Conditions: Erythematotelangiectatic Rosacea
Keywords: Erythema Rosacea Telangiectasia pulsed dye laser oxymetazoline hydrochloride 1% cream
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 34
Healthy volunteers: yes

Brief summary:
This study will compare treatment outcome with pulsed dye laser, when used used as an adjunctive treatment to oxymetazoline HCl 1% cream, compared to oxymetazoline HCL 1% cream alone, for patients with moderate or severe erythematotelangiectatic rosacea.

Detailed description:
This is a prospective, two-arm randomized, baseline-controlled, pilot study to evaluate treatment outcome of 3 Vbeam® Prima PDL treatments in subjects applying once-daily RHOFADE® topical oxymetazoline HCL 1.0% cream for improvement in erythematotelangiectatic rosacea. Treatment outcome will be compared to oxymetazoline HCL 1% cream alone.

Subjects with moderate or severe (Grade 3 or 4) erythematotelangiectatic rosacea on the validated Clinical Erythema Assessment (CEA) Scale and Subject Self-Assessment (SSA) Scale will be enrolled and randomized to one of two study arms:

Arm 1- 3 monthly treatments with Vbeam® PDL with daily RHOFADE® topical oxymetazoline HCL 1.0% cream.

Arm 2 -Treatment with daily RHOFADE® topical oxymetazoline HCL 1.0% cream only.

All subjects will apply RHOFADE® cream daily during the 6-month study. After 1-month of RHOFADE® cream, subjects in the combined treatment Arm 1 will receive the first of three monthly Vbeam® PDL treatments (at 4-week intervals) with a 3-day washout of cream before each treatment.

Investigators will assess erythema severity, global aesthetic improvement and vessel size improvement with treatment at 1, 2, 3 and 6-months' post-baseline. Subject satisfaction will be assessed. Safety assessments will be conducted at each study visit, and subjects in Arm 1 will also be assessed for treatment-associated discomfort and post-treatment response following PDL treatments.

Arms:
arm 1: Once daily application of pea-sized amount to face of Oxymetazoline HCL 1% Cream for 4 weeks prior to 1st of 3 monthly Vbeam® Prima PDL treatments. Subjects will continue with once daily application of Oxymetazoline HCL 1% Cream during the 6-month post-baseline study with a 3-day washout of cream prior to each of the 3 PDL treatments. arm 2: Once daily application of pea-sized amount to face of Oxymetazoline HCL 1% Cream during the 6-month study.

Interventions: intervention 1: The Vbeam® Prima System intervention 2: Oxymetazoline HCL 1% Cream
Intervention descriptions: intervention 1: 3 monthly Vbeam® Prima PDL treatments with a 3-day washout of topical Oxymetazoline HCL 1% cream before each treatment. intervention 2: Daily application of Oxymetazoline HCL 1% cream for the 6-month study.

Protocol document:
Prot_SAP_000.pdf: 
Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 1 of 28 
 
 
Title: 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser 
Treatment and RHOFADE™ (oxymetazoline hydrochloride) Topical 
Cream for Erythematotelangiectatic Rosacea 
Protocol Number: 
DHF24671 
 
 
Revision Date: 
June 11, 2018 
Study Type: 
Prospective, two-arm randomized, baseline-controlled, pilot study 
Study Device: 
VBeam® Prima Pulsed Dye Laser System 
 
Study Drug: 
RHOFADE™ (oxymetazoline hydrochloride) 
Sponsor:  
Candela Corporation 
530 Boston Post Road 
Wayland, MA 01778 
 
 
 
 
This document is the property of Candela Corporation No part of this document 
may be reproduced, stored in retrieval system, or transmitted in any form or any 
means, electronic, mechanical, photocopying, recording or otherwise without 
prior written permission from Candela Corporation. 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 2 of 28 
 
Contents 
ABBREVIATIONS ............................................................................................................................................ 4 
STUDY SYNOPSIS ........................................................................................................................................... 5 
Table 1 - Study synopsis ............................................................................................................................ 5 
BACKGROUND........................................................................................................................................... 6 
Study Device ......................................................................................................................................... 8 
Study Drug ............................................................................................................................................ 8 
STUDY DESIGN .......................................................................................................................................... 8 
Primary Efficacy Objective (Arm 1): ................................................................................................... 10 
Secondary Efficacy Objectives (Arms 1 and 2): .................................................................................. 10 
Safety Objectives (Arms 1 and 2): ...................................................................................................... 10 
Primary Efficacy Endpoint (Arm 1): .................................................................................................... 11 
Secondary Efficacy Endpoints (Arms 1 and 2): ................................................................................... 11 
Safety Endpoints (Arms 1 and 2): ....................................................................................................... 11 
Study Duration ................................................................................................................................... 11 
Subject Population ............................................................................................................................. 11 
Study Procedures ............................................................................................................................... 14 
Table 2: Study Schematics ...................................................................................................................... 14 
Data Recording ....................................................................................................................................... 18 
Protocol Revisions and/or Deviations .................................................................................................... 18 
ADVERSE EVENTS (AE) ................................................................................................................................. 19 
Anticipated Adverse Effects .................................................................................................................... 19 
Unanticipated Adverse Device Effects .................................................................................................... 19 
Reporting Adverse Events (AE) and Serious Adverse Events (SAE) ........................................................ 20 
MEASURES TAKEN TO PROTECT THE RIGHTS AND WELFARE OF SUBJECTS ............................................... 20 
RISK/BENEFIT ANALYSIS .............................................................................................................................. 21 
Risks ........................................................................................................................................................ 21 
Potential benefits to participating individuals ....................................................................................... 21 
Efficacy .................................................................................................................................................... 21 
Safety ...................................................................................................................................................... 21 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 3 of 28 
 
Interim and Final Data Analysis .............................................................................................................. 21 
ETHICS AND GOOD CLINICAL PRACTICE ...................................................................................................... 22 
QUALITY ASSURANCE AND STUDY MONITORING ....................................................................................... 22 
Study Monitoring/Auditing/Inspection .................................................................................................. 22 
ADMINISTRATIVE PROCEDURES.................................................................................................................. 22 
Control & Disposition of the Investigational Device ............................................................................... 22 
Informed Consent ................................................................................................................................... 23 
Monitoring Plan ...................................................................................................................................... 23 
REFERENCES ................................................................................................................................................ 23 
APPENDIX I – Photography Guidelines ....................................................................................................... 25 
APPENDIX II:  Clinical Erythema Assessment Scale (NRS)  and Subject Self-Assessment Scale .................. 26 
APPENDIX III:  Numerical Response Scale for Rating Pain (NRS) ................................................................ 26 
Appendix IV – Assessment scales................................................................................................................ 28 
 
