Facial Aesthetic Treatment
Conditions
Brief summary
The efficacy and safety, as well as subject satisfaction will be evaluated after single treatment with Azzalure alone or Restylane/Emervel filler alone followed by repeated combined treatment with Azzalure, Restylane/Emervel filler and Restylane Skinbooster. Subjects will be followed for up to 18 months after initial treatment.
Interventions
DRUGAzzalure
Glabellar lines
DEVICERestylane/Emervel filler
Facial tissue augmentation
DEVICERestylane Skinbooster
Facial skin rejuvenation
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects aged 35 to 50 years old * Subjects with the intention to undergo facial aesthetic treatment and who are likely to benefit from a combination of injection treatments and the benefit can be shown by improvements in their global facial aesthetic appearance and satisfaction. * Subjects with nasolabial folds assessed as mild or moderate. * Subjects with glabellar lines assessed as moderate or severe, when the severity of the lines has an important psychological impact on the subject. * Subjects with signed informed consent.
Exclusion criteria
* Subjects requiring treatment of forehead lines or crow´s feet. * Obvious facial sagging (major loss of facial fat/volume). * Signs or symptoms of eyelid ptosis or signs of compensatory frontalis muscle activity. * Heavily scarred or sun-damaged facial skin. * Active skin disease, inflammation or related conditions, such as infection, psoriasis and herpes zoster/herpes simplex near or on the areas to be treated. * Cancerous or pre-cancerous lesions in the areas to be treated. * Facial tissue augmenting therapy or revitalization treatment with hyaluronic acid (HA) or collagen, or botulinum toxin treatment during the last 12 months. * Procedures or treatments inducing an active dermal response such as laser, Intense Pulsed Light, chemical peeling, microdermabrasion, retinoids within the last 6 months. * Any aesthetic surgery of the face. * Permanent implant or aesthetic treatment with non-HA or non-collagen products in the face. * History of severe keloids and/or hypertrophic scars. * Neuromuscular junctional disorders (e.g. myasthenia gravis, Eaton Lambert syndrome or amyotrophic lateral sclerosis) or history of dysphagia and aspiration. * Known hypersensitivity to hyaluronic acid, botulinum toxin, lidocaine hydrochloride or other amide-type anesthetics. * History of autoimmune diseases. * Any medical condition that in the opinion of the investigator would make the subject unsuitable for inclusion (e.g. a chronic, relapsing or hereditary disease that may affect the general condition or may require frequent medical treatment). * Concomitant anticoagulant therapy and therapy with inhibitors of platelet aggregation (e.g. aspirin or other nonsteroidal anti-inflammatory drugs \[NSAIDs\]), Omega-3 or vitamin E within 10 days before study treatment, or a history of bleeding disorders. * Immunosuppressive therapy, chemotherapy, or systemic corticosteroids within the last 3 months prior to baseline visit. * Female subjects who are pregnant or plan to become pregnant within the study timeframe, or who are nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 7 Months (Review of Photographs) | 7 months | To evaluate Global facial aesthetic appearance at 7 months compared to at 1 month, blinded evaluator review of photographs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Month 1, Month 7, and Month 13 | The 5-graded GAIS is used to assess the facial aesthetic improvement from baseline by responding to the question: How would you describe the subject's global facial aesthetic appearance, compared to the photographs taken before treatment at baseline? The scale grades are Very much improved, Much improved, Somewhat improved, No change, Worse. Improved subjects are those graded as Very much improved, Much improved, and Somewhat improved. |
| Number of Subjects Satisfied With Overall Facial Appearance (Questionnaire) | Month 7 and Month 13 | Subjects answered the question How satisfied are you today with the appearance of your face? with Very/somewhat satisfied, Neither/nor, or Very/somewhat dissatisfied. Number of subjects satisfied are those that answered Very/somewhat satisfied. |
| Number of Subjects for Which the Investigator is Satisfied With Overall Facial Aesthetic Outcome | Month 7 and Month 13 | The Investigator answered the question How satisfied are you with the overall facial aesthetic outcome for the subject? with Very/somewhat satisfied, Neither/nor, or Very/somewhat dissatisfied. Satisfied criteria is met for those subjects that the Investigator answered Very/somewhat satisfied. |
| Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | 1, 7 and 13 months | To evaluate Global facial aesthetic appearance at 1, 7 and 13 months, blinded evaluator review of photographs from the respective visits. |
| Change in Perceived Age of Subjects | 1 and 7 months, and 1 and 13 months | To evaluate First impression and perceived age of subjects by evaluation of photos. Change between timepoints are reported. A negative value indicates that the participant is assessed to be younger at the specified visit compared to the assessment made at 1 month after single treatment. |
| Injected Filler Volume | Initial single treatment (baseline), first combined treatment (Month 6), and second combined treatment (Month 12) | To evaluate the filler volume injected at initial single treatment and at following repeated combined treatment |
| Adverse Event Reporting | 0-18 months | To evaluate safety throughout the study period |
