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

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

— ULTRA I  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04594213
• Other study ID #: M602011071
• Status: Completed
• Phase: Phase 3
• Start date: September 23, 2020
• Est. completion date: May 9, 2022

Study information

• Verified date: April 2024
• Source: Merz North America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 362
• Est. completion date: May 9, 2022
• Est. primary completion date: April 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• NT 201
Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% NaCl.
• Placebo
Solution for injection prepared by reconstitution of powder with percent (%) Sodium Chloride (NaCl).

Locations

Country	Name	City	State
United States	Merz Investigational Site	Aventura	Florida
United States	Merz Investigational Site	Boca Raton	Florida
United States	Merz Investigational Site	Encino	California
United States	Merz Investigational Site	Greenwood Village	Colorado
United States	Merz Investigational Site	Metairie	Louisiana
United States	Merz Investigational Site	Nashville	Tennessee
United States	Merz Investigational Site	New York	New York
United States	Merz Investigational Site	New York	New York
United States	Merz Investigational Site	New York	New York
United States	Merz Investigational Site	Newport Beach	California
United States	Merz Investigational Site	San Diego	California
United States	Merz Investigational Site	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Merz North America, Inc.	Merz Pharmaceuticals GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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".	Day 30
Primary	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".	Day 30
Primary	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".	Day 30
Secondary	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 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".	Day 30
Secondary	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 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".	Day 30
Secondary	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 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".	Day 30
Secondary	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 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".	Day 30
Secondary	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 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".	Day 30
Secondary	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 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".	Day 30
Secondary	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.	Day 30
Secondary	Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 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".	Day 30
Secondary	Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 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".	Day 30
Secondary	Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 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".	Day 30
Secondary	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.	Day 30
Secondary	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.	Up to 22 Weeks
Secondary	OLEX Period: Number of Subjects With Related TEAEs	TEAEs of the OLEX period are defined as 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.	Up to 39 Weeks