Trial Outcomes & Findings for Saypha® Volume LIdocaine in Nasolabial Folds (NCT NCT04883632)

Last Updated: 2025-04-03

Results Overview

The proportion of subjects with the NLF-SRS grade reduced by ≥1 point versus baseline at Week 24. This anaylsis is done per manufacturing site: C1 and HQ separately and for the overall population. A 'responder' is defined having at least ≥ 1 grade improvement as evaluated with the 5 point-validated NLF-SRS score on both sides of the face. Nasolabial Folds Severity Rating Scale (NLF-SRS) is a validated 5 grade scale where the lower number corresponds to: 0 = None/minimal: No visible/minimal nasolabial folds; 1. = Mild: Shallow but visible nasolabial fold with a slight indentation; 2. = Moderate: Moderately deep nasolabial fold; 3. = Severe: Very deep nasolabial fold with prominent facial feature; 4. = Extreme: Extremely deep and long nasolabial fold with skin redundancy Therefore, the lower the number, the better.

Recruitment status

COMPLETED

Study phase

Target enrollment

110 participants

Primary outcome timeframe

24 Weeks

Results posted on

2025-04-03

Participant Flow

Enrollment:110 (Subjects enrolled include subjects screened and randomized))

Participant milestones

Participant milestones
Measure	Saypha® VOLUME Lidocaine HQ Subjects who had administration of saypha® VOLUME Lidocaine manufactured in HQ	Saypha® VOLUME Lidocaine C1 Subjects who had administation of Sapha® VOLUME manufactured in C1
Overall Study STARTED	55	55
Overall Study COMPLETED	53	52
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Saypha® Volume LIdocaine in Nasolabial Folds

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Volume Lidocaine HQ n=54 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=55 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Total n=109 Participants Total of all reporting groups
Age, Continuous	49.5 years STANDARD_DEVIATION 10.1 • n=5 Participants	48.8 years STANDARD_DEVIATION 7.9 • n=7 Participants	49.2 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	50 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	53 Participants n=7 Participants	105 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator left side · 0 = None/minimal	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator left side · 1 = Mild	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator left side · 2 = Moderate	27 Participants n=5 Participants	30 Participants n=7 Participants	57 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator left side · 3 = Severe	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator left side · 4 = Extreme	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator right side · 0 = None/minimal	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator right side · 1 = Mild	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator right side · 2 = Moderate	33 Participants n=5 Participants	32 Participants n=7 Participants	65 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator right side · 3 = Severe	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Nasolabial fold severity scale - Grading by investigator right side · 4 = Extreme	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment, but for this analysis we have to consider the number of subjects with trial completion at Week 24, threfore an overal population of 106.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=53 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=53 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=106 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Responder Rate in Reduction of Nasolabial Folds	34 Participants	39 Participants	73 Participants	—

SECONDARY outcome

Timeframe: Week 4, week 36, week 52, week 65, week 78, week 104

The proportion of subjects with the NLF-SRS grade reduced by ≥1 point versus baseline at Week 4, Week 36, Week 52 and optional at Week 65, Week 78 and Week 104. A reduction in the score of the Nasolabial Folds Severity Rating Scale is considered an improvement as this reflects a decrease of the folds severity which is rated from 0 (none/minimal) to 4 (extreme). Individual NLF-SRS grades per visit calculated as the mean of grades assigned to the left and the right NLF, respectively On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=54 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=55 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Proportion of Responders at Other Time Points Week 4	46 Participants	46 Participants	92 Participants	—
Proportion of Responders at Other Time Points Week 36	27 Participants	32 Participants	59 Participants	—
Proportion of Responders at Other Time Points Week 52	10 Participants	13 Participants	23 Participants	—
Proportion of Responders at Other Time Points Week 65	3 Participants	3 Participants	6 Participants	—
Proportion of Responders at Other Time Points Week 78	1 Participants	0 Participants	1 Participants	—
Proportion of Responders at Other Time Points Week 104	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104

