A Multicenter, Single-Blind, Randomized, Parallel-Group, Controlled Study of the Safety and Effectiveness of JUVÉDERM VOLUMA® XC Injectable Gel for Correction of Temple Hollowing
Phase: NA
Conditions: Temple Hollowing
Sponsor: Allergan

 
 
NCT03166618 
 
Study ID: VOLUMA-007 
 
Title: A multicenter, single-blind, randomized, parallel-group, controlled study of the safety 
and effectiveness of JUVÉDERM VOLUMA® XC injectable gel for correction of temple 
hollowing 
 
Protocol Date: 24 Feb 2017 

 
 
Approval Date: 
 
01-Mar-2017
Allergan Confidential 
 
JUVÉDERM VOLUMA® XC 
Protocol VOLUMA-007 Amendment 3 
 
 
Page 1 of 75 
 
 
Title Page 
ALLERGAN – CONFIDENTIAL 
The following contains confidential, proprietary information 
that is the property of Allergan 
Study Title: 
A multicenter, single-blind, randomized, parallel-group, 
controlled study of the safety and effectiveness of 
JUVÉDERM VOLUMA® XC injectable gel for 
correction of temple hollowing 
Protocol Number: 
VOLUMA-007 Amendment 3 
Protocol Date 
24 Feb 2017 
Product Name: 
JUVÉDERM VOLUMA XC injectable gel 
Development Phase: 
Pivotal 
Sponsor: 
Allergan 
 
 
 
 
 
 
 
 
 
 
 
Names and contact information of Allergan study personnel are provided in the 
supplementary Study Contacts page.

 
 
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INVESTIGATOR SIGNATURE PAGE 
Study Title: 
A multicenter, single-blind, randomized, parallel-
group, controlled study of the safety and 
effectiveness of JUVÉDERM VOLUMA® XC 
injectable gel for correction of temple hollowing 
 
Protocol Number: 
VOLUMA-007 Amendment 3 
Protocol Date: 
24 Feb 2017 
Product Name: 
JUVÉDERM VOLUMA XC injectable gel 
Investigator: 
 
Study Location: 
 
 
I agree to: 
• Implement and conduct this study diligently and in strict compliance with this protocol, 
good clinical practices (GCP), and all applicable laws and regulations. 
• Maintain all information supplied by Allergan in confidence and, when this information 
is submitted to an Institutional Review Board (IRB) or another group, it will be submitted 
with a designation that the material is confidential. 
I have read this protocol in its entirety and I agree to all aspects. 
 
 
 
 
 
Investigator Printed Name 
 
Signature 
 
Date 
 
 
 
 
 
Investigator Printed Name 
 
Signature 
 
Date 
 
 
 
 
 
Investigator Printed Name 
 
Signature 
 
Date 
RETURN TO ALLERGAN 

 
 
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Synopsis 
 
NUMBER AND TITLE OF STUDY: 
VOLUMA-007:  A multicenter, single-blind, randomized, parallel-group, controlled study of the safety and 
effectiveness of JUVÉDERM VOLUMA® XC injectable gel for correction of temple hollowing 
DEVELOPMENT PHASE:  Pivotal 
STUDY CENTERS:  Up to 15 United States centers, including up to 3 centers for the feasibility phase 
NUMBER OF SUBJECTS:  Up to 189 subjects will be enrolled, including up to 30 subjects for the feasibility 
phase and up to 159 subjects for the pivotal phase 
OBJECTIVES:  The objectives of this study are to evaluate the safety and effectiveness of JUVÉDERM 
VOLUMA XC injectable gel in adult subjects seeking correction of temple hollowing. 
STUDY DESIGN: 
This is a prospective, multicenter, evaluator-blinded, randomized, parallel-group, controlled study to evaluate the 
safety and effectiveness of JUVÉDERM VOLUMA XC hyaluronic acid (HA) injectable gel to correct temple 
hollowing. 
 
 
 
 
 
At screening, after written informed consent has been given, the Treating Investigator (TI) will document the 
subject’s demographics, height, weight, vital signs, Fitzpatrick skin phototype, race, and history of sun exposure, 
smoking, and medical, surgical, dental, and cosmetic procedures.  Female subjects of childbearing potential will 
undergo urine pregnancy tests.  The Evaluating Investigator (EI) will rate subjects on the 5-point photonumeric 
Allergan Temple Hollowing Scale (ATHS) to determine eligibility for the study.  Subjects will be randomized 
2:1 to the treatment group or the control group and 1:1 to receive the first treatment in the right or left temple.  
The same order must be used for all treatments. 
FEASIBILITY PHASE: 
Treatment group:  
 
 
 
  Pretreatment 
anesthesia will be applied as necessary.  
 
 
.  
 
 
 
 
 
 Treatment of the second temple will follow the same treatment procedures as treatment of the first 
temple (
).  
 
.  Subjects will return for an office visit at 14 days after treatment of 
the second temple 
 

 
 
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  Thirty days after treatment of the second temple, the 
subject and the TI will discuss the results of the initial treatment and determine whether correction has been 
achieved.  If correction has not been achieved in 1 or both temples, the TI may perform a touch-up treatment.  
Touch-up treatment will be administered as described for initial treatment with each temple treated 1 or 2 days 
apart 
  The touch-up treatment visits, procedures, and 
follow-up are identical to those for the initial treatment. 
 
 
Routine follow-up visits for safety and effectiveness will occur at 1, 3, 6, 9, and 12 months after the last 
treatment.  At each visit, 
 
; the EI will rate 
subjects on the ATHS; the EI and subjects will separately assess improvement in the temple area using the 
Global Aesthetic Improvement Scale (GAIS); 
 
 
   
Control group:  Subjects randomized to the control group will complete a 3-month no-treatment control period 
 
, 
 and the EI will rate them on the 
ATHS and the GAIS at the month 1 and 3 visits. Subjects will exit the study after the month 3 procedures are 
complete.  
PIVOTAL PHASE: TBD 
Treatment group:  In the pivotal phase, subjects randomized to the treatment group will undergo the visit(s) and 
procedures prior to, during (initial, touch-up, and repeat treatments), and after treatment identical to those for 
subjects randomized to the treatment group in the feasibility phase.  Except that, in the pivotal phase, treatment 
of both temples from the same subject will occur on the same day, but will be separated by at least 30 minutes. 
Control group:  Pivotal phase subjects randomized to the control group will undergo the visit(s) and procedures 
during the no-treatment control period, prior to, during (optional initial and touch-up treatments), and after 
treatment identical to those for subjects randomized to the control group in the feasibility phase. 
DIAGNOSIS AND CRITERIA FOR INCLUSION/EXCLUSION: 
Adults with temple hollowing who are seeking restoration in the temple area 
INCLUSION: 
1. Age 22 or over and in good general health 
2. 
 
3. TI considers the subject’s temple hollowing to be amenable to temporary correction 
4. 
 
 
5. 
 
6. 
 
EXCLUSION: 
1. 
 
 
2. Has temple hollowing due to trauma, congenital malformations, or lipodystrophy, either congenital or 
acquired (eg, congenital myotonic dystrophy, HIV-associated lipodistrophy, or acquired generalized 
lipodystrophy) 
3. 
 

 
 
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4. Has ever received permanent facial implants (eg, polymethylmethacrylate, silicone, 
polytetrafluoroethylene) anywhere in the face or neck, or is planning to be implanted with any of these 
products during the study 
5. Has ever undergone fat injections above the subnasale or is planning to undergo this procedure during 
the study 
6. Has tattoos, piercings, facial hair (ie, beard, mustache), or scars above and including the subnasale that 
would interfere with visual assessment of the temple 
7. Has undergone semipermanent dermal filler treatment (eg, calcium hydroxyapatite, poly-L-lactic acid) 
in the temple or mid-face within 36 months before enrollment or is planning to undergo such treatment 
during the study 
8. Has undergone dermal filler injections above the subnasale within 24 months before enrollment or is 
planning to undergo this procedure during the study 
9. Has temporal arteritis or history of temporal arteritis 
10. Has temporomandibular joint dysfunction 
11. Has active or recurrent inflammation or infection in either eye 
 
) 
13. 
 
14. Has undergone mesotherapy or cosmetic treatment (laser, photomodulation, intense pulsed light, radio 
frequency, dermabrasion, moderate or greater depth chemical peel, liposuction, lipolysis, or other 
ablative procedures) anywhere in the face or neck or botulinum toxin injections above the subnasale 
within 6 months before enrollment or is planning to undergo any of these procedures during the study 
15. Has experienced trauma to the temple area within 6 months before enrollment or has residual 
deficiencies, deformities, or scarring 
16. Has a tendency to develop hypertrophic scarring 
17. Has a history of anaphylaxis or allergy to lidocaine (or any amide-based anesthetics), hyaluronic acid 
products, or Streptococcal protein, or is planning to undergo desensitization therapy during the term of 
the study 
18. Has porphyria or untreated epilepsy 
19. Has active autoimmune disease 
20. Has current cutaneous or mucosal inflammatory or infectious processes (eg, acne, herpes, gum disease), 
abscess, an unhealed wound, or a cancerous or precancerous lesion, above the subnasale (study device 
injection may be delayed for subjects with a history of recurrent oral herpes lesions who take 
prophylactic doses of antiviral/herpes medication for at least 2 days before study treatment 
administration) 
21. Is on a concurrent regimen of lidocaine or structurally-related local anesthetics (eg, bupivacaine) or is 
on a concurrent regimen of drugs that reduce or inhibit hepatic metabolism (eg, cimetidine, beta-
blockers) 
22. 
 
23. 
 
 
 
24. 
 