 
 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 4 of 28 
 
ABBREVIATIONS 
AE 
adverse event 
AIDS 
 
acquired immunodeficiency syndrome 
ANOVA 
analysis of variance 
CFR 
code of federal regulations  
cm 
centimeter 
DCD 
Candela’s dynamic cooling device 
FDA 
food and drug administration 
GCP 
good clinical practice 
HIV 
human immunodeficiency virus 
ICH 
international conference on harmonization 
IRB 
independent review board 
J 
Joule 
mJ 
milliJoule 
mm 
millimeter 
SAE 
serious adverse event 
SOP 
standard operating procedure 
Tx 
Treatment 
NSR 
PIH 
Non-Significant Risk 
post-inflammatory hyperpigmentation  
 
 
 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 5 of 28 
 
STUDY SYNOPSIS 
Table 1 - Study synopsis 
Proprietary Name 
Candela Vbeam® Prima Pulsed Dye Laser System  
Allergen RHOFADE™ (Oxymetazoline Hydrochloride) Cream  
Intended use 
Vbeam – treatment of benign cutaneous vascular lesions, such as facial and leg 
telangiectasia and rosacea. 
RHOFADE™ (oxymetazoline hydrochloride) cream, 1% is indicated for the topical 
treatment of persistent facial erythema associated with rosacea in adults. 
Design 
Prospective, two-arm randomized, baseline-controlled, pilot study. 
Study population 
Up to 60 healthy male or female adult volunteers seeking facial treatment for 
erythematotelangiectatic rosacea, 18 to 75 years of age. 
Study duration 
The expected total duration of this study is up to 1 year. 
Sites and 
Investigators 
Two investigational sites. 
Study Design:   
Subjects in this study will be randomized to one of two treatment arms:  
Arm 1: subjects will receive three (3) monthly Vbeam PDL facial treatments at 4-
week (± 1 week) intervals. Subjects will apply RHOFADE topical cream once daily 
for 4 weeks, with a 2-day wash-out period, prior to the 1st Vbeam PDL treatment. 
Subjects in Arm 1 will continue with daily use of RHOFADE topical cream during 
the study, according to the study protocol, with a 3-day wash-out period prior to 
each PDL treatment. Subjects in Arm 1 will apply RHOFADE topical cream in-
office immediately following each Vbeam PDL treatment. 
Arm 2: subjects will apply RHOFADE topical cream once daily for the duration of 
the 6-month study. Subjects will not receive laser therapy. 
At the 1-week post first PDL treatment follow-up visit (1wk Post Tx.1 FU), 
subjects will be assessed for immediate treatment response and duration of 
treatment response.  
Both arms will be evaluated at each study visit (1, 2, 3 and 6 months post 
baseline visit). The 6-month follow-up is at (2 months following the third PDL 
treatment for Arm 1 and after 6 months of continuous drug therapy for Arm 2. 
Methodology described in the protocol to evaluate efficacy and safety of 
treatments will be carried out at each visit at the clinic.  


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 6 of 28 
 
Primary Objective 
Evaluate the efficacy of combined Vbeam PDL and topical RHOFADE cream (Arm 
1) for improvement in erythematotelangiectatic rosacea at the 6-month follow-
up compared to baseline and compared to RHOFADE treatment alone at the 6-
month follow-up (Arm 2).   
Secondary 
Objectives 
• 
Evaluate the efficacy of combined Vbeam PDL and topical RHOFADE 
cream (Arm 1) for improvement in erythematotelangiectatic rosacea at 
each treatment visit (pre-treatments 2 and 3) compared to baseline.   
• 
Evaluate the efficacy of combined Vbeam PDL and topical RHOFADE 
cream (Arm 1) for improvement in erythematotelangiectatic rosacea 
compared to RHOFADE treatment only (Arm 2) at each study visit (pre-
treatments 2 and 3 and 6-month follow-up for Arm 1 and at the 2-, 3-, 
and 6-month follow-up visits for Arm 2).   
• 
Both arms: Evaluate improvement in vessel size at each study visit (1, 2, 
3 and 6 months post baseline visit). 
• 
Both arms: Evaluate subject satisfaction at each study visit (1, 2, 3 and 6 
months post baseline visit). 
• 
Both arms: Evaluate overall improvement (investigator and subject) at 
each study visit (1, 2, 3 and 6 months post baseline visit). 
Efficacy Endpoints 
• 
Clinician erythema assessment (CEA) – Appendix II. 
• 
Subject self-assessment (SSA) 5-point scale – Appendix II. 
• 
Investigator and subject assessment, using a Global Aesthetic 
Improvement (GAI) 5-point scale – Appendix IV, Table 4. 
• 
Investigator assessment of Improvement in vessel size – Appendix IV, 
Table 5. 
• 
Subject satisfaction 5-point scale – Appendix IV, Table 6. 
Safety Endpoints 
Evaluate the safety of the treatment (Arms 1 and 2): 
• 
Arm 1: Immediate treatment response – Appendix IV, Table 3. 
• 
Both Arms: Number, severity and type of any adverse event recorded 
throughout course of the study. 
• 
Arm 1: Discomfort level following PDL treatment – Appendix III.  
 
BACKGROUND 
Rosacea is a common chronic skin condition categorized into 4 subgroups based on clinical manifestations: 
erythematotelangiectatic, papulopustular, phymatous, and ocular [1]. Although the clinical features may 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 7 of 28 
 
