Moderate to Severe Nasolabial Folds
Conditions
Brief summary
Comparison of saypha Volume Lidocaine from 2 different manufacturing locations in correcting moderate to sever nasolabial folds
Detailed description
Following informed consent and screening, eligible subjects with moderate to severe nasolabial folds will be randomized to receive saypha® VOLUME Lidocaine from 1 of 2 manufacturing sites. The device will be injected into the deep dermis or supraperiostal, and subjects will return for follow-up assessments at Week 2, 4, 24, 36, 52 and optional at Week 65, 78 and 104 after the treatment. A Touch-up treatment may be done at Week 2, if deemed appropriate by the investigator. The performance of the investigational device will be evaluated by the investigator by assessing severity of nasolabial folds using the Nasolabial Folds Severity Rating Scale (NLF-SRS) at Week 4, 24, 36, 52 after the treatment and optional at Week 65, 78 and 104 and in comparison to Day 0. Telephone visits will be performed approximately 24 hours post-administration to monitor possible adverse events. In case any adverse events are reported during the telephone visits an unscheduled visit should be performed.
Interventions
COMBINATION_PRODUCTSaypha Volume Lidocaine
correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma. The amount injected depended on the size of the area to be corrected and the desired level of soft tissue augmentation. It was estimated that a maximum volume of 4 mL per treatment was needed but should not have exceeded 10 mL in total per treatment or 20 mL per year. and use in respective indications. The investigational device was administered to eligible subjects on investigation Day 0. A touchup treatment at Week 2 was optional at the investigator's discretion if full correction was
Sponsors
Croma-Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Subjects will be randomized to receive products from one of 2 productions sites. (C1 and HQ, respectively); as the products appear in an identical fashion only the batch numbers will allow identification of the production site; as the allocation of batch numbers to the respective site is not disclosed to the study site team, the entire team will be masked until break of blind
Intervention model description
prospective, randomized, double-blind, parallel-group, multi-center study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A subject must meet ALL of the following criteria to be eligible for the study: 1. Male or female 18 years of age or older 2. Presence of two fully visible, approximately symmetrical nasolabial folds, with each of the folds scored with 2 or 3 according to the 5-grade Nasolabial Folds Severity Rating Scale (NLF-SRS) as assessed by the investigator 3. Healthy skin in the facial area and free of diseases that could interfere in cutaneous aging evaluation 4. Willingness to abstain from any aesthetic or surgical procedures in the treatment area for the duration of the clinical investigation 5. Written signed and dated informed consent
Exclusion criteria
subject who meets ANY of the following criteria is NOT eligible for the study: 1. Pregnancy, lactation, planned pregnancy or unwillingness to use contraception at any time during the study (for women of child-bearing potential only) 2. History of mental disorders or emotional instability 3. History of allergic reaction or hypersensitivity to hyaluronic acid, lidocaine, or any amide-based anaesthetic 4. Presence of silicone implant or another non-absorbable substance (permanent fillers) in the nasolabial region 5. Any superficial or deep facial surgery or injection or implantation of any dermal fillers (including but not limited to hyaluronic acid, collagen, calcium hydroxylapatite, poly-l-lactic acid, polymethylmethacrylate, autologous fat injections), application of any absorbable and non-absorbable sutures (thread) for any purpose including wound care and facial lifting, any laser therapy (including but not limited to Neodym-YAG, KTP, IPL, Diode lasers as well as Erbium-YAG, CO2 or other ablative lasers), dermoabrasion, or botulinum toxin application in the nasolabial region within previous 12 months prior to enrolment, or any chemical peeling procedures (including but not limited to glycolic acid, trichloroacetic acid or phenolic peels) within previous 3 months prior to enrolment, or planning to undergo such procedures in the treatment area during the study 6. Presence of infectious, inflammatory, or proliferative lesions in the nasolabial region 7. Cutaneous lesions in the treatment area 8. Known human immune deficiency virus-positive individuals 9. History of allergies against aesthetic filling products and recurrent (3 times a year) herpes simplex in the treated area 10. Tendency to hypertrophic scars and/or keloid formation 11. History or presence of any autoimmune or connective tissue disease, or current treatment with immune therapy 12. Uncontrolled systemic diseases (such as diabetes mellitus) 13. Bariatric surgery within 12 months prior to enrollment or planned during the clinical investigation 14. Use of anticoagulant or thrombolytic medication