 
 
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25. 
 
 
26. 
 
27. 
 
28. 
 
 
TEST PRODUCT, DEVICE VOLUME, AND MODE OF ADMINISTRATION: 
JUVÉDERM VOLUMA XC (a hyaluronic acid injectable gel with lidocaine) will be administered via the 
supplied needles (27G ½″) to the temple area.  Appropriate injection volume for the temple will be determined 
by the TI
 
 
DURATION OF STUDY: 
Participation for each subject in the feasibility phase treatment group will encompass up to 1 month for 
screening, 1 month for treatment, and 12 months of follow-up after the last treatment (initial or touch-up). 
Participation for each subject in the feasibility phase control group will encompass up to 1 month for screening 
and 3 months for the no-treatment control period. 
RESPONSE MEASURES: 
Effectiveness:  The primary effectiveness measure is the EI assessment of temple hollowing using the ATHS (on 
a 5-point scale of convex to severe).  
 
 
 
 
Safety:  
 
 
 
 
STATISTICAL METHODS: 
Sample Size Calculation:  The sample size is determined to provide adequate power to demonstrate that the 
product is effective as well as safe.  A total of 90 subjects in the treatment group and 45 subjects in the control 
group will provide at least 90% power to detect a difference of 30% in the responder rates between the groups.  
 
 
 
 
 
 
 
 
 

 
 
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Effectiveness:  The primary effectiveness endpoint will be met if the responder rate for the treatment group is 
statistically greater than that for the control group at month 3 and the responder rate at month 3 for the treatment 
group is 60% or greater.  
 
 
 
 
 
 
 
 
 
 
 
 
Safety:  
 
 
 
 
 
 

 
 
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Table of Contents 
Synopsis .................................................................................................................................... 3 
Table of Contents ...................................................................................................................... 8 
List of Tables ........................................................................................................................... 11 
List of Figures ......................................................................................................................... 12 
1. 
Abbreviations and Terms ................................................................................................. 20 
2. 
Background, Risk and Benefit, and Clinical Rationale ................................................... 21 
2.1 
Background ............................................................................................................ 21 
2.2 
Risk and Benefit ..................................................................................................... 23 
2.3 
Clinical Rationale ................................................................................................... 24 
3. 
Study Objectives and Clinical Hypotheses ...................................................................... 25 
3.1 
Study Objectives .................................................................................................... 25 
3.2 
Clinical Hypothesis ................................................................................................ 25 
4. 
Study Design .................................................................................................................... 25 
4.1 
Structure ................................................................................................................. 25 
4.2 
Duration ................................................................................................................. 26 
4.3 
Treatment Groups and Treatment Regimen ........................................................... 26 
4.3.1  Study Treatment ......................................................................................... 26 
4.3.2  Control Treatment ...................................................................................... 26 
4.3.3  Methods for Blinding ................................................................................. 26 
4.3.4  Retreatment Criteria ................................................................................... 26 
4.4 
Permissible and Prohibited Medications/Treatments ............................................. 27 
4.4.1  Permissible Medications/Treatments ......................................................... 27 
4.4.2  Prohibited Medications/Treatments ........................................................... 27 
4.4.3  Special Diet or Activities ........................................................................... 28 
4.5 
Treatment Allocation Ratio .................................................................................... 29 
5. 
Study Population .............................................................................................................. 29 
5.1 
Number of Subjects ................................................................................................ 29 
5.2 
Study Population Characteristics ........................................................................... 29 
5.3 
Inclusion Criteria .................................................................................................... 29 
5.4 
Exclusion Criteria................................................................................................... 30 

 
 
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6. 
Procedures ........................................................................................................................ 32 
6.1 
Washout or Run-In Intervals .................................................................................. 32 
 
 
6.1.2  Run-in Intervals .......................................................................................... 32 
6.2 
Procedures to be Performed ................................................................................... 32 
6.2.1  Screening Visit ........................................................................................... 33 
6.2.2  Randomization Visit ................................................................................... 34 
6.2.3  Retinal Specialist Examination .................................................................. 34 
6.2.4  Treatment Group ........................................................................................ 35 
6.2.5  Control Group ............................................................................................ 38 
6.3 
Instructions for the Subjects ................................................................................... 40 
6.4 
Unscheduled Visits ................................................................................................. 41 
6.5 
Early Discontinuation of Subjects .......................................................................... 41 
6.6 
Withdrawal Criteria ................................................................................................ 42 
7. 
Response Measures and Summary of Data Collection Methods ..................................... 42 
7.1 
Effectiveness Measures .......................................................................................... 42 
7.1.1  Primary Effectiveness Measure .................................................................. 42 
7.1.2  Secondary Effectiveness Measures ............................................................ 43 
 
 
7.2 
Safety Measures ..................................................................................................... 44 
7.3 
Demographics and Baseline Characteristics .......................................................... 45 
7.4 
Treatment Characteristics ....................................................................................... 45 
7.5 
Summary of Methods of Data Collection .............................................................. 45 
8. 
Statistical Procedures ....................................................................................................... 46 
8.1 
Analysis Populations .............................................................................................. 46 
8.2 
Collection/Derivation of Primary and Secondary Effectiveness Assessments ...... 47 
8.2.1  Primary Effectiveness Variable .................................................................. 47 
8.2.2  Secondary Effectiveness Variables ............................................................. 47 
8.3 
Hypothesis and Methods of Analysis ..................................................................... 48 
8.3.1  Primary Effectiveness Analyses ................................................................. 48 
8.3.2  Secondary Effectiveness Analyses ............................................................. 48 
 
 
 
 
 
 

 
 
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8.5 
Sample Size Calculation ........................................................................................ 50 
 
 
9. 
Materials .......................................................................................................................... 51 
9.1 
Study Treatment ..................................................................................................... 51 
9.1.1  Product Description .................................................................................... 51 
9.1.2  Instructions for Use and Administration .................................................... 51 
9.1.3  Treatment Regimen Adjustments ............................................................... 52 
9.2 
Other Study Supplies .............................................................................................. 52 
10.  Study Administration Procedures .................................................................................... 53 
10.1  Subject Entry Procedures ....................................................................................... 53 
10.1.1  Overview of Entry Procedures ................................................................... 53 
10.1.2  Informed Consent and Subject Privacy ...................................................... 54 
10.1.3  Method for Assignment to Treatment Groups ............................................ 54 
10.2  Compliance with Protocol ...................................................................................... 55 
10.3  Pregnancy ............................................................................................................... 55 
10.4  Study Termination .................................................................................................. 55 
11.  Adverse Events ................................................................................................................ 57 
11.1  Definitions .............................................................................................................. 57 
11.1.1  Adverse Event ............................................................................................ 57 
11.1.2  Adverse Event of Special Interest .............................................................. 59 
11.1.3  Serious Adverse Event ............................................................................... 59 
11.1.4  Adverse Device Effect ............................................................................... 59 
11.1.5  Serious Adverse Device Effect ................................................................... 60 
11.1.6  Unanticipated Adverse Device Effect ........................................................ 60 
11.1.7  Device Deficiency ...................................................................................... 60 
11.1.8  Severity ...................................................................................................... 60 
11.1.9  Relationship to Treatment .......................................................................... 61 
11.2  Timelines for Reporting ......................................................................................... 61 
11.3  Procedures for Reporting an AE or ADE ............................................................... 61 
11.4  Procedures for Reporting an SAE or SADE .......................................................... 62 
12.  Administrative Issues ....................................................................................................... 62 
12.1  Protection of Human Subjects ................................................................................ 62 
12.1.1  Compliance with Informed Consent Regulations ...................................... 62 
12.1.2  Compliance with IRB Regulations............................................................. 63 

 
 
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12.1.3  Compliance with Good Clinical Practice ................................................... 63 
12.1.4  Financial Disclosure/Certification Form .................................................... 63 
12.1.5  Compliance with Electronic Records and Signature Regulations .............. 64 
12.2  Changes to the Protocol ......................................................................................... 64 
12.3  Subject Confidentiality and Privacy....................................................................... 64 
12.4  Documentation ....................................................................................................... 65 
12.4.1  Source Documents ..................................................................................... 65 
12.4.2  Case Report Form Completion................................................................... 66 
12.4.3  Investigator Reports ................................................................................... 66 
12.4.4  Retention of Documentation ...................................................................... 66 
12.5  Labeling, Packaging, Storage, and Return of Study Devices ................................. 67 
12.5.1  Labeling/Packaging .................................................................................... 67 
12.5.2  Storage of Study Devices ........................................................................... 67 
12.5.3  Study Device Accountability ...................................................................... 68 
12.5.4  Return of Study Devices ............................................................................ 68 
12.6  Monitoring by Allergan .......................................................................................... 68 
12.7  Testing of Biological Specimens ............................................................................ 69 
12.8  Publications ............................................................................................................ 69 
13.  References ........................................................................................................................ 69 
13.1  Study Report References ........................................................................................ 69 
13.2  Literature References ............................................................................................. 70 
14.  Protocol Amendment Summary ....................................................................................... 72 
 
List of Tables 
Table 1 
Schedule of Visits and Procedures:  Treatment Period for Treatment Group . 13 
Table 2 
Schedule of Visits and Procedures:  Posttreatment Follow-up Period for 
Treatment Group ............................................................................................. 15 
Table 3 
Schedule of Visits and Procedures:  Repeat Treatment and Follow-up for 
Pivotal Phase Treatment Group ...................................................................... 16 
Table 4 
Schedule of Visits and Procedures:  Control Period for Control Group ......... 17 
Table 5 
Schedule of Visits and Procedures:  Optional Treatment Period and Follow-up 
for Pivotal Phase Control Group ..................................................................... 18 

