner (refer to 
Section 5.6 for additional information) 
8. Able to understand the requirements of the study and be willing and able to follow all 
study procedures, attend all scheduled visits, and successfully complete the study. 
Exclusion Criteria: 
Subjects will not be eligible for study participation if they meet any of the following criteria: 
1. Any neurological condition that may place the subject at increased risk with exposure 
to botulinum toxin type A, including peripheral motor neuropathic diseases, such as 
amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional 
disorders, such as Lambert-Eaton syndrome and myasthenia gravis 
2. Any history of facial nerve palsy (e.g., Bell’s Palsy) or muscle weakness or paralysis in 
the treatment areas  
3. Active skin disease, infections, or inflammation at the injection sites 
4. History of or current significant facial asymmetry, eyelid ptosis or history of same, 
excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or inability of 
investigator to completely or almost eliminate the LCL by physically spreading lateral 
canthal area apart while at rest 
5. History of or current significant brow ptosis, significant brow asymmetry at rest or on 
brow elevation.  
6. A score of 2 or higher in any category of the Regional House-Brackmann Facial Nerve 
Grading System at screening 
7. Previous treatment with botulinum toxin type A in the face within 6 months prior to 
screening 
8. Has had within the last 6 months prior to screening, or plans to receive, any botulinum 
toxin treatment (other than study treatment)  
9. Has had within the last 6 months, or plans to receive, treatment with >200 U of any 
botulinum toxin anywhere in the body outside of the face within the last 6 months prior 
to screening through the end of the study 
 
 
 
 
 

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Overall Design: 
This is a phase 2a, multicenter, open-label, dose-escalation study to evaluate the safety and 
efficacy of DAXI for injection for the treatment of subjects with moderate to severe LCL. This 
study will be conducted at 4 sites in the United States. 
Approximately 64 subjects (18 to 65 years old) with moderate to severe LCL will be enrolled 
sequentially into 1 of 4 treatment cohorts (approximately 16 subjects per cohort) 
 
 
 Investigators will make all reasonable efforts to enroll equal proportions of subjects 
with moderate and severe LCL (based on baseline assessments) in each dosing cohort.  
The total study duration will be up to 38 weeks, including up to 2 weeks for screening. 
Subjects will be followed for a minimum of 24 weeks from LCL treatment and up to 36 weeks 
or until scores on the maximal expression IGA-LCWS and PLCWS return to baseline, 
whichever occurs first. Subjects will then have a Final Evaluation Visit. Baseline, unless 
otherwise stated, refers to the last available assessment prior to LCL treatment (Day 1 Visit). 
All treatments will be IM injections administered by the principal investigator (PI). 
 
 
  
 
 
 

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 Revance has this right to stop or terminate the study at any time for 
any reason at their discretion or in consultation with the DRC. 
Study Visits: 
Study visits will occur at the Screening Visit (Day -14), Treatment Visit (Day 1), a safety 
follow-up phone call at Week 1, and follow-up visits at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 
and 36. Baseline for all efficacy assessments, unless otherwise noted, will be the last available 
assessment prior to LCL treatment (Day 1 Visit). 
Efficacy Evaluations: 
• IGA-LCWS  
• PLCWS  
• GAIS  
• FASE 
• FACE-QTM Appraisal of Lines: Crow’s Feet Lines 
Baseline for all efficacy assessments associated with LCL severity, unless otherwise noted, 
refers to the last available assessment prior to LCL treatment (Day 1 Visit). Efficacy outcomes 
derived from the above list of assessments will be summarized descriptively by dose group 
and by timepoint. Count and proportion will be provided for responder endpoints (defined as 
proportion of subjects achieving certain status). Kaplan-Meier (KM) curves will be plotted by 
treatment group for each time-to-event endpoint to assess median duration of effect at 
maximum smile and at rest for selected endpoints. Dose-response will be explored using 
logistic regressions on the response rates (of key responder endpoints) and using log-rank test 
on the time-to-event endpoints. The effect of study center and baseline severity on the 
treatment outcome will also be explored. 
 
 

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Safety Evaluations: 
• Clinical laboratory tests (hematology, serum chemistry, prothrombin time [PT], 
urinalysis) 
 
 
 
 
• Injection site evaluation 
 
 
• Concomitant therapies/medications 
• Collection of adverse events (AEs) 
 
 
• Vital signs 
• Physical examination,
 
All TEAEs occurring during the study will be recorded and classified according to Medical 
Dictionary for Drug Regulatory Affairs (MedDRA) terminology. All reported TEAEs will be 
summarized, in terms of the number of subjects reporting events, system organ class, preferred 
term, severity, relationship to study drug, and severity. For summarization of event causality 
and severity, subjects will be counted only once within a system organ class or preferred term 
for a given event using the event with the greatest relationship for causality and the highest 
severity. A summary of AEs leading to discontinuation will also be provided. 
A by-subject listing of any SAEs will be provided and all SAEs will be summarized by 
severity and relationship to study treatment.  
All AEs, including TEAEs, and SAEs will be summarized for the study overall and by dose 
group.  
Clinical laboratory tests, including serum chemistry, hematology, PT (at the Screening Visit 
only), and urinalysis will be collected at the Screening Visit, Week 4, and Week 36 or Final 
Evaluation Visit, if applicable. 
 
. A UPT for all WOCBP will be performed at the Screening Visit, 
Day 1, and Week 36 or the Final Evaluation Visit, if applicable. 
 
 
 
 
 
 
 
 
 
 
 

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Other Evaluations:  
 
 
 
 
 
 
 
Number of Subjects:  
Approximately 64 subjects are expected to participate in this study. Refer to Section 9.2 for 
additional information on sample size determination. 
Disclosure Statement: This is an open-label, dose-escalation study with 4 treatment arms; 
neither subjects nor investigators/study staff will be blinded. All subjects will receive DAXI 
for injection for the treatment of moderate to severe LCL. 

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2. 
INTRODUCTION 
The formation of wrinkles at the corners of the eyes, which are referred to as crow’s feet lines or 
LCLs, are one of the primary signs of aging that can negatively impact the assessment of a 
person’s age. These dynamic lines appear during facial muscle contractions, like smiling, and 
over time can become permanent or static, meaning that they are still visible when without 
muscle contraction (Kane, 2015).  
Minimally-invasive injectable treatments have become the most common aesthetic procedure 
worldwide (Baumann, 2016) with an increase in frequency over the last decade since the first 
approval of botulinum neurotoxin Type A (OnabotulinumtoxinA; BOTOX® Cosmetic; [package 
insert]. Allergan, Inc., 2017). This is largely the result of an exceptional safety profile, as well as 
the ability of botulinum neurotoxin Type A to rejuvenate and enhance the facial area when 
compared with more invasive cosmetic procedures.  
Botulinum neurotoxin is produced by Clostridium botulinum, which is a gram-positive, spore-
forming, anaerobic bacterium (Carruthers, 2015a). There are 7 distinct types (A-G), only types A 
and B have established clinical uses due to a longer duration of action compared to the other 
types (De Boulle, 2007). Botulinum neurotoxin Type A blocks acetylcholine release into the 
neuromuscular junction, which prevents muscle contractions in the injected area. The onset of 
muscle weakening typically begins within 48 hours after treatment and usually lasts between 
4 and 5 months, although some patients have reported shorter or longer durations (Nestor, 2017; 
Carruthers, 2015; De Boulle, 2007). 
The presence of facial lines at rest result from a combination of factors, including repeated facial 
muscle contractions, structural skin remodeling that occurs with aging, and damage from 
excessive sun exposure (Carruthers, 2016). Carruthers, et.al., identified 4 distinct patterns for 
lateral canthal lines: full-fan, lower-fan, central-fan, and upper-fan. The description of these lines 
emphasizes the orientation of the lines in the lateral canthal area and nearby facial regions. As 
the dynamic patterns for LCL are further elucidated, it has become possible for experienced 
practitioners to customize treatment of the lateral canthal region to match the pattern of a 
patient’s lateral canthal lines.  
The efficacy and safety of onabotulinumtoxinA for the treatment of LCL has been evaluated in a 
large-scale clinical development program consisting of 3 phase 3 studies (Carruthers, 2015b). 
Study 1 evaluated onabotulinumtoxinA for the treatment of LCL alone. A total of 445 subjects 
with moderate to severe LCL were randomized to receive either onabotulinumtoxinA 24 U 
(N=222) or placebo (N=223) (Baumann, 2016). At baseline, 60.5% of subjects had severe LCL. 
The primary efficacy endpoint was investigator-assessed response of LCL at maximum smile on 
the Facial Wrinkle Severity (FWS) scale at Day 30. Responder rates were significantly higher in 
the onabotulinumtoxinA-treated groups when compared with placebo. Composite investigator- 
and subject-assessed improvement of at least 2 grades from baseline scores on the FWS at 
Day 30 were higher for the onabotulinumtoxinA-treated group (26.1%) when compared with 
placebo (1.3%) (Carruthers, 2015b).  
Study 2 was a 7-month, double-blind, randomized, placebo-controlled, parallel-group study with 
2 treatment cycles of onabotulinumtoxinA or placebo. A total of 917 subjects were enrolled: 