vary with rosacea, the most common primary feature of all subtypes is transient or persistent facial 
erythema [2,3]. Erythematotelangiectatic rosacea is primarily characterized by flushing and persistent 
central facial erythema [4].  
Early diagnosis and treatment based on subtype are recommended to halt progression of symptom 
severity [5]. Flushing is better prevented rather than treated, by avoiding specific triggers, decreasing 
transepidermal water loss by moisturizers, and blocking ultraviolet light [5]. Nonselective β-blockers and 
α2-adrenergic agonists decrease erythema and flushing [5], while pulsed dye laser [5, 6] and intense 
pulsed light are used for telangiectasias [5]. Pulsed dye laser also addresses the diffuse erythema and 
enlarged pores characteristic of rosacea [6]. 
Oxymetazoline hydrochloride 1% cream (RHOFADE™) is a newly FDA-approved topical medication for 
adult rosacea patients. A primarily alpha-1a agonist, oxymetazoline hydrochloride (HCl) is thought to 
diminish erythema through vasoconstriction [7]. RHOFADE was evaluated for the treatment of persistent 
erythema associated with rosacea in two identical, randomized, double-blind, vehicle-controlled, parallel-
group clinical trials [8]. A total of 489 subjects with persistent facial erythema associated with rosacea 
were treated with RHOFADE once daily for 4 weeks. An additional 440 subjects with persistent facial 
erythema associated with rosacea were also treated with RHOFADE once daily for up to one year in a long-
term (open-label) clinical trial [8]. Disease severity was graded by the clinician using a 5-point clinician 
erythema assessment (CEA) scale [4] and by the subject on a similar 5-point subject self-assessment (SSA) 
scale, on which subjects scored either “moderate” or “severe” on both scales. Composite success, defined 
as the proportion of subjects achieving at least a 2-grade improvement on both CEA and SSA, was 15% in 
Trial 1 and 12% in Trial 2 on Day 29 of treatment [8].   
Nonpurpuragenic pulsed dye laser (PDL) and intense pulsed light treatment have resulted in significant 
reduction in cutaneous erythema, telangiectasia and patient-reported associated symptoms of 
erythematotelangiectatic rosacea [9]. The PDL is an ideal energy-based device to treat the cutaneous 
vasculature of rosacea, since the 595nm wavelength is strongly taken up by the hemoglobin in blood 
vessels [6, 10].  With Vbeam 595nm PDL, ultra-long pulse durations reduce purpura while treating the 
telangiectasias associated with rosacea, which is more comfortable for patients [5, 6].  
The cutaneous manifestations of rosacea significantly impact patients’ well-being, social and emotional 
health [5], and alternatives to further improve management and treatment of this condition are 
necessitated.  
The objective of this pilot study is to evaluate the efficacy of Rhofade topical drug therapy combined with 
Vbeam PDL treatment. The study hypothesis is that a synergistic approach to treatment may improve the 
treatment course by a mechanism of action in which oxymetazoline acts as a vasoconstrictor, slowing 
down vascular flow and allowing for occlusion with PDL to close off the vessels quicker.  
   


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 8 of 28 
 
Study Device 
The Candela Family of Pulsed Dye Laser Systems, including the 595nm pulsed dye laser wavelength, are 
FDA-cleared systems (K051359; K050673). The Vbeam 595nm PDL is indicated for treatment of benign 
cutaneous vascular lesions, benign epidermal pigmented lesions and periorbital wrinkles. The Vbeam is 
also indicated for treatment of inflammatory acne vulgaris.  
The FDA-cleared Vbeam system includes spot sizes of 3, 5, 7, 10, 12 mm and 3x10 (elliptical). The study 
device is a modified version of the FDA-cleared system that includes an additional 15-mm spot size. The 
Vbeam and modified Vbeam are non-significant risk (NSR) devices. The modified Vbeam system provides 
epidermal cooling by either cryogen spray (Dynamic Cooling Device), as with the FDA-cleared system, or 
contact with a cooled window (termed contact-cooling). The modified Vbeam system (Vbeam Prima) 
recently received FDA clearance (K180593) on June 5, 2018. 
 
Study Drug 
RHOFADE™ is an alpha1A adrenoceptor agonist indicated for the topical treatment of persistent facial 
erythema associated with rosacea in adults [8]. 
There are no contraindications associated with topical use of RHOFADE for the topical treatment of 
persistent facial erythema associated with rosacea in adults. 
There are warnings and precautions associated with use of the 1% topical cream, as indicated in the FDA-
cleared package insert. These include the following: 
• 
Alpha-adrenergic agonists as a class may impact blood pressure. 
• 
Use with caution in patients with cerebral or coronary insufficiency, Raynaud’s phenomenon, 
thromboangiitis obliterans, scleroderma, or Sjögren’s syndrome. 
• 
Advise patients to seek immediate medical care if signs and symptoms of acute narrow-angle 
glaucoma develop. 
The most common adverse reactions (incidence > 1%) are application site dermatitis, worsening 
inflammatory lesions of rosacea, application site pruritus, application site erythema, and application site 
pain. In clinical trials, adverse reactions occurred in 1% - 2% of subjects treated with RHOFADE through 4 
weeks of treatment. In the long-term (open-label) clinical trial, the rates of adverse reactions over a one-
year treatment period were as follows: worsening inflammatory lesions of rosacea (3%), application site 
dermatitis (3%), application site pruritus (2%), application site pain (2%), and application site erythema 
(2%). Subjects with persistent erythema along with inflammatory lesions were allowed to use additional 
therapy for the inflammatory lesions of rosacea [8]. 
STUDY DESIGN 
This is a prospective, two-arm randomized, baseline-controlled, pilot study to evaluate the efficacy of 
combined Vbeam PDL and topical RHOFADE cream for improvement in erythematotelangiectatic rosacea.   


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 9 of 28 
 
Up to 60 healthy male or female subjects will be enrolled at two investigational sites. All subjects will 
undergo an assessment of their general health. Following enrollment, subjects will be randomized to a 
study arm. Subjects in Arm 1 will receive RHOFADE topical cream at the screening visit and will be 
instructed to apply it daily for 4 weeks prior to the first PDL facial treatment.  Arm 1 subjects will receive 
three (3) monthly PDL facial treatments at 4-week intervals. Subjects will apply RHOFADE topical cream 
once daily during the 6-month study, according to the study protocol, with a 3-day wash-out period 
prior to each PDL treatment. Immediately following the PDL treatment, subjects in Arm 1 will apply 
RHOFADE topical cream in-office. If subjects find it irritating to the skin to apply RHOFADE immediately 
after PDL treatment, then they may apply it within 24 hours of subsequent treatments.  
Arm 2 subjects will receive RHOFADE topical cream at the screening visit and will be instructed to apply 
it daily for 6 months of continuous use until the 6-month post-baseline follow-up visit. . Subjects in Arm 
2 will not receive laser therapy.  
A one-week post first PDL treatment safety follow-up visit will be conducted (1wk FU post Tx.1) for Arm 1 
subjects. In addition, efficacy and safety evaluations will be performed at each study visit (1, 2, 3 and 6 
months post-baseline visit), as shown in Figure 1 below..  
Erythema severity will be assessed at baseline and at each study visit. Improvement in erythema severity 
will be assessed at each post baseline visit. Additionally, investigator and subject questionnaires will be 
completed.  Photography will be performed at each study visit under visible light conditions of the front 
full face, right and left 45-degree profile and right and left 90-degree profile.  VISIA photography may also 
be performed for spectrometry measurements (optional). Safety assessments will be conducted at each 
study visit.  
 