from 10 days pre- to 3 days post injection 15. Any medical condition which, in the investigator's opinion, prohibits the inclusion in the study 16. Current or previous (within 30 days of enrolment) treatment with another investigational drug and/or medical device or participation in another clinical study 17. Previous enrolment in this clinical investigation 18. Subjects whose participation in clinical trials is prohibited by the Austrian Medical Devices Act (e.g., persons with a legal custodian appointed due to mental disability, prisoners, soldiers and other members of the armed forces, civil servants) 19. Any dental procedures one month before until one month after treatment with the investigational device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate in Reduction of Nasolabial Folds | 24 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Responders at Other Time Points | 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 |
| Change Versus Baseline in Nasolabial Fold Severitry | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | Weeks 4, 36, 52, 65, 78, and 104 | 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 |
| Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire Satisfaction With Outcome | Weeks 4, 24, 36, 52, 65, 78, and 104 | 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). |
| Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS | Day 0 and Week 2. | 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. |
| Percentage of Responders With a ≥2-point Improvement | Weeks 4, 24, 36, 52, 65, 78, and 104 | 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 |
| The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device | 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. |
| 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, 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 |
| Safety Outcome | Day 0 until week 65 | 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.- |
| Percentage of Subjects Having an Aesthetic Effect | 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. |
| Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Weeks 4, 24, 36, 52, 65, 78, and 104 | 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. |
| Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Weeks 4, 24, 36, 52, 65, 78, and 104 | 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. |
Countries
Austria
Participant flow
Recruitment details
Enrollment:110 (Subjects enrolled include subjects screened and randomized))
Participants by arm
| Arm | Count |
|---|---|
| Volume Lidocaine HQ 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 | 54 |
| 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 | 55 |
| Total | 109 |
Baseline characteristics
| Characteristic | Volume Lidocaine HQ | Volume Lidocaine C1 | Total |
|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 10.1 | 48.8 years STANDARD_DEVIATION 7.9 | 49.2 years STANDARD_DEVIATION 9 |
| Nasolabial fold severity scale - Grading by investigator left side 0 = None/minimal | 0 Participants | 0 Participants | 0 Participants |
| Nasolabial fold severity scale - Grading by investigator left side 1 = Mild | 0 Participants | 0 Participants | 0 Participants |
| Nasolabial fold severity scale - Grading by investigator left side 2 = Moderate | 27 Participants | 30 Participants | 57 Participants |
| Nasolabial fold severity scale - Grading by investigator left side 3 = Severe | 27 Participants | 25 Participants | 52 Participants |
| Nasolabial fold severity scale - Grading by investigator left side 4 = Extreme | 0 Participants | 0 Participants | 0 Participants |
| Nasolabial fold severity scale - Grading by investigator right side 0 = None/minimal | 0 Participants | 0 Participants | 0 Participants |
| Nasolabial fold severity scale - Grading by investigator right side 1 = Mild | 0 Participants | 0 Participants | 0 Participants |
| Nasolabial fold severity scale - Grading by investigator right side 2 = Moderate | 33 Participants | 32 Participants | 65 Participants |
| Nasolabial fold severity scale - Grading by investigator right side 3 = Severe | 21 Participants | 23 Participants | 44 Participants |
| Nasolabial fold severity scale - Grading by investigator right side 4 = Extreme | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 52 Participants | 53 Participants | 105 Participants |
| Sex: Female, Male Female | 52 Participants | 50 Participants | 102 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 55 | 0 / 109 |
| other Total, other adverse events | 16 / 54 | 14 / 55 | 30 / 109 |
| serious Total, serious adverse events | 1 / 54 | 2 / 55 | 3 / 109 |
Outcome results
Primary
Responder Rate in Reduction of Nasolabial Folds
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Volume Lidocaine HQ | Responder Rate in Reduction of Nasolabial Folds | 34 Participants |
| Volume Lidocaine C1 | Responder Rate in Reduction of Nasolabial Folds | 39 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Responder Rate in Reduction of Nasolabial Folds | 73 Participants |
Secondary
Change Versus Baseline in Nasolabial Fold Severitry
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.
