Abnormal Lip
Conditions
Keywords
Moderate to Severe Lip Volume Deficit
Brief summary
This is a prospective, open-label, multicentre, randomized study conducted to evaluate the effectiveness, safety and long-term safety of Saypha® FILLER Lidocaine for lip augmentation.
Detailed description
Following informed consent and screening, eligible subjects with moderate to severe deficiency of lip volume will be randomized to receive Saypha® FILLER Lidocaine from 1 of 2 manufacturing sites. The device will be injected into the submucosa of the lips, and subjects will return for follow-up assessments at Week 3, 6, 26, 52 and optional at Week 76 after the treatment. A Touch-up treatment may be done at Week 3, if deemed appropriate by the investigator. The performance of the investigational device will be evaluated by the investigator by assessing severity using the LFS, Lip Fullness Scale, at Week 6, 26, 52 after the treatment and optional at Week 76 and in comparison to Day 0. The upper and lower lip will be graded separately. 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® FILLER Lidocaine (HQ)
Saypha® FILLER Lidocaine is administered by injection into the lips. The volume applied depends on the size of the area which requires correction and will be selected by the investigator. A maximum volume of 2 mL for both lips in total (i.e., for upper plus lower lip) including touch up might be needed per treatment but the treatment should not exceed 10 mL in total per treatment or 20 mL per year.
COMBINATION_PRODUCTSaypha® FILLER Lidocaine (C1)
Saypha® FILLER Lidocaine is administered by injection into the lips. The volume applied depends on the size of the area which requires correction and will be selected by the investigator. A maximum volume of 2 mL for both lips in total (i.e., for upper plus lower lip) including touch up might be needed per treatment but the treatment should not exceed 10 mL in total per treatment or 20 mL per year.
Sponsors
Croma-Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Adult female or male subjects 18 years of age at Screening/Baseline visit (Visit 1) 2. Presence of approximately symmetrical very thin lips (minimal red lip shows) to moderately thick lips (moderate red lip shows) as assessed with the LFS (severity grade of 1 to 3 on both lips) as determined by the investigator at Visit 1 3. For females of childbearing potential only: negative urine pregnancy test at Visit 1, and must agree to use an highly effective method of contraception for the duration of the clinical investigation 4. Healthy skin in the treatment area and free of diseases that could interfere in evaluation of treatment 5. Willingness to abstain from any cosmetic or surgical procedures in the treatment area for the duration of the clinical investigation 6. Willingness to take part in this clinical investigation documented by a personally signed/dated informed consent.
Exclusion criteria
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. Prior surgery, scars or tattoo to the upper or lower lip or lip line; surgery and tattooing are prohibited until end of clinical investigation 5. Tooth gap, overbite, beard longer three-day beard, or excessive facial hair that could interfere in evaluation of treatment as judged by the investigator 6. Presence of any abnormal lip structure, such as a scar or lump or severe lip asymmetry, as judged by the investigator 7. Previous tissue augmenting therapy in the lip area (including lips, oral commissures, nasolabial folds, marionette and perioral lines) with HA or collagen filler, or laser treatment, chemical peeling, dermabrasion or mesotherapy within 12 months before Visit 1 and until end of clinical investigation 8. Previous permanent implant or treatment with non-HA or non-collagen filler in the lip area (including lips, oral commissures, nasolabial folds, marionette and perioral lines) and until end of the investigation 9. Previous toxin treatment in the lip area (including lips, oral commissures, nasolabial folds, marionette and perioral lines) within 9 months before Visit 1 and until end of clinical investigation 10. Presence of cutaneous lesions, inflammatory and/or infectious processes (e.g. acne, herpes, etc.) or proliferative lesions in the treatment area 11. Known human immune deficiency virus-positive individuals 12. History of allergies against aesthetic filling products and recurrent (3 times a year) herpes simplex in the treated area 13. Tendency to hypertrophic scars, keloid formation and/or pigmentation disorders 14. History or presence of any autoimmune or connective tissue disease, or current treatment with immune therapy 15. Uncontrolled systemic diseases (such as diabetes mellitus) 16. Use of anticoagulant, antiplatelet or thrombolytic medication (e.g. acetylsalicylic acid) from 10 days pre- to three days post IMD injections 17. Planned dental/oral surgery or modification (bridge-work, implants) within two weeks prior to initial IMD injection and to a minimum of four weeks post IMD injections 18. Any medical condition which, in the investigator's opinion, prohibits the inclusion in the study 19. Current or previous (within 30 days of enrolment) treatment with another investigational drug and/or medical device or participation in another clinical study 20. Previous enrolment in this clinical investigation 21. Any dependent relationship of the subject with the investigator, investigation site or Sponsor (e.g. employees or relatives) 22. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate in Lip Volume Improvement | Week 6 | The proportion of subjects ('responders') with the lip volume improved by ≥1 point versus baseline value at 6 weeks after initial treatment based on the investigator live assessment using the validated Lip Fullness Scale (LFS). Lip Fullness Scale (LFS) is a validated 5-point rating scale,that evaluates the Lip Volume Deficiency ranging from Grade 1 (minimal volume) to Grade 5 (very significant volume): In this case, the bigger the number, the better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6, Month 6, 12 and optional Month 18 | The percentage of responders based on the independent photographic reviewer´s assessments at Week 6, Month 6, 12 and optional Month 18 after initial treatment, based on photographs and using the validated LFS (compared to Baseline). Lip Fullness Scale (LFS) is a validated 5-point rating scale,that evaluates the Lip Volume Deficiency ranging from Grade 1 (minimal), Grade 2 (slight), Grade 3 (moderately thick), Grade 4 (thick), to Grade 5 (very significant): In this case, the bigger the number, the better. |
| Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6, Month 6, 12 and optional Month 18 | The percentage of subjects with an improvement relative to baseline photographs, (subjects who have been rated as very much improved or much improved or improved), based on the investigator assessment at Week 6, Month 6, 12 and optional Month 18 after initial treatment using the 5-point GAIS. |
| Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6, Month 6, 12 and optional Month 18 | The percentage of subjects with an improvement relative to baseline photographs (subjects who have been rated as very much improved or much improved or improved), based on subject assessment at Week 6, Month 6, 12 and optional Month 18 after initial treatment, using the 5-point GAIS with results ranging from 1 to 5 with lower numbers indicating better improvement |
| Subject Satisfaction Using Face-Q Questionnaire | Week 6, Month 6, 12 and optional Month 18 | The extent of subject´s satisfaction with overall outcome of the treatment, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q TM Questionnaire. The FACE-Q Satisfaction with Outcome scale is a patient-reported outcome measure designed to assess a patient's satisfaction with the results of a facial aesthetic procedure. This scale comprises six items, each with four response options: definitely agree, somewhat agree, somewhat disagree, and definitely disagree. The raw summed scale score is converted to a score from 0 to 100 by using the respective Conversion Tables available from Face Q authors. Higher scores reflect a better outcome (i.e., 0 (worst) to 100 (best)). |
| Percentage of Responders Based on the Investigator Live Assessment | 6, 12 and optional 18 months | The percentage of responders (with the Lip Volume Improved by \>=1 Point Versus Baseline Value,) based on the investigator live assessment at 6, 12 and optional 18 months after the initial treatment using the validated LFS. Lip Fullness Scale (LFS) is a validated 5-point rating scale,that evaluates the Lip Volume Deficiency ranging from Grade 1 (minimal volume) to Grade 5 (very significant volume): In this case, the bigger the number, the better. |
| Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Day1, Week 3 | Subject's perception of pain after initial and touch-up treatment with Saypha® FILLER Lidocaine using the 11-point Numeric Pain Rating Scale (NPRS), where 0 is no pain and 10 is the worst pain imaginable. |
| Percentage of Subjects Demonstrating an Aesthetic Effect | Week 6, Month 6, 12 and optional Month 18 | Percentage of subjects demonstrating an aesthetic effect at Week 6, Month 6, 12 and optional Month 18 based on the investigator's life assessment. A live assessment of the treated areas was performed and the treated areas compared to the subject's photographs obtained at the Baseline Visit. The presence of the aesthetic effect was recorded as either Yes or No |
| Injection Volume Required | Day1, Week 3 | Injection volume (initial and touch-up) required for an optimal augmentation of the lips with Saypha® FILLER Lidocaine. |
| Subject Satisfaction Using Face-Q TM Questionnaire Satisfaction With Lips | Week 6, Month 6, 12 and optional Month 18 | The extent of subject's satisfaction with augmentation of lips, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q TM Questionnaire Satisfaction with Lips, a 6-items Aesthetic Appearance Questionnaire with 5 pre-defined answer options between very satisfied and very dissatisfied. The extent of subject´s satisfaction with overall outcome of the treatment, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q. The raw summed scale score is converted to a score from 0 to 100 by using the respective Conversion Tables available from Face Q authors. Higher scores reflect a better outcome (i.e., 0 (worst) to 100 (best)). |
Countries
Austria
Participant flow
Recruitment details
Screened patients: N=121; Screening failures: N=7; Patients enrolled = Patients Treated with IMD: N= 114
Participants by arm
| Arm | Count |
|---|---|
| Saypha® FILLER HQ Eligible subjects will undergo bilateral lip augmentation treatments with Saypha® FILLER Lidocaine manufactured in the Croma Pharma HQ Facility in order to correct moderate to severe deficiency of lip volume.