 
 
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Table 6 
Allergan Temple Hollowing Scale .................................................................. 42 
Table 7 
Global Aesthetic Improvement Scale .............................................................. 43 
 
List of Figures 
Figure 1 
Example of Temple Hollowing ....................................................................... 22 
 

 
 
 
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1. 
Abbreviations and Terms 
Term/Abbreviation 
Definition 
3D 
3-dimensional 
ADE 
adverse device event 
AE 
adverse event 
ATHS 
Allergan Temple Hollowing Scale 
CE 
Conformité Européene 
CFR 
Code of Federal Regulations 
eCRF 
electronic case report form 
EI 
Evaluating Investigator 
DFU 
directions for use 
FDA 
Food and Drug Administration 
GAIS 
Global Aesthetic Improvement Scale 
GCP 
Good Clinical Practice 
HA 
hyaluronic acid 
HIPAA 
Health Insurance Portability and Accountability Act 
IC 
informed consent 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ISR 
injection site response 
IWRS 
interactive web response system 
mITT 
modified intent-to-treat 
PP 
per protocol 
PT 
preferred term 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SITA 
Swedish Interactive Threshold Algorithm 
SOC 
system organ class 
TI 
Treating Investigator 
UADE 
unanticipated adverse device effect 
US 
United States 

 
 
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2. 
Background, Risk and Benefit, and Clinical Rationale 
2.1 
Background 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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  These events were mild to 
moderate and resolved by week 2 (Moradi 2013). 

 
 
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2.2 
Risk and Benefit 
 
 
 

 
 
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. 
2.3 
Clinical Rationale 
JUVÉDERM VOLUMA XC was designed specifically for volumizing and has demonstrated 
effectiveness in restoring age-related mid-face volume deficit (Jones 2013).  The protocol is 
designed as a pivotal study to collect safety and effectiveness data associated with the 

 
 
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implantation of JUVÉDERM VOLUMA XC for temple hollowing in adult subjects seeking 
aesthetic improvement. 
3. 
Study Objectives and Clinical Hypotheses 
3.1 
Study Objectives 
The objectives of this study are to evaluate the safety and effectiveness of JUVÉDERM 
VOLUMA XC injectable gel in adult subjects seeking correction of temple hollowing. 
3.2 
Clinical Hypothesis 
The clinical hypothesis is that the percentage of pivotal phase subjects with a clinically 
significant change (defined as at least a 1-point improvement on the Allergan Temple 
Hollowing Scale [ATHS] score as assessed by the Evaluating Investigator [EI]) in temple 
hollowing from baseline to month 3 for both temples will be significantly greater in the 
JUVÉDERM VOLUMA XC treatment group than in the untreated control group and the 
percentage of the treatment group subjects with a clinically significant change in temple 
hollowing from baseline to month 3 for both temples will be 60% or greater. 
4. 
Study Design 
4.1 
Structure 
This is a prospective, multicenter, evaluator-blinded, randomized, parallel-group, controlled 
study to evaluate the safety and effectiveness of JUVÉDERM VOLUMA XC hyaluronic acid 
(HA) injectable gel to correct temple hollowing.  This study will be conducted in 2 phases:  
an initial feasibility phase involving up to 30 subjects at up to 3 investigational sites to assess 
short-term safety of the treatment and a pivotal phase involving additional subjects and sites 
to assess the long-term safety and effectiveness of the treatment.
 
 
 
 
 
 
 

 
 
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4.2 
Duration 
Participation for each subject in the feasibility phase treatment group will encompass up to 
1 month for screening, 1 month for treatment, and 12 months of follow-up after the last 
treatment (initial or touch-up). 
Participation for each subject in the feasibility phase control group will encompass up to 
1 month for screening and 3 months for the no-treatment control period. 
4.3 
Treatment Groups and Treatment Regimen 
4.3.1 
Study Treatment 
JUVÉDERM VOLUMA XC injectable gel 
4.3.2 
Control Treatment 
No treatment 
4.3.3 
Methods for Blinding 
The EI and the image analysis technician will be blinded to treatment until after the month 3 
visit when the control group subjects exit the study or receive the optional treatment.  
 
 
 
 
The TIs, study coordinators, and subjects will not be blinded to treatment, but they will 
secure the randomization and other records (eg, records of study treatments and prior study 
assessments) from potential discovery by the blinded EI.  The TI will not discuss the 
randomized treatment assignments with or in the presence of the EI. 
4.3.4 
Retreatment Criteria 
A subject may undergo a touch-up treatment 30 days after the initial treatment (ie, at the 
month 1 follow-up visit) if both the subject and TI determine that correction has not been 
achieved.  
  
 
 

 
 
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4.4 
Permissible and Prohibited Medications/Treatments 
4.4.1 
Permissible Medications/Treatments 
Topical or injectable anesthesia may be used during treatment according to routine practice, 
but it must be limited to the treatment areas only. 
 
 
 
The use of any concomitant medication, prescription or over-the-counter, is to be recorded on 
the subject’s electronic case report form (eCRF) at each visit along with the reason the 
medication is taken. 
Therapy considered necessary for the subject’s welfare may be given at the discretion of the 
TI.  If the permissibility of a specific medication/treatment is in question, please contact 
Allergan. 
4.4.2 
Prohibited Medications/Treatments 
 
 
 
 
 
 
 
 
 
 

 
 
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The decision to administer a prohibited medication/treatment is done with the safety of the 
study participant as the primary consideration.  When possible, Allergan is to be notified 
before the prohibited medication/treatment is administered. 
4.4.3 
Special Diet or Activities 
Within the first 24 hours after treatment, it is recommended that subjects avoid strenuous 
exercise, extensive sun or heat exposure, and alcoholic beverages.  Exposure to any of the 
above may cause temporary redness, swelling, and/or itching at the injection sites. 
 
 
 
 
 

 
 
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4.5 
Treatment Allocation Ratio 
Subjects are randomized at an allocation ratio of 2:1 to treatment with JUVÉDERM 
VOLUMA XC or no treatment control group. 
5. 
Study Population 
5.1 
Number of Subjects 
Up to 189 subjects will be enrolled at up to 15 sites, 
 
 
5.2 
Study Population Characteristics 
Adult subjects with temple hollowing who are seeking restoration will be recruited.  
 
 
 
5.3 
Inclusion Criteria 
The following are requirements for entry into the study: 
1. Age 22 or over and in good general health 
2. 
 
 
 
3. TI considers the subject’s temple hollowing to be amenable to temporary correction 
4. 
 
 
5. 
 
6. 
 

 
 
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5.4 
Exclusion Criteria 
The following are criteria for exclusion from participating in the study: 
1. 
 
 
2. 
 
 
 
3. Has atrophic skin in the temple area that might not be suitable for injection, in the 
opinion of the TI 
4. Has ever received permanent facial implants (eg, polymethylmethacrylate, silicone, 
polytetrafluoroethylene) anywhere in the face or neck, or is planning to be implanted 
with any of these products during the study 
5. Has ever undergone fat injections above the subnasale or is planning to undergo this 
procedure during the study 
6. Has tattoos, piercings, facial hair (ie, beard, mustache), or scars above and including 
the subnasale that would interfere with visual assessment of the temple 
7. Has undergone semipermanent dermal filler treatment (eg, calcium hydroxyapatite, 
poly-L-lactic acid) in the temple or mid-face within 36 months before enrollment or is 
planning to undergo such treatment during the study 
8. Has undergone dermal filler injections above the subnasale within 24 months before 
enrollment or is planning to undergo this procedure during the study 
9. Has temporal arteritis or history of temporal arteritis 
10. 
 
11. Has active or recurrent inflammation or infection in either eye 
12. Has a history of detached retina, retinal vascular occlusion (eg, vein or arterial 
occlusion), narrow angle glaucoma, or neovascular eye disease (eg, diabetic 
retinopathy, age-related wet macular degeneration) 
13. Has ever received a facelift, browlift, or facial reconstructive surgery or is planning to 
during the study 

 
 
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14. Has undergone mesotherapy or cosmetic treatment (laser, photomodulation, intense 
pulsed light, radio frequency, dermabrasion, moderate or greater depth chemical peel, 
liposuction, lipolysis, or other ablative procedures) anywhere in the face or neck or 
botulinum toxin injections above the subnasale within 6 months before enrollment or 
is planning to undergo any of these procedures during the study 
15. Has experienced trauma to the temple area within 6 months before enrollment or has 
residual deficiencies, deformities, or scarring 
16. Has a tendency to develop hypertrophic scarring 
17. Has a history of anaphylaxis or allergy to lidocaine (or any amide-based anesthetics), 
hyaluronic acid products, or Streptococcal protein, or is planning to undergo 
desensitization therapy during the term of the study 
18. Has porphyria or untreated epilepsy 
19. Has active autoimmune disease 
20. Has current cutaneous or mucosal inflammatory or infectious processes (eg, acne, 
herpes, gum disease), abscess, an unhealed wound, or a cancerous or precancerous 
lesion, above the subnasale (study device injection may be delayed for subjects with a 
history of recurrent oral herpes lesions who take prophylactic doses of antiviral/herpes 
medication for at least 2 days before study treatment administration) 
21. Is on a concurrent regimen of lidocaine or structurally-related local anesthetics 
(eg, bupivacaine) or is on a concurrent regimen of drugs that reduce or inhibit hepatic 
metabolism (eg, cimetidine, beta-blockers) 
22. 
 
23. 
 
 
 
 
24. 
 
 
25. 
 
 
 
 
 

 
 
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26. 
 
27.
 
