Aesthetics
Conditions
Brief summary
The efficacy and safety, as well as subject satisfaction will be evaluated after single treatment with Azzalure/Dysport alone or Restylane/Emervel filler alone followed by repeated combined treatment with Azzalure/Dysport, Restylane/Emervel filler and Restylane Skinbooster. Subjects will be followed for up to 18 months after initial treatment.
Interventions
DRUGAzzalure or Dysport
Glabellar lines
DEVICERestylane or 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 upper facial lines to be treated (at least two of glabellar lines, crow´s feet and/or forehead 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
* 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 |
|---|---|---|
| Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | 7 months | Percentage of subjects showing superior global facial aesthetic appearance at month 7 compared to month 1. Assessment of global facial aesthetic appearance was based on blinded evaluations of subject's youthful appearance (e.g. lack of facial volume loss, lack of static wrinkles and fine lines, good skin quality, and satisfactory result after aesthetic treatment). The blinded evaluators retrospectively reviewed photographs from visit for each subject and answered the following question: At which set of photographs does the subject show superior global facial aesthetic appearance?. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | 1, 7, and 13 months | The 5-graded GAIS was 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 following rating was used: Very much improved, Much improved, Somewhat improved, No change, or Worse. Criteria for improvement met for those subjects that were assessed as Very much improved, Much improved, or Somewhat improved. GAIS score was assessed by three blinded evaluators at Months 1, 7, and 13 (1 month after single treatment, 1 month after first combined treatment, and 1 month after second combined treatment). The blinded evaluators performed the evaluations retrospectively using 2D-photographs from each follow-up visit and from Baseline (Visit 1). |
| Number of Participants Satisfied With Facial Appearance | 7 and 13 months | The subjects were asked to answer the question How satisfied are you today with the appearance of your face? with Very/somewhat satisfied, Neither/nor, or Very/somewhat dissatisfied. Satisfied criteria is fulfilled for those subjects that answered Very/somewhat satisfied. |
| Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | 1, 7 and 13 months | Subjects showing superior Global facial aesthetic appearance at 1, 7 and 13 months. Assessment of global facial aesthetic appearance was based on blinded evaluations of subject's youthful appearance (e.g. lack of facial volume loss, lack of static wrinkles and fine lines, good skin quality, and satisfactory result after aesthetic treatment). The blinded evaluators retrospectively reviewed photographs from visit for each subject and answered the following question: At which set of photographs does the subject show superior global facial aesthetic appearance?. |
| Percentage of Subjects Improved in Wrinkle Severity Score | 7 and 13 months | The wrinkle severity of the Azzalure/Dysport treated glabellar lines at maximum frown was evaluated by the Investigator. A validated 5-graded photonumeric grading scale was used, where each severity grade was illustrated by a set of photographs. 0 = No glabella lines 1. = Mild glabella lines 2. = Moderate glabella lines 3. = Severe glabella lines 4. = Very severe glabella lines Improvement means going from higher score to lower score. |
| Injected Volume of Study Products at Initial Single Treatment | Baseline | Evaluation of Azzalure/Dysport (Group A)/Filler (Group B) volume injected at initial single treatment (baseline). |
| Number of Participants for Which the Investigator is Satisfied With the Outcome | 7 and 13 months | The Investigators 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 met for those subjects that the Investigator answered Very/somewhat satisfied. |
Countries
Brazil, France, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azzalure/Dysport as Single Treatment Azzalure/Dysport as single treatment at initial treatment
Azzalure or Dysport: Upper facial lines
Restylane or Emervel filler: Facial tissue augmentation
Restylane Skinbooster: Facial skin rejuvenation | 32 |
| Filler as Single Treatment Filler as single treatment at initial treatment
Azzalure or Dysport: Upper facial lines
Restylane or Emervel filler: Facial tissue augmentation
Restylane Skinbooster: Facial skin rejuvenation | 33 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Combination Treatment Phase (up to 18 m) | Withdrawal by Subject | 0 | 1 |
| Single Treatment Phase (6 Months) | Medical reason | 1 | 0 |
| Single Treatment Phase (6 Months) | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | Azzalure/Dysport as Single Treatment | Filler as Single Treatment | Total |
|---|---|---|---|
| Age, Continuous | 43.9 years | 44.8 years | 44.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 32 Participants | 33 Participants | 65 Participants |
| Region of Enrollment Brazil | 8 participants | 8 participants | 16 participants |
| Region of Enrollment France | 16 participants | 16 participants | 32 participants |
| Region of Enrollment Sweden | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 31 Participants | 32 Participants | 63 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
| Smoking | 13 Participants | 5 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 33 | 0 / 62 | 0 / 61 |
| other Total, other adverse events | 3 / 32 | 4 / 33 | 22 / 62 | 15 / 61 |
| serious Total, serious adverse events | 0 / 32 | 1 / 33 | 0 / 62 | 0 / 61 |
Outcome results
Primary
Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance
Percentage of subjects showing superior global facial aesthetic appearance at month 7 compared to month 1. Assessment of global facial aesthetic appearance was based on blinded evaluations of subject's youthful appearance (e.g. lack of facial volume loss, lack of static wrinkles and fine lines, good skin quality, and satisfactory result after aesthetic treatment). The blinded evaluators retrospectively reviewed photographs from visit for each subject and answered the following question: At which set of photographs does the subject show superior global facial aesthetic appearance?.