The average change versus baseline in the NLF-SRS (Nasolabial Folds Severity Rating Scale) grade at Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104 as evaluated by the investigator. A reduction in the score of the Nasolabial Folds Severity Rating Scale is considered an improvement as this reflects a decrease of the folds severity which is rated from 0 (none/minimal) to 4 (extreme). Nasolabial Folds Severity Rating Scale (NLF-SRS) is a validated 5 grade scale where the lower number corresponds to: 0 = None/minimal: No visible/minimal nasolabial folds; 1. = Mild: Shallow but visible nasolabial fold with a slight indentation; 2. = Moderate: Moderately deep nasolabial fold; 3. = Severe: Very deep nasolabial fold with prominent facial feature; 4. = Extreme: Extremely deep and long nasolabial fold with skin redundancy Therefore, the lower the number, the better.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=54 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=55 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Change Versus Baseline in Nasolabial Fold Severitry Week 4	1.4 score on a scale Standard Deviation 0.6	1.4 score on a scale Standard Deviation 0.6	1.4 score on a scale Standard Deviation 0.6	—
Change Versus Baseline in Nasolabial Fold Severitry Week 24	1.0 score on a scale Standard Deviation 0.90	1.2 score on a scale Standard Deviation 0.80	1.1 score on a scale Standard Deviation 0.90	—
Change Versus Baseline in Nasolabial Fold Severitry Week 36	0.7 score on a scale Standard Deviation 0.8	0.7 score on a scale Standard Deviation 0.7	0.7 score on a scale Standard Deviation 0.8	—
Change Versus Baseline in Nasolabial Fold Severitry Week 78	0.3 score on a scale Standard Deviation 0.5	0.0 score on a scale Standard Deviation 0.7	0.2 score on a scale Standard Deviation 0.6	—
Change Versus Baseline in Nasolabial Fold Severitry Week 104	0.0 score on a scale	—	0.0 score on a scale	—
Change Versus Baseline in Nasolabial Fold Severitry Week 52	0.2 score on a scale Standard Deviation 0.5	0.3 score on a scale Standard Deviation 0.5	0.2 score on a scale Standard Deviation 0.5	—
Change Versus Baseline in Nasolabial Fold Severitry Week 65	0.2 score on a scale Standard Deviation 0.7	0.1 score on a scale Standard Deviation 0.6	0.1 score on a scale Standard Deviation 0.6	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 4, 24, 36, 52, 65, 78, and 104

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups.

Percentage of responders with a ≥2-point improvement over Baseline on the 5-point NLF-SRS, based on investigator's live assessment at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment. On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Percentage of Responders With a ≥2-point Improvement Week 4	43 Participants	—	—	—
Percentage of Responders With a ≥2-point Improvement Week 24	32 Participants	—	—	—
Percentage of Responders With a ≥2-point Improvement Week 36	12 Participants	—	—	—
Percentage of Responders With a ≥2-point Improvement Week 52	0 Participants	—	—	—
Percentage of Responders With a ≥2-point Improvement Week 65	0 Participants	—	—	—
Percentage of Responders With a ≥2-point Improvement Week 78	0 Participants	—	—	—
Percentage of Responders With a ≥2-point Improvement Week 104	0 Participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 4, 24, 36, 52, 65, 78, and 104

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1

Percentage of subjects with aesthetic improvement using the 5-point Global Aesthetzic Improvement Scavel (GAIS) (subjects who have been rated as "very much improved" or "much improved" or "improved"), based on investigator's assessment at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment, for each treatment location (right NLF, left NLF) separately and overall.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 52 · Improvement	29 Participants	32 Participants	29 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 78 · No Improvement	10 Participants	10 Participants	10 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 78 · Improvement	1 Participants	1 Participants	1 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 104 · No Improvement	1 Participants	1 Participants	1 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 65 · No Improvement	19 Participants	20 Participants	20 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 65 · Improvement	10 Participants	9 Participants	9 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 4 · No Improvement	0 Participants	2 Participants	2 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 4 · Improvement	100 Participants	98 Participants	98 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 24 · No Improvement	17 Participants	16 Participants	18 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 24 · Improvement	89 Participants	90 Participants	88 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 36 · No Improvement	44 Participants	43 Participants	45 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 36 · Improvement	62 Participants	63 Participants	61 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 52 · No Improvement	76 Participants	73 Participants	76 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment Week 104 · Improvement	0 Participants	0 Participants	0 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 4, 24, 36, 52, 65, 78, and 104

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1.