 
28. 
 
 
 
6. 
Procedures 
6.1 
Washout or Run-In Intervals 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.1.2 
Run-in Intervals 
 
 
 
 
 
 
 
 
 
 
6.2 
Procedures to be Performed 
The TIs will be trained in the injection technique, and TIs and EIs will be trained in the use 
of the ATHS prior to initiating enrollment. 
Subjects will remove eyeglasses during all effectiveness assessments so that the eyeglasses 
do not obstruct the view of the temple area.  Contact lens use during effectiveness 
assessments is allowed.  The use of any corrective lenses during safety assessments of visual 
acuity is allowed, provided that the same lenses are used consistently throughout the study. 

 
 
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Throughout the study, to the extent possible, it is recommended that treatment and safety 
assessments for a particular subject be performed by the same TI, and effectiveness 
assessments (ATHS and Global Aesthetic Improvement Scale [GAIS]) be performed by the 
same EI.  If it is not possible to use the same evaluator to follow the subject, it is 
recommended that evaluations overlap (examine the subject together and discuss findings) 
for at least 1 visit. 
At each visit and safety telephone call, the TI (or designee) will solicit and record 
information about AEs and concomitant medications, therapies, and treatments.  The TI (or 
designee) will begin by asking the subject a general, non-directed question, “How have you 
been feeling since the last visit?”  
 
 
 
 
 
 
 
 
All reported AEs will be documented. 
6.2.1 
Screening Visit 
A subject is considered enrolled when he/she has signed the Informed Consent Form (ICF) in 
the presence of the TI or a qualified designee.  The site will then log onto the interactive web 
response system (IWRS) to obtain a unique subject number that will serve as the subject 
identification number on all study documents. 
The EI will evaluate the subject’s temple hollowing using the ATHS for each temple.  
Subjects who have an ATHS score of “Minimal”, “Moderate”, or “Severe” for each temple 
will be eligible for the study.  Although both temples must qualify, each temple can have a 
different score (eg, one temple can be “Minimal” severity and the other “Moderate”).  
Subjects will complete the Satisfaction with Temples and Satisfaction with Facial 
Appearance Overall modules of the FACE-Q questionnaire. 
The TI will ensure that each subject meets the study eligibility criteria and run-in and 
washout requirements (see Sections 5.3, 5.4, and 6.1).  The TI will record the reasons for 
those subjects who do not meet the inclusion/exclusion criteria and who withdraw consent 
before randomization. 

 
 
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The TI (or designee) will collect and record the subject’s demographic information, medical 
and surgical history, cosmetic and dental procedure history, smoking history, Fitzpatrick skin 
phototype, race, and sun exposure estimate.  Physical measurements (height and weight) and 
vital signs, including blood pressure (systolic and diastolic, while subject is seated), 
temperature, pulse, and respiratory rate will also be collected and recorded. 
A urine pregnancy test will be conducted for female subjects of childbearing potential.  If the 
test is positive, the subject will be exited from the study. 
The schedule of procedures to be conducted at screening are provided in Table 1 and Table 4. 
6.2.2 
Randomization Visit 
The randomization visit may occur on the same day as the screening visit and must occur 
within 30 days after screening/signing of the ICF.  Inclusion/exclusion criteria will be 
reviewed again to confirm subject eligibility, 
 
 
Subjects will be randomized in a 2:1 ratio to the treatment group or to the control group and 
1:1 to receive the first treatment in the right or left temple.  
 
 
Subjects randomized to the control group will finish the required procedures 
for the randomization visit and return for a month 1 and 3 visit during the control period. 
The schedule of procedures to be conducted at randomization are provided in Table 1 and 
Table 4. 
 
 
 
 
 
 
 
 
 
 
 

 
 
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6.2.4 
Treatment Group 
In both phases, subjects randomized to the treatment group will receive initial treatment, 
touch-up treatment if needed, and follow-up visits throughout the 12-month posttreatment 
study period. 
In the feasibility phase, treatment of the temples from the same subject will be staggered and 
separated by at least 1 day to allow for a retinal specialist examination after treatment of each 
temple.  In the pivotal phase, treatment of both temples from the same subject will occur on 
the same day, but will be separated by at least 30 minutes. 
6.2.4.1 
Initial Treatment 
The initial treatment visit will occur within 7 days after the retinal examination.  Before 
treatment of the first temple, inclusion/exclusion criteria will be reviewed again to confirm 
subject eligibility.  Female subjects of childbearing potential will take a urine pregnancy test; 
if the test is positive, the subject will not receive treatment and will be exited from the study.  
 
 
  The EI will not be present during any treatment 
procedures. 
Anesthesia will be administered following the standard practice at each investigational site.  
The application of ice and topical anesthesia is allowed to reduce injection discomfort.  
Injectable anesthesia must be limited to the treatment area only. The TI will use aseptic skin 
preparation and will administer injections to the first temple according to the VOLUMA-007 
DFU and Section 9.1.2 of this protocol. 
The TI will determine the appropriate volume to inject to achieve optimal correction (at least 
1-point improvement from baseline on the ATHS) based on clinical experience.  
 
 
 
 
 
 
 

 
 
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Subjects will receive instructions on how to evaluate the treatment areas, assess the 
procedural pain on an 11-point scale, and complete the daily safety diary to record the 
presence or absence and severity of injection site responses (ISRs) starting on the day of 
treatment and for approximately 30 days after treatment. 
Subjects will complete a safety follow-up telephone call at 3 days after treatment of the 
second temple.  Subjects will return for an office visit at 14 days after treatment of the second 
temple 
 
 
Thirty days after treatment of the second temple, the subject and the TI will discuss the 
results of the initial treatment and determine whether correction has been achieved.  If 
correction has not been achieved, the TI may perform a touch-up treatment. 
Details regarding anesthesia use, treatment areas injected, volume injected, kit numbers, 
needle gauge, characteristics of the procedure
 
and characteristics of the product 
 will be 
recorded on the eCRF. 
Concomitant medications, procedures, therapies, and AEs will be monitored continuously 
throughout the study.  The procedures and evaluations for the treatment period are listed by 
visit in Table 1. 

 
 
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6.2.4.2 
Touch-up Treatment 
If the TI and subject agree that 1 or both temples have not reached optimal correction 
(at least 1-point improvement on the ATHS) at the Day 30 visit, a touch-up treatment may be 
administered.  Touch-up treatment will be administered as described for initial treatment, 
with each temple treated 1 or 2 days apart 
 
 
.  Female 
subjects of childbearing potential will take a urine pregnancy test; if the test is positive, the 
subject will not receive touch-up treatment but will continue to be followed in the study. 
 
.  The TI (or designee) will review the subject’s 
daily safety diary and discuss any unusual signs/symptoms with the subject.  If an ISR is 
ongoing at the touch-up treatment, it will be recorded in the touch-up safety diary. 
The touch-up treatment visits, procedures, and follow-up are identical to those for the initial 
treatment.  The procedures and evaluations for the touch-up treatment are provided in 
Table 1. 
If no touch-up is needed, the subject will exit the treatment period and continue with the 
posttreatment follow-up visits and procedures. 
6.2.4.3 
Follow-up 
Treatment group subjects will attend follow-up visits for safety and effectiveness at month 1, 
3, 6, 9, and 12 after the last treatment (either initial treatment, if no touch-up is performed, or 
touch-up treatment).  Safety assessments will be performed at all posttreatment follow-up 
visits.  At all visits, 
 
, and the EI will evaluate the 
subject’s temple area using the ATHS and global aesthetic improvement of the temple area 
using the GAIS and comparing to the digital images of the subject captured at baseline.  
 
 
, and also rate treatment effectiveness using the GAIS.  
 
 
  At the 
month 3 and 12 visits, subject’s weight will be recorded and at the month 12 visit a urine 
pregnancy test will be administered to female subjects of childbearing potential.  Subjects in 

 
 
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the feasibility phase will be exited from the study after all month 12 visit procedures are 
completed. 
For the pivotal phase subjects, at the month 9 visit the TI and subject will discuss treatment 
results, and the subject will be offered a repeat treatment after completion of the month 12 
visit.
 
 
If the subject chooses not to receive repeat treatment the 
subject will be exited from the study after all month 12 visit procedures are completed. 
The procedures and evaluations to be performed during the follow-up period are listed by 
visit in Table 2. 
6.2.4.4 
Repeat Treatment 
 
  The order in which temples are treated will be the same as that for initial 
treatment.  Female subjects of childbearing potential will take a urine pregnancy test; if the 
test is positive, the subject will not receive repeat treatment and will be exited from the study.  
The repeat treatment visits and procedures are identical to those for the initial treatment 
during the pivotal phase.  The repeat treatment will be administered as described for initial 
treatment, with each temple treated approximately 30 minutes apart 
 
.  Subjects will be followed for 1 month after the repeat 
treatment and will exit the study. 
The procedures and evaluations to be performed during repeat treatment and follow-up are 
listed by visit in Table 3. 
6.2.5 
Control Group 
6.2.5.1 
Control Period 
In both phases, control group subjects will return to the investigational site at months 1 and 3 
after randomization. 
Feasibility phase subjects randomized to the control group will exit the study at the month 3 
visit. 
At the month 1 visit, the pivotal phase subjects randomized to the control group will be 
offered an optional treatment after completion of the month 3 visit.  
 