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305 subjects received onabotulinumtoxinA 44U (24 U to LCL area and 20 U to GL area), 
306 subjects received onabotulinumtoxinA 24 U (12 U to LCL Area and 0 U to GL area), and 
306 subjects received placebo (Moers-Carpi, 2015). The primary efficacy outcome was based on 
investigator and subject assessments of LCL severity at maximum smile at Day 30 using an 
FWS. Responder rates were calculated based on the proportion of subjects achieving a composite 
investigator- and subject-assessed improvement of at least 2 grades from baseline scores on the 
FWS at Day 30. For this endpoint scores were significantly higher for the LCL-treated group 
(20.3%), and the LCL and GL treated group (21.3%) when compared with placebo (0%). The 
proportion of responders achieving a score of 0 (none) or 1 (mild) on the FWS for LCL was 
significantly higher (as rated by both the investigator and the subject) at Day 30 (p <0.001) for 
the onabotulinumtoxinA group compared with the placebo group. Investigator-assessed 
responder rates were 59.0% and 54.9% in the onabotulinumtoxinA 44 U and 24 U groups, 
respectively. Subject responder rates at Day 30 were similar in the onabotulinumtoxinA-treated 
groups at 48.5% and 45.8%, respectively (Moers-Carpi, 2015). In general, when GL and LCL 
were treated simultaneously, responder rates were higher than those for LCL treatment alone.  
The reported AEs for both Study 1 and Study 2 were mild or moderate in severity, with 58.1% of 
subjects reporting at least 1 AE. Most AEs were not considered to be treatment-related. The most 
frequently reported treatment-related AEs included injection site hematoma (including bruises), 
headache, and injection site hemorrhage, all of which occurred at a frequency of ≤3.1% in each 
of the 4 treatment cycles. Further, the incidence of treatment-related AEs tended to decline with 
repeated treatment. None of the subjects discontinued treatment due to an AE or SAE 
(Carruthers, 2015b). 
Study 3 was a 5-month, double-blind, randomized, parallel-group, placebo-controlled extension 
study of the subjects who completed Study 2. Subjects who previously received 
onabotulinumtoxinA were eligible to receive the same dose in this study, while subjects who 
previously received placebo were randomized in a double-blind fashion to 1 of 2 treatment arms 
to receive either onabotulinumtoxinA 44 U or placebo. In this extension study, subjects were 
eligible to receive up to 2 additional treatment cycles. The endpoints were similar to Study 2 
with the primary response being the proportion of subjects achieving a score of 0 or 1 on the 
FWS at Day 30. A total of 684 subjects were enrolled: 260 to the 44 U onabotulinumtoxinA 
group, 227 to the onabotulinumtoxinA 24 U, 101 subjects who previously received placebo and 
were randomized to the onabotulinumtoxinA 44 U group, and 96 subjects who previously 
received placebo and were randomized to the placebo group. Results were consistent with Study 
2 with responder rates significantly higher in the onabotulinumtoxinA-treated groups at Day 30 
and at all other timepoints in cycles 3 and 4 when compared with placebo. During the 1-year 
assessment period, 58.2% of subjects experienced at least 1 AE; however, most were mild in 
intensity. Notably, the incidence of treatment-related AEs appeared to decline with repeated 
treatments. Treatment-related AEs, all occurring in <3.1% of subjects in each treatment cycle, 
included site hematoma, headache, and injection site hemorrhage.  
As minimally-invasive treatment becomes more widely used and accepted, and both men and 
women gain increased awareness of the recognition of facial aging and the aesthetic treatment 
options available, it is important to continue examining the potential benefits of such treatments 
in the context of unmet clinical need, improved self-satisfaction, and increased demand. 
Aesthetic products and procedures, while not medically necessary, can significantly improve 

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social and psychological functioning, as well as self-satisfaction, which can have a meaningful 
and significant impact on daily life and patient well-being (Fagien, 2008). 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
2.2. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of DAXI for injection may be found in the Investigator’s Brochure. 

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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
 
• To evaluate the efficacy 
and safety of DAXI for 
injection in the 
treatment of dynamic 
LCL 
• Proportion of subjects achieving a score or 0 or 1 
(none or mild) in LCL severity at maximum smile at 
Week 4 after LCL treatment on the IGA-LCWS 
• Incidence, severity, and relationship to study drug of 
TEAEs and SAEs during the overall study duration. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a phase 2a, multicenter, open-label, dose-escalation study to evaluate the safety and 
efficacy of DAXI for injection for the treatment of subjects with moderate or severe LCL. This 
study will be conducted at 4 sites in the United States. 
 Subjects 
will be screened for eligibility and enrolled into the study after providing informed consent. 
Approximately 64 subjects (18-65 years old) with moderate or severe LCL will be enrolled 
sequentially into 1 of 4 treatment cohorts (approximately 16 subjects per cohort)
 
. Investigators will make all 
reasonable efforts to enroll equal proportions of patients with moderate and severe LCL (based 
on baseline assessments) in each dosing cohort. The total study duration will be up to 38 weeks, 
including up to 2 weeks for screening. Subjects will be followed for a minimum of 24 weeks and 
up to 36 weeks or until scores on the maximal expression IGA-LCWS and PLCWS return to 
baseline (Day 1 Visit), or until Week 36, whichever occurs first. Subjects will then have the 
Final Evaluation Visit. 
Cohorts 1 and 2 will be enrolled simultaneously. Subsequent cohorts (3 and 4) will be enrolled 
sequentially and gated by the decision from the Data Review Committee (DRC) upon reviewing 
available data (including safety, efficacy, and photographs/videos) of previous cohorts. The DRC 
will convene to review data 4 weeks after LCL treatment for the last subject in Cohorts 1 and 2. 
The DRC will reconvene again after the last subject in Cohort 3 reaches the Week 4 Visit. 
Revance reserves the right to terminate or stop the study at any time. Refer to Sections 1.2 and 
9.5.1 for additional information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All treatments will be IM injections administered by the PI. 
 