Time frame: Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 104 | 0.0 score on a scale | — |
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 4 | 1.4 score on a scale | Standard Deviation 0.6 |
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 24 | 1.0 score on a scale | Standard Deviation 0.9 |
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 36 | 0.7 score on a scale | Standard Deviation 0.8 |
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 52 | 0.2 score on a scale | Standard Deviation 0.5 |
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 65 | 0.2 score on a scale | Standard Deviation 0.7 |
| Volume Lidocaine HQ | Change Versus Baseline in Nasolabial Fold Severitry | Week 78 | 0.3 score on a scale | Standard Deviation 0.5 |
| Volume Lidocaine C1 | Change Versus Baseline in Nasolabial Fold Severitry | Week 65 | 0.1 score on a scale | Standard Deviation 0.6 |
| Volume Lidocaine C1 | Change Versus Baseline in Nasolabial Fold Severitry | Week 4 | 1.4 score on a scale | Standard Deviation 0.6 |
| Volume Lidocaine C1 | Change Versus Baseline in Nasolabial Fold Severitry | Week 52 | 0.3 score on a scale | Standard Deviation 0.5 |
| Volume Lidocaine C1 | Change Versus Baseline in Nasolabial Fold Severitry | Week 36 | 0.7 score on a scale | Standard Deviation 0.7 |
| Volume Lidocaine C1 | Change Versus Baseline in Nasolabial Fold Severitry | Week 24 | 1.2 score on a scale | Standard Deviation 0.8 |
| Volume Lidocaine C1 | Change Versus Baseline in Nasolabial Fold Severitry | Week 78 | 0.0 score on a scale | Standard Deviation 0.7 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 104 | 0.0 score on a scale | — |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 24 | 1.1 score on a scale | Standard Deviation 0.9 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 36 | 0.7 score on a scale | Standard Deviation 0.8 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 52 | 0.2 score on a scale | Standard Deviation 0.5 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 78 | 0.2 score on a scale | Standard Deviation 0.6 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 4 | 1.4 score on a scale | Standard Deviation 0.6 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Change Versus Baseline in Nasolabial Fold Severitry | Week 65 | 0.1 score on a scale | Standard Deviation 0.6 |
Secondary
Proportion of Responders at Other Time Points
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
Time frame: Week 4, week 36, week 52, week 65, week 78, week 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Volume Lidocaine HQ | Proportion of Responders at Other Time Points | Week 4 | 46 Participants |
| Volume Lidocaine HQ | Proportion of Responders at Other Time Points | Week 36 | 27 Participants |
| Volume Lidocaine HQ | Proportion of Responders at Other Time Points | Week 52 | 10 Participants |
| Volume Lidocaine HQ | Proportion of Responders at Other Time Points | Week 65 | 3 Participants |
| Volume Lidocaine HQ | Proportion of Responders at Other Time Points | Week 78 | 1 Participants |
| Volume Lidocaine HQ | Proportion of Responders at Other Time Points | Week 104 | 0 Participants |
| Volume Lidocaine C1 | Proportion of Responders at Other Time Points | Week 104 | 0 Participants |
| Volume Lidocaine C1 | Proportion of Responders at Other Time Points | Week 4 | 46 Participants |
| Volume Lidocaine C1 | Proportion of Responders at Other Time Points | Week 65 | 3 Participants |
| Volume Lidocaine C1 | Proportion of Responders at Other Time Points | Week 78 | 0 Participants |
| Volume Lidocaine C1 | Proportion of Responders at Other Time Points | Week 36 | 32 Participants |
| Volume Lidocaine C1 | Proportion of Responders at Other Time Points | Week 52 | 13 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Proportion of Responders at Other Time Points | Week 36 | 59 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Proportion of Responders at Other Time Points | Week 52 | 23 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Proportion of Responders at Other Time Points | Week 104 | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Proportion of Responders at Other Time Points | Week 65 | 6 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Proportion of Responders at Other Time Points | Week 4 | 92 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Proportion of Responders at Other Time Points | Week 78 | 1 Participants |
Other Pre-specified
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')
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
Time frame: Week 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Volume Lidocaine HQ | 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 | — |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine C1 | 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 0.4 |
| Volume Lidocaine C1 | 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 | 0.2 score on a scale | Standard Deviation 0.5 |
| Volume Lidocaine C1 | 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 | 0.6 score on a scale | Standard Deviation 0.8 |
| Volume Lidocaine C1 | 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 | 0.3 score on a scale | Standard Deviation 0.8 |
| Volume Lidocaine C1 | 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 | 1.0 score on a scale | Standard Deviation 0.9 |
| Volume Lidocaine C1 | 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 | 1.3 score on a scale | Standard Deviation 0.7 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 1.0 score on a scale | Standard Deviation 0.8 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 0.6 score on a scale | Standard Deviation 0.8 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 0.3 score on a scale | Standard Deviation 0.7 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 0.2 score on a scale | Standard Deviation 0.5 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 0.2 score on a scale | Standard Deviation 0.7 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 1.4 score on a scale | Standard Deviation 0.6 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | — |
| Subgroup 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 65 | 0.0 score on a scale | Standard Deviation 0.6 |
| Subgroup 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 36 | 0.9 score on a scale | Standard Deviation 0.7 |
| Subgroup 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 24 | 1.2 score on a scale | Standard Deviation 0.9 |
| Subgroup 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 78 | 0.0 score on a scale | Standard Deviation 0 |
| Subgroup 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 0.4 |
| Subgroup 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 4 | 1.5 score on a scale | Standard Deviation 0.5 |
Other Pre-specified
Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
Other Pre-specified
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
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
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
Other Pre-specified
Percentage of Responders With a ≥2-point Improvement
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
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 4 | 43 Participants |
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 24 | 32 Participants |
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 36 | 12 Participants |
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 52 | 0 Participants |
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 65 | 0 Participants |
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 78 | 0 Participants |
| Volume Lidocaine HQ | Percentage of Responders With a ≥2-point Improvement | Week 104 | 0 Participants |
Other Pre-specified
Percentage of Subjects Having an Aesthetic Effect
Percentage of subjects having an aesthetic effect, based on the investigator's life assessment at Weeks 24, 36, 52, 65, 78, and 104.