 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 10 of 28 
 
Study Flowchart 
 
 
Primary Efficacy Objective: 
To evaluate the efficacy of combined Vbeam Prima PDL treatment and topical RHOFADE cream for 
improvement in erythematotelangiectatic rosacea, at the 6-month follow-up compared to baseline and 
compared to Arm 2 at the 6-month follow-up (RHOFADE drug therapy only). 
Secondary Efficacy Objectives: 
• 
Evaluate the efficacy of combined PDL and topical RHOFADE cream (Arm 1) for improvement in 
erythematotelangiectatic rosacea at each treatment visit (pre-treatments 2 and 3) compared to 
baseline.   
• 
Evaluate the efficacy of combined PDL and topical RHOFADE cream (Arm 1) for improvement in 
erythematotelangiectatic rosacea compared to topical RHOFADE cream only (Arm 2) at each 
study visit (pre-treatments 2 and 3 and 6-month follow-up for Arm 1 and at the 2-, 3-, and 6-
month follow-up visits for Arm 2).   
• 
Evaluate subject satisfaction at each study visit (1, 2, 3 and 6 months post-baseline). 
• 
Evaluate overall improvement (investigator and subject) at each study visit (1, 2, 3 and 6 months 
post-baseline).  
• 
Evaluate improvement in vessel size (investigator) at each study visit (1, 2, 3 and 6 months post 
baseline visit).  
Safety Objectives: 
• 
Evaluate the safety of combined PDL treatment and topical RHOFADE cream (Arm 1) during the 
study. 
• 
Evaluate comfort level associated with PDL treatment (Arm 1). 
Baseline
Day 0
Arms 1 & 2 
receive 
RHOFADE
~Day 30
1st PDL Tx 
(Arm 1) 
1-month FU 
(Arms 1 & 2)
~Day 37
1-week FU 
post Tx 1 
(Arm 1)
~Day 60
2nd PDL Tx 
(Arm 1) 
2-month FU 
(Arms 1 & 2)
~Day 90
3rd PDL Tx 
(Arm 1) 
3-month FU 
(Arms 1 & 2)
~Day 180
6-month FU 
(Arms 1 & 2)


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 11 of 28 
 
Comfort assessment will be performed independently by the subject using a numerical scale response 
(NSR) scale 0=No pain to 10=Worst possible pain (Appendix III). Subjects will be asked to fill out a 
questionnaire after each PDL treatment (Tx.1 – Tx.3). 
Primary Efficacy Endpoint: 
• 
Clinician erythema assessment (CEA): 5-point scale (0=Clear to 4=Severe) at 6-month follow-up 
compared to baseline.  
• 
Subject self-assessment (SSA) 5-point scale similar to CEA at 6-month follow-up compared to 
baseline. 
Secondary Efficacy Endpoints: 
• 
Investigator and subject assessment of overall changes in skin condition (skin texture, vessel 
size, flushing), using a Global Aesthetic Improvement (GAI) 5-point scale (0=Excellent 
improvement to 4=No difference) – Appendix IV, Table 4. 
• 
Investigator assessment of improvement in vessel size – Appendix IV, Table 5. 
• 
Subject satisfaction 5-point scale (0=Very satisfied to 4=Very dissatisfied) – Appendix IV, Table 6.   
Safety Endpoints: 
• 
The number, severity and type of any adverse event recorded throughout the study and post-
treatment (discomfort (pain), immediate and delayed response). 
• 
Occurrence of expected post-treatment immediate response following each treatment based on 
a predefined scale (Appendix IV, Table 3). 
• 
Discomfort (pain) level using a 10-point visual analog scale will also be recorded after each PDL 
treatment, using a Numerical Scale Response (NSR) – Appendix III. 
Study Duration 
The duration of the entire study from first subject enrollment to last subject completing the 6-month 
follow-up, is expected to be approximately 1 year.   
Subject Population  
Up to 60 healthy male and female adults (greater than 18 years of age), who meet the inclusion and 
exclusion criteria.   
Subjects enrolled in the study can discontinue their participation at any time, for any reason, without 
prejudice or reduction in the quality of their medical care.  In addition, the investigator or the sponsor can 
terminate a subject's participation in this study to protect the subject's health or if the subject is not 
compliant with the study protocol and schedule. Subjects may be replaced if withdrawn or lost from the 
study.   
All subjects enrolled into this study must meet the following criteria: 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 12 of 28 
 
Inclusion Criteria: 
1. Subject is a healthy male or female of 18 to 75 years of age. 
2. Subject has erythematotelangiectatic rosacea with clinician erythema assessment (CEA) and 
subject self-assessment (SSA) of “moderate” or “severe” (Grade 3 or 4).  
3. Fitzpatrick Skin Type I – VI. 
4. Subject must be able to read, understand and sign the Informed Consent Form. 
5. Subject must be willing and able to adhere to the treatment and follow-up schedule and post-
treatment care instructions. 
6. Subject must be willing to have limited sun exposure for the duration of the study, including the 
follow-up period up to 6 months post-baseline. 
7. Subject is willing to have photographs taken of the treated area that will be used, de-identified, 
in evaluations and may be used, de-identified, in presentations and/or publications. 
8. For female candidates – subject must be post-menopausal, or surgically sterilized, or using a 
medically acceptable form of birth control during the entire course of the study. 
Exclusion Criteria: 
1. Subject is pregnant or planning to become pregnant during the study duration. 
2. Subject has an active electrical implant anywhere in the body, such as a pacemaker or an internal 
defibrillator. 
3.    Subject has an implant in the treated area (such as metal plates or screws) or an injected chemical 
substance. 
4. Subject has a known collagen (connective tissue) disorder, vascular disease, scleroderma or other 
autoimmune disease (i.e. rheumatoid arthritis, lupus).  
5. Subject has a history of diseases stimulated by heat or sun exposure, such as recurrent Herpes 
Simplex in the treated area, unless treatment is conducted following a prophylactic regimen.  
6. Subject has a history of immunosuppression/immune deficiency disorders (including HIV infection 
or AIDS) or currently using immunosuppressive medications.  
7. Having or undergoing any form of treatment for active cancer or having a history of skin cancer 
or any other cancer in the areas to be treated, including presence of malignant or pre-malignant 
pigmented lesions.   
8. Subject is suffering from significant concurrent illness, such as such as cardiac disorders, diabetes 
(type I or II), or pertinent neurological disorders. 
9. Subject has an infection or is suffering from current or has a history of significant skin conditions 
in the treated area or inflammatory skin conditions, including, but not limited to: 
photodermatoses, active acne, excessive skin dryness, psoriasis, eczema, rash, open wounds, 
varicella scars, open lacerations or abrasions and active cold sores or herpes sores prior to 
treatment (duration of resolution as per the Investigator’s discretion) or during the treatment 
course.  