 
 
 
The area around the injection sites will be evaluated at the Screening Visit to assess for skin 
inflammation or active skin disease and at the Day 1, Week 2, and Week 4 Visits to determine if 
there is a cutaneous reaction to the investigational product. The assessment will be captured as a 

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global evaluation of the injection sites to assess for erythema, edema, burning or stinging 
sensation, itching, or bruising.  
All subjects will be evaluated for improvement in LCL severity using the Revance-validated 
4-point LCWS to assess LCL at rest and at maximum rest by both the investigator (IGA-LCWS) 
and the subject (PLCWS). An additional investigator- and subject-rated endpoint is the visual 
assessment of improvement from baseline in LCL severity on the GAIS at each post-treatment 
visit. Additional subject reported outcomes include responses to the FASE and FACE QTM: 
Appraisal of Lines: Crow’s Feet Lines questionnaires, as well as the Subject Global Satisfaction 
with Treatment questionnaire. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
4.4. 
Visit Schedule 
A Screening Visit will be conducted up to 2 weeks prior to enrollment, and subjects will receive 
investigational product at baseline (Day 1). Following treatment, subjects will complete a paper 
diary for 2 weeks to capture their assessment of improvement in the appearance of LCL. A 
follow-up safety phone call will be conducted at Week 1. Post-treatment on-site follow-up visits 

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will occur at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, and 36. The total study duration will be up to 
38 weeks, including up to a 2-week screening period. Subjects will be followed for a minimum 
of 24 weeks post-treatment and up to 36 weeks or until scores return to baseline for the maximal 
expression IGA-LCWS and PLCWS or until the Week 36 Visit, whichever occurs first. Subjects 
will then have a Final Evaluation Visit. 
Subjects will be evaluated for LCL severity using the Revance-validated 4-point IGA-LCWS and 
PLCWS at rest and at maximum smile effort. 

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5. 
STUDY POPULATION 
Approximately 64 female or male subjects, 18-65 years old, with moderate to severe LCL will be 
enrolled. Subjects must meet all of the inclusion criteria and none of the exclusion criteria to be 
eligible for the study 
5.1. 
Inclusion Criteria 
To be eligible for participation, subjects must: 
1. Provide written informed consent consistent with International Conference on 
Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines and local laws, including 
authorization to release health information, signed prior to any study procedures being 
performed 
2. Be outpatient, male or female subjects, in good general health, 18-65 years old 
3. Have a score of moderate (2) or severe (3) LCL at maximum smile effort as assessed by 
the IGA-LCWS (scores must be consistent bilaterally) 
4. Have a score of moderate (2) or severe (3) LCL at maximum smile effort as assessed by 
the PLCWS (scores must be consistent bilaterally) 
5. Have sufficient visual acuity without the use of eyeglasses (contact lens use is 
acceptable) to accurately assess their facial wrinkles 
6. Be willing to refrain from receiving facial fillers, laser treatments, use of any product that 
affects skin remodeling, or a product that may cause an active dermal response in the 
treatment areas (e.g., above the oral commissures) from screening through the end of the 
study 
7. All women of childbearing potential (WOCBP) must have a negative urine pregnancy 
test (UPT) result at the Screening and Baseline Visits and must practice an effective 
method of contraception throughout the study (e.g., oral contraceptive pill, injection, 
implant, patch, vaginal ring, intrauterine coil, intrauterine device, tubal ligation, barrier 
method) used WITH an additional form of contraception (e.g., sponge, spermicide or 
condom); abstinence; no heterosexual intercourse; or has a vasectomized partner (refer to 
Section 5.6 for additional information) 
8. Able to understand the requirements of the study and be willing and able to follow all 
study procedures, attend all scheduled visits, and successfully complete the study. 
5.2. 
Exclusion Criteria  
Subjects will not be eligible for study participation if they meet any of the following criteria: 
1. Any neurological condition that may place the subject at increased risk with exposure to 
botulinum toxin type A, including peripheral motor neuropathic diseases, such as 
amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional 
disorders, such as Lambert-Eaton syndrome and myasthenia gravis 
2. Any history of facial nerve palsy (e.g., Bell’s Palsy) or muscle weakness or paralysis in 
the treatment areas  
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4. History of or current significant facial asymmetry, eyelid ptosis or history of same, 
excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or inability of 
investigator to completely or almost eliminate the LCL by physically spreading lateral 
canthal area apart while at rest 
5. History of or current significant brow ptosis, significant brow asymmetry at rest or on 
brow elevation 
6. A score of 2 or higher in any category of the Regional House-Brackmann Facial Nerve 
Grading System at screening 
7. Previous treatment with botulinum toxin type A in the face within 6 months prior to 
screening through the end of the study 
8. Plans to receive any botulinum toxin treatment (other than study treatment) from 
screening through the end of the study 
9. Has had within the last 6 months, or plans to receive, treatment with >200 U of any 
botulinum toxin anywhere in the body outside of the face  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

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5.3. 
Informed Consent and Authorization to Release Health Information 
Written informed consent will be obtained from all subjects before any study-related procedures 
(including any screening procedures) are performed. The investigator may discuss the study and 
the possibility for entry with a potential subject without first obtaining consent. However, a 
subject wishing to participate must give written informed consent prior to any study-related 
procedures being conducted, including those performed solely for the purpose of determining 
eligibility for study participation, including withdrawal from current medication (if required prior 
to study entry). The investigator has both the ethical and legal responsibility to ensure that each 
subject being considered for inclusion in this study has been given a full explanation of the 

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procedures and expectations for study participation, as well as ample time to decide whether or 
not to participate and have all questions answered satisfactorily. 
Each subject will sign the consent form that has been approved by the same IRB/IEC that was 
responsible for protocol approval. Each informed consent document must adhere to the ethical 
principles stated in the Declaration of Helsinki and will include the elements required by FDA 
regulations in 21 CFR Part 50, as well as the elements required by ICH GCP guideline, and 
applicable federal and local regulatory requirements. The consent form must also include a 
statement that Revance, their designees, auditing and regulatory agencies will have direct access 
to the subject’s records and medical history for study related purposes. 
Once the appropriate essential information has been provided to the subject and fully explained 
by the investigator (or a qualified designee) and it is felt that the subject understands the 
implications and risks of participating in the study, the IRB/IEC approved consent document 
shall be signed and dated by both the subject and the person obtaining consent (investigator or 
designee), and by any other parties required by the IRB/IEC or other regulatory authorities. The 
subject will be given a copy of the signed informed consent document with the original kept on 
file by the Investigator. All of the above activities must be completed before any study related 
procedures are conducted (including any screening study procedures).  
5.4. 
Lifestyle Considerations 
While enrolled in this study, subjects must agree to refrain from receiving non-ablative laser or 
light treatments, microdermabrasion, or chemical peels (medium depth or deeper, for example 
TCA or phenol) in the treatment areas within 3 months before enrollment through the end of the 
study.  
 
 
Refer to Section 6.4 for a complete list of prohibited medications during the study. 
5.5. 
Protocol Deviations 
This study will be conducted as described in this protocol, except for emergency situations in 
which the protection, safety, and well-being of the subject requires immediate intervention, 
based on the judgment of the investigator (or a responsible, appropriately trained professional). 
In the event of a significant deviation from the protocol due to an emergency, accident, or 
mistake, the investigator or designee must contact Revance or designee by telephone at the 
earliest possible time. This will allow an early joint decision regarding the subject’s continuation 
in the study. This decision will be documented by the investigator and Revance or designee. 
5.6. 
Pregnancy 
All WOCBP must use an effective method of birth control during the course of the study (e.g., 
oral contraceptive pill, injection, implant, patch, vaginal ring, intrauterine coil, intrauterine 
device, tubal ligation, barrier method) used WITH an additional form of contraception (e.g., 
sponge, spermicide or condom); abstinence; no heterosexual intercourse; or has a vasectomized 

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partner. A female is considered to be of childbearing potential UNLESS she is post-menopausal 
(no menses for 12 consecutive months) or without a uterus and/or both ovaries. 
Before enrolling WOCBP in this study, investigators must review guidelines with the subject 
about study participation for WOCBP with the subject. The topics should generally include: 
• Informed consent document 
• Pregnancy prevention information 
• Risks to unborn child(ren) 
• Any drug interactions with hormonal contraceptives 
• Contraceptives in current use 
• Guidelines for the follow-up of a reported pregnancy 
Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy 
during participation in this study and the potential risk factors for an unintentional pregnancy. 
The subject must sign the informed consent document stating that the risk factors for 
unintentional pregnancy and the consequences were discussed with her. 
During the study, all WOCBP should be instructed to contact the investigator immediately 
(within 24 hours) if pregnancy is suspected (e.g., missed or late menstrual cycle). The 
investigator, or qualified designee, must immediately notify Revance or designee of any female 
subject who becomes pregnant any time during study participation, record the information on 
Revance or designee Pregnancy Notification Form and send the form to Revance or designee. 
The investigator will be asked to follow-up with the subject periodically during the pregnancy 
for ongoing health and safety information through term, as applicable.  
 