Time frame: 7 months
Population: One subject in Group A was excluded from the analysis due to the wrong photographs being used in the evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azzalure/Dysport as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | 66.7 percentage of subjects |
| Filler as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | 93.5 percentage of subjects |
Secondary
Injected Volume of Study Products at Initial Single Treatment
Evaluation of Azzalure/Dysport (Group A)/Filler (Group B) volume injected at initial single treatment (baseline).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azzalure/Dysport as Single Treatment | Injected Volume of Study Products at Initial Single Treatment | 118.8 Speywood Units/mL | Standard Deviation 13 |
| Filler as Single Treatment | Injected Volume of Study Products at Initial Single Treatment | 0.99 Speywood Units/mL | Standard Deviation 0.03 |
Secondary
Number of Participants for Which the Investigator is Satisfied With the Outcome
The Investigators 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 met for those subjects that the Investigator answered Very/somewhat satisfied.
Time frame: 7 and 13 months
Population: Number of analyzed subjects varied over time due to drop-out of study subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Azzalure/Dysport as Single Treatment | Number of Participants for Which the Investigator is Satisfied With the Outcome | Month 7 | 31 Participants |
| Azzalure/Dysport as Single Treatment | Number of Participants for Which the Investigator is Satisfied With the Outcome | Month 13 | 30 Participants |
| Filler as Single Treatment | Number of Participants for Which the Investigator is Satisfied With the Outcome | Month 7 | 31 Participants |
| Filler as Single Treatment | Number of Participants for Which the Investigator is Satisfied With the Outcome | Month 13 | 29 Participants |
Secondary
Number of Participants Satisfied With Facial Appearance
The subjects were asked to answer the question How satisfied are you today with the appearance of your face? with Very/somewhat satisfied, Neither/nor, or Very/somewhat dissatisfied. Satisfied criteria is fulfilled for those subjects that answered Very/somewhat satisfied.
Time frame: 7 and 13 months
Population: Number of analyzed subjects varied over time due to drop-outs from study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Azzalure/Dysport as Single Treatment | Number of Participants Satisfied With Facial Appearance | Month 7 | 31 Participants |
| Azzalure/Dysport as Single Treatment | Number of Participants Satisfied With Facial Appearance | Month 13 | 30 Participants |
| Filler as Single Treatment | Number of Participants Satisfied With Facial Appearance | Month 7 | 29 Participants |
| Filler as Single Treatment | Number of Participants Satisfied With Facial Appearance | Month 13 | 29 Participants |
Secondary
Number of Subjects Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator
The 5-graded GAIS was 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 following rating was used: Very much improved, Much improved, Somewhat improved, No change, or Worse. Criteria for improvement met for those subjects that were assessed as Very much improved, Much improved, or Somewhat improved. GAIS score was assessed by three blinded evaluators at Months 1, 7, and 13 (1 month after single treatment, 1 month after first combined treatment, and 1 month after second combined treatment). The blinded evaluators performed the evaluations retrospectively using 2D-photographs from each follow-up visit and from Baseline (Visit 1).
Time frame: 1, 7, and 13 months
Population: Number of analyzed subjects varied over time due to drop-outs from study. 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/Dysport as Single Treatment | Number of Subjects Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Month 1 | 65.1 % participants |
| Azzalure/Dysport as Single Treatment | Number of Subjects Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Month 7 | 90.3 % participants |
| Azzalure/Dysport as Single Treatment | Number of Subjects Improved on the Global Aesthetic Improvement Scale (GAIS) as Assessed by Blinded Evaluator | Month 13 | 88.3 % participants |
Secondary
Percentage of Subjects Improved in Wrinkle Severity Score
The wrinkle severity of the Azzalure/Dysport treated glabellar lines at maximum frown was evaluated by the Investigator. A validated 5-graded photonumeric grading scale was used, where each severity grade was illustrated by a set of photographs. 0 = No glabella lines 1. = Mild glabella lines 2. = Moderate glabella lines 3. = Severe glabella lines 4. = Very severe glabella lines Improvement means going from higher score to lower score.
Time frame: 7 and 13 months
Population: Number of analyzed subjects was reduced over time due to drop-out of study subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azzalure/Dysport as Single Treatment | Percentage of Subjects Improved in Wrinkle Severity Score | Month 7 | 100 percentage of participants |
| Azzalure/Dysport as Single Treatment | Percentage of Subjects Improved in Wrinkle Severity Score | Month 13 | 100 percentage of participants |
| Filler as Single Treatment | Percentage of Subjects Improved in Wrinkle Severity Score | Month 7 | 100 percentage of participants |
| Filler as Single Treatment | Percentage of Subjects Improved in Wrinkle Severity Score | Month 13 | 100 percentage of participants |
Secondary
Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance
Subjects showing superior Global facial aesthetic appearance at 1, 7 and 13 months. Assessment of global facial aesthetic appearance was based on blinded evaluations of subject's youthful appearance (e.g. lack of facial volume loss, lack of static wrinkles and fine lines, good skin quality, and satisfactory result after aesthetic treatment). The blinded evaluators retrospectively reviewed photographs from visit for each subject and answered the following question: At which set of photographs does the subject show superior global facial aesthetic appearance?.
Time frame: 1, 7 and 13 months
Population: Six subjects that were assessed differently by all three evaluators were excluded from the analysis. In addition, one subject was excluded from the analysis due to wrong photographs at Month 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azzalure/Dysport as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | Month 1 | 4.0 percentage of subjects |
| Azzalure/Dysport as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | Month 7 | 36.0 percentage of subjects |
| Azzalure/Dysport as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | Month 13 | 60.0 percentage of subjects |
| Filler as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | Month 1 | 3.6 percentage of subjects |
| Filler as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | Month 7 | 35.7 percentage of subjects |
| Filler as Single Treatment | Percentage of Subjects With Improvement in Global Facial Aesthetic Appearance | Month 13 | 60.7 percentage of subjects |