The treatment will be administered at the Baseline visit (Day 0).
Saypha® FILLER Lidocaine (HQ): Saypha® FILLER Lidocaine is administered by injection into the lips. The volume applied depends on the size of the area which requires correction and will be selected by the investigator. A maximum volume of 2 mL for both lips in total (i.e., for upper plus lower lip) including touch up might be needed per treatment but the treatment should not exceed 10 mL in total per treatment or 20 mL per year. | 57 |
| Saypha® FILLER C1 Eligible subjects will undergo bilateral lip augmentation treatments with Saypha® FILLER Lidocaine manufactured in the Croma Pharma C1 Facility in order to correct moderate to severe deficiency of lip volume.
The treatment will be administered at the Baseline visit (Day 0).
Saypha® FILLER Lidocaine (C1): Saypha® FILLER Lidocaine is administered by injection into the lips. The volume applied depends on the size of the area which requires correction and will be selected by the investigator. A maximum volume of 2 mL for both lips in total (i.e., for upper plus lower lip) including touch up might be needed per treatment but the treatment should not exceed 10 mL in total per treatment or 20 mL per year. | 57 |
| Total | 114 |
Baseline characteristics
| Characteristic | Saypha® FILLER HQ | Total | Saypha® FILLER C1 |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 13.78 | 43.2 years STANDARD_DEVIATION 15.03 | 44.4 years STANDARD_DEVIATION 16.22 |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 114 Participants | 57 Participants |
| Region of Enrollment Austria | 57 participants | 114 participants | 57 participants |
| Sex: Female, Male Female | 57 Participants | 114 Participants | 57 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Smoking habit current | 21 Participants | 43 Participants | 22 Participants |
| Smoking habit former | 4 Participants | 8 Participants | 4 Participants |
| Smoking habit never smoked | 32 Participants | 63 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 35 / 57 | 32 / 57 |
| serious Total, serious adverse events | 0 / 57 | 1 / 57 |
Outcome results
Primary
Responder Rate in Lip Volume Improvement
The proportion of subjects ('responders') with the lip volume improved by ≥1 point versus baseline value at 6 weeks after initial treatment based on the investigator live assessment using the validated Lip Fullness Scale (LFS). Lip Fullness Scale (LFS) is a validated 5-point rating scale,that evaluates the Lip Volume Deficiency ranging from Grade 1 (minimal volume) to Grade 5 (very significant volume): In this case, the bigger the number, the better.
Time frame: Week 6
Population: Population considered for this analysis is the Full Analysis Set (FAS) which comprises all subjects who received at least 1 administration of the IMD and who had at least 1 post-treatment evaluation of the LFS.~Individual LFS grades per visit are calculated separately for the upper and the lower lip.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Saypha® FILLER HQ | Responder Rate in Lip Volume Improvement | lower lip responders | 55 Participants |
| Saypha® FILLER HQ | Responder Rate in Lip Volume Improvement | upper lip responders | 53 Participants |
| Saypha® FILLER C1 | Responder Rate in Lip Volume Improvement | lower lip responders | 52 Participants |
| Saypha® FILLER C1 | Responder Rate in Lip Volume Improvement | upper lip responders | 53 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Responder Rate in Lip Volume Improvement | lower lip responders | 107 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Responder Rate in Lip Volume Improvement | upper lip responders | 106 Participants |
Secondary
Injection Volume Required
Injection volume (initial and touch-up) required for an optimal augmentation of the lips with Saypha® FILLER Lidocaine.
