Emervel® Deep Lidocaine vs. Juvederm® Ultra Plus in Treatment of Moderate to Severe Facial Wrinkles and Folds

Study Overview
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Brief Summary
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The purpose of the study was to compare the effectiveness and safety of Emervel Deep Lidocaine versus Juvederm Ultra Plus in the treatment of moderate to severe facial wrinkles and folds.

Detailed Description
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This was a randomized, evaluator-blinded, active-controlled, multi-center, split-face comparison study of Emervel Deep Lidocaine versus Juvederm Ultra Plus in the treatment of moderate to severe facial wrinkles and folds. Two physicians, an Unblinded Injecting Investigator and a Blinded Evaluating Investigator, were required at each study center. The Unblinded Injecting Investigator was different from the Blinded Evaluating Investigator.

Official Title
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A Pivotal USA Randomized, Evaluator-blinded, Active-controlled, Multi-center, Split-face Comparison Study of Emervel® Deep Lidocaine Versus Juvederm® Ultra Plus in the Treatment of Moderate to Severe Facial Wrinkles and Folds

Conditions
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Skin Wrinkling

Intervention / Treatment
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* Device: Emervel Deep Lidocaine
* Device: Juvederm Ultra Plus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject was a male or female 18 years of age or older The subject had bilateral nasolabial folds that, in the opinion of both the blinded evaluating investigator and the unblinded injecting investigator, was corrected with an injectable dermal implant The subject had the same Wrinkle Severity Rating Scale (WSRS) score of 3 or 4 (moderate or severe) for each nasolabial fold Exclusion Criteria: The subject had active skin disease or inflammation on or near a nasolabial fold that, in the principal investigator's opinion, would interfere with the study device injections and/or study assessments. The subject had a history of sensitivity to hyaluronic acid The subject had a history of sensitivity to lidocaine or other amide type anesthetics The subject was, in the principal investigator's opinion, at undue risk based on the precautions, warnings and contraindications for local lidocaine anesthetics.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emervel Deep Lidocaine<br>NLFs (Nasolabial Folds) were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine). | Device: Emervel Deep Lidocaine<br>* 20 mg/mL + 0.3% lidocaine<br>|
| Active Comparator: Juvederm Ultra Plus<br>NLFs were injected with Juvéderm Ultra Plus (24 mg/mL). | Device: Juvederm Ultra Plus<br>* 24mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies deep facial wrinkles (nasolabial folds). WSRS represents clinically meaningful change in NLF severity from the adjacent grades where 1= absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 millimeter (mm) visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 24 after final initial injection (Week 24 for participants without touch-up injection, Week 27 for participants with touch-up injection at Week 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 3 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies deep facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in nasolabial fold severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 3 after final initial injection (Week 3 for participants without touch-up injection, Week 6 for participants with touch-up injection at Week 3) | 
| Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 12 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies deep facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in nasolabial fold severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 12 after final initial injection (Week 12 for participants without touch-up injection, Week 15 for participants with touch-up injection at Week 3) | 
| Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 36 After Final Initial Injection | WSRS is a validated 5-point reference scale with photographs that classifies deep facial wrinkles (nasolabial folds). WSRS represents a clinically meaningful change in nasolabial fold severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 36 after final initial injection (Week 36 for participants without touch-up injection, Week 39 for participants with touch-up injection at Week 3) | 
| Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 48 After Final Initial Injection | WSRS is a nasolabial fold severity from the adjacent grades where 1 = absent (no visible fold; continuous skin line), 2 = mild (shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance), 3 = excellent (correction is expected from injectable implant), 4 = severe (very long and deep folds; prominent facial feature; less than 2 mm visible fold when stretched; significant improvement is expected from injectable implant), 5 = extreme (extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone). A negative change from baseline indicates improvement. | Baseline, Week 48 after final initial injection (Week 48 for participants without touch-up injection, Week 51 for participants with touch-up injection at Week 3) | 
| Mean Change From Baseline in Participant Self-Assessment of Wrinkle Severity at Week 24 After Final Initial Injection | Participants self-assessment was measured by using a wrinkle severity scale with 1 being absent and 5 being extreme. Each participant was to perform an assessment of the wrinkle severity based on self-assessment score: 1= Absent (No visible fold; continuous skin line), 2= Mild (Shallow but visible fold with a slight indentation), 3= Moderate (Moderately deep folds), 4= Severe (Very long and deep fold), 5= Extreme (Extremely deep and long folds). A negative change from baseline indicates improvement. | Baseline, Week 24 after final initial injection (Week 24 for participants without touch-up injection, Week 27 for participants with touch-up injection at Week 3) | 
| Participant Pain Assessment After the Initial Injection | Participant pain severity for each NLF was assessed at time 0, 15, 30, 45, 60 minutes and 24 hours after the initial injection using an 11-point Numeric Pain Intensity Scale (NPIS).The NPIS was a pain screening tool, commonly used to assess pain severity at that moment in time using a 0-10 scale, with 0 is no pain and 10 is the worst possible pain where a lower score correlates to better outcome for pain. | At 0 ,15, 30, 45, 60 minutes and 24 hours after the initial injection (Baseline) | 
| Participant Pain Assessment After the Initial Touch-up Injection | Participant pain severity for each NLF was assessed at time 0, 15, 30, 45, 60 minutes and 24 hours after the initial injection using NPIS. The NPIS was a pain screening tool, commonly used to assess pain severity at that moment in time using a 0-10 scale, with 0 is no pain and 10 is the worst possible pain where a lower score correlates to better outcome for pain. | At 0, 15, 30, 45, 60 minutes and 24 hours after the Initial Touch-up Injection (At 3 weeks after initial injection) | 
| Number of Participants With Adverse Event (AEs) | AE was defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Number of participants with AEs were reported. Event was unrelated to study product or injection procedure. If the treated side where an AE occurred was not applicable, this AE was summarized under each treatment group. | From start of study drug administration up to 62 weeks |