RHA® Redensity With New Anesthetic Agent - Perioral Rhytids

A Randomized, Controlled, Double-blinded, Within-subject (Split-face), Multicenter, Prospective Clinical Study to Compare the Level of Pain Using the Dermal Filler RHA® Redensity Formulated With Two Different Anesthetics in the Treatment of Perioral Rhytids

This is a randomized, controlled, double-blinded, within-subject (split-face), multicenter, prospective study to investigate whether RHA® Redensity with new anesthetic agent is non-inferior to RHA® Redensity with lidocaine in terms of injection site pain felt by the subject during injection.

At screening, the Treating Investigator (TI) evaluated subjects' perioral rhytid severity (using the Perioral Rhytid Severity Rating Scale; PR-SRS) to confirm eligibility and to establish a pre-treatment score for assessing aesthetic improvement.

At Visit 1, RHA® Redensity with new anesthetic agent was administered in a random sequence (first or second injection) and side of the mouth (left or right) and RHA® Redensity with lidocaine was administered to the other side. Study subjects and the TI injecting study devices were blinded.

Immediately after injection of an upper perioral quadrant, subjects rated the injection site pain experienced during injection using a 100 mm Visual Analog Scale (VAS). Injection site pain in each side of the mouth was also assessed at 15, 30, 45 and 60 minutes after injection of the upper quadrant.

Safety evaluation consisted of AE assessments, a 30-day CTR (Common Treatment Response) diary and a follow-up call performed by the study site at 72 hours after injection.

Subjects attended Visit 2 (30 days post-injection) where efficacy and safety assessments were conducted.

Subjects who presented with an unresolved clinically significant device related AE at Visit 2 received a optional follow-up phone call no later than 30 days after Visit 2.

If the clinically significant AE remained unresolved, the Investigator requested that the subject attended the optional in-clinic follow-up visit (i.e., Visit 3) within 5 working days. Follow-up of the clinically significant AE continued until the AE was resolved or the TI determines that additional follow-up was not necessary.

Study Overview

• Status: Completed
• Conditions: Pain; Aging
• Intervention / Treatment: Device: RHA® Redensity with new anesthetic agent; Device: RHA® Redensity with lidocaine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90120
      • California
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatient, male or female of any race, 22 years of age or older. Female subjects of childbearing potential must have a negative UPT at Visit 1 and practice a reliable method of contraception throughout the study.
2. Moderate to severe bilateral perioral rhytids (grade 2 or 3 on PR-SRS).
3. Perioral rhytids of the same PR-SRS grade on the left and right sides of the mouth.
4. Able to follow study instructions and complete all required visits.
5. Sign the IRB-approved ICF, Photographic Release Form, the Authorization for Use and release of Health and Research Study Information (HIPAA) form, and if applicable the California Experimental Research Subject's Bill of Rights prior to any study-related procedures being performed.

Exclusion Criteria:

1. Female subjects who are pregnant, breast-feeding, or of childbearing potential and not practicing reliable birth control.
2. Known hypersensitivity or previous allergic reaction to any component of the study devices.
3. Known sensitivity to local anesthetics of the amide type, history of multiple severe allergies, or history of anaphylactic shock.
4. Clinically significant active skin disease or infection in the perioral area within 6 months prior to study entry (TI discretion).
5. History of active chronic debilitating systemic disease that, in the opinion of the investigator, would make the subject a poor candidate in the study.
6. Malignancy (excluding non-melanoma skin cancer) within the past 5 years.
7. History or presence of condition or feature that may confound the interpretation of the results in the perioral region, for example, tattoo, significant facial hair, acne scaring, prior surgery in the area, potential for active disease or infection flare up such as herpes simplex.
8. History of skin cancer in the treatment area.
9. Elective, clinically significant facial procedures that may confound the interpretation of the results in the perioral region (TI discretion), prior to study enrollment.
10. Clinically active disease or infection in the perioral area or mouth (e.g., dental abscess).

