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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01205061

Enrollment

162

Registered

2010-09-20

Start date

2010-09-27

Completion date

2012-01-12

Last updated

2023-10-23

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 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

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.

Interventions

DEVICEEmervel Deep Lidocaine

20 mg/mL + 0.3% lidocaine

DEVICEJuvederm Ultra Plus

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 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.

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 (Week 24 for participants without touch-up injection, Week 27 for participants with touch-up injection at Week 3)	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.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 12 After Final Initial Injection	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)	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.
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 36 After Final Initial Injection	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)	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.
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 48 After Final Initial Injection	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)	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.
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 3 After Final Initial Injection	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)	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.
Participant Pain Assessment After the Initial Injection	At 0 ,15, 30, 45, 60 minutes and 24 hours after the initial injection (Baseline)	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.
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 (At 3 weeks after 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 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.
Number of Participants With Adverse Event (AEs)	From start of study drug administration up to 62 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 (Week 24 for participants without touch-up injection, Week 27 for participants with touch-up injection at Week 3)	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 11 sites in the United States from 27 September 2010 to 12 January 2012.

Pre-assignment details

A total of 184 participants were screened, of which 162 participants received treatment in this study.

Participants by arm

Arm	Count
Emervel Deep Lidocaine in Left NLF Followed by Juvederm Ultra Plus in Right NLF Participants received Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine) injection into the left NLF and Juvéderm Ultra Plus (24 mg/mL) in the right NLF.	80
Juvederm Ultra Plus in Left NLF Followed by Emervel Deep Lidocaine in Right NLF Participants received Juvéderm Ultra Plus (24 mg/mL) injection into the left NLF and Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine) injection in the right NLF.	82
Total	162

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	4
Overall Study	Clinical Investigational Plan Violation	1
Overall Study	Lost to Follow-up	9
Overall Study	Other	1
Overall Study	Withdrawal by Subject	11

Baseline characteristics

Characteristic	Juvederm Ultra Plus in Left NLF Followed by Emervel Deep Lidocaine in Right NLF	Total	Emervel Deep Lidocaine in Left NLF Followed by Juvederm Ultra Plus in Right NLF
Age, Continuous	54.0 years STANDARD_DEVIATION 8.09	53.7 years STANDARD_DEVIATION 8.68	53.4 years STANDARD_DEVIATION 9.29
Race/Ethnicity, Customized Race Black	11 Participants	20 Participants	9 Participants
Race/Ethnicity, Customized Race Caucasian	66 Participants	129 Participants	63 Participants
Race/Ethnicity, Customized Race Hispanic	5 Participants	10 Participants	5 Participants
Race/Ethnicity, Customized Race Other	0 Participants	3 Participants	3 Participants
Sex: Female, Male Female	78 Participants	156 Participants	78 Participants
Sex: Female, Male Male	4 Participants	6 Participants	2 Participants
Skin Type Type I	5 Participants	6 Participants	1 Participants
Skin Type Type II	12 Participants	28 Participants	16 Participants
Skin Type Type III	37 Participants	67 Participants	30 Participants
Skin Type Type IV	16 Participants	34 Participants	18 Participants
Skin Type Type V	8 Participants	19 Participants	11 Participants
Skin Type Type VI	4 Participants	8 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 162	0 / 162
other Total, other adverse events	16 / 162	16 / 162
serious Total, serious adverse events	7 / 162	7 / 162

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 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.

Time frame: 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)

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 Deep 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 Plus	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 0.68

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 (Week 24 for participants without touch-up injection, Week 27 for participants with touch-up injection at Week 3)