An Open-Label, Multi-Center Trial to Assess the Safety of Single and Repeat Treatments of DaxibotulinumtoxinA for Injection for Treatment of Moderate to Severe Glabellar Lines (SAKURA OPEN-LABEL SAFETY)
Phase: PHASE3
Conditions: Glabellar Frown Lines
Sponsor: Revance Therapeutics, Inc.

 
 
 
 
 
TITLE 
An Open-Label, Multi-Center Trial to Assess the Safety of 
Single and Repeat Treatments of DaxibotulinumtoxinA 
for Injection for Treatment of Moderate to Severe 
Glabellar Lines (SAKURA OPEN-LABEL SAFETY) 
PROTOCOL NUMBER 
1620303 
SPONSOR 
Revance Therapeutics, Inc. 
7555 Gateway Boulevard 
Newark, CA  94560 
Tel.: 510.742.3400 
Fax: 510.662.4903 
DOCUMENT TYPE 
Amended Protocol 
VERSION  
Amendment 1, 20 March 2017 
 
 
The trial 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The information contained in this document, particularly unpublished data, is 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, 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. 
 
 

Protocol 1620303  
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INVESTIGATOR’S AGREEMENT  
I have carefully read the protocol entitled: “An Open-Label, Multi-Center Trial to Assess 
the Safety of Single and Repeat Treatments of DaxibotulinumtoxinA for Injection for 
Treatment of Moderate to Severe Glabellar Lines” and,  
I will provide copies of the protocol, any subsequent protocol amendments and access to 
all information provided by the Sponsor to the trial personnel under my supervision. I 
will discuss this material with them to ensure that they are fully informed about the 
investigational drug and the trial protocol. 
I agree to conduct this clinical trial 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 
 
 
 
 
 
 
Printed Name 
 
Date 
Institution Name 
 
 
Address 
 
 
City, State  Postal Code, Country 
 
Phone Number 
 

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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
Revance Therapeutics, Inc. 
Name of Finished Product: 
DaxibotulinumtoxinA for Injection  
Name of Active Ingredient: 
daxibotulinumtoxinA 
Title of Trial:  
An Open-Label, Multi-Center Trial to Assess the Safety of Single and Repeat Treatments of 
DaxibotulinumtoxinA for Injection for Treatment of Moderate to Severe Glabellar Lines (SAKURA-OLS) 
Trial Center(s):  
Approximately 60 centers in the United States (US) and Canada  
Number of Subjects Planned: 
Approximately 1500 subjects will be enrolled for a single treatment in 
addition to approximately 600 roll over subjects from the phase 3 pivotal 
SAKURA-1 and -2 studies for a total of 2100 subjects. 
Trial Period:  
The duration of subject participation will vary depending on number of 
treatments and duration of follow-up. A subject may be on trial for a 
maximum of 86 weeks, inclusive of a two week screening period. 
Phase of Development: 
3 
Objective: 
To evaluate the long term safety of DaxibotulinumtoxinA for Injection for the treatment of moderate to 
severe glabellar lines following single and repeat administration. 
Design and Methodology: 
This is a phase 3, open label, multi-center trial to assess the safety of single and repeat administration of 
DaxibotulinumtoxinA for Injection in subjects with moderate to severe glabellar lines. Approximately 1500 
adult subjects will be enrolled for a single treatment; all subjects who have completed participation in either 
Revance protocol SAKURA-1 or SAKURA-2 will be rolled over for repeat treatments. Subjects will have 
the opportunity of receiving up to two repeat treatments in this trial. It is anticipated that approximately 400-
500 subjects will be treated with three treatments at selected centers.  
All subjects will be followed for at least 12 weeks, and up to 36 weeks, after each treatment for safety 
assessments. If both Patient Frown Wrinkle Severity (PFWS) and Investigator Global Assessment Frown 
Wrinkle Severity (IGA-FWS) scores at maximum frown return to baseline at the Week 12 visit, or at a visit 
between Weeks 12 and 36, the visit at which these two scores are recorded will be the Final Evaluation Visit, 
and for those subjects who receive multiple treatments (up to two), this visit will serve as a retreatment visit. 
Subjects with multiple treatments will have a Final Evaluation Visit at Week 12 following their final eligible 
treatment. 
All treatments will be intramuscular injections administered by a trained physician. Subjects will receive a 
total of 0.5mL of treatment, with of 0.1 mL administered per injection to five injection sites: two injections 
into each corrugator muscle and one injection in the procerus muscle. 
The duration of subject participation in this trial (SAKURA-OLS) will vary depending on the number of 
treatments and duration of follow-up. Subjects who completed participation in SAKURA-1 and SAKURA-2 
trials may be eligible for treatment on their last visit as long as written informed consent for the SAKURA-
OLS trial is obtained before any trial-related procedures (including any screening procedures) are performed 
and subjects meet eligibility criteria. Final Evaluation visit procedures of the controlled trials from which 
they are rolling over will serve as the baseline for this trial. A subject may be in SAKURA-OLS trial for a 
maximum of 86 weeks, inclusive of a two week screening period. The number of trial visits will vary per 
subject depending upon response to DaxibotulinumtoxinA for Injection. A subject may not be re-enrolled in 
the SAKURA-OLS trial after the Final Evaluation Visit (or after early discontinuation). 
Trial Visits: 

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Name of Sponsor/Company: 
Revance Therapeutics, Inc. 
Name of Finished Product: 
DaxibotulinumtoxinA for Injection  
Name of Active Ingredient: 
daxibotulinumtoxinA 
Screening (–Week 2), Treatment (Day 0), post the first treatment follow-up at Weeks 1, 2, 4, 8, and 12, then 
at Weeks 16, 20, 24, 28, 32, 36 or until the retreatment. Post the second treatment follow-up (for the subjects 
who are retreated) at Weeks 1, 2, 4, 8, and 12, then at Weeks 16, 20, 24, 28, 32, and 36 or until the 
retreatment.  Post the third treatment follow-up (for the subjects who receive the third treatment) at Weeks 1, 
2, 4, 8, and 12.  
Safety Evaluations:  
• 
Clinical laboratory tests (hematology, chemistry, prothrombin time [PT], urinalysis)  
 
  
 
  
• 
Injection Site Evaluation 
 
 
 
 
• 
Concomitant medications 
• 
Collection of adverse events (AEs) 
 
 
• 
Vital Signs  
• 
Physical Examination 
Effectiveness Evaluations:  
• 
Investigator Global Assessment Frown Wrinkle Severity (IGA-FWS)  
• 
Patient Frown Wrinkle Severity (PFWS)  
• 
Investigator and Patient Global Aesthetic Improvement Scale (GAIS) 
Other Evaluations: 
 
 
Diagnosis and Main Abbreviated Eligibility Criteria:  
Outpatient, male or non-pregnant, non-nursing females, 18 years of age or older, and in good general health 
with moderate (2) or severe (3) glabellar lines during maximum frown based on the IGA-FWS and PFWS. 
(Refer to Protocol Section 3.4 “Eligibility Criteria”). 
Test Article, Dose and Mode of Administration: 
DaxibotulinumtoxinA for Injection, 40 U, intramuscular injection, 0.5 mL 
Statistical Analyses: 
The trial subjects are eligible to receive up to three treatments.  For analysis purposes, the corresponding 
summary period will be defined for each treatment. For the trial-overall summary, all available data observed 
during the trial will be included. For analyses associated with a specific treatment, the summary will include 
all data observed since the treatment until the next treatment, or until the last visit of the trial when there is no 
subsequent treatment. To account for varying subject follow-up duration, the total follow-up duration (i.e., 
patient-years) will be calculated for each summary period. 
For the trial-overall summary, the baseline will be the last available value prior to the first treatment. For 
summaries associated with a specific treatment, the baseline will be the last available value prior to treatment 
(i.e., re-baselined). 
In addition to subjects who are directly enrolled, the trial also includes subjects rolling over from two pivotal 
phase 3 studies, SAKURA-1 and SAKURA-2.  For the roll over subjects who are in the active treatment 
group in the prior trial, the first daxibotulinumtoxinA treatment in this open-label safety trial will in fact be 
their second daxibotulinumtoxinA treatment.  Based on the subject’s prior exposure to DaxibotulinumtoxinA 

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Name of Sponsor/Company: 
Revance Therapeutics, Inc. 
Name of Finished Product: 
DaxibotulinumtoxinA for Injection  
Name of Active Ingredient: 
daxibotulinumtoxinA 
for Injection, the following two summary groups will be defined for the analysis: Group A and Group B. The 
former group will include all subjects who have received DaxibotulinumtoxinA for Injection in either 
protocol SAKURA-1 or SAKURA-2, and the latter group will include the remaining trial subjects. 
Safety Analyses: 
All treatment-emergent adverse events (AEs) occurring during the trial will be recorded and classified on the 
basis of MedDRA terminology. All reported treatment-emergent adverse events will be summarized, in terms 
of the number of subjects reporting events, system organ class, preferred term, severity, relationship to trial 
drug and seriousness. When summarizing events by causality and severity, each subject will be counted only 
once within a system organ class or a preferred term by using the event with the greatest relationship and 
highest severity within each classification. A list of AEs that lead to the subject’s premature discontinuation 
of the trial will be provided. 
Serious adverse events (SAEs) will be listed by subject. SAEs will be summarized by severity and 
relationship to trial treatment. 
The summaries of AEs and SAEs will be performed for the trial overall, and for each of the three treatment 
periods. For SAEs and key AEs 
, rate-per-injection and rate-
per-patient-year will be calculated. A 95% confidence interval will also be provided for the rate. 
Effectiveness Analyses: 
Effectiveness outcome measures, such as the Investigator Global Assessment Frown Wrinkle Severity (IGA-
FWS), Patient Frown Wrinkle Severity (PFWS), Investigator and Patient Global Aesthetic Improvement 
Scale (GAIS), are evaluated at maximum frown and at rest after maximum frown over time during the trial. 
Response rates and duration of the response, defined based on various definitions (see Section 7.3 for 
details), are calculated.  
Effectiveness data will be summarized as observed with no imputation for missing data. Descriptive statistics 
will be provided for all effectiveness variables at all timepoints for the summary group. 95% confidence 
intervals and/or p-values for comparing the difference between subgroups of interest (e.g., females vs. males, 
first treatment vs. second treatment, etc.) will be provided as appropriate. Kaplan-Meier curves will be 
plotted for the time-to-event endpoints. 
When comparisons (e.g., females vs. males, first treatment vs. second treatment, etc.) are performed, the tests 
will be done at a significant level of 0.05 with no adjustment for multiplicity.  
Sample Size Justification: 
This is a safety trial with all subjects treated with the same investigational product. The sample size of 
approximately 2,100 is considered to be adequate in assessing safety based on several approaches. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE 
adverse event 
ATC 
Anatomical Therapeutic Chemical 
BoNTA 
botulinum neurotoxin type A 
BP 
blood pressure 
CRF 
case report form 
CRO 
contract research organization 
CS 
clinically significant 
FDA 
Food and Drug Administration 
GAIS 
Global Aesthetic Improvement Scale 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GLSS 
Glabellar Line Severity Score 
HHS 
U.S. Department of Health and Human Services 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IGA-FWS 
Investigator Global Assessment Frown Wrinkle Severity 
IRB 
Institutional Review Board 
kDa 
kilodalton 
kg 
kilogram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
milliliter 
MRC 
Medical Research Council 
NCS 
not clinically significant 
PFWS 
Patient Frown Wrinkle Severity 
PP 
per protocol 
PT 
prothrombin time 
Revance 
Revance Therapeutics, Inc. 
RR 
respiration rate 
RT001 
DaxibotulinumtoxinA Topical Gel 
RT002 
DaxibotulinumtoxinA for Injection 
RTP004 
Novel excipient, inactive ingredient 
SAE 
serious adverse event 
SAS 
Statistical Analysis System 
SOP 
standard operating procedure 
 

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Abbreviation 
Definition 
TdP 
Torsade de Pointe 
U 
units 
UPT 
urine pregnancy test 
WHO 
World Health Organization 
WOCBP 
woman of child bearing potential 
 
 
 

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TABLE OF CONTENTS 
SIGNATURE PAGE ..........................................................................................................2 
INVESTIGATOR’S AGREEMENT ................................................................................3 
PROTOCOL SYNOPSIS ..................................................................................................4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................7 
TABLE OF CONTENTS ..................................................................................................9 
LIST OF TABLES ...........................................................................................................12 
LIST OF FIGURES .........................................................................................................12 
1 BACKGROUND ........................................................................................................13 
 
 
 
 
 
 
 
 
2 TRIAL OBJECTIVE .................................................................................................16 
3 TRIAL DESIGN.........................................................................................................17 
3.1 Overall Trial Design ...........................................................................................17 
3.1.1 Structure ..................................................................................................17 
3.1.2 Duration ..................................................................................................17 
3.1.3 Control ....................................................................................................18 
3.1.4 Dosage/Dose Regimen ............................................................................18 
3.1.5 Visit Schedule .........................................................................................18 
 
 
3.3 Population ...........................................................................................................19 
3.4 Eligibility Criteria ...............................................................................................19 
3.4.1 Informed Consent and Authorization to Release Health 
Information .............................................................................................19 
3.4.2 Inclusion Criteria ....................................................................................20 
3.4.3 Exclusion Criteria ...................................................................................20 
3.4.4 Eligibility Criteria for Retreatment .........................................................23 
4 TRIAL PROCEDURES ............................................................................................24 
4.1 Subject Entry Procedures ....................................................................................24 
4.1.1 Pregnancy................................................................................................24 
4.2 Schedule of Visits and Procedures ......................................................................25 
4.2.1 Screening Visit ........................................................................................25 
4.2.2 Treatment Visit (Day 0) ..........................................................................27 
4.2.3 Week 1 Follow-Up Visit .........................................................................29 
4.2.4 Follow-up Visits .....................................................................................30 

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4.2.5 Retreatment Procedures ..........................................................................31 
4.2.6 Final Evaluation Visit or Early Discontinuation.....................................32 
4.2.7 Unscheduled Visits .................................................................................33 
4.2.8 Discontinuation/Withdrawal Procedures ................................................33 
4.3 Variation from Scheduled Visit Days .................................................................34 
4.4 Schedule of Visits and Procedures ......................................................................34 
4.5 Safety Assessments .............................................................................................35 
4.5.1 Clinical Laboratory Data ........................................................................35 
4.5.2 Pregnancy Testing...................................................................................36 
4.5.3 Vital Signs...............................................................................................36 
4.5.4 Physical Exam.........................................................................................36 
4.5.5 Injection Site Evaluation .........................................................................36 
 
 
 
 
 