Percentage of subjects with aesthetic improvement using the 5-point Global Aesthetzic Improvement Scavel (GAIS) (subjects who have been rated as "very much improved" or "much improved" or "improved"), based on subject's assessment at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment, for each treatment location (right NLF, left NLF) separately and overall.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 36 · Improvement	80 Participants	84 Participants	80 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 104 · Improvement	0 Participants	0 Participants	0 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 4 · No improvement	3 Participants	2 Participants	3 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 4 · Improvement	103 Participants	104 Participants	103 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 24 · No improvement	12 Participants	13 Participants	13 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 24 · Improvement	95 Participants	94 Participants	94 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 36 · No improvement	26 Participants	22 Participants	26 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 52 · No improvement	51 Participants	49 Participants	51 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 52 · Improvement	54 Participants	56 Participants	54 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 65 · No improvement	17 Participants	17 Participants	17 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 65 · Improvement	12 Participants	12 Participants	12 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 78 · No improvement	6 Participants	6 Participants	6 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 78 · Improvement	5 Participants	5 Participants	5 Participants	—
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment Week 104 · No improvement	1 Participants	1 Participants	1 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 4, 36, 52, 65, 78, and 104

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1.

Percentage of responders with a ≥1-point improvement over Baseline on the 5-point NLF-SRS, based on evaluation by an independent reviewer of photographs for Weeks 4, 36, 52, 65, 78, and 104 after initial treatment. On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 104 : Response Rate with improvement 2 grades	0 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 4 : Response Rate with improvement 1 grade	24 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 4 : Response Rate with improvement 2 grades	3 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 24 : Response Rate with improvement 1 grade	24 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 24 : Response Rate with improvement 2 grades	0 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 36 : Response Rate with improvement 1 grade	21 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 36 : Response Rate with improvement 2 grades	0 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 52 : Response Rate with improvement 1 grade	19 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 52 : Response Rate with improvement 2 grades	1 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 65 : Response Rate with improvement 1 grade	8 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 65 : Response Rate with improvement 2 grades	1 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 78 : Response Rate with improvement 1 grade	4 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 78 : Response Rate with improvement 2 grades	0 Participants	—	—	—
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs Week 104 : Response Rate with improvement 1 grade	1 Participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 4, 24, 36, 52, 65, 78, and 104

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1.

Descriptive summary statistics for extent of subject satisfaction with outcome of the treatment, as assessed by the Face-Q questionnaire "Satisfaction with Outcome" at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment. Face-Q TM Questionnaire "Satisfaction with Outcome", a 6- tem, Health-related Quality of Life Questionnaire: The raw summed scale score is converted to a score from 0 to 100 by using the transformed sum score (Rasch model): Modified sum score ranges from 0 to 100 (low numbers correspond to low satisfaction).

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 104	59.0 score on a scale	—	—	—
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 4	76.8 score on a scale Standard Deviation 18.9	—	—	—
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 24	71.1 score on a scale Standard Deviation 23.7	—	—	—
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 36	62.2 score on a scale Standard Deviation 25.3	—	—	—
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 52	60.1 score on a scale Standard Deviation 27.9	—	—	—
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 65	83.9 score on a scale Standard Deviation 18.0	—	—	—
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome" Week 78	77.4 score on a scale Standard Deviation 23.1	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 and Week 2.

Population: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1.