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 13 of 28 
 
10. Having a known anticoagulative or thromboembolic condition or taking anticoagulation 
medications one week prior to and during the treatment course (to allow inclusion, temporary 
cessation of use might be requested as per the subject’s physician discretion). 
11. Use of non-steroidal anti-inflammatory drugs (NSAIDS, e.g., ibuprofen-containing agents) one 
week before and after each treatment session.  
12. Subject has a history of pigmentary disorders, particularly tendency for hyper- or hypo-
pigmentation.  
13. Subject has a history of keloid scarring or of abnormal wound healing. 
14. Subject has a known photosensitivity to the device’s laser wavelengths, history of ingesting 
medications known to induce photosensitivity, or history of seizure disorders due to light. 
15. Subject has undergone any surgical, light-based therapy or RF procedures in the treatment area 
within 3 months of treatment or during the study.  
16. Having undergone any other surgery in the treated area within 3 months of treatment (or more 
if skin has not healed completely) or during the study.  
17. Subject has a tattoo or permanent make-up in the treated area. 
18. Subject has systemically used retinoids or antioxidants within 1 month of treatment or during the 
study.  
19. Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning during the 
study. 
20. Participation in a study of another device or drug within three months prior to enrollment or 
during the study.  
21. As per the Investigator's discretion, any physical or mental condition which might make it unsafe 
for the subject to participate in this study. 
 
 


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
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Rev. Date 
June 11, 2018 
Page 14 of 28 
 
Study Procedures 
The following table provides a summary of the required study visits and the procedures and assessments 
performed at each visit. 
Table 2: Study Schematics 
Visit 
Screening 
/Baseline  
Tx 1* / 1-
month FU 
1-week (± 2 
days) Safety 
Evaluation 
Tx 2 - 3 / 2 
& 3-Month 
FU Visits 
(4± 1 
week) 
 
6-Month (± 
2 weeks) 
FU 
Informed Consent 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Inclusion/ Exclusion 
Criteria 
X 
 
 
 
 
Subject # Assignment 
X 
 
 
 
 
Randomization to Study 
Arm 
X 
 
 
 
 
Pregnancy Urine test 
X 
 
 
 
 
Vbeam PDL test spots, 
(optional) – Arm 1 
X 
X 
 
X 
 
Change to Medical 
History 
 
X 
X 
X 
X 
Photographs, prior to 
any treatments 
 
X 
X 
X 
X 
VISIA photographs, prior 
to any treatments 
(optional) 
 
X 
X 
X 
X 
Clinician erythema 
assessment (CEA), prior 
to any treatments 
X 
X 
 
X 
X 
Subject self-assessment 
(SSA), prior to any 
treatments 
X 
X 
 
X 
X 
Vbeam PDL Treatment – 
Arm 1 
 
X 
 
X 
 
Tx Pain Assessment – 
Arm 1 
 
X 
 
X 
 
Immediate Treatment 
Response – Arm 1 
 
X 
 
X 
 
 


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Visit 
Screening 
/Baseline  
 
Tx 1*/ 1-
month FU 
1-week (± 2 
days) Safety 
Evaluation 
Tx 2 - 3 / 2 
& 3-Month 
FU Visits 
(4± 1 
week) 
 
6-Month (± 
2 weeks) 
FU 
Photographs, 10 mins 
post any treatment 
(optional) – Arm 1 
 
X 
 
X 
 
Global Aesthetic 
Improvement (GAI) 
 
X 
 
X 
X 
Vessel size assessment 
 
X 
 
X 
X 
Subject Satisfaction 
Questionnaire 
 
X 
 
X 
X 
Adverse Events and 
Serious Adverse Events 
X 
X 
X 
X 
X 
End of participation 
(Termination) 
 
 
 
 
X 
*For Arm 1, the 1st PDL treatment will be scheduled at approximately 4 weeks following the screening 
visit.  
 
Screening Procedures 
• 
A brief relevant medical history will be obtained to address inclusion/exclusion criteria for the 
study. 
• 
Clinician erythema assessment (CEA) and subject self-assessment (SSA) will be obtained to 
address inclusion criteria for the study. Subjects with “moderate” or “severe” (Grade 3 or 4) are 
eligible for study participation (Appendix II). 
• 
Pregnancy will be assessed for female subjects based on their last menstrual period, ability to 
become pregnant (surgical sterilization, birth control), and whether they have plans to become 
pregnant during the 6-month study period.  
• 
The subject will undergo a standard skin exam to determine if they meet the study criteria. 
• 
If the subject meets the criteria for the study, he or she will discuss with the study staff the study 
procedures, risks, benefits, and commitments associated with enrollment into the study.  The staff 
will then review the consent form in detail with the subject, after which the subject will be given 
ample time to review the form.  The subject will sign a consent form after the subject fully 
understands the possible risks/benefits of the study and wants to participate in study.  The person 
conducting the session and the investigator will subsequently sign the consent form.  
• 
Once the consent form is signed, the subject will be assigned the next consecutive subject number 
and will be randomized to a treatment arm. 
• 
Women capable of childbearing will undergo a urine pregnancy test.  


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Page 16 of 28 
 
• 
Skin type will be recorded using the Fitzpatrick Scale. 
• 
Test spots may be performed (optional) for subjects in Arm 1 to determine the subject’s response 
to selected treatment parameters.  Test spot locations will be selected by the investigator.   
• 
Subjects in Arms 1 & 2 will be provided with RHOFADE topical cream and instructed to apply once 
daily, according to the drug insert instructions:  apply a pea-sized amount once daily in a thin layer 
to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. 
• 
The RHOFADE topical cream will be applied daily for 4 weeks prior to the first PDL facial treatment. 
• 
Subjects must discontinue topical use for a 3-day washout period prior to each PDL treatment.  
Pre-Treatment PDL Care 
In order to minimize pain during laser irradiation, subjects will be offered to use topical anesthetic 
cream (EMLA), which will be applied to the skin surface 30-60 minutes prior to laser irradiation.  
PDL Treatment Procedure 
• 
Treatments will be performed every 4 (±1) weeks.  Subjects in Arm 1 must discontinue topical use 
for a 3-day washout period prior to each PDL treatment. 
• 
Laser treatment procedures will conform to all laser safety instructions and should be conducted 
per the procedure described.   
• 
The investigator, all personnel in the treatment room and the subject will wear protective 
eyewear, appropriately rated for the device wavelength(s) being operated.  
• 
Based on the subject’s response to the test spot evaluation (optional) or experience from 
treatment of prior subjects in this study or in practice, the investigator will select the parameters 
used for treatment, based on the threshold for nonpurpuragenic settings. 
• 
Parameters include choice of: the 12 mm or 15 mm spot size, the laser fluence, the duration of 
the laser pulse exposures and the cooling procedure.  The investigator will treat the face with the 
parameters chosen and will document the parameters.  
• 
The treatment area will be photographed before each treatment and at each post-treatment 
follow-up visit. Optional photography can include photos at 10 minutes (approximately) after each 
treatment.  
• 
All subjects will be treated as follows:   
- 
The 12 mm or 15 mm spot size will be used. 
- 
Treatment pulses will be delivered at the threshold for nonpurpuragenic settings.  
• 
Subjects will be instructed to report any discomfort and/or comments during and post treatment.  
Discomfort will be rated on a scale from 0 = no pain to 10 = worst imaginable pain using the NRS 
scale (Appendix III).   
• 
Immediate clinical response post-treatment will be recorded for: purpura, edema, erythema, and 
blistering, based on a predefined scale (Appendix IV, Table 3).  
• 
Post-treatment photographs (optional) may be taken, approximately 10 mins post treatment, to 
document post treatment effects such as the collapse of blood vessels, or to document post 
treatment purpura, erythema, etc. 