 
4.5.9 Adverse Events .......................................................................................41 
 
4.6 Effectiveness Assessments..................................................................................43 
4.6.1 Patient Frown Wrinkle Severity (PFWS) ...............................................43 
4.6.2 Investigator Global Assessment Frown Wrinkle Severity ......................44 
4.6.3 Global Aesthetic Improvement Scale .....................................................44 
4.6.4 Additional Assessments ..........................................................................45 
4.7 Screen Failures ....................................................................................................45 
4.8 Protocol Deviations .............................................................................................45 
5 
 
5.1 Concomitant Medications ...................................................................................47 
 
 
6 EVALUATION OF ADVERSE EVENTS ...............................................................49 
6.1 Definitions...........................................................................................................49 
6.1.1 Clinical Laboratory Changes ..................................................................50 
6.1.2 Investigational Product Causality and Severity ......................................50 
6.2 Reporting Adverse Events ..................................................................................51 
6.3 Serious Adverse Events ......................................................................................51 
6.4 Procedure for Accessing the Randomization Code ............................................51 
6.5 Follow-up of Adverse Events .............................................................................52 
6.5.1 Follow-Up of Non-Serious Adverse Events ...........................................52 
6.5.2 Follow-Up of Post Trial Serious Adverse Events ...................................52 
7 STATISTICAL ANALYSIS .....................................................................................53 

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7.1 General Considerations .......................................................................................53 
7.2 Analysis Populations ...........................................................................................53 
7.3 Trial Endpoints....................................................................................................54 
7.4 Safety Analyses ...................................................................................................55 
7.4.1 Adverse Events .......................................................................................55 
7.4.2 Laboratory Tests .....................................................................................56 
7.4.3 Vital Signs and Physical Examination ....................................................56 
7.4.4 Injection Site Evaluation .........................................................................57 
 
 
 
 
7.4.7 Concomitant Therapies/Medications ......................................................57 
 
 
7.4.9 Effectiveness Analysis ............................................................................57 
7.4.10 Sample Size and Power Considerations..................................................57 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9 RECORDS MANAGEMENT ...................................................................................61 
9.1 Data Collection ...................................................................................................61 
9.2 File Management at the Trial Center ..................................................................63 
9.3 Records Retention at the Trial Center .................................................................63 
10 MONITORING, COMPLIANCE, AND QUALITY ..............................................64 
 
11 ETHICS AND RESPONSIBILITY ..........................................................................66 
 
 
 
 
 
 
 
 

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LIST OF TABLES 
Table 1: Allowed Variation from Scheduled Visit Days ...................................................34 
Table 2: Clinical Laboratory Tests ....................................................................................35 
Table 3: Injection Site Evaluation......................................................................................37 
 
 
 
 
Table 8: Patient Frown Wrinkle Severity (PFWS) ............................................................43 
Table 9: Investigator Global Assessment Frown Wrinkle Severity (IGA-FWS) ..............44 
Table 10: Global Aesthetic Improvement Scale ................................................................45 
Table 11: Prohibited Medications and Treatments ............................................................47 
 
LIST OF FIGURES 
Figure 1: Injection Sites .....................................................................................................71 
 

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1 
BACKGROUND 
The safety and effectiveness of botulinum toxin type A to act on the neuromuscular 
junction and relieve muscle spasm and its clinical effects such as strabismus, pain, and 
facial wrinkles has been well established for over 20 years (Scott, 1981; Carruthers, 
1992; Spencer, 2002). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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2 
TRIAL OBJECTIVE 
To evaluate the long term safety of DaxibotulinumtoxinA for Injection for the treatment 
of moderate to severe glabellar lines following single and repeat administration. 

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3 
TRIAL DESIGN 
3.1 
OVERALL TRIAL DESIGN 
3.1.1 STRUCTURE 
This is a phase 3, open label, multi-center trial to assess the safety of single and repeat 
administration of DaxibotulinumtoxinA for Injection in subjects with moderate to severe 
glabellar lines.   
Approximately 1500 adult subjects will be enrolled for a single treatment; all consenting 
subjects who have completed participation in either Revance protocol SAKURA-1 or 
SAKURA-2 may be eligible to roll over for repeat treatments in this trial (SAKURA-
OLS) on the last visit of the previous trial as long as written informed consent is obtained 
from all subjects before any trial-related procedures (including any screening procedures) 
are performed and subjects meet eligibility criteria.  Subjects, will have the opportunity 
of receiving up to one or two repeat treatments in this trial. Of all subjects enrolled in 
SAKURA-1, SAKURA-2 and SAKURA-OLS, it is anticipated that approximately 400-
500 total subjects will be treated for up to three treatments of DaxibotulinumtoxinA for 
Injection at select centers at the end of the trial; subjects from SAKURA-1 or SAKURA-
2 will have received one treatment in the parent trial and up to two treatments in 
SAKURA-OLS, and subjects who did not participate in either SAKURA-1 or SAKURA-
2 will have received between one and three treatments in the SAKURA-OLS. 
3.1.2 DURATION 
The duration of subject participation in this trial (SAKURA-OLS) will vary depending on 
the number of treatments and duration of follow-up. Subjects who completed 
participation in SAKURA-1 and SAKURA-2 trials may be eligible for participation in 
the SAKURA-OLS trial during their last visit as long as written informed consent for the 
SAKURA-OLS trial is obtained before any trial-related procedures (including any 
screening procedures) are performed and subjects meet eligibility criteria. Final 
Evaluation visit procedures of the controlled trials from which they are rolling over, end 
of trial PT, 
 will serve as the baseline for this trial. A 
subject may be in SAKURA-OLS trial for a maximum of 86 weeks, inclusive of a two 
week screening period. The number of trial visits will vary per subject depending upon 
response to DaxibotulinumtoxinA for Injection. A subject may not be re-enrolled in the 
SAKURA-OLS trial after the Final Evaluation Visit (or after early discontinuation). 

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3.1.3 CONTROL 
Not applicable. All subjects will be treated with DaxibotulinumtoxinA for Injection. 
3.1.4 DOSAGE/DOSE REGIMEN 
All treatments will be intramuscular injections administered by a trained physician.  
Injections must be performed only by the principal investigator contracted at the center. 
 
 
  
3.1.5 VISIT SCHEDULE 
A screening visit will be conducted up to two weeks prior to the first treatment.  
Following the first treatment at Day 0, subjects will have on-site post-treatment visits at 
Week 1, 2, 4, 8 and 12, then thereafter, monthly up to Week 36 or until both Patient 
Frown Wrinkle Severity (PFWS) and Investigator Global Assessment Frown Wrinkle 
Severity (IGA-FWS) scores at maximum frown return to baseline (or until the second 
treatment for the subjects who will receive multiple treatments).  Following the second 
treatment (if received), subjects will have on-site post-treatment visits at Week 1, 2, 4, 8 
and 12, then thereafter monthly up to Week 36 or until the third treatment.  Following the 
third treatment (if received), subjects will have on-site post-treatment visits at Week 1, 2, 
4, 8 and 12. Subjects who receive multiple treatments will have a Final Evaluation Visit 
twelve weeks after the final treatment.  
Starting at the Week 12 visit following the first (or the second) treatment, and evaluated 
thereafter monthly up to Week 36, subjects at selected centers may be retreated if 
retreatment criteria (see Section 3.4.4) are met.  Subjects at the selected centers will 
receive up to a total of up to three treatments (up to two treatments for roll over subjects) 
during SAKURA-OLS. 
 
