Dysport in the Treatment of Glabellar Lines in Chinese Subjects

Study Overview
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Brief Summary
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The objective of this study is to demonstrate the efficacy of Dysport for the improvement in appearance of moderate to severe glabellar lines and to assess the short term and long term safety of Dysport, used for the improvement in appearance of moderate to severe glabellar lines in Chinese subjects.

Detailed Description
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The first treatment cycle will be double blind and subjects will be randomised to receive Dysport, Botox or placebo. After the first treatment cycle, all subjects will receive a maximum of four treatment cycles with Dysport, occurring at intervals of no less than 84 Days (12 weeks) between each treatment cycle, depending upon individual duration of response to Dysport treatment.

Official Title
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A Phase III, Randomised, Double Blind and Open Label Phase, Multicentre, Active and Placebo Controlled Study to Investigate the Efficacy and Safety of Dysport Including a Comparison to Botox in the Treatment of Moderate to Severe Glabellar Lines, and to Assess the Long Term Efficacy and Safety of Dysport Following Repeated Treatments in This Indication

Conditions
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Glabellar Lines

Intervention / Treatment
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* Biological: Botulinum toxin type A
* Biological: Botulinum toxin type A
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent Male or female Chinese subjects who are between 18 to 65 years of age inclusive. Have moderate or severe wrinkles of vertical glabellar lines (Grade 2 or 3) at maximum frown at baseline (Day 1), as assessed by the subject using SSA. Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at baseline (Day 1), as assessed by the Investigator using ILA. Be Botulinum Toxin (BTX) naïve or have received their most recent BTX-A treatment more than 1 year prior to screening. Have a negative pregnancy test Have an understanding of the study Exclusion Criteria: Any prior surgery affecting corrugator supercilii, prior blepharoplasty or brow lift, dermal resurfacing, or any prior cosmetic procedures or scars within 36 months. Any prior treatment with permanent fillers in the upper face. Any prior treatment with nonpermanent dermal fillers in the upper face within the past 3 years and/or skin abrasions/resurfacing, photorejuvenation or skin/vascular laser intervention within the past 12 months. Any planned facial cosmetic surgery or procedures during the study period. Lack of capacity to frown. Facial conditions that could affect safety or efficacy results. History of facial nerve palsy. Marked asymmetry; ptosis; excessive dermatochalasis; deep dermal scarring; thick sebaceous skin; photodamage etc. Presence of any condition that could affect the safety, conduct or outcome of the study. Any subjects who have any psychiatric illness or are taking antidepressant, anxiolytic or antipsychotic medication. Pregnant and/or lactating female subjects. Female subjects of childbearing potential not willing to use contraceptive measures throughout the course of the study. History of drug or alcohol abuse. Treatment with an experimental drug or device within 30 days prior to screening for this study and during the conduct of this study. Requirement for BTX injection to site(s) for disorders other than glabellar lines. Known allergy or hypersensitivity to BTX. Any medical condition or laboratory finding from central laboratory results. The subject is unable and/or unwilling to comply fully with the protocol and the study. Mental incapacity, unwillingness or language barriers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AbobotulinumtoxinA<br>Dysport, 50 Units, divided into five injections into the glabellar area. Administered in double blind fashion at cycle 1 followed by up to 4 cycles Dysport, 50 Units administered with an interval period depending on response, no less than 12 weeks between each treatment cycle. | Biological: Botulinum toxin type A<br> <br> * Other names: AbobotulinumtoxinA (Dysport®);|
| Active Comparator: OnabotulinumtoxinA<br>Botox will be administered in treatment cycle 1 only. On Day 1, 20 Units, divided into five injections into the glabellar area. | Biological: Botulinum toxin type A<br> <br> * Other names: OnabotulinumtoxinA (Botox®);|
| Placebo Comparator: AbobotulinumtoxinA Placebo<br>Dysport placebo will be administered in treatment cycle 1 only. On Day 1, 50 Units, divided into five injections into the glabellar area. | Drug: Placebo<br>* 50 Units<br>|
| Placebo Comparator: OnabotulinumtoxinA Placebo<br>Botox placebo will be administered in treatment cycle 1 only. On Day 1, 20 Units, divided into five injections into the glabellar area. | Drug: Placebo<br>* 20 Units<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. | At Cycle 1, Day 29. | 
| Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period). | At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. | At Cycle 1, Day 29. | 
| Non-Inferiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Non Inferiority analysis of Dysport® versus Botox was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. | At Cycle 1, Day 29. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period). | Photographs of the glabellar region of subjects were taken at maximum frown at baseline (Cycle 1, Day 1) and at Cycle 1, Day 29. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity which rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of three readings by three independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment to placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. | At Cycle 1, Day 29. | 
| Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period). | On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score at Cycle 1, Day 29 is presented. | At Cycle 1, Day 29. | 
| The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period). | On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. | At Cycle 1, Day 29. |