Descriptive summary statistics for pain intensity, as evaluated by the subject using an 11-point NPRS (where 0 is no pain and 10 is the worst pain imaginable) immediately after the last injection and 15 minutes thereafter, at Day 0 and optional at Week 2.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS Injection at Day 0 - immediately after injection	1.4 units on a scale Standard Deviation 1.4	—	—	—
Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS Injection at Day 0 - 15 minutes after injection	0.0 units on a scale Standard Deviation 0.2	—	—	—
Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS Injection at Week 2 - immediately after injection	0.8 units on a scale Standard Deviation 1.1	—	—	—
Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS Injection at Week 2 - 15 minutes after injection	0.0 units on a scale Standard Deviation 0.0	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 24, 36, 52, 65, 78, and 104

Percentage of subjects having an aesthetic effect, based on the investigator's life assessment at Weeks 24, 36, 52, 65, 78, and 104.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=53 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=54 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=107 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Percentage of Subjects Having an Aesthetic Effect Week 104 · Aesthetic effect still present - no	1 Participants	0 Participants	1 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 24 · Aesthetic effect still present - yes	43 Participants	47 Participants	90 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 24 · Aesthetic effect still present - no	10 Participants	6 Participants	16 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 36 · Aesthetic effect still present - yes	30 Participants	35 Participants	65 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 36 · Aesthetic effect still present - no	23 Participants	18 Participants	41 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 52 · Aesthetic effect still present - yes	14 Participants	17 Participants	31 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 52 · Aesthetic effect still present - no	39 Participants	35 Participants	74 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 65 · Aesthetic effect still present - yes	5 Participants	5 Participants	10 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 65 · Aesthetic effect still present - no	8 Participants	11 Participants	19 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 78 · Aesthetic effect still present - yes	1 Participants	0 Participants	1 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 78 · Aesthetic effect still present - no	5 Participants	5 Participants	10 Participants	—
Percentage of Subjects Having an Aesthetic Effect Week 104 · Aesthetic effect still present - yes	0 Participants	0 Participants	0 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104

The proportion of subjects with the NLF-SRS grade reduced by ≥1 point versus Baseline at Weeks 4, 24, 36, 52, 65, 78, and 104 by injection technique (retrograde, bolus) and device (needle, cannula). A reduction in the score of the Nasolabial Folds Severity Rating Scale is considered an improvement as this reflects a decrease of the folds severity which is rated from 0 (none/minimal) to 4 (extreme). Nasolabial Folds Severity Rating Scale (NLF-SRS) is a validated 5 grade scale where the lower number corresponds to: 0 = None/minimal: No visible/minimal nasolabial folds; 1. = Mild: Shallow but visible nasolabial fold with a slight indentation; 2. = Moderate: Moderately deep nasolabial fold; 3. = Severe: Very deep nasolabial fold with prominent facial feature; 4. = Extreme: Extremely deep and long nasolabial fold with skin redundancy Therefore, the lower the number, the better.

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=58 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=51 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=63 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" n=46 Participants Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 4 after initial treatment	50 Participants	42 Participants	50 Participants	42 Participants
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 78 after initial treatment	1 Participants	0 Participants	1 Participants	0 Participants
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 104 after initial treatment	0 Participants	0 Participants	0 Participants	0 Participants
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 24 after initial treatment	40 Participants	33 Participants	40 Participants	33 Participants
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 36 after initial treatment	36 Participants	23 Participants	29 Participants	30 Participants
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 52 after initial treatment	13 Participants	10 Participants	15 Participants	8 Participants
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device Week 65 after initial treatment	2 Participants	4 Participants	5 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4, 24, 36, 52, 65, 78, and 104