| Number of Participants Who Had Improvement in Wrinkle Severity Score of Treated Glabellar Lines (Validated Photo Scales) | Month 7 and Month 13 | The wrinkle severity of the glabellar lines at maximum frown was evaluated by the investigator at baseline before first treatment and at follow-up visits. Validated photonumeric grading scales were used where each severity grade is illustrated by a set of photographs. The investigator performed the assessment live or by using 2D photographs from the present visit, together with the respective photo guide: 0 No glabella lines, 1 Mild glabella lines, 2 Moderate glabella lines, 3 Severe glabella lines, 4 Very severe glabella lines. Improved criteria is thus fulfilled for subjects receiving a lower score compared to baseline. |
Countries
France, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azzalure Alone as Initial Treatment Azzalulre alone as single treatment at initial treatment followed by two combined treatments with Azzalure, HA filler and Skinboosters at Month 6 and Month 12. | 29 |
| Filler Alone as Initial Treatment Filler alone as single treatment at initial treatment followed by two combined treatments with Azzalure, HA filler and Skinboosters at Month 6 and Month 12. | 31 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Medical reason | 0 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Filler Alone as Initial Treatment | Azzalure Alone as Initial Treatment |
|---|---|---|---|
| Age, Continuous | 44.7 years | 43.6 years | 45.9 years |
| Race/Ethnicity, Customized White | 22 Participants | 11 Participants | 11 Participants |
| Sex: Female, Male Female | 59 Participants | 30 Participants | 29 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
| Smoking Non smoker | 41 participants | 21 participants | 20 participants |
| Smoking Smoker | 19 participants | 10 participants | 9 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 29 | 4 / 31 | 15 / 28 | 13 / 28 | 9 / 28 | 9 / 28 |
| serious Total, serious adverse events | 0 / 29 | 1 / 31 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 7 Months (Review of Photographs)
To evaluate Global facial aesthetic appearance at 7 months compared to at 1 month, blinded evaluator review of photographs.
Time frame: 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Azzalure Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 7 Months (Review of Photographs) | 20 Participants |
| Filler Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 7 Months (Review of Photographs) | 25 Participants |
Secondary
Adverse Event Reporting
To evaluate safety throughout the study period
Time frame: 0-18 months
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azzalure Alone as Initial Treatment | Adverse Event Reporting | 36 Treatment related AEs |
| Filler Alone as Initial Treatment | Adverse Event Reporting | 26 Treatment related AEs |
Secondary
Change in Perceived Age of Subjects
To evaluate First impression and perceived age of subjects by evaluation of photos. Change between timepoints are reported. A negative value indicates that the participant is assessed to be younger at the specified visit compared to the assessment made at 1 month after single treatment.
Time frame: 1 and 7 months, and 1 and 13 months
Population: Five participants excluded from analysis due to incorrectly taken photographs.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azzalure Alone as Initial Treatment | Change in Perceived Age of Subjects | Difference Month 7/Month 1 | -1.7 years | Standard Deviation 4 |
| Azzalure Alone as Initial Treatment | Change in Perceived Age of Subjects | Differerence Month 13/Month 1 | -1.9 years | Standard Deviation 4.7 |
| Filler Alone as Initial Treatment | Change in Perceived Age of Subjects | Difference Month 7/Month 1 | -1.9 years | Standard Deviation 2.9 |
| Filler Alone as Initial Treatment | Change in Perceived Age of Subjects | Differerence Month 13/Month 1 | -2.4 years | Standard Deviation 2.9 |
Secondary
Injected Filler Volume
To evaluate the filler volume injected at initial single treatment and at following repeated combined treatment
Time frame: Initial single treatment (baseline), first combined treatment (Month 6), and second combined treatment (Month 12)
Population: For the initial single treatment, only the Filler alone as initial treatment participants received filler. At the two combination treatments, all subjects received filler. Data from the Filler alone as initial treatment participants are presented for the single treatment while data for all subjects are presented for the combination treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azzalure Alone as Initial Treatment | Injected Filler Volume | Single and first combined treatment | 0.98 mL | Standard Deviation 0.06 |
| Filler Alone as Initial Treatment | Injected Filler Volume | Single and first combined treatment | 1.92 mL | Standard Deviation 0.23 |
| Filler Alone as Initial Treatment | Injected Filler Volume | Second combined treatment | 1.72 mL | Standard Deviation 0.5 |
Secondary
Number of Participants Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator
The 5-graded GAIS is used to assess the facial aesthetic improvement from baseline by responding to the question: How would you describe the subject's global facial aesthetic appearance, compared to the photographs taken before treatment at baseline? The scale grades are Very much improved, Much improved, Somewhat improved, No change, Worse. Improved subjects are those graded as Very much improved, Much improved, and Somewhat improved.