 
 
 
 
 
 

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3.3 
POPULATION 
Approximately 2,100 female or male subjects, 18 years of age or older, in good general 
health, with moderate or severe glabellar lines will be enrolled. Subjects who completed 
participation in SAKURA-1 or SAKURA-2 may be eligible for participation in the 
SAKURA-OLS trial on the last visit of the previous trial as long as written informed 
consent is obtained from all subjects before any trial-related procedures (including any 
screening procedures) are performed and subjects meet eligibility criteria. Final 
Evaluation visit procedures of the previous trial, end of trial PT, 
 
will serve as the baseline for this trial. 
3.4 
ELIGIBILITY CRITERIA 
3.4.1 INFORMED CONSENT AND AUTHORIZATION TO RELEASE HEALTH 
INFORMATION 
Written informed consent will be obtained from all subjects before any trial-related 
procedures (including any screening procedures) are performed. The Investigator may 
discuss the trial 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 trial-related procedures being conducted, including those performed 
solely for the purpose of determining eligibility for trial participation, and including 
withdrawal from current medication (if required prior to trial entry). The Investigator has 
both the ethical and legal responsibility to ensure that each subject being considered for 
inclusion in this trial has been given a full explanation of the procedures and expectations 
for trial participation. 
The site-specific informed consent must be forwarded to Revance for approval prior to 
submission to an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
that is registered with the US Department of Health and Human Services (HHS) or 
applicable health authority. 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 the International Conference on Harmonisation (ICH) 
Good Clinical Practice (GCP) guideline, and applicable federal and local regulatory 
requirements. The consent form must also include a statement that Revance, their 
designees, and auditing regulatory agencies will have direct access to the subject’s 
records and medical history for trial related purposes. 

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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 trial, 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 trial related procedures are conducted (including 
any screening trial procedures).  
3.4.2 INCLUSION CRITERIA 
All subjects must meet the following inclusion criteria: 
1. Provide written informed consent including authorization to release health 
information 
2. Outpatient, male or non-pregnant, non-nursing females, 18 years of age or older, 
and in good general health  
3. Moderate (2) or severe (3) glabellar lines during maximum frown based on the 
Investigator Global Assessment Frown Wrinkle Severity (IGA-FWS) scale 
4. Moderate (2) or severe (3) glabellar lines during maximum frown based on the 
Patient Frown Wrinkle Severity (PFWS) scale  
5. 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 area from screening through the end of the trial 
6. Female subjects of childbearing potential must have a negative urine pregnancy 
test result at the Screening Visit and at the Treatment Visit, prior to 
investigational product administration, and practice an effective method of 
contraception throughout the trial (refer to section 4.1.1) 
7. Able to understand the requirements of the trial and sign informed consent 
including authorization to release health information 
8. Willing and able to follow all trial procedures, attend all scheduled visits, and 
successfully complete the trial 
9. In the opinion of the investigator, roll over subjects demonstrated compliance 
with the study procedures and visit requirements during SAKURA-1 or 
SAKURA-2 and are capable of complying with the study procedures and visit 
requirements in SAKURA-OLS 
3.4.3 EXCLUSION CRITERIA 
Subjects will not be enrolled if they meet any of the following exclusion criteria: 

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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. Muscle weakness or paralysis, in the area receiving trial treatment; or history of 
facial nerve palsy (e.g., Bell’s Palsy) 
3. Active skin disease, infections, or inflammation at the injection sites 
4. Significant facial asymmetry, eyelid ptosis or history of same, significant brow 
ptosis or history of same, excessive dermatochalasis, deep dermal scarring, thick 
sebaceous skin, or inability of Investigator to completely or almost completely 
eliminate glabellar lines by physically spreading medial brows apart while at rest 
5. A score of 2 or higher in any category of the Regional House-Brackman Facial 
Nerve Grading System at screening 
6. Previous treatment with botulinum toxin type A in the face within 24 weeks prior 
to screening  
7. Plan to receive botulinum toxin type A anywhere in the face through the duration 
of the trial 
8. Treatment with greater than 200 U botulinum toxin type A anywhere else in the 
body outside of the face within the last 3 months prior to screening and through 
the end of the trial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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No additional exclusions may be applied by the investigator in order to ensure that the 
trial population will be representative of all eligible subjects. 
Deviation from any entry criterion excludes a subject from enrollment into the trial. 

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3.4.4 ELIGIBILITY CRITERIA FOR RETREATMENT  
Subjects will have the opportunity of receiving up to two repeat treatments in this trial. It 
is anticipated that approximately 400-500 subjects will be treated with three treatments at 
selected centers. Assessment for retreatment will occur after subjects have completed at 
least 12 weeks of safety follow-up and when the following criteria are met:  
1. Return of IGA-FWS and PFWS severity scores to baseline 
2. Women of child-bearing potential (WOCBP) must have a negative urine 
pregnancy test (UPT) prior to treatment 
3. No active skin disease or infections or inflammation at the injection sites 
4. Subject has no condition or situation which, in the Investigator’s opinion, 
puts the subject at significant risk 

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4 
TRIAL PROCEDURES 
4.1 
SUBJECT ENTRY PROCEDURES 
Subject informed consent must be obtained prior to conducting screening procedures. 
At the screening visit, procedures including vital signs, physical examination, collection 
of samples for hematology, chemistry, prothrombin time (PT), 
 
urinalysis, urine pregnancy test (UPT) for WOCBP, collection of concomitant medication 
and medical history information, examination of the treatment area, PFWS, and IGA-
FWS must be completed. Results from clinical laboratory tests must be obtained and 
reviewed by the Investigator. Any WOCBP having a positive pregnancy test pre-
treatment will not be treated. The corresponding Final Evaluation Visit assessments may 
be used to determine eligibility for subjects rolling-over from Protocol SAKURA-1 or 
SAKURA 2. The 
 end of trial PT collected during 
studies SAKURA-1 or SAKURA-2, will serve as the baseline assessment for subjects 
rolling-over from these two studies.   
After the required screening procedures are completed and trial eligibility is confirmed as 
defined by the eligibility criteria in Sections 3.4.2 and 3.4.3, the subject will be enrolled 
in the trial and the investigational product will be prepared by the dose preparer and 
administered by the Investigator. 
4.1.1 PREGNANCY 
WOCBP must use an effective method of birth control during the course of the trial, such 
as the 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. 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 clinical trial, Investigators must review guidelines about 
trial participation for WOCBP. 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 

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• Guidelines for the follow-up of a reported pregnancy 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding 
pregnancy during participation in this clinical trial and the potential risk factors for an 
unintentional pregnancy. The subject must sign the informed consent document stating 
that the above-mentioned risk factors and the consequences were discussed with her. 
During the trial, all WOCBP should be instructed to contact the Investigator immediately 
(within 24 hours) if they suspect they might be pregnant (e.g., missed or late menstrual 
cycle). The Investigator must immediately notify Revance or designated Contract 
Research Organization (CRO) of any female subject who becomes pregnant any time 
during trial participation, record the information on the Pregnancy Notification Form, and 
send the form to the CRO. The trial center will be asked to follow up with the subject 
periodically during the pregnancy for ongoing health and safety information through 
term, as applicable. Subjects will remain on the trial until the end of the trial’s follow-up 
period. Pregnant subjects will not be eligible for retreatment. 
4.2 
SCHEDULE OF VISITS AND PROCEDURES 
It is recommended that trial visits be scheduled at approximately the same time of day 
throughout the trial. 
The IGA-FWS and Investigator GAIS should be performed by the same evaluator 
throughout the trial whenever possible. If it is not possible to use the same evaluator to 
follow the subject throughout the trial, two evaluators should examine the subject 
together and discuss findings for at least one prior visit. A schedule of trial assessments is 
provided in Appendix F. 
The progression of a subject through the trial will be dependent upon the duration of the 
effect (response). 
4.2.1 SCREENING VISIT 
The Screening Visit may take place within 14 days prior to investigational product 
administration at Day 0 (Treatment Visit). Subjects who completed participation in 
SAKURA-1 or SAKURA-2 may be eligible for participation in the SAKURA-OLS trial 
on the last visit of the previous trial as long as written informed consent is obtained from 
all subjects before any trial-related procedures (including any screening procedures) are 
performed and subjects meet eligibility criteria. Final Evaluation visit procedures of the 
previous trial, end of trial PT, 
 will serve as the 
baseline for this trial.  