Time frame: Weeks 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 24 | Aesthetic effect still present - yes | 43 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 24 | Aesthetic effect still present - no | 10 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 36 | Aesthetic effect still present - yes | 30 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 36 | Aesthetic effect still present - no | 23 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 52 | Aesthetic effect still present - yes | 14 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 52 | Aesthetic effect still present - no | 39 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 65 | Aesthetic effect still present - yes | 5 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 65 | Aesthetic effect still present - no | 8 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 78 | Aesthetic effect still present - yes | 1 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 78 | Aesthetic effect still present - no | 5 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 104 | Aesthetic effect still present - yes | 0 Participants |
| Volume Lidocaine HQ | Percentage of Subjects Having an Aesthetic Effect | Week 104 | Aesthetic effect still present - no | 1 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 104 | Aesthetic effect still present - no | 0 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 24 | Aesthetic effect still present - yes | 47 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 65 | Aesthetic effect still present - yes | 5 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 78 | Aesthetic effect still present - yes | 0 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 24 | Aesthetic effect still present - no | 6 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 52 | Aesthetic effect still present - no | 35 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 104 | Aesthetic effect still present - yes | 0 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 36 | Aesthetic effect still present - yes | 35 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 65 | Aesthetic effect still present - no | 11 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 52 | Aesthetic effect still present - yes | 17 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 36 | Aesthetic effect still present - no | 18 Participants |
| Volume Lidocaine C1 | Percentage of Subjects Having an Aesthetic Effect | Week 78 | Aesthetic effect still present - no | 5 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 36 | Aesthetic effect still present - no | 41 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 52 | Aesthetic effect still present - yes | 31 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 78 | Aesthetic effect still present - no | 10 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 52 | Aesthetic effect still present - no | 74 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 65 | Aesthetic effect still present - yes | 10 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 65 | Aesthetic effect still present - no | 19 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 104 | Aesthetic effect still present - yes | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 24 | Aesthetic effect still present - yes | 90 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 24 | Aesthetic effect still present - no | 16 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 78 | Aesthetic effect still present - yes | 1 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 36 | Aesthetic effect still present - yes | 65 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects Having an Aesthetic Effect | Week 104 | Aesthetic effect still present - no | 1 Participants |
Other Pre-specified
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment
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.
Time frame: 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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 78 | No Improvement | 10 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 36 | Improvement | 62 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 24 | No Improvement | 17 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 65 | Improvement | 10 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 52 | No Improvement | 76 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 4 | Improvement | 100 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 65 | No Improvement | 19 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 52 | Improvement | 29 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 78 | Improvement | 1 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 24 | Improvement | 89 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 104 | Improvement | 0 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 4 | No Improvement | 0 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 36 | No Improvement | 44 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 104 | No Improvement | 1 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 78 | No Improvement | 10 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 4 | No Improvement | 2 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 4 | Improvement | 98 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 24 | No Improvement | 16 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 24 | Improvement | 90 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 36 | No Improvement | 43 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 36 | Improvement | 63 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 52 | No Improvement | 73 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 52 | Improvement | 32 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 65 | No Improvement | 20 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 65 | Improvement | 9 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 78 | Improvement | 1 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 104 | No Improvement | 1 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 104 | Improvement | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 104 | No Improvement | 1 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 65 | Improvement | 9 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 36 | No Improvement | 45 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 24 | Improvement | 88 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 78 | No Improvement | 10 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 24 | No Improvement | 18 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 4 | No Improvement | 2 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 78 | Improvement | 1 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 4 | Improvement | 98 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 52 | Improvement | 29 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 52 | No Improvement | 76 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 104 | Improvement | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 65 | No Improvement | 20 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment | Week 36 | Improvement | 61 Participants |
Other Pre-specified
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment
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.