Time frame: Day1, Week 3
Population: The population considered for this analysis comprises all subjects who had at least 1 post-treatment evaluation using the Lip Fullness Scale and who received treatment with the Investigational Medical Device at the respective timepoints. 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 |
|---|---|---|---|---|
| Saypha® FILLER HQ | Injection Volume Required | Day 1 - initial treatment -lower lip | 0.79 ml | Standard Deviation 0.282 |
| Saypha® FILLER HQ | Injection Volume Required | Day 1 - Initial Treatment - Upper Lip | 0.80 ml | Standard Deviation 0.285 |
| Saypha® FILLER HQ | Injection Volume Required | Day 1 - initial treatment - both lips | 1.59 ml | Standard Deviation 0.516 |
| Saypha® FILLER HQ | Injection Volume Required | Week 3 - touch up treatment - lower lip | 0.50 ml | Standard Deviation 0.298 |
| Saypha® FILLER HQ | Injection Volume Required | Week 3 - touch up treatment - upper lip | 0.51 ml | Standard Deviation 0.305 |
| Saypha® FILLER HQ | Injection Volume Required | Week 3 - touch up treatment - both lips | 0.85 ml | Standard Deviation 0.604 |
Secondary
Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments
The percentage of responders based on the independent photographic reviewer´s assessments at Week 6, Month 6, 12 and optional Month 18 after initial treatment, based on photographs and using the validated LFS (compared to Baseline). Lip Fullness Scale (LFS) is a validated 5-point rating scale,that evaluates the Lip Volume Deficiency ranging from Grade 1 (minimal), Grade 2 (slight), Grade 3 (moderately thick), Grade 4 (thick), to Grade 5 (very significant): In this case, the bigger the number, the better.
Time frame: Week 6, Month 6, 12 and optional Month 18
Population: FAS - see primary endopoint for FAS definition
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6 - Lower Lip | 25 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6 - Upper Lip | 17 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 6 - Lower Lip | 20 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 6 - Upper Lip | 15 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 12 - Lower Lip | 20 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 12 - Upper Lip | 20 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 18 - Lower Lip | 15 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 18 - Upper Lip | 13 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 6 - Lower Lip | 19 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 18 - Lower Lip | 16 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 6 - Upper Lip | 24 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 12 - Lower Lip | 15 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 12 - Upper Lip | 26 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6 - Lower Lip | 30 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6 - Upper Lip | 25 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 18 - Upper Lip | 21 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 6 - Lower Lip | 39 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6 - Upper Lip | 42 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Week 6 - Lower Lip | 55 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 6 - Upper Lip | 39 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 18 - Lower Lip | 31 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 12 - Upper Lip | 46 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 12 - Lower Lip | 35 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Independent Photographic Reviewer´s Assessments | Month 18 - Upper Lip | 34 Participants |
Secondary
Percentage of Responders Based on the Investigator Live Assessment
The percentage of responders (with the Lip Volume Improved by \>=1 Point Versus Baseline Value,) based on the investigator live assessment at 6, 12 and optional 18 months after the initial treatment using the validated LFS. Lip Fullness Scale (LFS) is a validated 5-point rating scale,that evaluates the Lip Volume Deficiency ranging from Grade 1 (minimal volume) to Grade 5 (very significant volume): In this case, the bigger the number, the better.
Time frame: 6, 12 and optional 18 months
Population: FAS (defined in the Analyis Population description of the primary outcome measure) was considered for the analysis of the secondary endpoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Saypha® FILLER HQ | Percentage of Responders Based on the Investigator Live Assessment | Month 6 Lower Lips | 48 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Investigator Live Assessment | Month 6 Upper Lips | 49 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Investigator Live Assessment | Month 12 Lower Lips | 41 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Investigator Live Assessment | Month 12 Upper Lips | 38 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Investigator Live Assessment | Month 18 Lower Lips | 28 Participants |
| Saypha® FILLER HQ | Percentage of Responders Based on the Investigator Live Assessment | Month 18 Upper Lips | 24 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Investigator Live Assessment | Month 18 Upper Lips | 19 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Investigator Live Assessment | Month 6 Lower Lips | 50 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Investigator Live Assessment | Month 12 Upper Lips | 36 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Investigator Live Assessment | Month 18 Lower Lips | 23 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Investigator Live Assessment | Month 6 Upper Lips | 50 Participants |
| Saypha® FILLER C1 | Percentage of Responders Based on the Investigator Live Assessment | Month 12 Lower Lips | 36 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Investigator Live Assessment | Month 6 Upper Lips | 99 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Investigator Live Assessment | Month 12 Lower Lips | 77 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Investigator Live Assessment | Month 18 Upper Lips | 43 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Investigator Live Assessment | Month 12 Upper Lips | 74 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Investigator Live Assessment | Month 6 Lower Lips | 98 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Responders Based on the Investigator Live Assessment | Month 18 Lower Lips | 51 Participants |
Secondary
Percentage of Subjects Demonstrating an Aesthetic Effect