12. Exposure to any other investigational drug/device within 90 days of entering the study.

13. Clinically significant alcohol or drug abuse, or history of poor cooperation or unreliability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RHA® Redensity with new anesthetic agent; Split-face injection of RHA® Redensity with new anesthetic agent in the perioral rhytids on one side of the mouth and RHA® Redensity with lidocaine in the perioral rhytids in the other side of the mouth. Up to 3 mL injected per side.	Device: RHA® Redensity with new anesthetic agent; A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 15 mg/g and 0.3% w/w of new anesthetic agent in a physiologic buffer.
Experimental: RHA® Redensity with lidocaine; Split-face injection of RHA® Redensity with lidocaine in the perioral rhytids on one side of the mouth and RHA® Redensity with new anesthetic agent in the perioral rhytids in the other side of the mouth. Up to 3 mL injected per side.	Device: RHA® Redensity with lidocaine; A sterile, biodegradable, biocompatible, viscoelastic, clear, colorless, homogenized gel implant. It consists of cross-linked hyaluronic acid produced by fermentation of Streptococcus zooepidemicus, formulated to a concentration of 15 mg/g and 0.3% w/w lidocaine in a physiologic buffer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of RHA® Redensity With New Anesthetic Agent Versus RHA® Redensity With Lidocaine in Terms of Reducing Pain During Device Injection Into the Upper Perioral Rhytids.	Injection pain during injection was measured on the 100 mm Visual Analog Scale (VAS), as assessed by subjects immediately after injection of each upper perioral quadrant. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain	Visit 1 - During Injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference Between RHA® Redensity With New Anesthetic Agent Versus RHA® Redensity With Lidocaine in Term of Reducing Pain at 15, 30, 45 and 60 Minutes Post-injection in Each Side of the Mouth.	Injection pain was measured on the 100 mm Visual Analog Scale (VAS), as assessed by subjects in each side of the mouth. VAS is a 100 mm Visual Analog Scale with 0 meaning no pain and 100 meaning intolerable pain	Visit 1 - 15, 30, 45 and 60 minutes post-injection
Change From Baseline of PR-SRS Score for RHA® Redensity With New Anesthetic Agent Vs RHA® Redensity With Lidocaine for the Correction of Perioral Rhytids as Assessed by the Treating Investigator (TI)	PR-SRS (Perioral Rhytids Severity Rating Scale) is a validated 4-grade scale with 0 being "Absent" and 3 being "Severe"	Visit 1 (Baseline, pre-injection) - Visit 1 (post-injection), Visit 2 (Day 30)
Percentage of Responders Based on the Intra-individual Improvement of at Least One Grade on the Perioral Rhytids Severity Rating Scale (PR-SRS) Compared to Baseline, as Assessed by the TI	A responder corresponds to a subject with an intra-individual improvement of at least one grade on the PR-SRS compared to Baseline	Visit 1 - Baseline (pre-injection), Visit 1 (post-injection), Visit 2 (Day 30)
Subject's Perception of Treatment Effectiveness as Per the FACE-Q (Perioral Rhytids Domain) Questionnaire.	The FACE-Q measures the experience and outcomes of aesthetic facial procedures from the patient's perspective. FACE-Q questionnaire is composed of 6 questions with a score linked to answers (1 being 'Not at all' and 4 being 'Extremely'). The subject will be instructed as follows: ""These questions ask about how you look right now. For each question, circle only one answer. With the area around your lips in mind, in the past week, how much have you been bothered by:", and will provide response. To calculate the FACE-Q, outcomes from all 6 questions were pooled, data were transformed so that higher scores reflected a superior outcome, and adapted to a scale of 100 units (i.e. lowest score = 0, highest score = 100).	Visit 1 (Baseline) and Visit 2 (Day 30)
Number of Subjects Scored Either "Much Improved" or "Improved" on Global Aesthetic Improvement (GAI) by the Treating Investigator (TI)	Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of "much improved, improved, no change, worse, and much worse". GAI will bewas assessed using the baseline photograph. Each side of the mouth were assessed independently.	Visit 1 (post-injection) and Visit 2 (Day 30)
Number of Global Aesthetic Improvement (GAI) Responders (i.e., Scoring Either "Much Improved" or "Improved") on GAI Scale According to Subject's Self-assessment	Global Aesthetic Improvement (GAI) is a subjective 5-grade scale comprised of "much improved, improved, no change, worse, and much worse". GAI was assessed using the baseline photograph. Subjects were instructed as follows: "Use a mirror to compare your face to the photograph provided to you and rate the degree of aesthetic improvement by using the following scale". Each side of the face was assessed independently.	Visit 1 (post-injection) and Visit 2 (Day 30)
Number of Both "Satisfied" or "Very Satisfied" Subjects With Study Treatment Using the Subject's Satisfaction Scale	The Subject Satisfaction Scale is a subjective, balanced, 5-point scale assessing subject satisfaction with study treatment. Possible scores range from with 1 (very satisfied) to 5 (very dissatisfied). Proportion of subjects who were Satisfied (i.e., 1-Very Satisfied + 2-Satisfied) was compared to the proportion of subjects who were Not Satisfied (i.e., 3-Neither Satisfied nor dissatisfied + 4-Dissatisfied + 5-Very Dissatisfied)	Visit 1 (post-injection) and Visit 2 (Day 30)
Number of Subjects With Post Injection Treatment Responses (From Common Treatment Responses (CTR) Diary) for Safety Evaluation of RHA® Redensity With New Anesthetic Agent Versus RHA® Redensity With Lidocaine	The subjects will receive a diary booklet and instructions for recording his/her observations of the Common Treatment Responses to the study treatments within 30 days following the treatment. The diary will be discussed during follow-up phone-call and visit. Subjects were instructed to complete the diary at approximately the same time each day (i.e., am or pm). The subject diary captured the following Common Treatment Responses (CTR) that occur following the injection of a dermal filler; specifically, redness, pain, tenderness, firmness, swelling, lumps/bumps, bruising, itching, discoloration, and "other". The 30-day patient CTR diary included a detailed glossary describing all signs/symptoms listed in the diary; an option was provided to report "other" reactions if the subject experienced a sign/symptom that was not listed.	During 30 days after injection

Collaborators and Investigators

• Sponsor: Teoxane SA

Publications and helpful links

General Publications

• Kaufman-Janette J, Joseph JH, Dayan SH, Smith S, Eaton L, Maffert P. Patient Comfort, Safety, and Effectiveness of Resilient Hyaluronic Acid Fillers Formulated With Different Local Anesthetics. Dermatol Surg. 2022 Oct 1;48(10):1065-1070. doi: 10.1097/DSS.0000000000003541. Epub 2022 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2019
• Primary Completion (Actual): February 24, 2020
• Study Completion (Actual): November 9, 2020

Study Registration Dates

• First Submitted: August 23, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Lidocaine; Hyaluronic Acid; Perioral rhytids; Anesthetic
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Anesthetics; Lidocaine
• Other Study ID Numbers: TEO-RHA-1801

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No