If an SAE occurs in conjunction with the pregnancy such as untoward outcome of the pregnancy 
or of the offspring (spontaneous abortion, or abnormality in the offspring) then the reporting time 
frame for an SAE must be met and SAE reporting procedures followed. In the event of a normal 
birth, follow-up with the subject will occur with a phone call until the first well visit, at which 
time, active follow-up to the pregnancy will cease.  
 

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6. 
STUDY INTERVENTION 
The active pharmaceutical ingredient, daxibotulinumtoxinA, is a purified 150 kilodalton (kDa) 
botulinum neurotoxin type A, derived from the Hall strain C. botulinum. Produced by C. 
botulinum as a single inactive polypeptide chain of 150 kDa, daxibotulinumtoxinA undergoes 
proteolytic cleavage by proteases present in the fermentation culture to yield the active di-chain 
molecule comprised of a 100 kDa heavy chain and a 50 kDa light chain linked via both 
non-covalent interactions and a disulfide bond (Aoki, 2001). The heavy chain plays a role in 
binding, internalization, and translocation of daxibotulinumtoxinA into neuronal cells. The light 
chain acts as a site-specific metalloprotease causing selective cleavage and inactivation of the 
25 kDa synaptosome associated protein (SNAP-25), which is a cell membrane localized 
component of the vesicular release machinery. This cleavage of SNAP-25 by the light chain of 
botulinum toxin type A blocks the synaptic vesicle exocytosis and subsequent release of 
acetylcholine, thus leading to a dose-dependent weakening of the target muscle. 
6.1. 
Study Intervention(s) Administered 
This is an open-label, nonrandomized study for the treatment of moderate or severe LCL. 
Subjects will be sequentially enrolled by cohort. All subjects will receive DAXI for injection on 
Day 1 according to their assigned cohort.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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6.2.4. 
Investigational Product Administration 
Investigational product will be administered by the PI to injection site in the designated treatment 
areas bilaterally while the subject is in a sitting position 
 
. 
1. Wear protective gloves for investigational product administration 
2. Pull subject’s hair away from the treatment areas (lateral canthal region) 
3. Wipe all injection sites with alcohol 
 
 
  
 
 
 
 
 
 
 
 
 

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6.3. 
Concomitant Medications/Therapies 
Concomitant medications are any prescription or over-the-counter preparations used by subjects 
during participation in the study. Use of concomitant medications will be recorded on the 
Concomitant Medications electronic case report form (eCRF) beginning at the Screening Visit 
(and anything taken during the previous 30 days) until the Final Evaluation Visit.  
The dose and dosing regimen of all prescription and non-prescription therapies and medications, 
including herbs, vitamins, or other nutritional supplements administered will be documented. 
 
 
 
 
 

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6.5. 
Dose Modification 
Subjects will receive a single dose (consisting of 3 variable volume injections) according to 
assigned dose cohort in this study. The DRC will convene to review available data (including 
safety and photographs/videos) for Cohorts 1 and 2 prior to making a decision about the 
treatment of Cohort 3. The DRC will also convene to review applicable data (safety and 
photographs/video) prior to making a decision about the treatment of Cohort 4. 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1. 
Subject Discontinuation/Withdrawal from the Study 
A subject may voluntarily withdraw from study participation at any time. If the subject 
withdraws consent and discontinues from the study, the Investigator will attempt to determine 
the reason for discontinuation and record the reason in the subject’s study records and on the 
eCRF. If a subject withdraws consent because of an AE, that AE should be indicated as the 
reason for withdrawal. In the event of early discontinuation, (i.e., prior to the Final Evaluation) 
and consent is withdrawn, the subject should be asked to return to the study center to complete 
the assessments specified in the Final Evaluation Visit. Subjects who withdraw from the study 
will not be replaced. Subjects who withdraw from the study, but agree to continued follow-up, 
must be reconsented by the investigator for this limited participation in the study (unless this 
situation was adequately described in the original informed consent form [ICF]). 
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 from study participation at any time if medically necessary or 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. Prior to discontinuing a subject from study participation, the Investigator 
will discuss his/her intentions with the Medical Monitor or designee. 
All subjects who fail to return to the study center for the required follow-up visits will be 
contacted by phone to determine the reason(s) why the subject failed to return for the necessary 
visit or elected to discontinue from the study. If a subject is unreachable by telephone after a 
minimum of 2 documented attempts (1 attempt on 2 different days), a registered letter will be 
sent requesting that contact be made with the Investigator.  
Revance has the right to terminate or to stop the study at any time. Should this be necessary, both 
Revance and the Investigator will ensure that proper study discontinuation procedures are 
completed. 
7.2. 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study center. 
Before a subject is deemed lost-to-follow-up, the study center should make every effort to 
contact the subject (refer to Section 7.1) and reschedule the missed visit as soon as possible. The 
subject should be counseled on the importance of visit compliance and should be questioned as 
to whether he or she wishes to continue in the study. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. Subject Entry Procedures  
Subject informed consent must be obtained prior to conducting screening procedures. Each 
signature must be personally dated by each signatory and the original retained by the PI as part 
of the study record. A signed copy must be provided to each subject (refer to Section 5.3). 
8.2. Schedule of Visits and Procedures 
It is recommended that study visits be scheduled at approximately the same time of day 
throughout the study. The IGA-LCWS and Investigator GAIS should be performed by the same 
evaluator throughout the study whenever possible. If it is not possible to use the same evaluator 
throughout the study, two evaluators should examine the subject together and discuss findings 
for at least 1 prior visit. The SOA is provided in Section 1.3. 
8.2.1. 
Screening Visit 
The Screening Visit must take place within 14 days prior to the LCL treatment visit (Day 1 
Visit).  
The following procedures must be performed and recorded at this visit: 
1. Review study procedures and information regarding the study and obtain written 
informed consent and privacy authorization (as applicable) 
2. Review eligibility criteria 
3. Obtain medical/surgical history, including prior toxin use, and demographic 
information, including Fitzpatrick skin phototype 
4. Once the investigator has confirmed eligibility, the subject will be enrolled 
5. Conduct patient education: Discuss the potential effect of DAXI for injection 
treatment, explain the PLCWS measurement and the categories of the severity 
assessment scales, and instruct the subjects to consider depth of lines for LCL 
severity. Use the provided Patient Education Brochure 
 
 
 
 
 
 
 
 
 
8. Perform a physical examination,
 
 
 
 
 
 
 

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10. Measure and record vital signs (body temperature, respiratory rate, sitting radial 
pulse, and sitting systolic and diastolic blood pressure); subjects must sit for at 
5 minutes prior to having pulse and blood pressure measurements taken 
 
 
12. Collect blood and urine samples for clinical safety laboratory tests (hematology, 
serum chemistry, PT, and urinalysis)  
 
 
 
 
 
 
 