The average change versus Baseline in the NLF-SRS grade at Weeks 4, 24, 36, 52, 65, 78, and 104 as evaluated by the investigator by injection technique ('retrograde', 'bolus') and device ('needle', 'cannula') On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=58 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=51 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=63 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" n=46 Participants Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 52	0.3 score on a scale Standard Deviation 0.5	0.2 score on a scale Standard Deviation 0.5	0.2 score on a scale Standard Deviation 0.5	0.3 score on a scale Standard Deviation 0.4
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 65	0.1 score on a scale Standard Deviation 0.6	0.3 score on a scale Standard Deviation 0.8	0.2 score on a scale Standard Deviation 0.7	0.0 score on a scale Standard Deviation 0.6
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 24	1.1 score on a scale Standard Deviation 0.9	1.0 score on a scale Standard Deviation 0.9	1.0 score on a scale Standard Deviation 0.8	1.2 score on a scale Standard Deviation 0.9
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 78	0.2 score on a scale Standard Deviation 0.8	0.2 score on a scale Standard Deviation 0.4	0.3 score on a scale Standard Deviation 0.7	0.0 score on a scale Standard Deviation 0.0
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 104	0.0 score on a scale	—	0.0 score on a scale	—
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 4	1.5 score on a scale Standard Deviation 0.5	1.3 score on a scale Standard Deviation 0.7	1.4 score on a scale Standard Deviation 0.6	1.5 score on a scale Standard Deviation 0.5
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula') Week 36	0.8 score on a scale Standard Deviation 0.7	0.6 score on a scale Standard Deviation 0.8	0.6 score on a scale Standard Deviation 0.8	0.9 score on a scale Standard Deviation 0.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 until week 65

Population: All safety analyses will be based on the safety analysis set, defined as all subjects who received the investigational device (109 subjects). TEAEs is defined as treatment-emergent adverse event, that can be local and non local. Local TEAEs are the AEs in treatment area or just around treatment area; Non-Local: are AEs accredited to an IMD dose, if the start of AE is at the time point of application or later. In the below data local and non-local are reported together under TEAEs.

Occurrence and frequency of adverse events within each manufacturing site - HQ and C1 separately and for the overall population (HQ +C1). The safety of the investigational device will be monitored throughout the investigation, from visit 1 (Day 0 - baseline / treatment) until the final visit ( week 65 / visit 9). AEs were collected at each visit. In addition, the subjects were instructed to immediately contact the investigator by phone in case of occurrence of any untoward event between the visits.-

Outcome measures

Outcome measures
Measure	Volume Lidocaine HQ n=54 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=55 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=109 Participants Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities	Subgroup "Cannula" Subjects randomized to be treated with Saypha Volume Lidocaine The investigational device was administered with a cannula
Safety Outcome TEAES (local) - SAEs	0 Participants	0 Participants	0 Participants	—
Safety Outcome TEAES (non -local) - SAEs	1 Participants	2 Participants	3 Participants	—
Safety Outcome TEAES (local) - number of AEs reported	11 Participants	4 Participants	15 Participants	—
Safety Outcome TEAES ( non-local) - number of AEs reported	10 Participants	14 Participants	24 Participants	—
Safety Outcome TEAES (local)- Causal Relationship with IMP (probable + definite)	6 Participants	4 Participants	10 Participants	—
Safety Outcome TEAES (non-local)- Causal Relationship with IMP (probable + definite)	0 Participants	0 Participants	0 Participants	—
Safety Outcome TEAES (local) - Causal Relationship with Procedure (probable + definite)	8 Participants	4 Participants	12 Participants	—
Safety Outcome TEAES (non-local) - Causal Relationship with Procedure (probable + definite)	0 Participants	0 Participants	0 Participants	—

Adverse Events

Volume Lidocaine HQ

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Volume Lidocaine C1

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Overall Population (Saypha Volume Lidocaine HQ + C1)

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Volume Lidocaine HQ n=54 participants at risk Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Volume Lidocaine C1 n=55 participants at risk Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma	Overall Population (Saypha Volume Lidocaine HQ + C1) n=109 participants at risk Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities
Musculoskeletal and connective tissue disorders intervertebral disc protrusion	0.00% 0/54 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.	1.8% 1/55 • Number of events 1 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.	0.92% 1/109 • Number of events 1 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.
Musculoskeletal and connective tissue disorders vertebral foraminal stenosis,	0.00% 0/54 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.	1.8% 1/55 • Number of events 1 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.	0.92% 1/109 • Number of events 1 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.
Infections and infestations appendicitis	1.9% 1/54 • Number of events 1 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.	0.00% 0/55 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.	0.92% 1/109 • Number of events 1 • 65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65). AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.

Other adverse events

Additional Information

Clinical Development - Head of Clinical Operations

Croma Pharma

Phone: +432262684680

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place