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1. Review trial procedures and information regarding the trial and obtain written 
informed consent 
2. Review eligibility criteria 
3. Obtain medical/surgical history, including prior toxin use, and demographic 
information including Fitzpatrick skin type 
4. Conduct patient education: Discuss the potential effect of DaxibotulinumtoxinA 
for Injection treatment, explain the PFWS measurement and the categories of the 
severity assessment scales, and instruct the subjects to consider depth of lines for 
severity of their glabellar lines. Use the provided Patient Education Brochure 
5. Measure and record vital signs (body temperature, respiratory rate, sitting radial 
pulse, and sitting systolic and diastolic blood pressure) 
 
7. Collect blood samples for clinical safety laboratory tests (hematology, chemistry, 
and PT)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 treatment. 

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4.2.2 TREATMENT VISIT (DAY 0) 
The Treatment Visit must be performed within 14 days of the Screening Visit. The 
following procedures must be performed and recorded:  
Prior to Investigational Product Administration 
1. Review eligibility criteria and confirm that all screening visit procedures have 
been completed, results reviewed, and recorded 
2. Update medical/surgical history 
3. Conduct patient education: Discuss the potential effect of DaxibotulinumtoxinA 
for Injection treatment, explain the PFWS measurement and the categories of the 
severity assessment scales, and instruct the subjects to consider depth of lines for 
severity of their glabellar lines. Use the provided Patient Education Brochure 
4. Measure and record vital signs (body temperature, respiratory rate, sitting radial 
pulse, and sitting systolic and diastolic blood pressure) 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

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17. Once the Investigator has confirmed subject eligibility, enroll the subject 
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 (Appendix A) 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 area (forehead) 
3. Wipe all injection sites with alcohol 
4. Inject a dose of 
 
 
 
 
After Investigational Product Administration 
1. 
 obtain 
vital signs (body temperature, respiratory rate, sitting radial pulse, and sitting 
systolic and diastolic blood pressures) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4.2.3 WEEK 1 FOLLOW-UP VISIT  
At Week 1, following treatment, the subject will return to the office 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:  
1. Query subject about concomitant therapy/medication 
2. Query subject about any AEs 
 
 
 
 
 
 
 
 
 
 
 
 
7. Conduct patient education: discuss the potential effect of DaxibotulinumtoxinA 
for Injection treatment, explain the PFWS measurement and the categories of the 
severity assessment scales, and instruct the subjects to consider depth of lines for 
severity of their glabellar lines. Use the provided Patient Education Brochure 
 
 
 
 
 
 
 
 
 

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4.2.4 FOLLOW-UP VISITS  
At Week 2 following treatment, and Weeks 4, 8, 12, and monthly until subject qualifies 
for retreatment or Final Evaluation Visit, the following procedures must be performed 
and recorded: 
1. Conduct patient education: discuss the potential effect of DaxibotulinumtoxinA 
for Injection treatment, explain the PFWS measurement and the categories of the 
severity assessment scales, and instruct the subjects to consider depth of lines for 
severity of their glabellar lines. Use the provided Patient Education Brochure 
2. At Week 2 only, measure and record vital signs (body temperature, respiratory 
rate, sitting radial pulse, and sitting systolic and diastolic blood pressure) 
 
  
 
 
 
6. At Week 4 only, collect blood samples for clinical safety laboratory tests 
(hematology and chemistry)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
15. Assess AEs 
 
 
 

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4.2.5 RETREATMENT PROCEDURES  
At select centers, subjects may be eligible for retreatment up to two times. In addition to 
the procedures performed during the follow-up visit, the following retreatment 
procedures should also be performed: 
Prior to Investigational Product Administration 
 
 
2. Measure and record vital signs (body temperature, respiratory rate, sitting radial 
pulse, and seated systolic and diastolic blood pressure)  
 
 
 
 
 
 
 
7. Once the Investigator has confirmed subject eligibility for retreatment, the subject 
will be treated. The trained dose preparer will prepare the assigned investigational 
product according to trial-specific instructions 
After Investigational Product Administration 
1. 
 obtain 
vital signs (body temperature, respiratory rate, sitting radial pulse, and seated 
systolic and diastolic blood pressure) 
 

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3. Assess for AEs 
 
 
 
 
 
 
 
 
 
 
 
4.2.6 FINAL EVALUATION VISIT 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 safety until at least 
Week 12 and up to Week 36 with monthly visits until both IGA-FWS and PFWS scores 
have returned to baseline. The subject will then have a Final Evaluation Visit. If a subject 
has received multiple treatments, the Final Evaluation Visit will occur at Week 12 
following the final treatment. 
1. Conduct patient education: Discuss the potential effect of DaxibotulinumtoxinA 
for Injection treatment, explain the PFWS measurement and the categories of the 
severity assessment scales, and instruct the subjects to consider depth of lines for 
severity of their glabellar lines. Use the provided Patient Education Brochure 
2. Measure and record vital signs (body temperature, respiratory rate, sitting radial 
pulse, and sitting systolic and diastolic blood pressure) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15. Assess AEs 
 
 
 
 
 
 
 
 
 
 
 
If there are no safety concerns, the subject’s participation in the trial is complete at this 
visit. 
4.2.7 UNSCHEDULED VISITS 
If an AE occurs that in the Investigator’s opinion requires a clinical examination for 
further assessment, the subject should be brought in for an unscheduled visit. If signs of 
suspected ptosis are reported or observed, obtain photographs of subject in primary gaze 
with brow relaxed, and in primary gaze with brow elevated. 
4.2.8 DISCONTINUATION/WITHDRAWAL PROCEDURES 
A subject may voluntarily withdraw from trial participation at any time. If the subject 
withdraws consent and discontinues from the trial, the Investigator will attempt to 
determine the reason for discontinuation and record the reason in the subject’s trial 
records and on the case report form (CRF). If a subject withdraws consent because of an 
AE, that AE should be indicated as the reason for withdrawal. In the event of early 

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discontinuation, (i.e., prior to the Final Evaluation) and whenever possible, the subject 
should be asked to return to the trial center to complete the assessments specified in the 
Final Evaluation Visit. Subjects who withdraw from the trial will not be replaced. 
If at any time during the trial, 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 trial participation at any time if medically 
necessary or if the subject has failed to follow trial procedures or to keep follow-up 
appointments. Appropriate documentation in the subject’s trial record and CRF regarding 
the reason for discontinuation must be completed. Prior to discontinuing a subject from 
trial participation, the Investigator will discuss his/her intentions with the Medical 
Monitor or designee. 
All subjects who fail to return to the trial 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 trial. If a subject is unreachable by 
telephone after a minimum of two documented attempts (one attempt on two different 
days), a registered letter will be sent requesting that contact be made with the 
Investigator. 
Revance has the right to terminate or to stop the trial at any time. Should this be 
necessary, both Revance and the Investigator will ensure that proper trial discontinuation 
procedures are completed. 
4.3 
VARIATION FROM SCHEDULED VISIT DAYS 
To allow for scheduling flexibility, limited variation will be permitted from the specified 
time of each visit (Table 1). 
Table 1: Allowed Variation from Scheduled Visit Days 
Scheduled Visit (Post Each Treatment) 
Allowed Variation 
Week 1  
+ 2 days 
Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, and 36 
+/- 3 days 
 
4.4 
SCHEDULE OF VISITS AND PROCEDURES 
A schedule of visits and procedures is provided in Appendix F. 
 
 

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4.5 
SAFETY ASSESSMENTS 
4.5.1 CLINICAL LABORATORY DATA 
As outlined in Table 2, non-fasting samples for hematology, chemistry, PT (Screening 
only) and urinalysis will be collected at Screening, Week 4 visits, prior to Retreatment (as 
applicable), and at the Final Evaluation Visit. 
 
. 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 trial center 
using supplies provided by the sponsor. 
Table 2: 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) 
Urine Pregnancy 
(WOCBP only)* 
 
 
 
 
*If positive at timepoints after trial 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 (NCS) or 
Clinically Significant (CS) 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. Refer to Section 6.1.1 for further information. 
 
 

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4.5.2 PREGNANCY TESTING 
All WOCBP will have a UPT at the Screening Visit, prior to any treatment and Final 
Evaluation Visit or Early Discontinuation, if applicable. If any result is positive prior to 
treatment, the subject will not be allowed to participate. The results of the UPTs for 
WOCBP will be evaluated at the trial center. Refer to Section 4.1.1 for further 
information. 
4.5.3 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, Treatment Visit 
(pre- and post-treatment), Week 2, Final Evaluation or Early Discontinuation Visits,
 
. 
4.5.4 PHYSICAL EXAM 
A physical examination, in addition to vital signs,
 
, general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, 
heart, lungs, abdomen, lymph nodes, and extremities will be conducted at Screening, 
Week 2 and Final Evaluation or Early Discontinuation Visits. Significant physical 
examination findings that are present prior to investigational product administration are 
to be included on the Medical History page. 
Significant physical examination findings which meet the definition of an adverse event 
will be recorded on the adverse event page post-treatment. 
4.5.5 INJECTION SITE EVALUATION 
Injection sites will be evaluated at the Screening Visit, Treatment Visit pre- and post-
treatment (to determine if there is an immediate reaction to the investigational product), 
Follow-up Visits, and Final Evaluation Visit or Early Discontinuation Visit, if applicable. 
The assessment will be done as a global evaluation of the five injection sites (Table 3).  

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Table 3: 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 
 
 
 
 
 

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4.5.9 ADVERSE EVENTS 
Adverse Events (AEs) will be graded as mild, moderate, or severe as defined in 
Section 6.1.2 of this protocol. 
AEs will be evaluated at the Treatment Visit post-treatment, Follow-up Visits, and Final 
Evaluation Visit or Early Discontinuation Visit, if applicable. Section 6 outlines the 
procedures for recording and reporting AEs. 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4.6 
EFFECTIVENESS ASSESSMENTS 
Effectiveness assessments will include Investigator assessment of glabellar line severity 
and glabellar line improvement, subject assessment of glabellar line severity and 
improvement. Effectiveness assessments will be conducted with the subject in a sitting 
position. In order to have 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). 
4.6.1 PATIENT FROWN WRINKLE SEVERITY (PFWS) 
At each clinic visit as designated in the Schedule of Trial Assessments (Appendix F), the 
subject will assess the visual appearance (at maximum frown and at rest after maximum 
frown) of the glabellar lines using the following 4 point scale for subject’s assessment of 
Patient Frown Wrinkle Severity (Appendix B, Table 8). The assessment form will be 
provided directly to the subject to complete while reviewing the glabellar treatment area 
using the supplied handheld mirror as outlined in Appendix B. Subjects with contact 
lenses should view their glabellar lines with contacts. Subjects wearing glasses should be 
advised to view their glabellar lines without glasses if possible. If glasses are needed for 
the subject to see their glabellar lines, then glasses can be worn for the assessment. The 
subject assessment must be completed before the Investigator completes the IGA-FWS 
assessment. 
Table 8: Patient Frown Wrinkle Severity 
(PFWS) 
Rating Score  
Frown Wrinkle 
Severity  
Description  
0 
None 
No wrinkles 
1 
Mild 
Very shallow wrinkles 
2 
Moderate 
Moderate wrinkles 
3 
Severe 
Deep wrinkles 
 
 
 
 
  
 
 

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4.6.2 INVESTIGATOR GLOBAL ASSESSMENT FROWN WRINKLE SEVERITY 
At each clinic visit as designated in the Schedule of Trial Assessments (Appendix F), the 
Investigator will assess the visual appearance (at maximum frown and at rest after 
maximum frown) of the glabellar lines using the IGA-FWS with the following 4 point 
scale (Table 9). 
Table 9: Investigator Global Assessment Frown Wrinkle Severity 
(IGA-FWS) 
Rating Score 
Frown Wrinkle Severity  
Description  
0 
None 
No wrinkles 
1 
Mild 
Very shallow wrinkles 
2 
Moderate 
Moderate wrinkles 
3 
Severe 
Deep and furrowed wrinkles 
 
 
 
 
 
 
 
 
4.6.3 GLOBAL AESTHETIC IMPROVEMENT SCALE 
The Investigator and subject will assess the visual appearance (at maximum frown and at 
rest after maximum frown) of the glabellar line improvement from the baseline condition 
using the following 7 point severity Global Aesthetic Improvement Scale (GAIS, 
Table 10). Assessments will be made as designated in the Schedule of Trial Assessments 
(Appendix F).  
The Patient GAIS assessment form (Appendix D) will be provided directly to the subject 
to complete while reviewing the glabellar treatment area (at maximum frown and at rest 
after maximum frown) using the supplied handheld mirror as outlined in Appendix D. 
Subjects with contact lenses should view their glabellar lines with contacts. Subjects 
wearing glasses should be advised to view their glabellar lines without glasses if possible. 
If glasses are needed for the subject to see their glabellar lines, then glasses can be worn 
for the assessment. The subject assessment must be completed before the Investigator 
completes the IGA-FWS assessment. 

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Table 10: 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 
 
4.6.4 ADDITIONAL ASSESSMENTS  
 
 
 
 
 
 
 
   
 
 
 
 
 
 
  
4.7 
SCREEN FAILURES 
A screen failure subject will be a person from whom informed consent is obtained and is 
documented in writing (i.e., subject signs an informed consent form), but who does not 
meet the trial eligibility requirements.  
4.8 
PROTOCOL DEVIATIONS 
This trial will be conducted as described in this protocol, except for an emergency 
situation in which the protection, safety, and well-being of the subject requires immediate 

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intervention, based on the judgment of the Investigator (or a responsible, appropriately 
trained professional designated by the Investigator). In the event of a significant deviation 
from the protocol due to an emergency, accident, or mistake, the Investigator or designee 
must contact Revance at the earliest possible time by telephone.  This will allow an early 
joint decision regarding the subject’s continuation in the trial. This decision will be 
documented by the Investigator and the Sponsor.   