 
The Screening Visit clinical laboratory test results and UPT must be reviewed and signed by the 
investigator; any abnormal results must be determined to be not clinically significant by the 
investigator prior to enrollment. 
8.2.2. 
Treatment Visit (Baseline/Day 1) 
The LCL treatment visit at Baseline (Day 1 Visit) must be performed within 14 days of the 
Screening Visit. The LCL dose is administered at this visit. The following procedures must be 
performed and recorded for each visit:  
Prior to Investigational Product Administration 
1. Confirm that all screening procedures have been completed, results reviewed, and 
recorded 
2. Review eligibility criteria 
3. Update medical/surgical history  
 
 
 
 
 
 
 
7. Conduct patient education: Discuss the potential effect of DAXI for injection 
treatment, explain the PLCWS measurement and the categories of the severity 
assessment scales, and instruct the subjects to consider depth of lines for LCL 
severity. Use the provided Patient Education Brochure 
 
 
 
 
 
 
 

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11. Physical examination 
 
 
 
 
 
 
13. Measure and record vital signs (body temperature, respiratory rate, sitting radial 
pulse, and sitting systolic and diastolic blood pressure); subjects must sit for 5 
minutes prior to having pulse and blood pressure measurements taken 
 
 
 
 
 
 
 
 
16. Update concomitant therapy/medications since the Screening documenting the dose 
and dosing regimen of all prescription and non-prescription therapies and 
medications, including herbs, vitamins, or other nutritional supplements 
(Section 6.3). 
Investigational Product Preparation 
The assigned investigational product will be prepared by the trained dose preparer according to 
trial-specific instructions. The prepared investigational product will be provided in a syringe to 
the investigator for administration. 
Investigational Product Administration 
Investigational product will be administered by the investigator to injection site in the designated 
treatment area (Refer to Appendix 2) while the subject is in a seated position.  
1. Wear protective gloves for investigational product administration. 
2. Pull subject’s hair away from the treatment area.  
3. Wipe all injection sites with alcohol. 
 
 
 
 
 
 
 
 
 

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After Investigational Product Administration 
 
 obtain vital signs 
(body temperature, respiratory rate, sitting radial pulse, and sitting systolic and diastolic 
blood pressures) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.2.3. 
Week 1 Follow-up Phone Call  
At the Week 1 follow-up phone call, the subject will be contacted by the site staff for a health 
status check, concomitant therapy/medication check, and a query about AEs that may have 
occurred.  
The following procedures must be performed and recorded:  
 
 
 
  
 
 
 
 
3. Query subject about any new or ongoing AEs since the last visit 
 
 
 
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8.2.4. 
Follow-up Visits  
At Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32, the following procedures must be performed and 
recorded: 
 
 
 
 
3. Conduct patient education: discuss the potential effect of DAXI for injection treatment, 
explain the PLCWS measurement and the categories of the severity assessment scales, 
and instruct the subjects to consider depth of lines for severity of their LCL. Use the 
provided Patient Education Brochure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
13. Collect blood and urine samples for clinical safety laboratory tests (hematology, serum 
chemistry, and urinalysis) (Week 4 Visit only) 
 
 
 
 
 
 
 
 
17. Assess any new or ongoing AEs since the last visit  
 
 
 

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8.2.5. 
Final Evaluation Visit (Week 36) or Early Discontinuation 
The following procedures must be performed and recorded at the Final Evaluation Visit for each 
subject. Following treatment, subjects will be followed for at a minimum of 24 weeks from LCL 
treatment and up to 36 weeks for safety or until maximal expression scores on the IGA-LCWS 
and PLCWS return to baseline or Week 36, whichever occurs first. Subjects will then have a 
Final Evaluation Visit at which time the following procedures must be performed and recorded:  
 
 
2. Conduct patient education: Discuss the potential effect of DAXI for injection treatment, 
explain the PLCWS measurement and the categories of the severity assessment scales, 
and instruct the subjects to consider depth of lines for severity of their LCL. Use the 
provided Patient Education Brochure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10. Perform a physical examination 
 
 
 
12. Measure and record vital signs (body temperature, respiratory rate, sitting radial pulse, 
and sitting systolic and diastolic blood pressure) 
 
 
 
14. Collect blood and urine samples for clinical safety laboratory tests (hematology, serum 
chemistry, and urinalysis) 
 
 
 
 
 
 
 
 
 

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If there are no safety concerns, the subject’s participation in the study is complete at this visit.  
8.2.6. 
Variation from Scheduled Visit Days 
To allow for scheduling flexibility, limited variation will be permitted from the specified time of 
each visit (Table 3). 
Table 3: Allowed Variation from Scheduled Visit Days 
Scheduled Visit 
Allowed Variation 
Week 1  
+ 2 days 
Week 2 
± 2 days 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36  
±4 days 
8.3. 
Efficacy Assessments 
Effectiveness assessments will include investigator assessment of LCL severity and 
improvement, as well as subject assessment of severity and improvement. Effectiveness 
assessments will be conducted with the subject in a sitting position. To ensure consistent eye 
positioning during the assessment, the investigator should ask the subject to focus on a fixed 
point in the examination room. The assessment should be conducted in a room with good 
overhead lighting or natural light from a window (but not direct sunlight). Investigator 
assessments of improvement should be performed by the same evaluator throughout the study for 
a given subject. (Refer to Section 8.2.) 
8.3.1. 
Investigator Global Assessment of Lateral Canthal Wrinkle Severity 
At each clinic visit as designated in the SOA (Section 1.3), the investigator will assess the visual 
appearance (at rest and at maximum smile) of the LCL on each side of the face using the 
IGA-LCWS with the following 4-point scale (Table 4).  
Table 4: Investigator Global Assessment Lateral Canthal Wrinkle Severity 
 
Rating Score 
Lateral Canthal Wrinkle 
Severity  
Description  
0 
None 
None to minimally visible line(s) lateral to 
the lateral canthus 
1 
Mild 
Visible, shallow line(s) lateral to the lateral 
canthus 
2 
Moderate 
Clearly visible, moderately deep line(s) 
lateral to the lateral canthus 
3 
Severe 
Clearly visible, deep line(s) lateral to the 
lateral canthus with redundancy of skin 
 
 
 

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8.3.2. 
Patient Lateral Canthal Wrinkle Severity Scale 
Subjects will complete the PLCWS scale at rest and at maximum smile, to assess the severity of 
the LCL on each side of the face at the Screening Visit, Day 1 Visit (Baseline), follow-up visits, 
and the Week 36 Visit or the Final Evaluation Visit, if applicable.  
The subject assessment form will be provided directly to the subject to complete while reviewing 
his or her LCL using the supplied handheld mirror. Scores at screening and baseline must be 
consistent bilaterally. 
Refer to Appendix 4 for additional information. 
 
Table 5: Patient Lateral Canthal Wrinkle Severity 
Rating 
Score  
Lateral 
Canthal 
Wrinkle 
Severity  
Description  
0 
None 
No line(s) lateral to the lateral canthus 
1 
Mild 
Barely visible, shallow line(s) lateral to the 
lateral canthus 
2 
Moderate 
Clearly visible, moderately deep line(s) 
lateral to the lateral canthus 
3 
Severe 
Clearly visible deep line(s) lateral to the 
lateral canthus with redundancy of skin 
 
8.3.3. 
Global Aesthetic Improvement Scale (GAIS) 
The investigator and subject will assess the visual appearance (at maximum smile) of the LCL 
improvement from the baseline condition on each side of the face using the following 7-point 
severity GAIS (Table 6). Subjects will use the baseline assessment photograph for comparison 
when reviewing the visual appearance for LCL to assess improvement following treatment. 
Assessments will be made as designated in the SOA (Section 1.3).  
The Patient GAIS Assessment Form (Appendix 4) will be provided directly to the subject to 
complete while reviewing the lateral canthal treatment areas (at maximum smile) using the 
supplied handheld mirror as outlined in Appendix 5. Subjects with contact lenses should view 

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their treatment areas while wearing their contact lenses. Subjects who wear glasses must have 
sufficient visual acuity to be able to view their treatment areas without the use of glasses. The 
subject assessment must be completed before the investigator completes the IGA-LCWS 
assessment. 
 
