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

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 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.

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

Conditions
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Facial Aesthetic Treatment

Intervention / Treatment
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* Drug: Azzalure
* Device: Restylane/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 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.

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 alone as single treatment<br>Azzalure alone as single treatment at initial treatment followed by two combined treatments with Azzalure, HA filler and Skinboosters at Month 6 and Month 12. | Drug: Azzalure<br>* Glabellar lines<br>* Other names: Botulinum toxin;Device: Restylane/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 alone as single treatment<br>HA 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. | Drug: Azzalure<br>* Glabellar lines<br>* Other names: Botulinum toxin;Device: Restylane/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 |
| --- | --- | --- |
| 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. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1, 7 and 13 months | 
| 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. | Month 1, Month 7, and Month 13 | 
| 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. | Month 7 and Month 13 | 
| 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. | Month 7 and Month 13 | 
| 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. | Month 7 and Month 13 | 
| 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. | 1 and 7 months, and 1 and 13 months | 
| Injected Filler Volume | To evaluate the filler volume injected at initial single treatment and at following repeated combined treatment | Initial single treatment (baseline), first combined treatment (Month 6), and second combined treatment (Month 12) | 
| Adverse Event Reporting | To evaluate safety throughout the study period | 0-18 months |