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5 
PROHIBITED THERAPIES AND MEDICATIONS 
5.1 
CONCOMITANT MEDICATIONS 
Concomitant medications are any prescription or over-the-counter preparations used by 
subjects during participation in the trial. Use of concomitant medications will be recorded 
on the Concomitant Medications case report form (CRF) beginning at the Screening Visit 
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 
EVALUATION OF ADVERSE EVENTS 
6.1 
DEFINITIONS 
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 trial 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 clinically significant change in the trial safety evaluations, (e.g., vital signs, injection 
site evaluation, 
 
) post-treatment 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) 

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• 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 prevent one of the outcomes listed above (i.e., is a significant or 
important medical event) 
6.1.1 CLINICAL LABORATORY CHANGES 
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. This determination, however, does not necessarily need to be 
made the first time an abnormal value is observed; the Investigator may repeat the 
laboratory test or request additional tests to verify the results of the original laboratory 
test. If this laboratory value is determined to be a clinically significant result for that 
subject, this may be considered an AE to be assessed according to severity.  
The Investigator must sign and date all written laboratory reports (e.g., urinalysis, 
hematology, chemistry, PT, and pregnancy tests) and note Not Clinically Significant 
(NCS) or Clinically Significant (CS) for each out of range laboratory value. 
6.1.2 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 

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• 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 trial; treatment or other 
intervention usually needed  
6.2 
REPORTING ADVERSE EVENTS 
The Investigator will assess subjects post-treatment and at each subsequent trial visit for 
the occurrence of AEs. In order to avoid bias in eliciting AEs, subjects should be asked 
the following non leading question: “How have you felt since your last visit?” All AEs 
(serious and non-serious) reported by the subject must be recorded on the source 
documents and CRFs.  
In addition, an Investigator must report an SAE to Revance within 24 hours of their 
awareness of the event according to the procedure outlined below. All fatal or life-
threatening SAEs should be telephoned to Revance or the authorized representative as 
soon as the investigator learns of the event. 
6.3 
SERIOUS ADVERSE EVENTS 
An Investigator must report an SAE to Revance or the designated CRO’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 
 If the event is fatal or life-threatening, telephone Revance or the authorized 
representative as soon as the investigator learns of the event 
 Obtain and maintain all pertinent medical records (discharge summary, autopsy 
report, etc.) and medical judgments of medical personnel who assisted in subject’s 
treatment and follow-up 
 Provide follow-up information to Revance or the authorized representative 
Regulatory authorities, IRBs/IEC, and Investigators will be notified of SAEs in 
accordance with applicable regulations and requirements (e.g., GCPs, ICH Guidelines, 
national regulations and local requirements). 
6.4 
PROCEDURE FOR ACCESSING THE RANDOMIZATION CODE 
Not Applicable: open label trial. 

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6.5 
FOLLOW-UP OF ADVERSE EVENTS  
6.5.1 FOLLOW-UP OF NON-SERIOUS ADVERSE EVENTS 
Non-serious AEs that are identified during the last scheduled trial visit (or early 
discontinuation, if applicable) must be recorded on the AE CRF 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, trial related abnormalities at the end of the trial, 
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. 
6.5.2 FOLLOW-UP OF POST TRIAL SERIOUS ADVERSE EVENTS 
SAEs that are identified on the last scheduled contact (or early discontinuation, if 
applicable) must be recorded on the AE CRF page and reported to the CRO and Revance 
according to the reporting procedures outlined in Section 6.3. This may include 
unresolved previously reported SAEs, or new SAEs. The Investigator should follow these 
SAEs until the events are resolved, or the subject is lost to follow-up. The Investigator 
should continue to report any significant follow-up information to the Medical Monitor, 
Revance 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 and the 
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7 
STATISTICAL ANALYSIS 
7.1 
GENERAL CONSIDERATIONS 
The analysis of data from the trial will be performed when all subjects have completed 
the trial or discontinued prematurely, and all data are in the database and have been 
cleaned and verified. All statistical programming will be performed using statistical 
analysis system (SAS) version 9.4 or higher.   
The trial has up to three treatments. Depending on the analysis purpose, the 
corresponding summary period will be defined for each treatment. For the trial-overall 
summary, all available data observed during the trial will be included. For analyses 
associated with a specific treatment, the summary will include all data observed since the 
treatment until the next treatment, or until the last visit of the trial when there is no 
subsequent treatment. To account for varying subject follow-up duration, the total follow-
up duration (i.e., patient-years) will be calculated for each summary period. 
For the trial-overall summary, the baseline will be the last available value prior to the first 
treatment. For summaries associated with a specific treatment, the baseline will be the 
last available value prior to treatment (i.e., re-baselined). 
7.2 
ANALYSIS POPULATIONS 
The Safety-Evaluable population will include all subjects who are exposed to the 
investigational product and who provide any post-treatment safety information. 
Analyses specifically associated with each of the three treatment periods will be 
performed on a subset of the safety-evaluable population, including only those subjects 
who receive trial treatment and have post-treatment safety information for the specific 
treatment.  These safety-evaluable sub-populations will be respectively identified as 
Treatment-1-Evaluable, Treatment-2-Evaluable, or Treatment-3-Evaluable. 
In addition to subjects who are directly enrolled, the trial also includes subjects rolling 
over from two pivotal phase 3 studies, SAKURA-1 and SAKURA-2.  For the roll over 
subjects who are in the active treatment group in the prior trial, the first 
daxibotulinumtoxinA treatment in this open-label safety trial will in fact be their second 
daxibotulinumtoxinA treatment.  Based on the subject’s prior exposure to 
DaxibotulinumtoxinA, the following two summary groups will be defined for the 
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• Group A: all subjects who have received DaxibotulinumtoxinA for injection in 
SAKURA-1 or SAKURA-2 
• Group B: all subjects in the trial who are not in Group A  
7.3 
TRIAL ENDPOINTS 
Safety Endpoints: 
• Incidence, severity and relationship to trial drug of treatment-emergent adverse 
events during each treatment and the trial overall 
• Incidence, severity and relationship to trial drug of treatment-emergent serious 
adverse events during each treatment and the trial overall 
Effectiveness Endpoints: 
Unless specified otherwise, all endpoints associated with IGA-FWS, PFWS or GAIS 
henceforth will be based on assessments at maximum frown.  When applicable, similar 
endpoints based on assessments at rest after maximum frown will also be summarized. 
For the endpoints that are derived from a comparison with the baseline, two derivation 
rules using different reference timepoints as the baseline (i.e., trial baseline or treatment 
baseline) will be applied separately. 
• Time to retreatment since the first trial treatment (on Treatment-1-Evaluable only) 
• Time to retreatment since the second trial treatment (on Treatment-2-Evaluable 
only) 
• Time to return to, or worse than, baseline on both IGA-FWS and PFWS 
• Time to return to 2 or 3 (moderate or severe) on both IGA-FWS and PFWS 
• Proportion of subjects with a ≥2 point improvement from baseline on both IGA-
FWS and PFWS at each visit over time 
• Proportion of subjects with a score of 0 or 1 (none or mild) on IGA-FWS at each 
visit over time  
• Proportion of subjects with a score of 0 or 1 (none or mild) on PFWS at each visit 
over time  
• Proportion of subjects with a ≥1 point improvement from baseline on both IGA-
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• Proportion of subjects with a ≥1 point improvement (i.e., improved, much 
improved, or very much improved) on GAIS at each visit over time (with 
investigator’s assessment and subject’s self-assessment summarized separately) 
• Proportion of subjects with a ≥2 point improvement (i.e., much improved, or very 
much improved) on GAIS at each visit over time (with investigator’s assessment 
and subject’s self-assessment summarized separately)  
• Proportion of subjects with a ≥3 point improvement (i.e., very much improved) on 
GAIS at each visit over time (with investigator’s assessment and subject’s self-
assessment summarized separately) 
• Mean GAIS score at each visit over time (with investigator’s assessment and 
subject’s self-assessment summarized separately) 
7.4 
SAFETY ANALYSES 
Safety data collected for the overall trial period will be summarized for the Safety-
Evaluable population. Summaries associated with each of the three treatment periods will 
be performed on the corresponding sub-population (i.e., Treatment-1-Evaluable, 
Treatment-2-Evaluable or Treatment-3-Evaluable).  To account for varying subject 
follow-up duration, the total follow-up duration (i.e., patient-years) will be calculated for 
each summary period. 
Descriptive statistics will be presented to summarize the safety data. 
7.4.1 ADVERSE EVENTS 
All AEs will be recorded and classified on the basis of MedDRA terminology. 
Treatment-emergent AEs are those AEs with an onset on or after the date and time of trial 
treatment. All treatment-emergent AEs will be summarized by system organ class, 
preferred term, severity, relationship, and seriousness. When summarizing events by 
causality and severity, each subject will be counted only once within a system organ class 
or a preferred term by using the event with the greatest relationship and highest severity 
within each classification. 
All information pertaining to AEs noted during the trial will be listed by subject, detailing 
the verbatim description given by the Investigator, preferred term, system organ class, 
start date, stop date, severity, action taken regarding trial drug, corrective treatment, 
outcome, and drug relatedness. The event onset relative (in number of days) to the date of 
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administration prior to the event, will be provided. In addition, a list of adverse events 
that lead to the subject’s premature discontinuation of the trial will also be provided. 
Serious adverse events (SAEs) will be listed by subject. SAEs will be summarized by 
severity and relationship to trial treatment.  Each subject will be counted only once within 
a system organ class or a preferred term using the event with the greatest relationship and 
greatest severity. 
The summaries of AEs and SAEs will be performed for the trial overall, and for each of 
the three treatment periods.  For SAEs and key AEs 
 
