Emervel Classic Lidocaine Versus Juvederm® Ultra in Treatment of Moderate to Severe Facial Wrinkles and Folds

A Pivotal USA Randomized, Evaluator-blinded, Active-controlled, Multi-center, Split-face Comparison Study of Emervel Classic Lidocaine Versus Juvederm® Ultra in the Treatment of Moderate to Severe Facial Wrinkle Folds

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01205048

Enrollment

171

Registered

2010-09-20

Start date

2010-09-30

Completion date

2012-01-19

Last updated

2023-07-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Skin Wrinkling

Brief summary

The purpose of this study is to compare the effectiveness and safety of Emervel Classic Lidocaine versus Juvederm® Ultra in the treatment of moderate to severe facial wrinkles and folds.

Interventions

DEVICEEmervel Classic Lidocaine

20 mg/mL + 0.3% lidocaine

DEVICEJuvederm® Ultra

24mg/mL

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* The subject is a male or female 18 years of age or older * The subject has bilateral nasolabial folds that, in the opinion of both the Blinded Evaluating Investigator and the Unblinded Injecting Investigator, can be corrected with an injectable dermal implant * The subject has the same Wrinkle Severity Rating Scale (WSRS) score of 3 or 4 (moderate or severe) for each nasolabial fold

Exclusion criteria

* The subject has 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 has a history of sensitivity to hyaluronic acid * The subject has a history of sensitivity to lidocaine or other amide type anesthetics * The subject is, in the Principal Investigator's opinion, at undue risk based on the precautions, warnings and contraindications for local lidocaine anesthetics.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection	Baseline, Week 24 after final initial injection	WSRS is a validated 5-point reference scale with photographs that classifies 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.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 12 After Final Initial Injection	Baseline, Week 12 after final initial injection	WSRS is a validated 5-point reference scale with photographs that classifies 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.
Mean Change From Baseline in Wrinkle Severity Scale (WSRS) at Week 36 After Final Initial Injection	Baseline, Week 36 after final initial injection	WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a 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 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.
Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 48 After Final Initial Injection	Baseline, Week 48 after final initial injection	WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a 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 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.
Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 3 After the Final Initial Injection	Baseline, Week 3 after final initial injection	WSRS is a validated 5-point reference scale with photographs that classifies facial wrinkles (nasolabial folds). WSRS represents a 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 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.
Participant Pain Assessment After the Initial Injection	At 0 ,15, 30, 45, 60 minutes and 24 hours 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.
Participant Pain Assessment After the Initial Touch-up Injection	At 0, 15, 30, 45, 60 minutes and 24 hours 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 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.
Number of Participants With Adverse Events (AEs)	From start of study drug administration up to 56 weeks	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.
Mean Change From Baseline in Participant Self-Assessment of Wrinkle Severity at Week 24 After Final Initial Injection	Baseline, 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.

Countries

United States

Participant flow

Recruitment details

The study was conducted at 12 centers in the United States from September 2010 to January 2012.

Pre-assignment details

A total of 171 participants were enrolled, of which 170 participants received treatment in this study.

Participants by arm

Arm	Count
Emervel Classic Lidocaine in Left NLF Followed by Juvederm Ultra in Right NLF Participants received Emervel Classic Lidocaine (20 mg/mL with 0.3% lidocaine) injection into the left NLF and Juvéderm Ultra (24 mg/mL) in the right NLF.	84
Juvederm Ultra in Left NLF Followed by Emervel Classic Lidocaine in Right NLF Participants received Juvéderm Ultra (24 mg/mL) injection into the left NLF and Emervel Classic Lidocaine (20 mg/mL with 0.3% lidocaine) injection in the right NLF.	86
Total	170

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Clinical Investigation Plan Violation	1
Overall Study	Lost to Follow-up	4
Overall Study	Other	2
Overall Study	Withdrawal by Subject	14

Baseline characteristics

Characteristic	Total	Emervel Classic Lidocaine in Left NLF Followed by Juvederm Ultra in Right NLF	Juvederm Ultra in Left NLF Followed by Emervel Classic Lidocaine in Right NLF
Age, Continuous	53.9 years STANDARD_DEVIATION 8.22	54.1 years STANDARD_DEVIATION 8.82	53.6 years STANDARD_DEVIATION 7.64
Fitzpatrick Skin Type Skin Type I	6 Participants	3 Participants	3 Participants
Fitzpatrick Skin Type Skin Type II	39 Participants	19 Participants	20 Participants
Fitzpatrick Skin Type Skin Type III	52 Participants	29 Participants	23 Participants
Fitzpatrick Skin Type Skin Type IV	55 Participants	27 Participants	28 Participants
Fitzpatrick Skin Type Skin Type V	9 Participants	4 Participants	5 Participants
Fitzpatrick Skin Type Skin Type VI	9 Participants	2 Participants	7 Participants
Race/Ethnicity, Customized Black	15 Participants	5 Participants	10 Participants
Race/Ethnicity, Customized Caucasian	116 Participants	58 Participants	58 Participants
Race/Ethnicity, Customized Hispanic	38 Participants	20 Participants	18 Participants
Race/Ethnicity, Customized Other	1 Participants	1 Participants	0 Participants
Sex: Female, Male Female	160 Participants	79 Participants	81 Participants
Sex: Female, Male Male	10 Participants	5 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 170	0 / 170
other Total, other adverse events	10 / 170	11 / 170
serious Total, serious adverse events	2 / 170	2 / 170

Outcome results

Primary

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 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.

Time frame: Baseline, Week 24 after final initial injection

Population: Intent to Treat (ITT) population included participants who were randomized and received an injection on both treatment sides.

Arm	Measure	Value (MEAN)	Dispersion
Emervel Classic Lidocaine	Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection	-1.1 Score on a scale	Standard Deviation 0.75
Juvederm Ultra	Mean Change From Baseline in Wrinkle Severity Rating Scale (WSRS) at Week 24 After Final Initial Injection	-1.2 Score on a scale	Standard Deviation 0.76

Secondary

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.

Time frame: Baseline, Week 24 after final initial injection