Percentage of subjects demonstrating an aesthetic effect at Week 6, Month 6, 12 and optional Month 18 based on the investigator's life assessment. A live assessment of the treated areas was performed and the treated areas compared to the subject's photographs obtained at the Baseline Visit. The presence of the aesthetic effect was recorded as either Yes or No
Time frame: Week 6, Month 6, 12 and optional Month 18
Population: The population considered for this analysis comprises all subjects who received at least 1 administration of the Investigational Medical Device and who had at least 1 post-treatment evaluation using the Lip Fullness Scale. 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) |
|---|---|---|---|
| Saypha® FILLER HQ | Percentage of Subjects Demonstrating an Aesthetic Effect | Week 6 | 110 Participants |
| Saypha® FILLER HQ | Percentage of Subjects Demonstrating an Aesthetic Effect | Month 6 | 106 Participants |
| Saypha® FILLER HQ | Percentage of Subjects Demonstrating an Aesthetic Effect | Month 12 | 86 Participants |
| Saypha® FILLER HQ | Percentage of Subjects Demonstrating an Aesthetic Effect | Month 18 | 59 Participants |
Secondary
Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS
The percentage of subjects with an improvement relative to baseline photographs (subjects who have been rated as very much improved or much improved or improved), based on subject assessment at Week 6, Month 6, 12 and optional Month 18 after initial treatment, using the 5-point GAIS with results ranging from 1 to 5 with lower numbers indicating better improvement
Time frame: Week 6, Month 6, 12 and optional Month 18
Population: FAS - please see primary endpoint description
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 6 - Lower Lips | 51 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6 - lower lips | 55 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 6 - Upper Lips | 53 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 18 - Upper Lips | 34 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6 - upper lips | 56 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 12 - Lower Lips | 45 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 18 - Lower Lips | 37 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 12 - Upper Lips | 44 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6 - upper lips | 54 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 12 - Upper Lips | 44 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6 - lower lips | 54 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 18 - Lower Lips | 34 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 18 - Upper Lips | 35 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 6 - Lower Lips | 53 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 6 - Upper Lips | 53 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 12 - Lower Lips | 44 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 6 - Upper Lips | 106 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6 - lower lips | 109 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Week 6 - upper lips | 110 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 6 - Lower Lips | 104 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 18 - Upper Lips | 69 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 12 - Lower Lips | 89 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 12 - Upper Lips | 88 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on Subject Assessment Using GAIS | Month 18 - Lower Lips | 71 Participants |
Secondary
Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS
The percentage of subjects with an improvement relative to baseline photographs, (subjects who have been rated as very much improved or much improved or improved), based on the investigator assessment at Week 6, Month 6, 12 and optional Month 18 after initial treatment using the 5-point GAIS.
Time frame: Week 6, Month 6, 12 and optional Month 18
Population: FAS - Please see primary endpoint for definition
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6 -Lower Lip | 56 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6 - Upper Lip | 56 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 6 - Lower Lip | 53 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 6 - Upper Lip | 53 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 12- Lower Lip | 44 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 12 - Upper Lip | 44 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 18 - Lower Lip | 30 Participants |
| Saypha® FILLER HQ | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 18 -Upper Lip | 30 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 6 - Lower Lip | 53 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 18 - Lower Lip | 26 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 6 - Upper Lip | 53 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 12- Lower Lip | 41 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 12 - Upper Lip | 40 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6 -Lower Lip | 54 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6 - Upper Lip | 54 Participants |
| Saypha® FILLER C1 | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 18 -Upper Lip | 21 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 6 - Lower Lip | 106 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6 - Upper Lip | 110 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Week 6 -Lower Lip | 110 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 6 - Upper Lip | 106 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 18 - Lower Lip | 56 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 12 - Upper Lip | 84 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 12- Lower Lip | 85 Participants |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Percentage of Subjects With an Improvement Based on the Investigator Assessment Using GAIS | Month 18 -Upper Lip | 51 Participants |
Secondary
Subject Satisfaction Using Face-Q Questionnaire
The extent of subject´s satisfaction with overall outcome of the treatment, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q TM Questionnaire. The FACE-Q Satisfaction with Outcome scale is a patient-reported outcome measure designed to assess a patient's satisfaction with the results of a facial aesthetic procedure. This scale comprises six items, each with four response options: definitely agree, somewhat agree, somewhat disagree, and definitely disagree. The raw summed scale score is converted to a score from 0 to 100 by using the respective Conversion Tables available from Face Q authors. Higher scores reflect a better outcome (i.e., 0 (worst) to 100 (best)).