 
 
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who accept optional treatment will have a retinal specialist examination done within 7 days 
before the month 3 visit.  Control group subjects who decline optional treatment will exit the 
study after the month 3 visit.  The control period concludes after completion of the month 3 
procedures. 
The procedures and evaluations for the control group during the control period are listed by 
visit in Table 4. 
6.2.5.2 
Optional Treatment 
In the pivotal phase, control group subjects who have optional treatment will be followed for 
safety only; no effectiveness assessments will be performed. 
A urine pregnancy test will be conducted for female subjects of childbearing potential prior 
to the optional treatment.  If the test is positive, the subject will not receive optional treatment 
and will be exited from the study. 
The optional treatment can occur on the same day as the month 3 visit, 
 
 
If the month 3 visit and optional treatment occur on the same day, 
all pretreatment study procedures that overlap with the month 3 procedures do not need to be 
repeated.  If the optional treatment visit occurs after the month 3 visit, optional treatment 
must occur within 2 weeks after the month 3 visit or the start of the pivotal phase (whichever 
is last) 
 
The optional treatment visits, procedures, and follow-up are identical to those for the initial 
treatment of the treatment group in the pivotal phase, including the 30-minute waiting period 
between temples.  The preparation process and performance of procedures after treatment 
administration will be the same as that described for the initial treatment of the treatment 
group in the pivotal phase.  The procedures and evaluations for the optional treatment of the 
control group are listed by visit in Table 5. 
6.2.5.3 
Touch-up Treatment 
Thirty days after the optional initial treatment, the subject and the TI will discuss the results 
of the initial treatment and determine whether correction has been achieved.  If correction has 
not been achieved in 1 or both temples, the TI may perform a touch-up treatment.  Female 
subjects of childbearing potential will take a urine pregnancy test; if the test is positive, the 
subject will not receive touch-up treatment but will continue to be followed in the study.  The 
touch-up treatment visits, procedures, and follow-up are identical to those for the touch-up 

 
 
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treatment of the treatment group in the pivotal phase.  The procedures and evaluations for 
touch-up treatment are listed by visit in Table 5. 
6.2.5.4 
Follow-up 
All treated control group subjects will be followed for 12 months for safety only.  The 
procedures and safety assessments to be performed at the month 1, 3, 6, 9, and 12 visits after 
the last treatment (ie, either initial or touch-up) are listed by visit in Table 5. 
6.3 
Instructions for the Subjects 
At the screening visit, the TI (or designee) will discuss alternative treatments that may be 
available with any subject who is interested in participating in the study; he/she will counsel 
the subject regarding his/her treatment goals and the potential benefits, risks (including 
potential risks to vision), and limitations of study treatment.  After counseling, if the subject’s 
expectations are achievable within the parameters of the study, the TI (or designee) will 
proceed with obtaining the subject’s signature on the ICF and will continue the subject in the 
study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Subjects will also be instructed to contact the TI or his/her research staff to report any 
unexpected symptoms or to ask questions about the study. 
6.4 
Unscheduled Visits 
An unscheduled visit may occur for safety purposes 
 
Applicable procedures will be performed and recorded 
on the eCRF. 
 
 
6.5 
Early Discontinuation of Subjects 
Each subject reserves the right to withdraw from the study at any time without jeopardy to 
his/her future medical care.  The procedures to be performed at early exit visits/final study 
visits are specified in Table 1 to 5.  Subjects may also be administratively withdrawn if they 
do not return for follow-up visits through the final study visit.  For any subject who 
withdraws from the study, the date and reason for withdrawal will be recorded on the eCRF.  
If an AE is ongoing at the time of withdrawal and is related to the study treatment, the TI will 
attempt to follow the subject until the AE has been resolved or follow-up is no longer 
possible.  The TI shall ask for the subject’s permission to follow his/her status/condition 
outside the study. 

 
 
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If a subject fails to return for 1 or more scheduled study visits, the TI (or designee) will 
attempt to contact the subject to determine and document the reason the subject has failed to 
return, and to encourage compliance with the study visit schedule. 
6.6 
Withdrawal Criteria 
If a female subject has a positive urine pregnancy test at the time of the initial treatment visit, 
the subject will not be eligible for treatment and will be withdrawn from the study.  The 
pregnancy will be followed as described in Section 10.3. 
 
 
 
 
 
 
 
7. 
Response Measures and Summary of Data Collection Methods 
7.1 
Effectiveness Measures 
7.1.1 
Primary Effectiveness Measure 
The primary effectiveness measure is the EI’s assessment of temple hollowing using the 
ATHS described in Table 6. 
Table 6 
Allergan Temple Hollowing Scale 
Score 
Grade 
Description 
0 
Convex 
Rounded temple 
1 
Flat 
Flat temple; temporal fusion line may be visible 
2 
Minimal 
Shallow depression or concavity with minimal volume loss; temporal fusion line may be 
visible 
3 
Moderate 
Moderate depression or concavity with moderate volume loss; moderate prominence of 
temporal fusion line 
4 
Severe 
Deeply recessed, sunken appearance; marked prominence of temporal fusion line and 
zygomatic arch 
 
The ATHS is a 5-point ordinal scale developed by Allergan to grade the severity of temple 
hollowing.  The ATHS contains photographic images of subjects representing different 

 
 
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Fitzpatrick skin types, race categories, and severities of temple hollowing (0 = Convex, 
1 = Flat, 2 = Minimal, 3 = Moderate, 4 = Severe).  A scale validation study (Study FSV-001) 
was conducted to assess the inter- and intra-rater reliability of the ATHS.  Each of the 
8 trained clinicians independently evaluated the subjects in-person and assigned each subject 
an ATHS grade based on the live evaluation.  Three weeks later, the same 8 trained clinicians 
re-evaluated the same subjects, and assigned each subject an ATHS grade based on the live 
evaluation and without reliance on prior memory.  Both the inter- and intra-rater agreement 
were substantial (> 0.60), indicating substantial agreement among the raters as well as within 
the raters between the 2 in-person evaluation sessions, respectively.  Additionally, the results 
demonstrate that a 1-point difference or higher is clinically significant.  Therefore, results 
confirmed that the ATHS is validated and appropriate to be used as a primary effectiveness 
measure for this study. 
7.1.2 
Secondary Effectiveness Measures 
The secondary effectiveness measures include independent, noncollaborative assessments by 
both the EI and the subject of global aesthetic improvement in the temple area using the 
5-point GAIS (Table 7). 
Table 7 
Global Aesthetic Improvement Scale 
Score 
Grade 
Description 
2 
Much Improved 
Marked improvement in appearance 
1 
Improved 
Improvement in appearance, but a touch-up or retreatment is indicated 
0 
No Change 
The appearance is essentially the same as the original condition 
-1 
Worse 
The appearance is worse than the original condition 
-2 
Much Worse 
The appearance is much worse than the original condition 
 
7.1.3 
Other Effectiveness Measures 
 
 
 
 
 
 
 

 
 
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• 
 
 
 
 
 
 
 
7.2 
Safety Measures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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7.3 
Demographics and Baseline Characteristics 
Subject demographics and baseline characteristics to be collected include sex, age, race, 
height, weight, vital signs, 
 
medical/surgical/cosmetic/dental procedure history, and prior medications. 
7.4 
 
 
 
 
7.5 
Summary of Methods of Data Collection 
Electronic data capture will be used to collect study-specific information, 
 
 
  
 
Investigators will provide access to hospital files, medical 
records, and other source documents containing subject clinical/medical information.  Source 
document verification will be performed. 
 
 
  
 
 
 
The clinical database or a subset of the clinical database will be locked prior to initiation of 
statistical analysis.  All data review and verification procedures and resolution of queries 
must be completed prior to database lock. 

 
 
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Allergan will permit trial-related monitoring, audits, Institutional Review Board (IRB) 
review, and regulatory inspections, and will provide direct access to source documents, 
which will be retained for at least 2 years after the last approval of a marketing application 
and until there are no pending or contemplated marketing applications in an International 
Conference on Harmonisation (ICH) region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. 
8. 
Statistical Procedures 
A separate statistical analysis plan will be prepared to provide specifications for all analyses.  
The plan will be finalized and approved prior to clinical database lock.  The database will be 
locked and analyzed at the end of study (all data collected through the end of the study). 
 
 
 
 
 
Every attempt will be made to collect complete data and limit the occurrence of missing data.  
No imputation of missing data will be performed.  Deviations from the analyses planned in 
the statistical plan will be documented in the clinical study report. 
8.1 
Analysis Populations 
The following analysis populations will be used in the analyses for this study: 
• modified intent-to-treat (mITT) population:  subjects who are randomized to study 
treatment (treatment group) and receive at least 1 study device treatment, and subjects 
who are randomized to the control group 
• per-protocol (PP) population:  all mITT subjects who do not have any significant 
protocol deviations affecting the primary effectiveness endpoint 
• safety population:  subjects who receive at least 1 study device treatment or are 
randomized to the control group 
Unless specified otherwise, effectiveness analyses, whether performed on the mITT or PP 
population, will use the “as-randomized” assignment for each subject (eg, if a subject 
randomized to the control group is treated inadvertently at the start of the study, the 

 
 
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assessments for that subject will nonetheless be included in the control group analysis).  The 
PP population will be used to perform sensitivity analyses for the primary effectiveness 
variable.  All safety analyses will be conducted on the safety population, using the “as-
treated” grouping for each subject (eg, if a subject randomized to the control group is treated 
at the start of the study, the subject will be analyzed in the treatment group). 
8.2 
Collection/Derivation of Primary and Secondary Effectiveness 
Assessments 
8.2.1 
Primary Effectiveness Variable 
The primary effectiveness variable, the ATHS response, is derived from the EI’s assessment 
of temple hollowing using the ATHS (on a 5-point scale of convex to severe, Section 7.1.1).  
 
