Study to Investigate the Safety and Duration of Effect of Different Botulinum Toxin A (NT 201) Dose Groups Following the Treatment of Glabellar Frown Lines

Study Overview
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Brief Summary
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The purpose of the study is to investigate the safety and duration of effect following different doses of Botulinum Toxin A (NT 201) in the treatment of glabellar frown lines (GFL).

Detailed Description
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This prospective, randomized, double-blind, multi-Center clinical study consists of a two stage experimental main period comparing different dose groups, followed by an optional open-label extension period (20 Units follow-up treatment).

Official Title
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A Prospective, Randomized, Double-blind, Multicenter Study to Investigate the Safety and Duration of Effect of Different NT 201 Dose Groups Following the Treatment of Glabellar Frown Lines

Conditions
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Moderate to Severe Glabellar Frown Lines

Intervention / Treatment
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* Drug: NT 201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participant 18 years or over. Moderate (score=2) to severe (score=3) GFL at maximum frown as assessed by investigator on the 4-point facial wrinkle scale (FWS). Moderate (score=2) to severe (score=3) GFL at maximum frown as assessed by participant on the 4-point FWS. Exclusion Criteria: Previous treatment with Botulinum neurotoxin (BoNT) of any serotype in the facial area within the last 12 months before injection. Previous treatment with any facial cosmetic procedure (example, chemical peeling, photo rejuvenation, mesotherapy, photodynamic therapy, laser treatment, tattooing of eyebrows) in the glabellar area within the last 12 months before injection. Previous treatment with any biodegradable filler in the glabellar area within the last 12 months before injection. Inability to substantially reduce GFL by physically spreading them apart as assessed by the investigator. Excessively thick sebaceous skin or hypertrophic muscles in the upper third part of the face. Any surgery or scars in the glabellar area. Marked facial asymmetry. Eyelid ptosis. Marked brow ptosis and/or dermatochalasis. Ongoing severe or unstable medical conditions, example, systemic infection, or pulmonary disease, at the discretion of the investigator.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NT 201 Dose group 1<br>Stage 1 and 2. Intramuscular injection into the glabellar area. | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% unpreserved Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Experimental: NT 201 Dose group 2<br>Stage 1. Intramuscular injection into the glabellar area. | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% unpreserved Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Experimental: NT 201 Dose group 3<br>Stage 1. Intramuscular injection into the glabellar area. | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% unpreserved Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Experimental: NT 201 Dose group 4<br>Stage 2. Intramuscular injection into the glabellar area. | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% unpreserved Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Experimental: NT 201 Dose group 5<br>Open Label Extension Period. Intramuscular injection into the glabellar area. | Drug: NT 201<br>* Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% unpreserved Sodium Chloride (NaCl).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Effect Defined as Time Between Treatment and Relapse to Baseline Status Assessed by the Investigator on the FWS | Duration of effect: time between treatment and first occurrence of relapse to baseline status. If no effect was observed, duration of effect was set to 0. Effect: any improvement (at least 1 point) at maximum frown as assessed by investigator on FWS. Investigator's FWS assessed status of GFL according to 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for investigator's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). Duration of effect was analyzed using Kaplan-meier analysis, and 95 percent (%) confidence interval (CI) were calculated using log-log transformation. | From the time of first treatment up to Day 360 | 
| Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) |  | From the time of first treatment up to Day 390 | 
| Number of Participants With at Least One Treatment-emergent Serious Adverse Event (TESAE) |  | From the time of first treatment up to Day 390 | 
| Number of Participants With at Least One Treatment-emergent Adverse Event of Special Interest (TEAESI) |  | From the time of first treatment up to Day 390 | 
| Number of Participants With at Least One Treatment Related TEAE |  | From the time of first treatment up to Day 390 | 
| Number of Participants With at Least One Treatment Related TESAE |  | From the time of first treatment up to Day 390 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Effect Whereby Effect Was Defined as Score of None (0) or Mild (1) at Maximum Frown as Assessed by the Investigator According to FWS | Duration of effect was defined as time between treatment and first point in time when score was moderate or severe again. If no effect was observed, duration of effect was set to 0. Effect was defined by a score of none (0) or mild (1) at maximum frown as assessed by investigator according to FWS. Investigator's FWS assessed status of GFL according to 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for investigator's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). Duration of effect was analyzed using Kaplan-meier analysis, and 95% CI were calculated using log-log transformation. | From the time of first treatment up to Day 360 | 
| Duration of Effect Whereby Effect Was Defined by 2-point Improvement From Baseline at Maximum Frown as Assessed by the Investigator According to FWS | Duration of effect: time between treatment and first point in time when improvement was less than 2 points again. If no effect was observed, duration of effect was set to 0. Effect: at least a 2-point improvement from baseline at maximum frown as assessed by investigator on the FWS. Investigator's FWS assessed status of GFL according to 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for investigator's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). Duration of effect was analyzed using Kaplan-meier analysis, and 95% CI were calculated using log-log transformation. | From the time of first treatment up to Day 360 | 
| Percentage of Participants Rated as None (0) or Mild (1) at Maximum Frown by Investigator's Rating on FWS | Investigator's FWS assessed status of GFL according to the 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for investigator's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). 95% CIs for percentage of participants were based on Pearson-clopper method. | At Day 180 | 
| Percentage of Participants Rated as None (0) or Mild (1) at Maximum Frown by Participant's Rating on FWS | Participant's FWS assessed status of GFL according to the 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for participant's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). 95% CI for percentage of participants were based on Pearson-clopper method. | At Day 180 | 
| Percentage of Participants Rated as at Least 1-point Improvement Compared to Baseline at Maximum Frown by Investigator's Rating on FWS | Investigator's FWS assessed status of GFL according to the 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for investigator's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). 95% CI for percentage of participants were based on Pearson-clopper method. | At Day 180 | 
| Percentage of Participants Rated as at Least 1-point Improvement Compared to Baseline at Maximum Frown by Participant's Rating on FWS | Participant's FWS assessed status of GFL according to the 4-point severity grades at maximum frown as: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Descriptors of each severity grade for participant's FWS assessment at maximum frown were as: 0 (no muscle action at all), 1 (some even slight muscle action possible [that is, visible furrows]), 2 (moderately strong muscle action possible [that is, visible muscle bulges]), 3 (strong muscle action possible which may cause local pallor). 95% CI for percentage of participants were based on Pearson-clopper method. | At Day 180 |