Safety and Efficacy of the Full Face Applications of Variable Doses of a Commercial Botulinum Toxin Type a (Dysport®)
Condition: Sun-induced Wrinkles
Study type: Interventional
Phase: Phase 4

Summary: 
      This is an open-label and phase IV study of full face injections of variable doses of
      botulinum toxin type A (BT-A). As it is an open-label and not blind study, both investigator
      and subjects will know the injection local and doses of the study drug. Patients will be
      randomized into 3 different groups. Each group will receive a specific dose according with
      the indication evaluated by the investigator. Six visits will be schedule in this study.
    

Detailed description: 
      4.2 Methodology

      4.2.1 Patient evaluation After providing written informed consent, subject's eligibility will
      be assessed at a Screening Visit. The subject's general medical history will be recorded.
      This includes demographic data, history of surgical and cosmetic procedures, dermatological
      assessment, physical examination, and prior concomitant medications. A pregnancy test will
      also be performed.

      4.2.1.1 Severity of wrinkles

      One sub-investigator will rate the wrinkles with the following validated severity scales for
      the main areas of the face at Baseline, Week 4, Week 8, Week 16 and Week 24:

        -  Clinical 0-3 score for standardized assessment of facial wrinkles in the glabella area
           (from GLADYS study)

        -  Photometric Atlas for the Assessment of Crow's Feet Severity

        -  Facial Wrinkle Scale, for forehead lines (Carruthers A, et al. Dermatol Surg.
           2003;29(5):461-7)

      4.2.1.2 Standard set of photographs will be taken

      At Screening , 2, 3, 4 and 5 visits, photographs will be taken:

      All the photographs will be taken in a standardized photographic mode with fixed position of
      the camera. A guideline with examples of standardized photos with delimit standardized
      positions will be provided to the person responsible to take the photos.

      In the photographs, each research subject will be identified by a tag containing a reference
      to the study, the number of the research subject and the control date. The research subjects
      should wash their faces before the photographic procedure to remove excess oil and all make
      up will be removed. All the pictures will be taken at the same room and under same
      parameters.

      The photograph set consist of

        -  Full face frontal view relaxed;

        -  One set of photographs relaxed and contracted of each indication that patient will be or
           was treated in this study.

      At the end of the study, two independent evaluators (dermatologists) will assess before and
      after pictures in a blinded manner. This evaluation will be done to assess the efficacy of
      BT-A in the injected areas not assessed by the scales.

      4.2.3 Groups of treatment

      Subjects will be assigned to one of the three following treatment groups, according with the
      total dose received in visit 1:

        -  Group 1: 30 subjects who received 125 to 170 U of BT-A (Dysport®)

        -  Group 2: 30 subjects who received 171 to 210 U of BT-A (Dysport®)

        -  Group 3: 30 subjects who received 211 to 250 U of BT-A (Dysport®)

      4.2.4 Reconstitution of the study product and Treatment Administration An independent,
      experienced and registered pharmacist will be the assigned to carry through the
      reconstitution of the products. She will prepare the dilutions and the syringes of the
      product (DYSPORT®) immediately prior to the injections.

      The dilutions of DYSPORT® 500 units per vial will be made with 2 mL of 0.9% sterile saline,
      using 3 mL syringes and a 21 gauge needle, giving a concentration of 250 units/mL or 2.5
      units/0.01 mL of the reconstituted product.

      An experienced dermatologist in the use of botulinum toxins (principal investigator - DH)
      will perform all the injections according to the indications and total number of units that
      will be injected according to the treatment plan, which aims to obtain the best results. She
      will only perform the injections and will not participate in other phases of this study.

      The application of the BT-A will be made with Becton, Dickinson and Company (BD) Ultra-fine
      II 0.3 cc syringes, with a 29 gauge needle, 0.5 cm in length (short needle).

      Immediately after the application, the side effects will be verified and if needed, will be
      registered and managed.
    

Intervention name(s): Botulinum toxin
Intervention type(s): Drug
Intervention description(s): Drug: Botulinum toxin
Indications for eligibility and total doses that will be applied in each part of the face, at visit 1:
Upper face:
Crow's feet wrinkles - 70 units
Glabella - 50 units
Forehead - 40 units
Mid face:
Lower eyelid - 5 units
Nasal wrinkles - 20 units
Malar wrinkles - 10 units
Lower face:
Peri-oral wrinkles - 15 units
Asymmetric smile or gummy smile - 5 units
"Cellulitic chin" - 20 units
Marionette lines - 25 U According to the patients needs, the doses can vary ±10% in terms of the amount of units that will be injected.
Patients will be allocated in each group and receive the doses described above at visit 1. At visit 2, all the patients will receive a touch-up of a standard dose of 25 U, distributed on the treated areas according patient's needs.
Other intervention name(s): Dysport
Intervention MeSH terms: Botulinum Toxins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Botulinum Toxin; Rejuvenation; Facial dynamic wrinkles