 
 
 
 
 
The primary effectiveness endpoint is the proportion of ATHS responders at month 3. 
8.2.2 
Secondary Effectiveness Variables 
The 2 secondary effectiveness variables are: 
• GAIS responder based on EI assessment of global aesthetic improvement
 
 
 
• GAIS responder based on subject assessments of global aesthetic improvement 
 
 
 

 
 
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8.3 
Hypothesis and Methods of Analysis 
8.3.1 
Primary Effectiveness Analyses 
The primary effectiveness analysis will be performed on the mITT population.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.3.2 
Secondary Effectiveness Analyses 
 
 
 
 
 
GAIS) at the month 3 visit 
  

 
 
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8.3.3 
Other Effectiveness Analyses 
 
 
 
 
 
 
 
 
 
 
 
 
8.3.4 
Safety Analyses 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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8.5 
Sample Size Calculation 
The sample size is determined to provide adequate power to demonstrate that the product is 
effective as well as safe.  A total of 90 subjects in the treatment group and 45 subjects in the 
control group will provide at least 90% power to detect a difference of 30% in the responder 
rates between the groups.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 

 
 
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9. 
Materials 
9.1 
Study Treatment 
9.1.1 
Product Description 
JUVÉDERM VOLUMA XC is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, 
colorless, homogeneous, HA gel implant (dermal filler).  
 
 
 
 
9.1.2 
Instructions for Use and Administration 
 
 
 
  
 
 
 
 
The TIs will use aseptic injection technique, and the following procedures must be used to 
ensure subject safety.  The detailed recommended injection technique is provided in the 
VOLUMA-007 DFU included in the Site Study Binder. 

 
 
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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
severe pain. 
 
 
 
 
 
 
 
 
 
9.1.3 
Treatment Regimen Adjustments 
Up to 2 treatment sessions (initial and touch-up) per temple are allowed; 
 
 
 
 
 
 
 
9.2 
Other Study Supplies 
 
 
 
 

 
 
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pressure cuff, and internet connection for eCRF completion and IWRS).  The retinal 
specialist is responsible for supplies related to retinal exams (eg, retinal imaging equipment, 
Humphrey visual field analyzer). 
10. 
Study Administration Procedures 
The clinical study shall not begin until the required approvals from the appropriate regulatory 
authorities and IRBs have been obtained. 
10.1 
Subject Entry Procedures 
10.1.1 
Overview of Entry Procedures 
Prospective subjects as defined by the criteria in Sections 5.3 and 5.4 (inclusion/exclusion 
criteria) will be considered for entry into this study.  A subject is considered to have entered 
the study upon signing the ICF, which will occur prior to any screening procedures.  
: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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10.1.2 
Informed Consent and Subject Privacy 
The purpose, procedures, risks, benefits, and alternatives to study participation will be 
discussed with each potential subject.  The subject must also give Authorization for Use and 
Release of Health and Research Study Information, including digital images and other 
written documentation in accordance with the relevant country and local privacy 
requirements (where applicable) prior to any study-related procedures or change in treatment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
10.1.3 
Method for Assignment to Treatment Groups 
At the time of randomization (ie, at or within 30 days after screening/signing of the ICF), 
eligible subjects will be assigned to 1 of 2 treatment groups (treatment and control) in a 
2:1 ratio to receive JUVÉDERM VOLUMA XC or to the control group.  
 
 
 
 
 
 

 
 
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The IWRS will 
provide the site with the specific kit number(s) for each randomized subject at the time of 
randomization and at each subsequent treatment visit.  Sites will dispense treatment 
according to the IWRS instructions provided by the system. 
10.2 
Compliance with Protocol 
The TI is responsible for compliance with the protocol at the investigational site.  A 
representative of Allergan will make frequent contact with the TI and his/her research staff 
and will conduct regular monitoring visits at the site to review subject and device 
accountability records for compliance with the protocol.  Any protocol deviations will be 
discussed with the TI upon identification.  The use of the data collected for the subject will 
be discussed to determine if the data is to be included in the analysis.  All protocol deviations 
will be reported to the IRB according to the IRBs reporting requirements. 
10.3 
Pregnancy 
If a female subject becomes pregnant after treatment, the TI will notify Allergan immediately 
after the pregnancy is confirmed.  The TI will (1) instruct the subject to notify her physician 
of the presence of the investigational device and (2) will follow the pregnancy to term.  Best 
practices are to be followed in order to ensure the welfare of the subject and the fetus.  The 
Medical Safety Physician will contact the TI to obtain information about the pregnancy 
outcome.  The subject will continue to be followed for safety, and the pregnancy will be 
documented as a protocol deviation. 
Pregnancy by itself will not be considered an AE or serious adverse event (SAE).  
Hospitalization for a normal delivery or elective abortion of a normal fetus does not 
constitute an SAE.  However, the occurrence of an adverse pregnancy outcome for the 
mother or child may constitute an AE or SAE, and these are to be reported as described in 
Sections 11.1.4 and 11.1.5. 
10.4 
Study Termination 
If conditions arise during the study that indicate that the study or an investigational site needs 
to be terminated, Allergan, the TI, Monitor, IRB, and/or regulatory agencies will discuss the 
situation and take appropriate action after consultation.  
 
 

 
 
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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
Per International Organization for Standardization (ISO) 14155, if a study is prematurely 
terminated or suspended due to safety issues, Allergan shall inform all Investigators and the 
regulatory authorities of the termination or suspension and the reason(s) for the termination 
or suspension.  The IRB is also to be informed promptly and provided the reason(s) for the 
termination or suspension by Allergan or by the Investigator, as specified by the applicable 
regulatory requirements.  If a premature termination or suspension occurs, Allergan shall 
remain responsible for providing resources to fulfill the protocol obligations and existing 
agreements for follow-up of subjects enrolled in the study, and each investigator or 
authorized designee shall promptly inform enrolled subjects, if applicable. 

 
 
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11. 
Adverse Events 
Throughout the course of the study, all AEs will be monitored and reported on an AE eCRF, 
including seriousness, severity, action taken, and relationship to study treatment.  If AEs 
occur, the first concern will be the safety of the study participants. 
 
  
 
 
 
 
. 
For a description of potential AEs, see Sections 2.2, 11.1.1, and the VOLUMA-007 DFU. 
11.1 
Definitions 
11.1.1 
Adverse Event 
An AE is defined in accordance with ISO 14155 as “any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal laboratory 
findings) in subjects, users, or other persons, whether or not related to the investigational 
medical device.”  This definition includes events related to the investigational medical device 
or comparator and events related to the procedures involved except for events in users or 
other persons, which only include events related to investigational medical devices. 
Disease signs and symptoms that existed prior to the study treatment are not considered AEs 
unless the condition recurs after the subject has recovered from the pre-existing condition or 
the condition worsens in intensity or frequency during the study. 
AEs will be monitored throughout the study beginning with signing of the ICF.  At each 
postscreening visit, the TI (or designee) will begin querying for AEs by asking each subject a 
general, non-directed questions,  “Have you had any changes to your condition since your 
last visit?”  
 
 
 
 
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therapy/concomitant medications are to be updated.  Directed questioning and examination 
will then be done as appropriate.  All reportable AEs and clinically significant abnormal 
laboratory findings will be documented on the appropriate eCRF. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unforeseeable risks or results are also a possibility.  The risk of developing a serious 
complication is small.  If a complication occurs, subjects will be advised to contact the TI 
who will use his/her medical judgment to do whatever is necessary to treat the subject. 

 
 
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11.1.2 
Adverse Event of Special Interest 
An AE of special interest is defined as any vision-related AE.  See Section 11.3 for 
procedures for reporting an AE of special interest. 
11.1.3 
Serious Adverse Event 
An SAE is defined in accordance with ISO 14155 as an AE that: 
a) led to death, 
b) led to serious deterioration in the health of the subject, that either resulted in 
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient or prolonged hospitalization, or 
4. medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect 
NOTE:  Allergan considers all cancer AEs as SAEs.  Abortion is also considered an SAE 
except for elective abortion of a normal fetus. 
NOTE:  Planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol, without serious deterioration in health, is not considered an SAE. 
See Section 11.4 for procedures for reporting an SAE/serious adverse device effect (SADE). 
11.1.4 
Adverse Device Effect 
An adverse device effect (ADE) is defined in accordance with ISO 14155 as “an adverse 
event related to the use of an investigational medical device.”  This definition includes any 
AEs resulting from insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device as well as 
any event resulting from use error (per ISO 62366) or from intentional misuse of the 
investigational medical device. 
See Section 11.3 for procedures for reporting an ADE. 