Table 6: Global Aesthetic Improvement Scale 
Rating Score 
Wrinkle Improvement  
-3 
Very Much Worse 
-2 
Much Worse 
-1 
Worse 
0 
No Change 
1 
Improved 
2 
Much Improved 
3 
Very Much Improved 
 
8.3.4. 
Facial Age Self Evaluation (FASE) 
At each clinic visit designated in the SOA (Section 1.3), the subject will be asked to rate their 
perceived age on a FASE questionnaire (Appendix 7). Following the subject’s completion of the 
Patient GAIS, the subject will be given the FASE questionnaire to rate their perception of how 
old they think they look following treatment. 
8.3.5. 
FACE-QTM Appraisal of Lines: Crow’s Feet Lines 
At each follow-up visit designated in the SOA (Section 1.3), the subject will be asked to rate 
their perception of themselves on the FACE-Q Appraisal of Lines: Crow’s Feet Lines (Appendix 
9). This questionnaire asks subjects to rate how bothered they are by their LCL using 7 questions 
about general appearance using a rating scale of 1 to 4 with 1 representing Not Bothered and 4 
representing Extremely Bothered. Refer to Appendix 9 for additional information. 
 
 
 
 
 
 
 
 
 

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8.3.6.1.2. Subject Global Satisfaction with Treatment Questionnaire 
The subject will be asked to provide a rating of their satisfaction with the treatment results at the 
at all timepoints after treatment using the Subject Global Satisfaction with Treatment 
Questionnaire. Following the subject’s completion of the Patient GAIS, the subject will be given 
the questionnaire to rate their satisfaction with the treatment results. Subjects will be asked how 
satisfied or dissatisfied they are with how the treated area of the face looks (Appendix 8).  
8.4. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SOA (Section 1.3). 
8.4.1. 
Physical Examination  
A targeted physical examination, 
, will be 
conducted at the Screening Visit, Day 1 Visit, and Week 36 Visit or the Final Evaluation Visit, if 
applicable. Significant physical examination findings that are present prior to investigational 
product administration are to be included on the Medical History eCRF. 
Significant physical examination findings after investigational product administration, which 
meet the definition of an AE, will be recorded on the AE eCRF post-treatment. 
8.4.2. 
Vital Signs 
Vital signs (i.e., body temperature, respiration rate, sitting radial pulse rate, and sitting systolic 
and diastolic blood pressures) will be obtained at the Screening Visit, Day 1 Visit, and Week 2 
and Week 36 or the Final Evaluation Visit, if applicable. Subjects must sit for 5 minutes prior to 
having pulse and blood pressure measurements taken. Any new abnormal findings or worsening 
from baseline at subsequent assessments, if judged clinically significant, should be recorded as 
an AE on the AE eCRF page. 
 
 
 
 
 

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8.4.3. 
Pregnancy Testing 
A UPT is required for all WOCBP at screening, baseline (pre-treatment) and Week 36 or Final 
Evaluation Visit. A positive result prior to treatment will exclude the subject from study 
participation. The results of the UPT will be evaluated at each study center. If any subject has a 
positive UPT, a serum pregnancy test is required for confirmation. 
 
If a female subject becomes pregnant while participating in the study, the investigator or site 
designee must complete the Pregnancy Report Notification Form provided by Revance or 
designee as soon as the pregnancy is confirmed (see Section 5.6). 
8.4.4. 
Injection Site Evaluation 
Injection sites will be evaluated at the Screening Visit to assess for skin inflammation or active 
skin disease and at the Day 1, Week 2, and Week 4 Visits to determine if there is an immediate 
reaction to the investigational product. The assessment will be done as a global evaluation of the 
3 injection sites for LCL on each side of the face (Table 7). Refer to Appendix 2 for additional 
information. 
 
Table 7: Injection Site Evaluation 
Assessment Descriptor 
Present? 
 
Yes 
No 
Erythema 
 
 
Edema 
 
 
Burning or Stinging (sensation as described by 
subject) 
 
 
Itching (sensation as described by subject) 
 
 
Bruising 
 
 
 
If the subject answers yes to any of these items, it should be captured and recorded as an AE in the 
eCRF.  
8.4.5. 
Clinical Safety Laboratory Assessments 
As outlined in Table 8, non-fasting samples for hematology, chemistry, PT (screening only) and 
urinalysis will be collected at the Screening Visit and the Week 4 and 36 Visits, or Final 
Evaluation Visit if applicable. 
 
. Blood and urine specimens will be collected using applicable 
safety precautions and will be processed according to the central clinical laboratory’s 
instructions. Urinalysis will be evaluated at the study center using supplies provided by Revance 
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Table 8: Clinical Laboratory Tests 
Serum Chemistry 
Hematology 
Urinalysis 
Additional Tests 
Glucose 
Total bilirubin 
Alanine aminotransferase 
Aspartate 
aminotransferase 
Alkaline phosphatase 
Blood urea nitrogen 
Hemoglobin 
Hematocrit 
Leukocyte Count 
(total) 
Leukocyte Count 
(differential) 
Red Blood Cell 
Count 
Platelet Count 
Specific gravity 
pH 
Glucose 
Protein 
Blood 
Bilirubin 
Ketones 
Prothrombin time (PT) 
(screening only) 
UPT (WOCBP only)* 
 
 
 
 
 
*If positive at timepoints after study treatment, confirm by serum pregnancy test 
It is the investigator’s responsibility to review the results of all laboratory tests as they become 
available. For each laboratory test result outside the reference range, the investigator must 
ascertain if the abnormal lab result is a clinically significant result for that individual subject. 
Likewise, if laboratory tests are taken at follow-up visits, the investigator must ascertain if this is 
an abnormal and clinically significant change from pretreatment for that individual subject. The 
investigator may repeat the laboratory test or request additional tests to verify the results of the 
original laboratory test.  
The investigator must sign and date all written laboratory results (e.g., urinalysis, hematology, 
chemistry, PT, and pregnancy tests) and note Not Clinically Significant or Clinically Significant 
for each out of range laboratory value. If a laboratory value is determined to be a clinically 
significant result for that subject, this may be considered an AE.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.5. 
Adverse Events and Serious Adverse Events 
8.5.1. 
Evaluation of Adverse Events and Serious Adverse Events 
For this protocol, an adverse event (AE) is any untoward medical occurrence (e.g., sign, 
symptom, disease, syndrome, intercurrent illness, clinically significant abnormal laboratory 
finding, injury or accident) that emerges or worsens following administration of investigational 
product and until the end of study participation that may not necessarily have a causal 
relationship to the administration of the investigational product. An AE can therefore be any 
unfavorable and/or unintended sign (including a clinically significant abnormal laboratory 
result), symptom, or disease temporally associated with the use of an investigational product, 
whether or not considered related to the investigational product. A treatment-emergent AE is one 
that occurs after any period of exposure to treatment. 
Pre-existing conditions, which increase in frequency or severity or a change in nature as a 
consequence of an investigational product use will also be considered an adverse event. 
An unexpected AE is an adverse reaction, the nature or severity of which is not consistent with 
the applicable product information (e.g., Investigator’s Brochure for an unapproved 
investigational product or package insert/summary of product characteristics for an approved 
product). 
Any change in the study safety evaluations, (e.g., vital signs, injection site evaluation, 
 
) post-treatment determined to be clinically significant by the 
investigator must be reported as an AE. 
A serious adverse event (SAE) is any untoward medical occurrence that results in any of the 
following outcomes: 
• Death 
• Life-threatening, (i.e., the subject was, in the opinion of the Investigator, at immediate 
risk of death from the event as it occurred. It does not apply to an AE that hypothetically 
might have caused death if it were more severe) 
• Persistent or significant disability/incapacity or substantial disruption of the subject’s 
ability to carry out normal life functions 
• Requires in-patient hospitalization or prolongs hospitalization (i.e., a prolonged 
hospitalization beyond the expected length of stay; hospitalizations for elective 
medical/surgical procedures, scheduled treatments, or routine check-ups are not SAEs by 
this criterion) 
• Congenital anomaly/birth defect (i.e., an adverse outcome in a child or fetus of a subject 
exposed to the molecule or investigational product before conception or during 
pregnancy) 
• Does not meet any of the above serious criteria but based upon appropriate medical 
judgement may jeopardize the subject or may require medical or surgical intervention to 
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8.5.2. 
Assessment and Reporting Requirements 
The investigator will assess each subject post-treatment and at each subsequent study visit for the 
occurrence of AEs. In order to avoid bias in eliciting AEs, subjects should be asked the following 
non-leading question: “How have you felt since your last visit?” All AEs (serious and non-
serious) will be collected from the signing of the ICF until the Final Evaluation Visit. Any AE 
reported by the subject must be recorded on the source documents and eCRFs.  
All AEs will be collected from Day 1 until Week 36 or the Final Evaluation Visit at all 
timepoints as specified in the SOA (Section 1.3). Medical occurrences that begin before the start 
of study intervention but after obtaining informed consent will be recorded as well. 
 
All SAEs will be recorded and reported to Revance or designee immediately within 24 hours of 
their awareness of the event. All fatal or life-threatening SAEs should be telephoned to Revance 
or the designee’s authorized representative as soon as the investigator learns of the event. 
8.5.3. 
Serious Adverse Events 
The investigator must report an SAE to Revance or the designee’s authorized representative 
within 24 hours of their awareness of the event: 
 Complete and return an SAE Form with all information known to date; including the 
investigator’s assessment of causality 
 Contact Revance or the authorized representative for a fatal or life-threatening event as 
soon as the investigator or study staff are aware of the event 
 Obtain and maintain all pertinent medical records (e.g., discharge summary, autopsy 
report) and medical judgments of medical personnel who assisted in subject’s treatment 
and follow-up 
 Provide follow-up information to Revance or designee within 24 hours of awareness 
Regulatory Authorities, IRBs/ IECs, and investigators will be notified of SAEs in accordance 
with applicable regulations and requirements (e.g., ICH-GCP, national regulations and local 
requirements). 
 
 
 
 
  
 
 
 
 

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8.5.5. 
Follow-up of Non-Serious Adverse Events 
All AEs that are identified during the last scheduled study visit (or the Final Evaluation Visit, if 
applicable) must be recorded on the AE eCRF as ongoing. 
Any clinically significant abnormal test results, (e.g., laboratory findings), at the final assessment 
should be followed to resolution or until determined by the investigator to be stabilized. Repeat 
tests may be indicated to establish this. 
If a subject has any clinically significant, study-related abnormalities at the end of the study, the 
Medical Monitor should be notified and every effort made by the investigator to arrange follow-
up evaluations at appropriate intervals to document the course of the abnormalities unless the 
Medical Monitor determines that follow-up is sufficient. 
8.5.6. 
Follow-up of Post-Study Serious Adverse Events 
Any SAEs that are identified on the last scheduled contact (or at early discontinuation, if 
applicable) must be recorded on the AE eCRF and reported to Revance or designee according to 
the reporting procedures outlined in Section 8.5.2. This may include unresolved previously 
reported SAEs or new SAEs. The investigator should follow these SAEs until the events are 
resolved, or the subject is lost-to-follow-up. The investigator should continue to report any 
significant follow-up information to the Medical Monitor, Revance or designee and the IRB/IEC 
up to the point the event has been resolved. Resolution means the subject has returned to the 
baseline state of health, or the Investigator does not expect any further improvement or 
worsening of the subject’s condition. 
Any new SAEs reported by the subject to the investigator that occur after the last scheduled 
contact and are determined by the investigator to be reasonably associated with the 
administration of investigational product should be reported to Revance or designee and the 
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8.5.7. 
Investigational Product Causality and Severity 
Relationship of an AE to investigational product will be assessed as follows: 
• Definite: There is a clinically plausible time sequence between the onset of the AE and 
the administration of investigational product; when the event responds to withdrawal of 
investigational product and/or recurs with re-administration of investigational product 
• Probable: There is a clinically plausible time sequence between the onset of the AE and 
the administration of investigational product; the AE is unlikely to be caused by the 
concurrent/underlying illness, other drugs or procedures 
• Possible: There may or may not be a clinically plausible time sequence between the onset 
of the AE and the administration of investigational product and a cause cannot be ruled 
out 
• Unrelated: There is not a temporal or causal relationship to investigational product 
administration 
The investigator is responsible for evaluating all AEs and determining the severity of the event. 
Severity will be categorized as mild, moderate or severe according to the following definitions: 
• Mild: Event may be noticeable to subject; does not influence daily activities; usually 
does not require intervention 
• Moderate: Event may be of sufficient severity to make subject uncomfortable; 
performance of daily activities may be influenced; intervention may be needed  
• Severe: Event may cause severe discomfort; usually interferes with daily activities; 
subject may not be able to continue in the study; treatment or other intervention usually 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The data from the study running sequentially in cohorts with dose-escalation can be used to 
assess the maximal tolerable dose level in treating the LCL. It can also be used to assess the 
effective doses and the potential dose-response. When assessing the dose-response on a 
responder endpoint, the null hypothesis will be that each dose group has the same rate of 
response and the alternative hypothesis will be that not all doses groups have the same response 
rate.  That is, 
H0: r1 = r2 =  r3 = r4 = r5    versus  
Ha: ri ≠ rj for at least a pair of dose groups (i, j), i=1, 2, 3 or 4 and j=i+1 to 5, 
Where ri is the response rate for dose group i.  
9.2. 
Sample Size Determination 
The sample size is not determined by the power of formal hypothesis tests.  
 
 
 
 
 
 
  
9.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined and the summary groups for 
analysis will be based on the actual dose for LCL received (which is expected to be consistent 
with the enrollment cohorts): 
Population 
Description 
Enrolled  
All subjects who receive the LCL treatment 
LCL-Evaluable 
All enrolled subjects who have any post-LCL treatment 
assessment of IGA-LCWS at maximum smile  
Safety 
All enrolled subjects 
9.4. 
Statistical Analyses 
The statistical analysis plan will be developed and finalized before database lock and will 
describe the detailed methods of analysis, the subject populations to be included in the analyses, 
and procedures for accounting for missing, unused, and spurious data. This section is a summary 
of the planned statistical analyses of the primary and secondary endpoints. 
In general, descriptive summaries will include means, standard deviations, and range for 
continuous variables, and counts and proportions for categorical measures. Unless otherwise 

