Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study II

Randomized Double Blind Phase 3 Study to Assess the Efficacy and Safety of BoNT/A-DP in the Treatment of Glabellar Lines in Comparison With Placebo Followed by an Open Label Extension Study

The aim of this study is to assess the efficacy and safety of BoNT/a-DP in the treatment of glabellar lines in comparison with placebo, including efficacy after repeat treatments and long term safety.

This multicenter Phase 3 study is comprised of two parts. The first part of the study is a randomized, double blind, placebo-controlled, phase which aims to demonstrate efficacy and safety of BoNT/A-DP compared with placebo. The second part is an open label extension phase to evaluate efficacy after repeat treatments and long term safety. Subjects can receive a maximum of four treatment cycles over the duration of the study, a single treatment in the first cycle compared with placebo, and up to three subsequent treatments in the open label extension study.

Inclusion Criteria:

• Aged ≥ 18 years or older at time of screening on FWS) as determined by in-clinic assessments by both the investigator and the subject(where: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe').
• Subject has a stable medical condition with no uncontrolled systemic disease.
• Female subjects of childbearing potential must test negative for pregnancy and agree to use effective birth control during the course of the study.
• Subjects who wear glasses must be able to adequately self-assess the severity of their glabellar lines (according to the FWS), without glasses obstructing the forehead area.
• The moderate to severe glabellar lines have an important psychological impact on the subject, as indicated by scores >0 on either the Emotional or the Social Functioning subscale of the modified Skindex-16 (GL-QoL).

Exclusion Criteria:

• Previous treatment with any serotype of botulinum toxin for any indication within the 12 months prior to screening, or any planned treatment with botulinum toxin of any serotype for any reason during the trial (other than the investigational treatment).
• Known hypersensitivity to the study medication or its excipients.
• Any medical condition that may place the subject at increased risk due to exposure to botulinum toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, profound atrophy or weakness in the target muscles, or any other condition (at the investigator's discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy.
• Facial laser or light treatment, microdermabrasion, superficial peels or retinoid therapy within the 3 months prior to screening or planned during the study.
• Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers,) within 12 months prior to screening or planned during the study.
• Previous insertion of permanent material in the glabellar area or planned during the study.
• Any surgery, or history of surgery, in the glabellar area including surgical removal of the corrugator, procerus or depressor supercili muscles or a combination of these, or scars in the glabellar area, or such surgery planned during the study.
• Active skin disease/infection or irritation at the treatment area.
• Inability to substantially lessen glabellar frown lines even by physically spreading them apart.
• Use of a muscle relaxant, , within 2 weeks prior to screening or planned during the study.
• Marked facial asymmetry or ptosis of eyelid and/or eyebrow, or current facial palsy or neuromuscular junction disorders as judged by the investigator.
• Pregnant, breastfeeding or planning to become pregnant during the trial.
• Use of prohibited medication including anticholinergic drugs, or drugs which could interfere with neuromuscular function, including aminoglycoside antibiotics and curare-like compounds within 2 weeks prior to screening or planned during the study.
• Planned surgery with general anaesthetic (use of local anaesthetic outside the glabellar area is permitted).
• Participation in another clinical study within one month of screening and throughout the trial.
• Previous participation in another botulinum toxin aesthetic study which involved the treatment of glabellar lines in combination with canthal lines and/or forehead lines in the previous 18 months.
• Chronic drug or alcohol abuse (as per investigator discretion).

Eligibility Criteria for re-treatment: The following criteria MUST be met for re-treatment:

• At time of re-treatment subject does not have relevant changes to their health status from enrollment, which would have prevented subject's entry into the study according to the inclusion and exclusion criteria
• The subject must have been randomized to receive treatment and must have received at least one treatment (BoNT/A-DP or placebo).
• A minimum of 12 weeks must have elapsed since the previous study treatment.
• The subject's glabellar lines at maximum frown must have relapsed to a FWS score of 2 or 3 as determined by the investigator and the subject.
• No relevant infection or inflammation in the planned injection area.
• Negative urine pregnancy test, in women of child-bearing potential.
• The subject must have received fewer than four study treatments.
• The subject must agree and consent to re-treatment.
• Re-treatment will be performed at the latest by week 48.