Time frame: 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 78 | No improvement | 6 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 36 | Improvement | 80 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 24 | No improvement | 12 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 65 | Improvement | 12 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 52 | No improvement | 51 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 4 | Improvement | 103 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 65 | No improvement | 17 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 52 | Improvement | 54 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 78 | Improvement | 5 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 24 | Improvement | 95 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 104 | Improvement | 0 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 4 | No improvement | 3 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 36 | No improvement | 26 Participants |
| Volume Lidocaine HQ | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 104 | No improvement | 1 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 78 | No improvement | 6 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 4 | No improvement | 2 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 4 | Improvement | 104 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 24 | No improvement | 13 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 24 | Improvement | 94 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 36 | No improvement | 22 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 36 | Improvement | 84 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 52 | No improvement | 49 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 52 | Improvement | 56 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 65 | No improvement | 17 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 65 | Improvement | 12 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 78 | Improvement | 5 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 104 | No improvement | 1 Participants |
| Volume Lidocaine C1 | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 104 | Improvement | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 104 | No improvement | 1 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 65 | Improvement | 12 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 36 | No improvement | 26 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 24 | Improvement | 94 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 78 | No improvement | 6 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 24 | No improvement | 13 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 4 | No improvement | 3 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 78 | Improvement | 5 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 4 | Improvement | 103 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 52 | Improvement | 54 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 52 | No improvement | 51 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 104 | Improvement | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 65 | No improvement | 17 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment | Week 36 | Improvement | 80 Participants |
Other Pre-specified
Safety Outcome
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.-
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Volume Lidocaine HQ | Safety Outcome | TEAES ( non-local) - number of AEs reported | 10 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (local) - SAEs | 0 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (local) - number of AEs reported | 11 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (non -local) - SAEs | 1 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (non-local) - Causal Relationship with Procedure (probable + definite) | 0 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (local)- Causal Relationship with IMP (probable + definite) | 6 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (non-local)- Causal Relationship with IMP (probable + definite) | 0 Participants |
| Volume Lidocaine HQ | Safety Outcome | TEAES (local) - Causal Relationship with Procedure (probable + definite) | 8 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (non-local) - Causal Relationship with Procedure (probable + definite) | 0 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES ( non-local) - number of AEs reported | 14 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (local)- Causal Relationship with IMP (probable + definite) | 4 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (local) - SAEs | 0 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (local) - number of AEs reported | 4 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (non-local)- Causal Relationship with IMP (probable + definite) | 0 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (non -local) - SAEs | 2 Participants |
| Volume Lidocaine C1 | Safety Outcome | TEAES (local) - Causal Relationship with Procedure (probable + definite) | 4 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (non -local) - SAEs | 3 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (local) - number of AEs reported | 15 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES ( non-local) - number of AEs reported | 24 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (local)- Causal Relationship with IMP (probable + definite) | 10 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (non-local)- Causal Relationship with IMP (probable + definite) | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (local) - Causal Relationship with Procedure (probable + definite) | 12 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (non-local) - Causal Relationship with Procedure (probable + definite) | 0 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | Safety Outcome | TEAES (local) - SAEs | 0 Participants |
Other Pre-specified
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire Satisfaction With Outcome
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire Satisfaction With Outcome | Week 104 | 59.0 score on a scale | — |
Other Pre-specified
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device
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.
Time frame: Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine HQ | 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 |
| Volume Lidocaine C1 | 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 | 0 Participants |
| Volume Lidocaine C1 | 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 | 10 Participants |
| Volume Lidocaine C1 | 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 | 23 Participants |
| Volume Lidocaine C1 | 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 | 4 Participants |
| Volume Lidocaine C1 | 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 |
| Volume Lidocaine C1 | 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 | 33 Participants |
| Volume Lidocaine C1 | 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 | 42 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 15 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 29 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 | 5 Participants |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 |
| Overall Population (Saypha Volume Lidocaine HQ + C1) | 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 |
| Subgroup Cannula | 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 | 30 Participants |
| Subgroup Cannula | 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 |
| Subgroup Cannula | 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 | 0 Participants |
| Subgroup Cannula | 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 | 33 Participants |
| Subgroup 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 | 42 Participants |
| Subgroup Cannula | 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 | 1 Participants |
| Subgroup Cannula | 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 | 8 Participants |