Safety and Efficacy of Azzalure/Dysport, Restylane/Emervel Filler and Restylane Skinbooster Treatment

Study Overview
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Brief Summary
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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.

Official Title
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An Evaluator-blinded Multi-center Study of Combined Treatment With Azzalure/Dysport, Restylane/Emervel Filler and Restylane Skinbooster as Compared to Single Treatment With Either Azzalure/Dysport Alone or Restylane/Emervel Filler Alone

Conditions
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Aesthetics

Intervention / Treatment
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* Drug: Azzalure or Dysport
* Device: Restylane or Emervel filler
* Device: Restylane Skinbooster


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azzalure/Dysport as single treatment<br>Azzalure/Dysport as single treatment at initial treatment | Drug: Azzalure or Dysport<br>* Glabellar lines<br>* Other names: Botulinum toxin;Device: Restylane or Emervel filler<br>* Facial tissue augmentation<br>* Other names: Hyaluronic acid;Device: Restylane Skinbooster<br>* Facial skin rejuvenation<br>* Other names: Hyaluronic acid;|
| Experimental: Filler as single treatment<br>Filler as single treatment at initial treatment | Drug: Azzalure or Dysport<br>* Glabellar lines<br>* Other names: Botulinum toxin;Device: Restylane or Emervel filler<br>* Facial tissue augmentation<br>* Other names: Hyaluronic acid;Device: Restylane Skinbooster<br>* Facial skin rejuvenation<br>* Other names: Hyaluronic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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?. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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?. | 1, 7 and 13 months | 
| 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). | 1, 7, and 13 months | 
| 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. | 7 and 13 months | 
| 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. | 7 and 13 months | 
| 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 = Mild glabella lines = Moderate glabella lines = Severe glabella lines = Very severe glabella lines Improvement means going from higher score to lower score. | 7 and 13 months | 
| 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). | Baseline |