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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Glabellar Frown Lines

Intervention / Treatment
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* Drug: Botulinum Toxin A
* Drug: Placebo
* Drug: Botulinum Toxin A - Open Label


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years or older at time of screening Has moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on FWS) as determined by in-clinic assessments by both the investigator and the subject(where: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe'). Exclusion Criteria: 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. 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). Active skin disease/infection or irritation at the treatment area. Pregnant, breastfeeding or planning to become pregnant during the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum toxin A<br>Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into glabellar area. | Drug: Botulinum Toxin A<br>* Injection, 20 Units divided in five 0.1mL i.m injections into the glabellar area<br>* Other names: BoNT/A-DP;|
| Placebo Comparator: Placebo<br>Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. | Drug: Placebo<br>* injection, sodium chloride 0.9% divided in five 0.1 mL i.m. injections into the glabellar area<br>* Other names: sodium chloride 0.9 %;|
| Experimental: Botulinum toxin A open label extension phase<br>Open Label Extension Phase for all Subjects of Arm 1 and 2 for up to 3 treatment cycles | Drug: Botulinum Toxin A - Open Label<br>* Open Label Extension Phase with Experimental Drug; Injection, 20 Units divided in five 0.1mL i.m injections into the glabellar area<br>* Other names: BoNT/A-DP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate at Week 4 | Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit relative to baseline, based on both the investigators'and the subjects'in-clinic assessments. | week 4 relative to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of responders at maximum frown at week 12 | Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement ≥2 points in FWS score (at maximum frown) at the week 12 visit relative to baseline, based on both the investigator's and the subject's in-clinic assessment | week 12 | 
| Percentage of responders at week 16 | Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement ≥2 points in FWS score (at maximum frown) at the week 16 visit relative to baseline, based on both the investigator's and the subject's in-clinic assessment | week 16 | 
| Subjects with a ≥ 1 point reduction in FWS score | The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 based separately on the investigators'and the subjects'in-clinic assessments | week 4 | 
| Percentage of responders at week 20 or later | Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement ≥2 points in FWS score (at maximum frown) at the week 20 visit (or later) relative to baseline, based on both the investigator's and the subject's in-clinic assessment | week 20 | 
| Safety Evaluation | Frequency, severity and causal relationship of AEs, SAes and AESIs | trough study completion (60 weeks) |