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

Merz North America, Inc.368 enrolled

Overview

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 (OLEX) period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

368

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 to severe 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.

Locations (12)

Merz Investigational Site

Bad Soden, Germany

Merz Investigational Site

Berlin, Germany

Merz Investigational Site

Bochum, Germany

Merz Investigational Site

Drensteinfurt, Germany

Merz Investigational Site

Düsseldorf, Germany

Merz Investigational Site

Hamburg, Germany

Merz Investigational Site

Hamburg, Germany

Merz Investigational Site

Mannheim, Germany

Merz Investigational Site

München, Germany

Merz Investigational Site

München, Germany

...and 2 more locations

Outcomes

Primary Outcomes

Main Period: Percentage of Glabellar Frown Line (GFL) Responders at Day 30

The Merz aesthetics scales (MAS) are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. GFL-response was defined as a score of 0 (no) or 1 (mild) and at least two-grade improvement from baseline to Day 30 of main period on MAS for GFL at maximum contraction as assessed by both the investigator and the subject. The MAS for GFL ranged as 0 to 4 where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".

Time frame: Day 30

Main Period: Percentage of Horizontal Forehead Lines (HFL) Responders at Day 30

The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. HFL-response was defined as a score of 0 (no) or 1 (mild) and at least two-grade improvement from baseline to Day 30 of main period on MAS for HFL at maximum contraction as assessed by both the investigator and the subject. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Percentage of Lateral Canthal Lines (LCL) Responders at Day 30

The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. LCL-response was defined as a score of 0 (no) or 1 (mild) and at least two-grade improvement from baseline to Day 30 of main period on MAS for both left and right LCL at maximum contraction as assessed by both the investigator and the subject. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Secondary Outcomes

Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for GFL at Maximum Contraction as Assessed by the Investigator at Day 30

The MAS are 5-point scales used to identify responders in clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. MAS for GFL ranged as 0 to 4, where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".

Time frame: Day 30

Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for HFL at Maximum Contraction as Assessed by the Investigator at Day 30

The MAS are 5-point scales used to identify responders in clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Percentage 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 Day 30

The MAS are 5-point scales used to identify responders in clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for GFL at Maximum Contraction as Assessed by the Subject at Day 30

The MAS are 5-point scales used to identify responders in clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for GFL ranged as 0 to 4, where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".

Time frame: Day 30

Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for HFL at Maximum Contraction as Assessed by the Subject at Day 30

The MAS are 5-point scales used to identify responders in clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Percentage 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 Subject at Day 30

The MAS are 5-point scales used to identify responders in clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Subjects

The GAIS is a 7-point Likert scale capturing the global aesthetic improvement ranging from +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the subject. GAIS as assessed by the subject at Day 30 was analyzed using an analysis of covariance (ANCOVA) model.

Time frame: Day 30

Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 of Main Period on MAS for GFL at Maximum Contraction as Assessed by the Investigator

The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph- based outcome instruments designed specifically for assessment of each upper facial area. The MAS for GFL ranged as 0 to 4 where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".

Time frame: Day 30

Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 of Main Period on MAS for HFL at Maximum Contraction as Assessed by the Investigator

The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 of Main Period on MAS for Both Left and Right LCL at Maximum Contraction as Assessed by the Investigator

The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".

Time frame: Day 30

Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator

The GAIS is a 7-point Likert scale capturing the global aesthetic improvement ranging from +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the investigator. GAIS as assessed by the investigator at Day 30 was analyzed using an ANCOVA model.

Time frame: Day 30

Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs)

TEAEs during the Main Period are defined as adverse events (AEs) with onset or worsening on or after date and time of first dose of study treatment and before date and time of first administration of study treatment in the OLEX period or the final study visit, if subject was not treated in the OLEX period. An AE is considered to be related if a causal relationship between study treatment and the AE is at least reasonably possible.

Time frame: Up to 22 weeks

OLEX: Number of Subjects With Related TEAEs

TEAEs of the OLEX period are defined as adverse events (AEs) with onset or worsening on or after date and time of first dose of study treatment in the OLEX period up to and including the final study visit. An AE is considered to be related if a causal relationship between study treatment and the AE is at least reasonably possible.

Time frame: Up to 39 weeks