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Protocol # 
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Rev. Date 
June 11, 2018 
Page 17 of 28 
 
• 
Subjects will be instructed on post-treatment care, including the use of sunscreen.  
• 
Subjects in Arm 1 will apply RHOFADE topical cream immediately (in-office) following the PDL 
treatment. If subjects find it irritating to the skin to apply Rhofade immediately after PDL 
treatment, then they may apply it within 24 hours of subsequent treatments. 
1-Week Post-Treatment 1 Safety Evaluation:  
Subjects in Arm 1 will be scheduled for a 1-week (±2 days) safety evaluation following the first PDL 
treatment. The following procedures will be conducted during this visit: 
• 
A brief relevant medical history review for any changes from baseline.  
• 
Skin evaluation of treatment area. 
• 
Photographs of treatment area. 
• 
Adverse event reporting. 
Follow-up Study Visits:  
The following procedures will be conducted during the 1-, 2-, 3- and 6-month study visits for subjects in 
both Arms 1 & 2: 
• 
A brief relevant medical history review for any changes from baseline.  
• 
Skin evaluation of treatment area. 
• 
Photography will be performed according to the same procedure used at the baseline visit.  
• 
VISIA photography (optional) may be performed according to the same procedure used at the 
baseline visit. 
• 
Clinician erythema assessment (CEA) and subject self-assessment (SSA) will be recorded prior to 
treatment (Appendix II). 
• 
Assessment of improvement (pretreatment) will be recorded by the investigator and subject using 
the Global Aesthetic Improvement Scale (GAI) —Appendix IV, Table 4. 
• 
Improvement in vessel size will be evaluated by investigator—Appendix IV, Table 5. 
• 
Subject satisfaction will be reported —Appendix IV, Table 6. 
• 
Treatment will be performed (Arm 1).   
• 
Subjects will be instructed to report any discomfort and/or comments during and post treatment 
(Arm 1).  Discomfort will be rated on a scale from 0 = no pain to 10 = worst imaginable pain using 
the NRS scale (Appendix III).   
• 
Immediate clinical response post-treatment (Arm 1) will be recorded for: purpura, edema, 
erythema, and blistering, based on a predefined scale (Appendix IV, Table 3).  
• 
Post-treatment photographs (approximately 10 minutes post treatment) may be taken to 
document post treatment effects (Arm 1) such as the collapse of blood vessels in the lesion, or to 
document post treatment purpura, erythema, etc. (optional). 
• 
Subjects in Arm 1 will be instructed on post-treatment care.  


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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
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Rev. Date 
June 11, 2018 
Page 18 of 28 
 
• 
Subjects in Arm 1 will apply RHOFADE topical cream immediately (in-office) following the PDL 
treatment. If subjects find it irritating to the skin to apply Rhofade immediately after PDL 
treatment, then they may apply it within 24 hours of subsequent treatments. 
• 
Adverse event reporting. 
Study Termination Procedure  
The study termination visit occurs in parallel with the last follow-up visit.  The only additional procedure 
required for the termination evaluation is to complete the study termination case report form (CRF). 
Photographs 
Photographs will be taken at each study visit, before and approximately 10 minutes after (optional) each 
treatment for subjects in Arm 1, and at the 6-month follow-up (2 months following the final PDL treatment 
for subjects in Arm 1).  Photography will be standardized for reproducibility of photos (Appendix I): i.e., 
same photographer for each subject’s study visits, use of the same camera, background, position of 
camera with respect to the treated area, same lighting and exposure conditions. These photographs will 
be taken for documentation, as well as for the investigator and subject assessments.   
Post-treatment Care 
After treatment, no special care is usually necessary for the treatment site. Aquaphor (similar to Vaseline) 
may be supplied to the subject to be applied to any area that feels irritated. The subject will also be 
instructed to apply cool compresses if they have any areas of swelling after treatment and to wash the 
treated area with soap or a gentle cleanser as they normally would for the week following treatment. The 
subject will be able to continue with their preferred routine skin care, excluding any method of wrinkle 
removal, the day after treatment. Sunscreen should be worn.  
Data Recording 
All data will be recorded in source documents and transcribed onto Case Report Forms (CRFs). Site will be 
monitored by Syneron staff or designees to assure adherence to the clinical trial requirements, subject 
safety, protocol procedures, and for data accuracy. The Case Report Forms and images will be reviewed 
and retrieved during the monitoring visit.  All source documentation will remain in the subject's files at 
the site. 
Protocol Revisions and/or Deviations 
With the exception of emergency situations, no changes or deviations in the conduct of this protocol will 
be permitted without the prior approval of the sponsor. 
The IRB/IEC that granted original approval for the study must be notified of all changes in the protocol 
and will approve any change or deviation that may increase risk to the subject, and/or that may adversely 
affect the rights of the subject or validity of the investigation. 


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
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In the event of an emergency, the Investigator will institute any medical procedures deemed appropriate. 
However, all such procedures must be promptly reported to the sponsor and the IRB/IEC. 
ADVERSE EVENTS (AE) 
An adverse event (AE) is any adverse change in health or side effect that occurs in a study participant 
during their participation in the study. 
Anticipated Adverse Effects 
Anticipated adverse effects of laser-based treatments include: hyperpigmentation, blistering, crusting, 
bruising, scabbing, scarring, hypopigmentation, infection, and pinpoint bleeding.  While unlikely, some 
adverse events may be permanent. 
An adverse event (AE) is any undesired clinical occurrence in a study subject as indicated by signs, 
symptoms, illnesses, events that develop or worsen in severity in association with the study when deemed 
by the Investigator to be related to use of the device or study procedures. The Investigator will document 
all adverse signs and symptoms regardless of severity or frequency that are either volunteered by subjects 
or observed during the course of the study that are related to the device.  The Investigator will also record 
adverse experiences of subjects resulting from concurrent illnesses, reactions to concurrent medications, 
or progression of disease states that the Investigator deems related to the device. Included in the 
description will be the nature of the sign or symptom, the date of onset, whether the event was serious, 
the severity, the relationship to study procedures or investigational device, the action taken, the date of 
resolution, and the outcome. The Principal Investigator will then determine the relationship of the adverse 
device effect to the investigational device. 
Unanticipated Adverse Device Effects 
For device studies, part 21 CFR 812.3(s) uses the term unanticipated adverse device effect which is defined 
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. 
An unanticipated adverse effect will be graded as follows: 
Mild: 
Sign or symptom, usually transient, non-life-threatening requiring no special 
treatment and generally not interfering with usual activities. 
Moderate: 
Sign or symptom, non-life-threatening which may be ameliorated by simple 
therapeutic measures and may interfere with usual activity. 