 
 
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11.1.5 
Serious Adverse Device Effect 
A SADE is defined in accordance with ISO 14155 as “an adverse device effect that has 
resulted in any of the consequences characteristic of a serious adverse event.” 
See Section 11.4 for procedures for reporting a SADE. 
11.1.6 
Unanticipated Adverse Device Effect 
An unanticipated adverse device effect (UADE) is defined in accordance with 21 Code of 
Federal Regulations (CFR) 812.3 as “any serious adverse effect on health or safety or any 
life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in 
the investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, safety, 
or welfare of subjects.” 
11.1.7 
Device Deficiency 
A device deficiency is defined in accordance with ISO 14155 as “inadequacy of a medical 
device with respect to its identity, quality, durability, reliability, safety, or performance.”  
Device deficiencies include malfunctions, use errors, and inadequate labeling. 
If a device deficiency occurs, the TI will notify Allergan using the fax number or email on 
the front page of the protocol.  Device deficiencies shall be documented throughout the study 
and appropriately managed by Allergan.  Allergan shall review all device deficiencies and 
determine and document in writing whether they could have led to a SADE.  These shall be 
reported to the regulatory authorities and IRBs as required by national regulations. 
11.1.8 
Severity 
Severity is a clinical determination of the intensity of an AE.  The severity assessment for a 
clinical AE is to be completed using the following definitions as guidelines: 

 
 
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Mild 
Awareness of sign or symptom, but easily tolerated 
Moderate 
Discomfort affecting daily activity 
Severe 
Disabling with inability to do usual daily activities 
11.1.9 
Relationship to Treatment 
Relationship to a treatment refers to a determination of the relationship (if any) between an 
AE and the device or treatment procedure.  A causal relationship is present if the TI 
determines that there is a reasonable possibility that the AE may have been caused by the 
device or is associated with the procedure, such as an event that can be attributed to other 
products, surgical techniques, or medications required specifically for the procedure.  
Relationship to the treatment must be determined by the TI and cannot be delegated to other 
study staff. 
11.2 
Timelines for Reporting 
The TI (or designee) is to adhere to the following schedule in reporting different types of 
AEs. 
Adverse Event 
Type 
Reporting to Allergan 
Start of 
Collection 
End of Collection 
AEs, ADEs 
Record on AE eCRF upon awareness for 
review by the Clinical Monitor 
Signing ICF 
Last subject visit 
SAEs, SADEs 
Record on SAE Form and fax to Allergan 
within 24 hours of awareness 
Signing ICF 
Last subject visit 
AEs of Special 
Interest 
Record on AE eCRF and notify Allergan by 
phone/email within 24 hours of awareness 
Signing ICF 
Last subject visit 
11.3 
Procedures for Reporting an AE or ADE 
All AEs or ADEs occurring during the study period (beginning with signing ICF) are to be 
recorded on the appropriate eCRF by the TI.  Any AE that is ongoing at the exit visit must be 
followed up as appropriate. 
The TI will report AEs of special interest to Allergan within 24 hours of awareness of the 
event by completing an AE eCRF and notifying Allergan study management personnel and 
the Medical Safety Physician by phone or email.  Allergan will notify FDA of any AEs of 
special interest within 10 days of Allergan’s awareness of the event. 

 
 
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11.4 
Procedures for Reporting an SAE or SADE 
All SAEs and SADEs occurring during the study period (from signing ICF) or through the 
last subject visit are to be immediately reported to an Allergan representative at a fax 
number/e-mail address listed on the cover page and recorded on the appropriate eCRFs.  All 
subjects with an SAE/SADE must be followed up and the outcomes reported.  The TI is to 
supply Allergan and the IRB with any additional requested information (eg, hospital 
discharge summary, autopsy reports and terminal medical reports).  Allergan will evaluate all 
SADEs and determine and document in writing whether they meet the definition of a UADE.  
These shall be reported to all participating TIs, the regulatory authorities, and IRBs as 
required by national regulations. 
In the event of an SAE/SADE, the TI must: 
1. Notify Allergan immediately by fax/email using the SAE/SADE reporting forms.  For 
the SAE/SADE fax number/email address, see the front page of the protocol. 
2. Obtain and maintain in his/her files all pertinent medical records, information, and 
medical judgments from colleagues who assisted in the treatment and follow-up of 
the subject. 
3. Provide Allergan with a complete, written case history which includes a statement as 
to whether the event was or was not related to the use of the investigational device. 
4. Promptly inform the governing IRB of the event, if it is treatment-related.  For other 
SAEs, notify the governing IRB as required by the IRB, local regulations, and the 
governing health authorities. 
12. 
Administrative Issues 
12.1 
Protection of Human Subjects 
12.1.1 
Compliance with Informed Consent Regulations 
Written IC is to be obtained from each subject prior to enrollment into the study, and/or from 
the subject’s legally authorized representative according to 21 CFR 50. 

 
 
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12.1.2 
Compliance with IRB Regulations 
This study is to be conducted in accordance with IRB regulations (21 CFR 56).  The TI must 
obtain approval from a properly constituted IRB prior to initiating the study and re-approval 
or review at least annually.  Allergan is to be notified immediately if the responsible IRB has 
been disqualified or if proceedings leading to disqualification have begun.  Copies of all IRB 
correspondence with the TI are to be provided to Allergan. 
12.1.3 
Compliance with Good Clinical Practice 
This protocol is to be conducted in compliance with Good Clinical Practice (GCP) guidelines 
and with ethical principles for clinical research. 
12.1.4 
Financial Disclosure/Certification Form 
In accordance with 21 CFR 54.4, the Investigator and any Sub-Investigators who are directly 
involved in the treatment or evaluation of subjects must complete the Financial Disclosure 
Form disclosing completely and accurately any financial interests or arrangements that apply 
to themselves, their spouse, or their dependent children. 
• Any financial arrangement entered into between Allergan and the Investigator 
involved in the conduct of a covered clinical trial, whereby the value of the 
compensation to the Investigator for conducting the study could be influenced by the 
outcome of the study 
• Any significant payments of other sorts from Allergan, such as a grant to fund 
ongoing research, compensation in the form of equipment, retainer for ongoing 
consultation, or honoraria 
• Any proprietary interest in the tested product held by any Investigator involved in a 
study 
• Any significant equity interest in Allergan held by any Investigator involved in any 
clinical study 
• Any steps taken to minimize the potential for bias resulting from any of the disclosed 
arrangements, interests, or payments. 

 
 
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The Investigator shall provide to Allergan accurate financial information on an annual basis, 
with prompt updates if any relevant changes occur over the course of the investigation, and at 
1 year following completion of this study. 
12.1.5 
Compliance with Electronic Records and Signature 
Regulations 
This study is to be conducted in compliance with the regulations on electronic records and 
electronic signature. 
12.2 
Changes to the Protocol 
The TI is not to implement any deviation from or changes to the protocol without approval 
by Allergan and prior review and documented approval/favorable opinion from the IRB of a 
protocol amendment, except where necessary to eliminate immediate hazards to study 
subjects, or when the changes involve only logistical or administrative aspects of the study 
(eg, change in monitors, change of telephone numbers).  Allergan may amend the protocol 
during the course of the study.  The amended protocol shall be distributed to the TIs and 
IRBs upon approval by regulatory authorities. 
12.3 
Subject Confidentiality and Privacy 
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the study device may ultimately be marketed, but the 
subject’s name will not be disclosed in these documents.  The subject’s name may be 
disclosed to Allergan, the governing health authorities, or the FDA, if they inspect the study 
records.  Appropriate precautions will be taken to maintain confidentiality of medical records 
and personal information. 
Written Authorization and other documentation in accordance with the relevant country and 
local privacy requirements (where applicable) are to be obtained from each subject prior to 
enrollment into the study, and/or from the subject’s legally authorized representative in 
accordance with the applicable privacy requirements (eg, Health Insurance Portability and 
Accountability Act Standards for Privacy of Individually Identifiable Health Information 
[HIPAA]). 

 
 
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In accordance with HIPAA requirements, additional purposes of this study include the 
following:  to publish anonymous subject data from the study and to create and maintain a 
data repository. 
12.4 
Documentation 
12.4.1 
Source Documents 
Source documents may include a subject’s medical records, hospital charts, laboratory notes, 
 
 
 
 
 and any other 
diagnostic tests that may be performed, 
 
If the Serious Adverse Event Form and Pregnancy Surveillance Form are 
used in this study, they are also considered source documents.  The TI’s copies of the eCRFs 
serve as part of the TI’s record of a subject’s study-related data. 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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12.4.2 
Case Report Form Completion 
The TI is responsible for ensuring that data are properly recorded on each subject’s eCRFs 
and related documents.  The TI who has signed the protocol signature page or his/her 
authorized designee is to personally sign the eCRFs (as indicated on the eCRF) to validate 
that the observations and findings are recorded on the eCRFs correctly and completely.  The 
eCRFs are to be submitted to Allergan in a timely manner at the completion of the study, or 
as otherwise specified by Allergan. 
The data reported on the eCRFs shall be derived from source documents and be consistent 
with these source documents, and any discrepancies shall be explained in writing.  Any 
change or correction to data reported on an eCRF shall be dated, initialed and explained, if 
necessary, and shall not obscure the original entry (ie, an audit trail shall be maintained); this 
applies to both written and electronic changes or corrections. 
12.4.3 
Investigator Reports 
In accordance with 21 CFR 812.150, the TI shall prepare and submit complete, accurate, and 
timely reports as follows:  report to Allergan within 5 working days a withdrawal of IRB 
approval, study progress reports to Allergan and IRB at least annually, and a final report to 
Allergan and IRB within 3 months after study termination or completion. 
12.4.4 
Retention of Documentation 
All study related correspondence, subject records, consent forms, subject privacy 
documentation, records of the distribution and use of all investigational products, and copies 
of eCRFs are to be maintained on file. 