Time frame: Week 6, Month 6, 12 and optional Month 18
Population: The population considered for this analysis comprises all subjects who received at least 1 administration of the Investigational Medical Device, who had at least 1 post-treatment evaluation using the Lip Fullness Scale and who have Face-Q measurements available for the respective timepoints. 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 |
|---|---|---|---|---|
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q Questionnaire | Week 6 | 85.8 score on Face Q questionnaire | Standard Deviation 17.88 |
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q Questionnaire | Month 6 | 80.0 score on Face Q questionnaire | Standard Deviation 20.61 |
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q Questionnaire | Month 12 | 71.7 score on Face Q questionnaire | Standard Deviation 25.53 |
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q Questionnaire | Month 18 | 78.3 score on Face Q questionnaire | Standard Deviation 25.76 |
Secondary
Subject Satisfaction Using Face-Q TM Questionnaire Satisfaction With Lips
The extent of subject's satisfaction with augmentation of lips, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q TM Questionnaire Satisfaction with Lips, a 6-items Aesthetic Appearance Questionnaire with 5 pre-defined answer options between very satisfied and very dissatisfied. The extent of subject´s satisfaction with overall outcome of the treatment, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q. The raw summed scale score is converted to a score from 0 to 100 by using the respective Conversion Tables available from Face Q authors. Higher scores reflect a better outcome (i.e., 0 (worst) to 100 (best)).
Time frame: Week 6, Month 6, 12 and optional Month 18
Population: The population considered for this analysis comprises all subjects who received at least 1 administration of the Investigational Medical Device, who had at least 1 post-treatment evaluation using the Lip Fullness Scale and who have Face-Q measurements available for the respective timepoints. 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 |
|---|---|---|---|---|
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q TM Questionnaire Satisfaction With Lips | Week 6 | 90.9 score Face Q questionnaire | Standard Deviation 11.96 |
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q TM Questionnaire Satisfaction With Lips | Month 6 | 84.9 score Face Q questionnaire | Standard Deviation 17.24 |
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q TM Questionnaire Satisfaction With Lips | Month 12 | 76.2 score Face Q questionnaire | Standard Deviation 22.69 |
| Saypha® FILLER HQ | Subject Satisfaction Using Face-Q TM Questionnaire Satisfaction With Lips | Month 18 | 78.3 score Face Q questionnaire | Standard Deviation 20.45 |
Secondary
Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale
Subject's perception of pain after initial and touch-up treatment with Saypha® FILLER Lidocaine using the 11-point Numeric Pain Rating Scale (NPRS), where 0 is no pain and 10 is the worst pain imaginable.
Time frame: Day1, Week 3
Population: FAS-please see primary endpoint population definition
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saypha® FILLER HQ | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Initial Treatment - Immediately after treatment | 3.3 score on a scale | Standard Deviation 1.71 |
| Saypha® FILLER HQ | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Initial Treatment - 15 min post treatment | 0.5 score on a scale | Standard Deviation 0.92 |
| Saypha® FILLER HQ | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Touch up (Week 3) - Immediately after treatment | 2.9 score on a scale | Standard Deviation 1.48 |
| Saypha® FILLER HQ | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Touch up (Week 3 ) - 15 min post treatment | 0.4 score on a scale | Standard Deviation 0.65 |
| Saypha® FILLER C1 | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Touch up (Week 3 ) - 15 min post treatment | 0.4 score on a scale | Standard Deviation 0.77 |
| Saypha® FILLER C1 | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Initial Treatment - Immediately after treatment | 3.6 score on a scale | Standard Deviation 1.75 |
| Saypha® FILLER C1 | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Touch up (Week 3) - Immediately after treatment | 2.7 score on a scale | Standard Deviation 1.52 |
| Saypha® FILLER C1 | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Initial Treatment - 15 min post treatment | 0.7 score on a scale | Standard Deviation 1.05 |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Touch up (Week 3 ) - 15 min post treatment | 0.3 score on a scale | Standard Deviation 0.53 |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Initial Treatment - 15 min post treatment | 0.3 score on a scale | Standard Deviation 0.73 |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Touch up (Week 3) - Immediately after treatment | 3.0 score on a scale | Standard Deviation 1.46 |
| Overall Population (Saypha® FILLER HQ + Saypha® FILLER C1) | Subject's Perception of Pain Using the 11-point Numeric Pain Rating Scale | Initial Treatment - Immediately after treatment | 3.0 score on a scale | Standard Deviation 1.62 |