Trial Outcomes & Findings for Emervel® Deep Lidocaine vs. Juvederm® Ultra Plus in Treatment of Moderate to Severe Facial Wrinkles and Folds (NCT NCT01205061)

NCT ID: NCT01205061

Last Updated: 2023-10-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

162 participants

Primary outcome timeframe

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)

Results posted on

2023-10-23

Participant Flow

The study was conducted at 11 sites in the United States from 27 September 2010 to 12 January 2012.

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

Participant milestones

Participant milestones
Measure
All Participants
Participants were randomized to receive either Emervel Deep Lidocaine (20 milligram per milliliter \[mg/mL\] with 0.3% lidocaine) injection in the left nasolabial fold (NLF) and Juvederm Ultra Plus (24 mg/mL) injection in to the right NLF or Juvederm Ultra Plus (24 mg/mL) injection in the left NLF and Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine) injection in the right NLF.
Overall Study
STARTED
162
Overall Study
Emervel Deep Lidocaine in Left NLF Followed by Juvederm Ultra in Right NLF
80
Overall Study
Juvederm Ultra in Left NLF Followed by Emervel Deep Lidocaine in Right NLF
82
Overall Study
COMPLETED
136
Overall Study
NOT COMPLETED
26

Reasons for withdrawal

Reasons for withdrawal
Measure
All Participants
Participants were randomized to receive either Emervel Deep Lidocaine (20 milligram per milliliter \[mg/mL\] with 0.3% lidocaine) injection in the left nasolabial fold (NLF) and Juvederm Ultra Plus (24 mg/mL) injection in to the right NLF or Juvederm Ultra Plus (24 mg/mL) injection in the left NLF and Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine) injection in the right NLF.
Overall Study
Adverse Event
4
Overall Study
Withdrawal by Subject
11
Overall Study
Clinical Investigational Plan Violation
1
Overall Study
Lost to Follow-up
9
Overall Study
Other
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Emervel Deep Lidocaine in Left NLF Followed by Juvederm Ultra Plus in Right NLF
n=80 Participants
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.
Juvederm Ultra Plus in Left NLF Followed by Emervel Deep Lidocaine in Right NLF
n=82 Participants
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.
Total
n=162 Participants
Total of all reporting groups
Age, Continuous
53.4 years
STANDARD_DEVIATION 9.29 • n=5 Participants
54.0 years
STANDARD_DEVIATION 8.09 • n=7 Participants
53.7 years
STANDARD_DEVIATION 8.68 • n=5 Participants
Sex: Female, Male
Female
78 Participants
n=5 Participants
78 Participants
n=7 Participants
156 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
4 Participants
n=7 Participants
6 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Caucasian
63 Participants
n=5 Participants
66 Participants
n=7 Participants
129 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Black
9 Participants
n=5 Participants
11 Participants
n=7 Participants
20 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Hispanic
5 Participants
n=5 Participants
5 Participants
n=7 Participants
10 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Other
3 Participants
n=5 Participants
0 Participants
n=7 Participants
3 Participants
n=5 Participants
Skin Type
Type I
1 Participants
n=5 Participants
5 Participants
n=7 Participants
6 Participants
n=5 Participants
Skin Type
Type II
16 Participants
n=5 Participants
12 Participants
n=7 Participants
28 Participants
n=5 Participants
Skin Type
Type III
30 Participants
n=5 Participants
37 Participants
n=7 Participants
67 Participants
n=5 Participants
Skin Type
Type IV
18 Participants
n=5 Participants
16 Participants
n=7 Participants
34 Participants
n=5 Participants
Skin Type
Type V
11 Participants
n=5 Participants
8 Participants
n=7 Participants
19 Participants
n=5 Participants
Skin Type
Type VI
4 Participants
n=5 Participants
4 Participants
n=7 Participants
8 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
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
-1.1 Score on a scale
Standard Deviation 0.68

SECONDARY outcome

Timeframe: 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)

Population: ITT population included participants who were randomized and received an injection on both treatment sides.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 3 After Final Initial Injection
-1.6 Score on a scale
Standard Deviation 0.62
-1.6 Score on a scale
Standard Deviation 0.64

SECONDARY outcome

Timeframe: 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)

Population: ITT population included participants who were randomized and received an injection on both treatment sides.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 12 After Final Initial Injection
-1.3 Score on a scale
Standard Deviation 0.70
-1.3 Score on a scale
Standard Deviation 0.74

SECONDARY outcome

Timeframe: 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)

Population: ITT population included participants who were randomized and received an injection on both treatment sides.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 36 After Final Initial Injection
-1.1 Score on a scale
Standard Deviation 0.67
-1.1 Score on a scale
Standard Deviation 0.68

SECONDARY outcome

Timeframe: 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)

Population: ITT population included participants who were randomized and received an injection on both treatment sides.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Mean Change From Baseline in Wrinkle Severity Rating Score (WSRS) at Week 48 After Final Initial Injection
-0.8 Score on a scale
Standard Deviation 0.66
-0.9 Score on a scale
Standard Deviation 0.66