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stated otherwise, a 95% confidence interval will be provided for means and proportions. No 
formal hypothesis tests are planned, but group comparisons may be performed as exploratory 
analyses. No multiplicity adjustments or imputation of missing data are planned. 
9.4.1. 
Efficacy Analyses 
Unless otherwise noted, baseline for all efficacy assessments refers to the last available 
assessment prior to LCL treatment. Efficacy outcomes will be summarized. Descriptive statistics 
will be provided for all efficacy variables at all timepoints. 
The primary efficacy endpoint will be the proportion of subjects achieving a score or 0 or 1 
(none or mild) in LCL severity assessed by IGA-LCWS at maximum smile. The LCLs will be 
evaluated on both sides of the face and both scores will be recorded. If different ratings are 
obtained from the left and the right sides of the face, subjects will be scored using the higher 
(i.e., more severe) rating. The dose response in the proportion of responders at Week 4 will be 
explored using the logistic regression stratified by baseline LCWS severity and study center. 
Additional measures to assess the effectiveness outcomes will include the investigator GAIS 
evaluated at maximum smile at each visit. Various responder endpoints associated with the 
LCWS, such as achieving certain status or certain magnitude of improvement from baseline, will 
be derived from these effectiveness outcomes for each visit. These responder endpoints will be 
analyzed by statistical models similar to that for the primary endpoint. 
Duration of response will be evaluated by various time-to-event endpoints. Kaplan-Meier (KM) 
curves will be plotted by dose group for each time-to-event endpoint.  
Responder and time-event endpoints defined based on subject assessments for LCL wrinkle 
severity (such as PLCWS and the subject GAIS for LCL) will be summarized in the same way as 
those by investigator assessments. Similarly, the endpoints defined based on scores assessed at 
rest will be summarized in the same way as those on scores assessed at maximum smile.  
9.4.2. 
Safety Analyses 
All AEs occurring during the study will be recorded and classified according to MedDRA 
terminology. Those occurring during or after treatment are considered as treatment-emergent. All 
reported TEAEs will be summarized, in terms of the number of subjects reporting events, system 
organ class, preferred term, severity, relationship to study drug, and seriousness. For 
summarization of event causality and seriousness, subjects will be counted only once within a 
system organ class or preferred term using the event with the event with the greatest relationship 
for causality and the event with the highest severity. A summary of TEAEs leading to 
discontinuation will also be provided. 
A by-subject listing of any SAEs will be provided and all SAEs will be summarized by severity 
and relationship to study treatment.  
Clinical laboratory test results will be summarized by visit and if applicable a shift table will be 
used to evaluate the shift in status from baseline at each visit. 
9.5. 
Interim Analyses  
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9.5.1. 
Data Review Committee (DRC) 
Cohorts 1 and 2 will be enrolled simultaneously. Safety data and subject photographs will be 
evaluated by the DRC at 4 weeks after LCL treatment in Cohorts 1 and 2 before a decision is 
made to move forwarded with the next and subsequent doses. The DRC will reconvene again 
after the last subject in Cohort 3 reaches the Week 4 Visit. Safety data will be monitored 
throughout the study by the DRC at regular intervals. 
Dose escalation for LCL may be stopped at the discretion of the DRC as outlined in the DRC 
Charter. 
The full details for the roles and responsibilities of the DRC will be detailed in the study-specific 
DRC charter. 
 

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10. 
Records Management 
10.1. 
Data Collection 
For this study, all protocol-specified data will be recorded in the source documents, and data will 
be entered on the eCRFs from the source documents. In addition to signature confirmation that a 
subject meets the study eligibility criteria, upon each subject’s completion of the study, the 
investigator will sign a statement indicating that all pages of the subject’s case report have been 
reviewed. Signature stamps and “per signatures” are not acceptable.  
It is Revance’s policy that the study data be verifiable with the source data which necessitates 
access to all original recordings, laboratory reports, and other records for each subject. The 
investigator must, therefore, agree to allow access to subjects’ records, and source data must be 
made available for all study data. Subjects (or their legal representatives) must also allow access 
to their medical records. Subjects will be informed of the importance of increased record access 
and permission granted by signature on the informed consent document prior to any screening 
procedures. 
Checks will be performed to ensure the quality, consistency, and completeness of the data. 
Instances of missing or un-interpretable data will be resolved with the investigator or study 
coordinator. Data queries will be sent to the study center. Site personnel will be responsible for 
providing resolutions to the data queries and for correcting the eCRFs, as appropriate. All unused 
Revance or designee study materials and binders must be returned to Revance or designee upon 
completion of the study. 
The investigator must keep written or electronic source documents for every subject participating 
in the clinical study. The subject file that identifies the study in which the subject is participating 
must include the subject’s available demographic and medical information including:  
• Name 
• Contact information 
• Date of birth 
• Sex 
• Medical history 
• Concomitant diseases 
• Concomitant therapies/medication 
• Study visit dates 
• Performed examinations, evaluations, and clinical findings 
• Investigational product administration 
• AEs, SAEs, or pregnancy (as applicable) 
Additionally, any other documents with source data, especially original printouts of data that 
were generated by technical equipment must be included in the subject’s source document (e.g., 
laboratory value listings). All these documents must have at least the subject’s initials, study 
number, and the date of the evaluation.  

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The data recorded during the study will be documented in the eCRF and/or the study-specific 
forms. Before or at study termination, all data must be forwarded to Revance or designee. The 
data will be recorded, evaluated, and stored in anonymous form in accordance with data-
protection regulations. 
Subjects will authorize the use of their protected health information (PHI) during the informed 
consent process in accordance with the applicable privacy requirements. Subjects who deny 
permission to use and disclose PHI will not be eligible to participate in the study. The 
investigator will ensure that the study documents forwarded to Revance or their designee, and 
any other documents, contain no subject names or other PHI, such as medical record number or 
date of birth. 
Any amendments and corrections necessary will be undertaken in both the source documents and 
eCRFs (as appropriate) and countersigned by the investigator, or documented designee, stating 
the date of the amendment/correction. Errors must remain legible and may not be deleted with 
correction aids. The investigator must state his/her reason for the correction of any data. In the 
case of missing data/remarks, the entry spaces provided in the eCRF should be cancelled out to 
avoid unnecessary follow-up inquiries. 
Regulatory authorities, the IRB/IEC and/or Revance’s Quality Assurance department (or 
designee) may request access to all source documents, eCRFs, and other study documentation for 
on-site audit or inspection. The investigator must guarantee direct access to these documents. 
eCRFs will be kept by Revance or designee in a secured area. Clinical data will be recorded in a 
computer format for subsequent statistical analyses. Data files will be stored on electronic media 
with a final master data file kept by Revance or designee after descriptive and statistical analyses 
and reports have been generated and are complete.  
10.2. 
File Management at the Study Center 
It is the responsibility of the investigator to ensure that the study center maintains all source and 
essential documents in accordance with ICH Guidance for Industry E6 Good Clinical Practice: 
Consolidated Guidance, Section 8 – Essential Documents for the Conduct of a Clinical Study. 
10.3. 
Records Retention at the Study Center 
It is a Revance requirement that all investigators participating in clinical studies maintain 
detailed clinical data for one of the following periods: 
• Country-specific requirements, or 
• A period of at least 2 years following the last approval of a marketing application 
approved by a Regulatory Authority in an ICH region or until there are no pending or 
contemplated marketing applications in an ICH region, or, 
• A period of 2 years after Revance notifies the investigator that the data will not be 
submitted for review by any Regulatory Authority  
Regardless of applicable retention period, the investigator must not dispose of any records or 
essential documents relevant to this study without either (1) written permission from Revance, or 
(2) providing an opportunity for Revance to collect such records. The investigator shall take 
responsibility for maintaining adequate and accurate electronic or hard copy source documents of 

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all observations and data generated during this study. Such documentation is subject to 
inspection by Revance or designee and relevant regulatory agencies. If the investigator 
withdraws from the study (e.g., relocation, retirement) all study-related records should be 
transferred to a mutually agreed upon designee. Notice of such transfer will be provided to 
Revance in writing.  
 

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12. 
ETHICS AND RESPONSIBILITY 
This study must be conducted in compliance with the protocol, the ICH Guidance for Industry 
E6 (R2) Good Clinical Practice: Consolidated Guidance and the applicable regulatory 
requirements. investigators must submit all essential regulatory documentation, as required by 
local and national regulations (including IRB/IEC approval of the protocol and ICF) to Revance 
or designee before investigational product will be shipped to the study center.  

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Protocol    1820205 Version: Amendment 2 
 
Revance Therapeutics, Inc.  
14 August 2019 
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