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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Major: 
Sign or symptom that is intense or debilitating but non-life-threatening and that 
interferes with usual activities. Recovery is usually aided by therapeutic measures 
and the discontinuation of the study device may be required. 
Severe: 
Any untoward medical occurrence that at any time results in death or life-
threatening illness, resulting in persistent or significant disability/incapacity.   
The relationship of the adverse effect to the study is defined as follows: 
Probable: 
An adverse event has a strong temporal relationship to study device, and another 
etiology is unlikely or significantly less likely. 
Possible: 
An adverse event has a strong temporal relationship to the study device, and an 
alternative etiology is equally or less likely compared to the potential relationship 
to study device.  
Probably not: 
An adverse event has little or no temporal relationship to the study device and/or 
a more likely alternative etiology exists. 
Not related: 
An adverse event has no temporal relationship to study device or has a much more 
likely alternative etiology.  
Reporting Adverse Events (AE) and Serious Adverse Events (SAE) 
The Investigator must report all unanticipated adverse device effects that are serious in nature to the 
clinical study monitor immediately or within twenty-four hours by telephone (see below). If such an 
unanticipated adverse device effect is reported after normal working hours, the Investigator will leave a 
voice message at the monitor’s telephone number with accompanying report of the unanticipated 
adverse device effect faxed or sent to the fax number/e-mail address below:             
 
Sharon Timberlake, Global VP of Clinical and Regulatory Affairs 
Telephone Number (mobile): +1 (617) 957-1434 
 Email: sharont@syneron-candela.com 
  
A written report prepared by the Principal Investigator must follow within five working days to both the 
IRB and to Candela and should include a full description of the event and sequence. 
MEASURES TAKEN TO PROTECT THE RIGHTS AND WELFARE OF SUBJECTS 
Research records will be available to study personnel, and the Institutional Review Board, where 
applicable.  Research records may be used for purposes of medical education, after removal of patient 
names or other identifying information. Subjects will be required to provide permission for the 


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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
June 11, 2018 
Page 21 of 28 
 
photographs taken of the treatment area during the study to be made available to the investigator and 
the sponsor for research and marketing purposes, after removal of identifying information.  These 
photographs may be used for lectures, presentations or publications. 
RISK/BENEFIT ANALYSIS 
Risks 
The use of the device used in this clinical study has been determined to present a non-significant risk in 
accordance with 21 CFR 812.3 for the intended use in this study. 
Potential benefits to participating individuals  
Subjects may benefit by achieving visual improvement of their erythematotelangiectatic rosacea as a 
result of treatment in this study.  Not all subjects may have complete clearance of their 
erythematotelangiectatic rosacea.   
DATA ANALYSIS 
Copies of Case Report Forms and photographs will be collected by the sponsor during the monitoring visit 
when appropriate and will be used for analysis of efficacy and safety.  
Efficacy 
The efficacy of combined Vbeam Prima PDL and topical RHOFADE cream for improvement in 
erythematotelangiectatic rosacea compared to baseline will be assessed by clinician erythema 
assessment, subject self-assessment, and Investigator and subject assessment, using a Global Aesthetic 
Improvement 5-point scale and subject satisfaction 5-point scale. 
Safety 
Safety of treatments will be evaluated throughout this study.  Each treatment area will be evaluated for 
severity of purpura, edema, erythema, hyperpigmentation, hypopigmentation, blistering and scarring.  All 
clinical response and complications observed either immediately following each treatment or at follow-
up visits will be noted on the data forms. These data will be descriptively tabulated by treatment area.   
Pain scores will also be assessed for safety.   
Interim and Final Data Analysis 
Interim analysis can be performed at any time and used to terminate the study should it seem necessary 
to do so.   


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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
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Page 22 of 28 
 
ETHICS AND GOOD CLINICAL PRACTICE 
This study will be carried out in compliance with the following: 
• 
Syneron Candela Standard Operating Procedures. 
• 
Declaration of Helsinki, concerning medical research in humans (Recommendations Guiding 
Physicians in Biomedical Research Involving Human Subjects, Helsinki 1964, amended Tokyo, 
1975, Venice 1983, Hong Kong 1989, Seoul 2008 and Brazil 2013). 
• 
US Code of Federal Regulations (Title 21CFR including parts 50, 56 and 812 governing informed 
consent and IRB regulations) 
• 
International Conference on Harmonization (ICH) Harmonized Tripartite Guideline for Good 
Clinical Practice (GCP), 1996. 
QUALITY ASSURANCE AND STUDY MONITORING 
Study Monitoring/Auditing/Inspection 
The Study Monitor will be responsible for monitoring the study sites to review the data being collected. 
The sponsor shall implement and maintain quality control and quality assurance procedures with written 
standard operating procedures (SOPs) to ensure that the trial is being conducted and data are generated, 
documented and reported in compliance with the protocol, Good Clinical Practice (GCP) and applicable 
regulatory requirements. Visits will be made prior to the initiation of the study, at scheduled intervals 
throughout the study, and at termination of the study. 
Once enrollment and treatments have begun, monitoring visits will take place more frequently pending 
enrollment and study activities.    
The sponsor and site will maintain regular phone and e-mail correspondence throughout the study to 
confirm compliance of study procedures.   
The investigator/institution agrees to allow the monitor and other authorized personnel direct access to 
source data/documents for trial related monitoring, the clinical supplies storage/dispensing area and to 
provide all documents in the Investigator Regulatory Binder for review, and to assist site auditors in their 
activities if requested. Requests by the United States Food and Drug Administration (FDA) or regulatory 
agencies of other countries to inspect the study site may be made after adequate notification. The 
investigator may be required to assist the regulatory inspectors in their duties, if requested. 
ADMINISTRATIVE PROCEDURES 
Control & Disposition of the Study Device 
The study device will be used according to the instructions of the Sponsor.     