SECONDARY outcome

Timeframe: 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: ITT population included participants who were randomized and received an injection on both treatment sides.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Mean Change From Baseline in Participant Self-Assessment of Wrinkle Severity at Week 24 After Final Initial Injection
-1.2 Score on a scale
Standard Deviation 0.91
-1.3 Score on a scale
Standard Deviation 0.75

SECONDARY outcome

Timeframe: At 0 ,15, 30, 45, 60 minutes and 24 hours after the initial injection (Baseline)

Population: ITT population included participants who were randomized and received an injection on both treatment sides. Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given timepoints.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Participant Pain Assessment After the Initial Injection
At 0 Minutes
3.1 Score on a scale
Standard Deviation 2.1
5.3 Score on a scale
Standard Deviation 2.3
Participant Pain Assessment After the Initial Injection
At 15 Minutes
0.5 Score on a scale
Standard Deviation 0.9
1.8 Score on a scale
Standard Deviation 1.8
Participant Pain Assessment After the Initial Injection
At 30 Minutes
0.2 Score on a scale
Standard Deviation 0.6
1.0 Score on a scale
Standard Deviation 1.5
Participant Pain Assessment After the Initial Injection
At 45 Minutes
0.1 Score on a scale
Standard Deviation 0.4
0.5 Score on a scale
Standard Deviation 1.0
Participant Pain Assessment After the Initial Injection
At 60 Minutes
0.1 Score on a scale
Standard Deviation 0.3
0.3 Score on a scale
Standard Deviation 0.8
Participant Pain Assessment After the Initial Injection
At 24 Hours
0.9 Score on a scale
Standard Deviation 1.5
0.9 Score on a scale
Standard Deviation 1.6

SECONDARY outcome

Timeframe: At 0, 15, 30, 45, 60 minutes and 24 hours after the Initial Touch-up Injection (At 3 weeks after initial injection)

Population: ITT population included participants who were randomized and received an injection on both treatment sides. Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given timepoints.

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.

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=86 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=80 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Participant Pain Assessment After the Initial Touch-up Injection
At 0 Minutes
3.3 Score on a scale
Standard Deviation 2.2
4.8 Score on a scale
Standard Deviation 2.4
Participant Pain Assessment After the Initial Touch-up Injection
At 15 Minutes
0.7 Score on a scale
Standard Deviation 1.2
1.2 Score on a scale
Standard Deviation 1.6
Participant Pain Assessment After the Initial Touch-up Injection
At 30 Minutes
0.3 Score on a scale
Standard Deviation 0.7
0.5 Score on a scale
Standard Deviation 1.0
Participant Pain Assessment After the Initial Touch-up Injection
At 45 Minutes
0.1 Score on a scale
Standard Deviation 0.4
0.2 Score on a scale
Standard Deviation 0.7
Participant Pain Assessment After the Initial Touch-up Injection
At 60 Minutes
0.1 Score on a scale
Standard Deviation 0.3
0.1 Score on a scale
Standard Deviation 0.5
Participant Pain Assessment After the Initial Touch-up Injection
At 24 Hours
0.5 Score on a scale
Standard Deviation 0.9
0.6 Score on a scale
Standard Deviation 1.3

SECONDARY outcome

Timeframe: From start of study drug administration up to 62 weeks

Population: Safety population included all participants who received at least one injection.

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."

Outcome measures

Outcome measures
Measure
Emervel Deep Lidocaine
n=162 Participants
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 Participants
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Number of Participants With Adverse Event (AEs)
66 Participants
67 Participants

Adverse Events

Emervel Deep Lidocaine

Serious events: 7 serious events
Other events: 16 other events
Deaths: 0 deaths

Juvederm Ultra Plus

Serious events: 7 serious events
Other events: 16 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Emervel Deep Lidocaine
n=162 participants at risk
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 participants at risk
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Infections and infestations
Herpes Zoster
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Infections and infestations
Diarrhoea infections
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Gastrointestinal disorders
Small intestinal obstruction
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Infections and infestations
Lumbar Spinal stenosis
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Reproductive system and breast disorders
Ovarian Cyst
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
0.62%
1/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.

Other adverse events

Other adverse events
Measure
Emervel Deep Lidocaine
n=162 participants at risk
NLFs were injected with Emervel Deep Lidocaine (20 mg/mL with 0.3% lidocaine).
Juvederm Ultra Plus
n=162 participants at risk
NLFs were injected with Juvéderm Ultra Plus (24 mg/mL).
Infections and infestations
Upper respiratory tract infection
3.7%
6/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
3.7%
6/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Infections and infestations
Sinusitis
3.1%
5/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
3.1%
5/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
Nervous system disorders
Migraine
3.1%
5/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.
3.1%
5/162 • From start of study drug administration up to 62 weeks
The safety population included all participants who received at least one injection.

Additional Information

Clinical Scientist

Galderma

Phone: +46184749000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER