Safety and Efficacy Study of the Simultaneous Treatment of Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines and Lateral Canthal Lines) in Subjects With Moderate to Severe Upper Facial Lines

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and efficacy of NT 201 (active ingredient: Botulinum (neuro)toxin type A, free from complexing proteins) in the combined treatment of wrinkles in the upper face (Upper Facial Lines [UFL]): Horizontal Forehead Lines [HFL], Glabellar Frown Lines [GFL], and Lateral Canthal Lines [LCL]). It is a prospective, randomized, double-blind, placebo-controlled, multicenter study with a placebo-control main period (MP) followed by an open-label extension period (OLEX).

Official Title
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A Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Simultaneous Treatment of Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)

Conditions
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Moderate to Severe Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)

Intervention / Treatment
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* Drug: NT 201
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients (male or female) 18 years of age or older. Horizontal forehead lines [HFL], glabellar frown lines [GFL], and symmetrical lateral canthal lines [LCL] of moderate (score 2) to severe (score 3) intensity at maximum contraction as assessed by the investigator and subject according to Merz Aesthetics Scales [MAS]. Exclusion Criteria: Previous treatment with botulinum neurotoxin [BoNT] of any serotype in the face within the last 12 months before injection. Any facial cosmetic procedure within the last 12 months before baseline injection. Previous treatment with any biodegradable filler in the face within the last 12 months before injection. Any previous insertion of permanent material in the face (regardless of the time between previous treatment and this study). Any medical condition that may put the subject at increased risk with exposure to NT201.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP: NT 201 (incobotulinumtoxinA): UFL<br>Intramuscular injection | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing protein;|
| Experimental: MP: NT201 (incobotulinumtoxinA): GFL/HFL; Placebo: LCL<br>Intramuscular injection | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing protein;Drug: Placebo<br>* Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).<br>|
| Placebo Comparator: MP: Placebo: UFL<br>Intramuscular injection | Drug: Placebo<br>* Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).<br>|
| Experimental: OLEX: NT201 (incobotulinumtoxinA): UFL<br>Intramuscular injection | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing protein;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Glabella Frown Line (GFL) responders at Day 30 | Merz Aesthetics Scale (MAS - 5-point scale) will be used to identify responders | Day 30 | 
| Proportion of Horizontal Forehead Lines (HFL) responders at Day 30 | Merz Aesthetics Scale (MAS - 5-point scale) will be used to identify responders | Day 30 | 
| Proportion of Lateral Canthal Lines (LCL) responders at Day 30 | Merz Aesthetics Scale (MAS - 5-point scale) will be used to identify responders | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for GFL at maximum contraction as assessed by the investigator at post-baseline visits of MP | Merz Aesthetics Scale (MAS) is a 5-point scale. | Week 1, 4, 8, 12, and 16 | 
| Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for HFL at maximum contraction as assessed by the investigator at post-baseline visits of MP | Merz Aesthetics Scale (MAS) is a 5-point scale. | Week 1, 4, 8, 12, and 16 | 
| Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for both left and right LCL at maximum contraction as assessed by the investigator at post-baseline visits of MP | Merz Aesthetics Scale (MAS) is a 5-point scale. | Week 1, 4, 8, 12, and 16 | 
| Global Aesthetic Improvement Scale (GAIS) as assessed by the subject at Day 30 of MP |  | Day 30 | 
| Proportion of subjects with at least one-grade improvement from baseline to Day 30 of MP on MAS for GFL at maximum contraction as assessed by the investigator | Merz Aesthetics Scale (MAS) is a 5-point scale. | Day 30 | 
| Proportion of subjects with at least one-grade improvement from baseline to Day 30 of MP on MAS for HFL at maximum contraction as assessed by the investigator | Merz Aesthetics Scale (MAS) is a 5-point scale. | Day 30 | 
| Proportion of subjects with at least one-grade improvement from baseline to Day 30 of MP on MAS for both left and right LCL at maximum contraction as assessed by the investigator | Merz Aesthetics Scale (MAS) is a 5-point scale. | Day 30 | 
| Global Aesthetic Improvement Scale (GAIS) as assessed by the investigator at Day 30 of MP |  | Day 30 | 
| Incidence of related treatment-emergent adverse events (TEAEs) in the MP |  | Baseline to week 16 | 
| Incidence of related treatment-emergent adverse events (TEAEs) in the OLEX period |  | Week 16 to 48 |