 
 
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Allergan-specific essential documents are to be retained until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since 
the formal discontinuation of clinical development of the investigational product.  These 
documents are to be retained for a longer period, however, if required by the applicable 
regulatory requirements or if needed by Allergan. 
Allergan requires notification in writing if the TI wishes to store study documents off-site or 
to relinquish the study data records so that mutually agreed-upon arrangements can be made 
for transfer of the data records to a suitably qualified, responsible person.  Notification is to 
go to Allergan, Attn: Clinical Research Dept., 2525 Dupont Drive, Irvine, CA 92612. 
12.5 
Labeling, Packaging, Storage, and Return of Study Devices 
12.5.1 
Labeling/Packaging 
 
 
 
 
 
 
 
 
 
 
12.5.2 
Storage of Study Devices 
The study device must be stored in a secure area accessible to delegated study personnel only 
and administered only to subjects entered into the clinical study, at no cost to the subject, in 
accordance with the conditions specified in this protocol. 
JUVÉDERM VOLUMA XC must be stored at room temperature 
 with a 
continuous temperature monitoring device.  Use of the device is required to ensure that the 

 
 
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study product is being maintained within the acceptable storage-range conditions.  If the 
storage temperature varies from the programmed limits, the device alarm will trigger 
indicating an excursion that may impact the stability of the study product.  Sites must report 
any alarmed temperature excursion to Allergan, and avoid administering the impacted study 
product, by isolating the product, until receiving further instructions from Allergan.  Do not 
freeze or expose to extreme heat.  Do not use if the package is open or damaged or if the 
product is not clear. 
12.5.3 
Study Device Accountability 
The TI (or designee) must keep an accurate accounting of the number of study devices 
received from Allergan, dispensed to subjects, and returned to Allergan during and at the 
completion of the study.  A detailed inventory must be completed for the study devices 
including subject initials, device serial/lot number, date of implantation, and date of 
explantation if applicable.  Study device accountability will be performed within IWRS 
according to the instructions provided by the system.  The study product must be dispensed 
to study subjects by an appropriately qualified person and is to be used in accordance with 
the protocol under the direct supervision of a study TI. 
12.5.4 
Return of Study Devices 
Upon completion of the treatment period, the quantities of all used and unused study devices 
will be reconciled.  Used syringes and needles will be disposed of onsite.  Unused syringes 
will be returned to Allergan unless other disposition arrangements are agreed upon in writing 
with Allergan. 
Devices that are damaged during shipment or at the site or that malfunction during use 
(eg, faulty syringe or plunger) must be accounted for and returned.  The TI will promptly 
notify Allergan’s Clinical Research department of any device malfunction.  The Clinical 
Research or Product Support representative will provide instruction for the return of any 
faulty syringe for evaluation. 
12.6 
Monitoring by Allergan 
Appropriately trained representatives of Allergan will monitor the conduct of the trial at each 
investigational site, including visits to the site to review, audit, and retrieve copies of study-
related documents.  It is the responsibility of the TI to be present or available for consultation 

 
 
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and to assure that Allergan has access to all study-related records during scheduled 
monitoring visits. 
Allergan will review device accountability records and completed eCRFs to ensure 
completeness and consistency with the source records and compliance with the protocol 
requirements. 
Allergan representatives will meet with the TI(s) and appropriate staff at mutually convenient 
times to discuss study-related data and questions. 
12.7 
Testing of Biological Specimens 
At screening and before each study treatment (initial and touch-up), a trained research staff 
member will perform pregnancy testing on urine samples of female subjects of childbearing 
potential.  The test employed must have a sensitivity of at least 50 mIU/mL for human 
chorionic gonadotropin. 
12.8 
Publications 
This study will be registered and results posted on www.clinicaltrials.gov.  Allergan, as the 
Sponsor, has proprietary interest in this study.  Authorship and manuscript composition will 
reflect joint cooperation between study Investigators and Allergan personnel.  Authorship 
will be established prior to the writing of the manuscript.  As this study involves multiple 
centers, no individual publications will be allowed prior to completion of the final report of 
the multicenter study except as agreed with Allergan. 
13. 
References 
13.1 
Study Report References 
Data from the following study are on file at Allergan. 
Study Number 
Study Title 
FSV-001 
Validation of Multiple Photonumeric Scales for Use in the Evaluation of Volume 
Deficits and Aging 

 
 
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13.2 
Literature References 
Alam M, Gladstone H, Kramer EM, Murphy JP Jr, Nouri K, Neuhaus IM, et al.  American 
Society for Dermatologic Surgery.  ASDS guidelines of care:  injectable fillers.  Dermatol 
Surg. 2008;34 Suppl 1:S115-S148. 
Atherton DD, Joshi N, Kirkpatrick N.  Augmentation of temporal fossa hollowing with 
Mersilene mesh.  J Plast Reconstr Aesthet Surg.  2010;63(10):1629-1634. 
Beer KR, Julius H, Dunn M, Wilson F.  Remodeling of periorbital, temporal, glabellar, and 
crow’s feet areas with hyaluronic acid and botulinum toxin.  J Cosmet Dermatol.  
2014;13(2):143-150. 
Breithaupt AD, Jones DH, Braz A, Narins R, Weinkle S.  Anatomical basis for safe and 
effective volumization of the temple.  Dermatol Surg.  2015;41 Suppl 1:S278-S283. 
Callan P, Goodman GJ, Carlisle I, Liew S, Muzikants P, Scamp T, et al.  Efficacy and safety of 
a hyaluronic acid filler in subjects treated for correction of mid-face volume deficiency:  A 24 
month study.  Clin Cosmet Investig Dermatol.  2013;6:81-89. 
Carruthers J, Fagien S, Dolman P.  Retro or peribulbar injection techniques to reverse visual 
loss after filler injections.  Dermatol Surg.  2015;41 Suppl 1:S354-357. 
Clauser LC, Tieghi R, Galie M, Carinci F.  Structural fat grafting:  facial volumetric 
restoration in complex reconstructive surgery.  J Craniofac Surg.  2011;22(5):1695-1701. 
Gosain AK.  Hydroxyapatite cement paste cranioplasty for the treatment of temporal 
hollowing after cranial vault remodeling in a growing child.  J Craniofac Surg.  
1997;8(6):506-511. 
Guo J, Tian W, Long J, Gong H, Duan S, Tang W.  A retrospective study of traumatic temporal 
hollowing and treatment with titanium mesh.  Ann Plast Surg.  2012;68(3):279-285. 
Jones D, Flynn T.  Hyaluronic acids: clinical applications.  In: Jones D, editor.  Injectable 
fillers: principles and practice.  Oxford, UK:  Wiley-Blackwell;2010. p. 158-174. 
Jones D, Murphy DK.  Volumizing hyaluronic acid filler for midface volume deficit:  2-year 
results from a pivotal single-blind randomized controlled study.  Dermatol Surg. 
2013;39(11):1602-1612. 

 
 
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Kim S, Matic DB.  The anatomy of temporal hollowing:  the superficial temporal fat pad.  
J Craniofac Surg.  2005;16(4):651-654. 
Lowe NJ, Maxwell CA, Lowe P, Shah A, Patnaik R.  Injectable poly-l-lactic acid:  3 years of 
aesthetic experience.  Dermatol Surg.  2009;35(1 Suppl):344-349. 
McNichols CH, Hatef DA, Cole P, Hollier LH, Thornton JF.  Contemporary techniques for the 
correction of temporal hollowing:  augmentation temporoplasty with the classic dermal fat 
graft.  J Craniofac Surg.  2012;23(3):e234-e238. 
Moradi A, Shirazi A, Moradi J.  A 12-month, prospective, evaluator-blinded study of small gel 
particle hyaluronic acid filler in the correction of temporal fossa volume loss.  J Drugs 
Dermatol.  2013;12(4):470-475. 
Moradi A, Shirazi A, Perez V.  A guide to temporal fossa augmentation with small gel particle 
hyaluronic acid dermal filler.  J Drugs Dermatol.  2011;10(6):673-676. 
Philip-Dormston WG, Hilton S, Nathan M.  A prospective, open-label, multicenter, 
observational, postmarket study of the use of a 15 mg/mL hyaluronic acid dermal filler in the 
lips.  J Cosmet Dermatol.  2014;13(2):125-134. 
Raspaldo H.  Volumizing effect of a new hyaluronic acid sub-dermal facial filler:  a 
retrospective analoysis based on 102 cases.  J Cosmet Laser Ther.  2008;10(3):134-142. 
Rose AE, Day D.  Esthetic rejuvenation of the temple.  Clin Plast Surg.  2013;40(1):77-89. 
Ross JJ, Malhotra R.  Orbitofacial rejuvenation of temple hollowing with Perlane injectable 
filler.  Aesthet Surg J.  2010;30(3):428-433. 
Sykes JM.  Applied anatomy of the temporal region and forehead for injectable fillers.  
J Drugs Dermatol.  2009;8(10 Suppl):s24-s27. 
Sykes JM, Cotofana S, Trevidic P, Solish N, Carruthers J, Carruthers A, et al.  Upper face: 
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2015;136(5 Suppl):204S-218S. 

 
 
Approval Date: 
 
01-Mar-2017
Allergan Confidential 
 
JUVÉDERM VOLUMA® XC 
Protocol VOLUMA-007 Amendment 3 
 
 
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14. 
Protocol Amendment Summary 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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01-Mar-2017
Allergan Confidential 
 
JUVÉDERM VOLUMA® XC 
Protocol VOLUMA-007 Amendment 3 
 
 
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Version Date/ 
Amend. No. 
Changes to Protocol 
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Approval Date: 
 
01-Mar-2017
Allergan Confidential 
 
JUVÉDERM VOLUMA® XC 
Protocol VOLUMA-007 Amendment 3 
 
 
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Version Date/ 
Amend. No. 
Changes to Protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Approval Date: 
 
01-Mar-2017
Allergan Confidential 
 
JUVÉDERM VOLUMA® XC 
Protocol VOLUMA-007 Amendment 3 
 
 
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Version Date/ 
Amend. No. 
Changes to Protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Approval Date: 
 
01-Mar-2017
ALLERGAN 
 
 
 
 
 
 
 
 
 
Date (DD/MMM/YYYY)/Time (PT) 
Signed by: 
Justification 
  
 
 
            
 
           
 
            
 
           
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
Protocol VOLUMA-007 Amd 3
01-Mar-2017 16:02 GMT-080