Time frame: Month 1, Month 7, and Month 13
Population: Number of analyzed subjects decreased over time due to drop-out of study subjects.~Data not presented Per Arm, since statistical analysis was only performed on both groups combined after the combination treatments (since the groups receive the exact same treatment during the combination treatment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azzalure Alone as Initial Treatment | Number of Participants Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Improved Month 1 | 35 participants |
| Azzalure Alone as Initial Treatment | Number of Participants Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Improved Month 7 | 42 participants |
| Azzalure Alone as Initial Treatment | Number of Participants Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Improved Month 13 | 47 participants |
Secondary
Number of Participants Who Had Improvement in Wrinkle Severity Score of Treated Glabellar Lines (Validated Photo Scales)
The wrinkle severity of the glabellar lines at maximum frown was evaluated by the investigator at baseline before first treatment and at follow-up visits. Validated photonumeric grading scales were used where each severity grade is illustrated by a set of photographs. The investigator performed the assessment live or by using 2D photographs from the present visit, together with the respective photo guide: 0 No glabella lines, 1 Mild glabella lines, 2 Moderate glabella lines, 3 Severe glabella lines, 4 Very severe glabella lines. Improved criteria is thus fulfilled for subjects receiving a lower score compared to baseline.
Time frame: Month 7 and Month 13
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azzalure Alone as Initial Treatment | Number of Participants Who Had Improvement in Wrinkle Severity Score of Treated Glabellar Lines (Validated Photo Scales) | Improved Month 7 | 27 participants |
| Azzalure Alone as Initial Treatment | Number of Participants Who Had Improvement in Wrinkle Severity Score of Treated Glabellar Lines (Validated Photo Scales) | Improved Month 13 | 27 participants |
| Filler Alone as Initial Treatment | Number of Participants Who Had Improvement in Wrinkle Severity Score of Treated Glabellar Lines (Validated Photo Scales) | Improved Month 7 | 28 participants |
| Filler Alone as Initial Treatment | Number of Participants Who Had Improvement in Wrinkle Severity Score of Treated Glabellar Lines (Validated Photo Scales) | Improved Month 13 | 28 participants |
Secondary
Number of Subjects for Which the Investigator is Satisfied With Overall Facial Aesthetic Outcome
The Investigator answered the question How satisfied are you with the overall facial aesthetic outcome for the subject? with Very/somewhat satisfied, Neither/nor, or Very/somewhat dissatisfied. Satisfied criteria is met for those subjects that the Investigator answered Very/somewhat satisfied.
Time frame: Month 7 and Month 13
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azzalure Alone as Initial Treatment | Number of Subjects for Which the Investigator is Satisfied With Overall Facial Aesthetic Outcome | Satisfied Month 7 | 28 participants |
| Azzalure Alone as Initial Treatment | Number of Subjects for Which the Investigator is Satisfied With Overall Facial Aesthetic Outcome | Satisfied Month 13 | 28 participants |
| Filler Alone as Initial Treatment | Number of Subjects for Which the Investigator is Satisfied With Overall Facial Aesthetic Outcome | Satisfied Month 7 | 28 participants |
| Filler Alone as Initial Treatment | Number of Subjects for Which the Investigator is Satisfied With Overall Facial Aesthetic Outcome | Satisfied Month 13 | 28 participants |
Secondary
Number of Subjects Satisfied With Overall Facial Appearance (Questionnaire)
Subjects answered the question How satisfied are you today with the appearance of your face? with Very/somewhat satisfied, Neither/nor, or Very/somewhat dissatisfied. Number of subjects satisfied are those that answered Very/somewhat satisfied.
Time frame: Month 7 and Month 13
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azzalure Alone as Initial Treatment | Number of Subjects Satisfied With Overall Facial Appearance (Questionnaire) | Satisfied Month 7 | 23 participants |
| Azzalure Alone as Initial Treatment | Number of Subjects Satisfied With Overall Facial Appearance (Questionnaire) | Satisfied Month 13 | 24 participants |
| Filler Alone as Initial Treatment | Number of Subjects Satisfied With Overall Facial Appearance (Questionnaire) | Satisfied Month 7 | 26 participants |
| Filler Alone as Initial Treatment | Number of Subjects Satisfied With Overall Facial Appearance (Questionnaire) | Satisfied Month 13 | 27 participants |
Secondary
Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs)
To evaluate Global facial aesthetic appearance at 1, 7 and 13 months, blinded evaluator review of photographs from the respective visits.
Time frame: 1, 7 and 13 months
Population: Incorrectly taken photographs for six participants were excluded from analysis. Additionally two participants excluded because they were assessed different by all three evaluators.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Azzalure Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | Superior Month 1 | 5 Participants |
| Azzalure Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | Superior Month 7 | 5 Participants |
| Azzalure Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | Superior Month 13 | 13 Participants |
| Filler Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | Superior Month 1 | 0 Participants |
| Filler Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | Superior Month 7 | 11 Participants |
| Filler Alone as Initial Treatment | Number of Subjects With Improvement in Global Facial Aesthetic Appearance at 1, 7 and 13 Months (Review of Photographs) | Superior Month 13 | 14 Participants |