Efficacy and Safety of Clostridium Botulinum Toxin Type A to Improve Appearance of Moderate to Severe Glabellar Lines
Condition: Moderate to Severe Glabellar Lines
Intervention: Botulinum toxin type A; Placebo
Intervention description: A solution containing 50 U in 0.25 mL (200 U/mL). Each vial contained 0.625 mL of deliverable volume of solution. A volume of 0.25 mL, containing 50 U of BTX-A-HAC NG (i.e. 10 U/0.05 mL) was withdrawn from the vial into a syringe for administration. The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection), each of which was to be administered into predefined sites across the glabellar region (two injections into each corrugator muscle and one injection into the procerus muscle).; A solution containing only the excipients of BTX-A-HAC NG (identical in appearance to the active product). Each vial contained 0.625 mL of deliverable volume of solution. A volume of 0.25 mL was withdrawn from the vial into a syringe for administration. The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection), each of which was to be administered into predefined sites across the glabellar region (two injections into each corrugator muscle and one injection into the procerus muscle).
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 185.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Moderate to Severe

Summary:

      The purpose of this study was to demonstrate the safety and the efficacy of a single
      treatment of an injectable liquid form of Clostridium botulinum toxin type A haemagglutinin
      complex (BTX-A-HAC; hereafter referred to as BTX-A-HAC Next Generation (BTX-A-HAC NG)), used
      for the improvement in the appearance of moderate to severe glabellar lines (the lines
      between the eyebrows).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of written informed consent prior to any study related procedures.

          2. Male or female between 18 and 65 years of age, inclusive.

          3. Had moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at
             baseline (Day 1), as assessed by the ILA using a validated 4-point photographic scale.

          4. Had moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at
             baseline (Day 1), as assessed by the SSA using a validated 4-point categorical scale.

          5. Were dissatisfied or very dissatisfied (Grade 2 or 3) with their glabellar lines at
             baseline (Day 1), as assessed by the subject's level of satisfaction.

          6. Had a negative pregnancy test (for females of childbearing potential only).
             Nonchildbearing potential was defined as post menopausal for at least 1 year, surgical
             sterilisation at least 3 months before entering the study, or hysterectomy.

          7. Had both the time and the ability to complete the study and comply with study
             instructions.

        Exclusion Criteria:

          1. Previous treatment with any serotype of botulinum toxin (BTX).

          2. Any prior treatment with permanent fillers in the upper face including the glabellar
             lines area.

          3. Any prior treatment with long lasting dermal fillers in the upper face including the
             glabellar lines area within the past 3 years and/or skin abrasions/resurfacing
             (whatever the interventional technic used) within the past 5 years, or
             photorejuvenation or skin/vascular laser intervention within the past 12 months.

          4. Any planned facial cosmetic surgery during the study.

          5. A history of eyelid blepharoplasty or brow lift within the past 5 years.

          6. An inability to substantially reduce glabellar lines by physically spreading them
             apart or lack of capacity to frown.

          7. An active infection or other skin problems in the upper face including the glabellar
             lines area (e.g. acute acne lesions or ulcers).

          8. Use of concomitant therapy which, in the Investigator's opinion, would have interfered
             with the evaluation of the safety or efficacy of the study treatment, including
             medications affecting bleeding disorders (antiplatelet agents and/or anticoagulants
             given for treatment or prevention of cardiovascular/cerebrovascular diseases).

          9. Pregnant women, nursing mothers, or women who were planning a pregnancy during the
             study, or believed they may be pregnant at the start of the study. Throughout the
             course of the study, women of childbearing potential had to use a reliable form of
             contraception (e.g. oral contraceptives for more than 12 consecutive weeks, or
             spermicide and condoms).

         10. A history of drug or alcohol abuse.

         11. Treatment with an experimental drug or use of any experimental device within 30 days
             prior to the start of the study and during the conduct of the study.

         12. Known allergy or hypersensitivity to any serotype of BTX or any component of BTX-A-HAC
             NG.

         13. Clinically diagnosed significant anxiety disorder, or any other significant
             psychiatric disorder (e.g. depression) that might interfere with the subject's
             participation in the study.

         14. Use of medications that affect neuromuscular transmission, such as curare like
             nondepolarising agents, lincosamides, polymyxins, anticholinesterases and
             aminoglycoside antibiotics, within the past 30 days.

         15. A history of facial nerve palsy.

         16. Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or
             thick sebaceous skin.

         17. The presence of any other condition (e.g. neuromuscular disorder or other disorder
             that could interfere with neuromuscular function), laboratory finding or circumstance
             that, in the judgement of the Investigator, might increase the risk to the subject or
             decrease the chance of obtaining satisfactory data to achieve the objectives of the
             study.