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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
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Informed Consent 
The Study Personnel will obtain written Informed Consent prior to the subject’s participation in any study 
procedures.  The Study Personnel will inform the subjects about the experimental procedure to be utilized 
and assure the subjects that their decision regarding participation in the study will have no bearing on the 
quality of medical care received, and that their decision whether to participate in the study is strictly 
voluntary.  
During the initial interview, subjects will be assured that they are free to change their mind and that their 
decision to participate in (or withdraw later from) the study will have no effect on their standard medical 
care.   
Monitoring Plan 
At least 3 monitoring visits are projected over the course of the study. The frequency of those visits will 
depend upon enrollment, study activities and the study visit schedule.  The first visit is scheduled at the 
initiation of the study prior to the first subject treatment in the study.  The second visit is scheduled after 
enrollment and treatment has been initiated and a third visit will be for a close-out visit for the study.  
Further interim visits may be conducted as needed to assure compliance to the study protocol and 
regulatory requirements.  The number and frequency of monitoring visits may also be increased per the 
sponsor decision to collect data and images post treatment.  
REFERENCES 
1. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: Report of the National 
Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad 
Dermatol. 2002 Apr;46(4):584-7. 
2. Steinhoff M, Schmelz M, Schauber J. Facial Erythema of Rosacea - Aetiology, Different 
Pathophysiologies and Treatment Options. Acta Derm Venereol. 2016 Jun 15;96(5):579-86. 
3. Del Rosso JQ. Management of facial erythema of rosacea: what is the role of topical α-
adrenergic receptor agonist therapy? J Am Acad Dermatol. 2013 Dec;69(6 Suppl 1):S44-56. 
4. Tan J, Liu H, Leyden JJ, Leoni MJ. Reliability of Clinician Erythema Assessment grading scale. J Am 
Acad Dermatol. 2014 Oct;71(4):760-3. 
5. Abokwidir M, Feldman SR. Rosacea Management. Skin Appendage Disord. 2016 Sep;2(1-2):26-
34. 
6. Bernstein EF, Kligman A. Rosacea treatment using the new-generation, high-energy, 595 nm, 
long pulse-duration pulsed-dye laser. Lasers Surg Med. 2008 Apr;40(4):233-9. 
7. Patel NU, Shukla S, Zaki J, Feldman SR. Oxymetazoline hydrochloride cream for facial erythema 
associated with rosacea. Expert Rev Clin Pharmacol. 2017 Aug 24:1-6. 
8. U.S. Food & Drug Administration New Drug Application (NDA): 208552: 
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=
208552. Accessed August 28, 2017. 


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
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Page 24 of 28 
 
9. Neuhaus IM, Zane LT, Tope WD. Comparative efficacy of nonpurpuragenic pulsed dye laser and 
intense pulsed light for erythematotelangiectatic rosacea. Dermatol Surg. 2009 Jun;35(6):920-8.  
10. Alam M, Dover JS, Arndt KA.  Treatment of facial telangiectasia with variable-pulse high-fluence 
pulsed-dye laser: comparison of efficacy with fluences immediately above and below the 
purpura threshold.  Dermatol Surg 2003; 29(7): 681–684. 
11. Bernstein EF.  The new-generation, high-energy, 595-nm, long pulse-duration pulsed-dye laser 
improves the appearance of photodamaged skin.  Lasers Surg Med 2007; 39(2): 157–163. 
 
 
 


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
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Rev. Date 
June 11, 2018 
Page 25 of 28 
 
APPENDIX I – Photography Guidelines 
 
At each time point (before the treatments and at the follow‐up visits), photographs of the treated facial 
areas should be taken in a standardized manner. 
o Photographs should be taken in a private room or area of the clinic under controlled conditions, 
including the distance from the camera to the subject, height of the camera, background, camera 
positioning, subject's positioning and lighting in order to achieve high quality before & after sets. 
o For consistency purposes, the same person should ideally take all study photographs, especially 
per subject. 
o Subject’s hair should be pulled by from the face with a hairband or shower cap.  
o The digital files should follow a consistent standard naming scheme (including: date, subject study 
ID, subject initials, for example: 001TS_Tx.1_Mar 21 2015, etc.). 
Specific photography details for facial area: 
o Front face 
o 90º right profile and left profile 
o 45º right profile and left profile 
 
 


Candela Corporation 
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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
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APPENDIX II:  Clinical Erythema Assessment Scale (NRS) *  
 
 
❑ 0 = Clear 
Clear skin with no signs of erythema 
❑ 1 = Almost clear 
Almost clear; slight redness 
❑ 2 = Mild 
Mild erythema; definite redness 
❑ 3 = Moderate 
Moderate erythema; marked redness 
❑ 4 = Severe 
Severe erythema; fiery redness 
 
*Tan J, Liu H, Leyden JJ, Leoni MJ. Reliability of Clinician Erythema Assessment grading scale. J Am Acad 
Dermatol. 2014 Oct;71(4):760-3. 
Subject Self-Assessment Scale (SSA)** 
❑ 0 = Clear of unwanted redness 
❑ 1 = Nearly clear of unwanted redness 
❑ 2 = Somewhat more redness than I prefer 
❑ 3 = More redness than I prefer 
❑ 4 = Completely unacceptable redness 
 
** DuBois J, Dover JS, Jones TM, et al. Phase 2 Randomized, Dose-Ranging Study of Oxymetazoline 
Cream for Treatment of Persistent Facial Erythema Associated With Rosacea. J Drugs Dermatol. 2018 
Mar 1;17(3):308-316.  
 


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Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
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Rev. Date 
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Page 27 of 28 
 
APPENDIX III:  Numerical Response Scale for Rating Pain (NRS) 
 
Please define how much pain you felt during the treatment by choosing a number from 0 to 10, with 0 
being no pain and 10 - the worst pain imaginable.   
 
 
 
Reference:  
Williamson A and Hoggart B.  Pain: a review of three commonly used pain rating scales.  J Clin 
Nurs 2005; 14(7): 798-804. 
Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Breivik Hals EK, Kvarstein G, 
Stubhaug A.  Assessment of pain.  Br J Anaesthesia 2008; 101(1): 17-24. 
 
 


Candela Corporation 
Confidential 
Pilot Study to Evaluate Combined Vbeam® Pulsed Dye Laser Treatment and RHOFADE™ 
(oxymetazoline hydrochloride) Topical Cream for Erythematotelangiectatic Rosacea  
Protocol # 
DHF24671 
Rev. Date 
June 11, 2018 
Page 28 of 28 
 
Appendix IV – Assessment scales 
Table 3 – Post-treatment Side Effect Severity Scale 
(0) Absent / None 
❑ 
(1) Mild 
❑ 
(2) Moderate 
❑ 
(3) Severe 
❑ 
Table 4 – Global Aesthetic Improvement (GAI) Scale 
(0) Excellent improvement 
❑ 
(1) Good improvement 
❑ 
(2) Moderate improvement 
❑ 
(3) Slight improvement 
❑ 
(4) No change 
❑ 
Table 5 – Improvement in Vessel Size  
(0) 76–100% improvement (excellent) 
❑ 
(1) 51–75% improvement (marked) 
❑ 
(2) 26–50% improvement (moderate) 
❑ 
(3) 1–25% improvement (mild) 
❑ 
(4) No response 
❑ 
 
Table 6 – Satisfaction Scale 
(0) Very Satisfied  
❑ 
(1) Satisfied  
❑ 
(2) No Opinion 
❑ 
(3) Dissatisfied 
❑ 
(4) Very Dissatisfied 
❑