, rate-per-injection and rate-per-patient-year will be 
calculated.  A 95% confidence interval will also be provided for the rate. 
7.4.2 LABORATORY TESTS 
Laboratory test results will be summarized with descriptive statistics by visit. Change 
from Screening to Final Evaluation Visit will be summarized for continuous test results. 
Shift tables will be presented to summarize laboratory test results at Screening and Final 
Evaluation Visit. Normal ranges established by the central laboratory will be used to 
determine shifts. A listing of all out-of-range laboratory test results at any evaluation will 
also be provided. Determination of clinical significance for all out-of-range laboratory 
values will be made by each investigator and included in the listing. In addition, a listing 
of all clinically significant laboratory test results will be provided. 
 
 
 
 
 
 
  
UPTs will be summarized for all treated subjects in the category of WOCBP and 
presented in the data listings. 
7.4.3 VITAL SIGNS AND PHYSICAL EXAMINATION 
Vital signs and abnormal findings from the physical examination will be summarized 
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7.4.4 INJECTION SITE EVALUATION 
Outcomes of the injection site evaluations will be tabulated by visit for each treatment. 
 
 
 
 
 
 
7.4.7 CONCOMITANT THERAPIES/MEDICATIONS 
Concomitant therapies/medications used at Screening and during the trial will be coded 
using the World Health Organization (WHO) drug dictionary and summarized by 
treatment group, Anatomical Therapeutic Chemical (ATC) second level term, and 
preferred name for the Safety-Evaluable population. 
 
 
 
  
7.4.9 EFFECTIVENESS ANALYSIS 
Effectiveness data will be summarized as observed with no imputation for missing data.  
Descriptive statistics will be provided for all effectiveness variables at all timepoints by 
the summary group.  95% confidence intervals and/or p-values for comparing the 
difference between subgroups of interest (e.g., females vs males) will be provided as 
appropriate.  Kaplan-Meier curves will be plotted for the time-to-event endpoints defined 
in Section 7.3.   
When comparisons (e.g., females vs males, Treatment 1 vs Treatment 2, etc.) are 
performed, the tests will be done at a significant level of 0.05 with no adjustment for 
multiplicity. 
7.4.10 SAMPLE SIZE AND POWER CONSIDERATIONS 
This is a safety trial with all subjects treated with the same investigational product.  The 
sample size of approximately 2,100 is considered to be adequate in assessing the safety 
based on several approaches.  
 

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9 
RECORDS MANAGEMENT 
9.1 
DATA COLLECTION 
For this trial, all protocol-specified data will be recorded in the source documents, and 
data will be entered on the CRFs from the source documents. In addition to signature 
confirmation that a subject meets the trial eligibility criteria, upon each subject’s 
completion of the trial, 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 trial data be verifiable with the source data that 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 trial 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 Screening. 
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 Trial Coordinator. Data queries will be sent to the trial center. Trial center personnel 
will be responsible for providing resolutions to the data queries and for correcting the 
CRFs, as appropriate. All unused Revance source documents and binders must be 
returned to Revance upon completion of the trial. 
The Investigator must keep written or electronic source documents for every subject 
participating in the clinical trial. The subject file that identifies the trial 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 
• Trial visit dates 
• Performed examinations, evaluations, and clinical findings 

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• 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, trial number, and the date of the evaluation.  
The data recorded during the course of the trial will be documented in the CRF and/or the 
trial-specific forms. Before or at trial termination, all data must be forwarded to Revance. 
The data will then be recorded, evaluated, and stored in anonymous form in accordance 
with data-protection regulations. 
Subjects will authorize the use of their protected health information during the informed 
consent process in accordance with the applicable privacy requirements. Subjects who 
deny permission to use and disclose protected health information will not be eligible to 
participate in the trial. The Investigator will ensure that the trial documents forwarded to 
Revance, and any other documents, contain no mention of subject names. 
Any amendments and corrections necessary will be undertaken in both the source 
documents and CRFs (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 CRF should be cancelled out so as to avoid unnecessary follow-up 
inquiries. 
Regulatory authorities, the IRB/IEC and/or the Revance’s Quality Assurance group (or 
designee) may request access to all source documents, CRFs, and other trial 
documentation for on-site audit or inspection. The Investigator must guarantee direct 
access to these documents. CRFs will be kept by Revance or an authorized 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 after descriptive and statistical analyses and reports have been 
generated and are complete.  

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9.2 
FILE MANAGEMENT AT THE TRIAL CENTER 
It is the responsibility of the Investigator to ensure that the trial center file is maintained 
in accordance with ICH Guidance for Industry E6 Good Clinical Practice: Consolidated 
Guidance, Section 8 – Essential Documents for the Conduct of a Clinical Trial. 
9.3 
RECORDS RETENTION AT THE TRIAL 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 two years after Revance notifies the Investigator that the data will not 
be submitted for review by any Regulatory Authority  
The Investigator must not dispose of any records or essential documents relevant to this 
trial 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 all 
observations and data generated during this trial. Such documentation is subject to 
inspection by Revance and relevant regulatory agencies. If the Investigator withdraws 
from the trial (e.g., relocation, retirement) all trial-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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10 MONITORING, COMPLIANCE, AND QUALITY 
All aspects of the trial will be monitored by Revance or authorized representatives of 
Revance according to Good Clinical Practices (GCP) and Standard Operating Procedures 
(SOPs) for compliance with applicable government regulations, (i.e., Informed Consent 
Regulations and Institutional Review Board regulations).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 ETHICS AND RESPONSIBILITY 
This trial must be conducted in compliance with the protocol, the ICH Guidance for 
Industry E6 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 informed consent form) to Revance before investigational product will be shipped to 
the trial center.  

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