Efficacy and Safety of Clostridium Botulinum Toxin Type A to Improve Appearance of Moderate to Severe Glabellar Lines

A Phase III, Double Blind, Randomised, Placebo Controlled Study To Assess The Efficacy And Safety Of A Single Treatment Of Clostridium Botulinum Toxin Type A To Improve The Appearance Of Moderate To Severe Glabellar Lines

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).

At the Baseline Visit (Day 1), subjects were randomised in a ratio of 2:1 to receive either BTX-A-HAC NG solution (50 U) or placebo. Randomisation was stratified according to gender and severity of glabellar lines at maximum frown (moderate to severe) at Baseline. A single dose of BTX-A-HAC NG solution 50 U or placebo was injected on Day 1. Subjects were then monitored at the study centre for 30 minutes. On Day 4, subjects were contacted by telephone for adverse event monitoring and to record concomitant medications and treatments.

Subjects attended follow-up visits at the study centre on Days 8, 15, 29, 57, 85, 113, 148 and 183. The Day 183 follow-up visit was the end of study visit; all subjects who had completed the Day 183 Visit were considered to have completed the study.

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.