Trial Outcomes & Findings for 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 (NCT NCT04594213)
NCT ID: NCT04594213
Last Updated: 2024-05-08
Results Overview
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".
COMPLETED
PHASE3
362 participants
Day 30
2024-05-08
Participant Flow
Subjects were recruited at 12 investigational sites in the United States.
Of the 420 screened subjects, 58 subjects exited as screen failures and 362 subjects were randomized and enrolled to receive a treatment with NT 201 or placebo in the main period of the study. Out of 350 subjects who completed the main period, only 303 subjects received treatment in the open-label extension (OLEX) period of the study.
Participant milestones
| Measure |
Main Period: Placebo (Group P)
Subjects received placebo injection in all three upper facial lines (UFL) (glabellar frown lines \[GFL\], horizontal forehead lines \[HFL\] and lateral canthal lines \[LCL\]) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
Subjects received a total of 64 Units (U) of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
OLEX: NT 201 (Main Period: Group P)
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group U)
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group G and H)
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
|---|---|---|---|---|---|---|
|
Main Period (Up to 22 Weeks)
STARTED
|
91
|
179
|
92
|
0
|
0
|
0
|
|
Main Period (Up to 22 Weeks)
COMPLETED
|
88
|
172
|
90
|
0
|
0
|
0
|
|
Main Period (Up to 22 Weeks)
NOT COMPLETED
|
3
|
7
|
2
|
0
|
0
|
0
|
|
OLEX Period (Up to 39 Weeks)
STARTED
|
0
|
0
|
0
|
86
|
144
|
73
|
|
OLEX Period (Up to 39 Weeks)
COMPLETED
|
0
|
0
|
0
|
66
|
100
|
60
|
|
OLEX Period (Up to 39 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
20
|
44
|
13
|
Reasons for withdrawal
| Measure |
Main Period: Placebo (Group P)
Subjects received placebo injection in all three upper facial lines (UFL) (glabellar frown lines \[GFL\], horizontal forehead lines \[HFL\] and lateral canthal lines \[LCL\]) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
Subjects received a total of 64 Units (U) of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
OLEX: NT 201 (Main Period: Group P)
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group U)
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group G and H)
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
|---|---|---|---|---|---|---|
|
Main Period (Up to 22 Weeks)
Withdrawal by Subject
|
2
|
6
|
1
|
0
|
0
|
0
|
|
Main Period (Up to 22 Weeks)
Physician Decision
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Main Period (Up to 22 Weeks)
Lost to Follow-up
|
1
|
0
|
1
|
0
|
0
|
0
|
|
OLEX Period (Up to 39 Weeks)
Adverse Event
|
0
|
0
|
0
|
0
|
2
|
0
|
|
OLEX Period (Up to 39 Weeks)
Lost to Follow-up
|
0
|
0
|
0
|
4
|
6
|
2
|
|
OLEX Period (Up to 39 Weeks)
Pregnancy
|
0
|
0
|
0
|
0
|
0
|
1
|
|
OLEX Period (Up to 39 Weeks)
Other eligibility criteria for re-injection not met
|
0
|
0
|
0
|
1
|
0
|
0
|
|
OLEX Period (Up to 39 Weeks)
Protocol Violation
|
0
|
0
|
0
|
1
|
0
|
0
|
|
OLEX Period (Up to 39 Weeks)
Withdrawal by Subject
|
0
|
0
|
0
|
6
|
11
|
4
|
|
OLEX Period (Up to 39 Weeks)
No need for re-injection
|
0
|
0
|
0
|
7
|
22
|
5
|
|
OLEX Period (Up to 39 Weeks)
Other
|
0
|
0
|
0
|
1
|
3
|
1
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Main Period: Placebo (Group P)
n=91 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=179 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
Total
n=362 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.5 years
STANDARD_DEVIATION 12.99 • n=5 Participants
|
47.2 years
STANDARD_DEVIATION 13.21 • n=7 Participants
|
47.8 years
STANDARD_DEVIATION 13.47 • n=5 Participants
|
47.4 years
STANDARD_DEVIATION 13.19 • n=4 Participants
|
|
Sex: Female, Male
Female
|
79 Participants
n=5 Participants
|
154 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
308 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
28 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
106 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
63 Participants
n=5 Participants
|
130 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
256 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
79 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
309 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 30Population: Target population of main primary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
Main Period: Percentage of Glabellar Frown Line (GFL) Responders at Day 30
|
0 percentage of subjects
|
52.3 percentage of subjects
|
—
|
PRIMARY outcome
Timeframe: Day 30Population: Target population of main primary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
Main Period: Percentage of Horizontal Forehead Lines (HFL) Responders at Day 30
|
0 percentage of subjects
|
66.5 percentage of subjects
|
—
|
PRIMARY outcome
Timeframe: Day 30Population: Target population of main primary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
Main Period: Percentage of Lateral Canthal Lines (LCL) Responders at Day 30
|
0 percentage of subjects
|
51.7 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
0 percentage of subjects
|
88.6 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
0 percentage of subjects
|
92.0 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
3.3 percentage of subjects
|
81.3 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
2.2 percentage of subjects
|
75.6 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
1.1 percentage of subjects
|
77.3 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
3.3 percentage of subjects
|
65.9 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: Target population of main key secondary estimand included subjects with HFL, GFL and LCL of moderate to severe intensity at maximum contraction as assessed by investigator and subject according to MAS, as randomized in this study: Subset of subjects randomized to UFL (Group U) or to placebo (Group P) groups, grouped by randomized treatment assignment.
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.
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=90 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=176 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Subjects
|
0.08 score on a scale
Interval -0.06 to 0.23
|
2.24 score on a scale
Interval 2.14 to 2.35
|
—
|
SECONDARY outcome
Timeframe: Day 30Population: FAS. Here "overall number of subjects analyzed" were subjects who had non-missing data for this outcome measure.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=89 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=173 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
1.1 percentage of subjects
|
96.5 percentage of subjects
|
96.7 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 30Population: FAS. Here "overall number of subjects analyzed" were subjects who had non-missing data for this outcome measure.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=89 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=173 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
2.2 percentage of subjects
|
96.0 percentage of subjects
|
96.7 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 30Population: FAS. Here "overall number of subjects analyzed" were subjects who had non-missing data for this outcome measure.
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".
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=89 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=173 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
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
|
7.9 percentage of subjects
|
89.0 percentage of subjects
|
29.3 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 30Population: FAS. Here "overall number of subjects analyzed" were subjects who had non-missing data for this outcome measure.
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.
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=89 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=172 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator
|
0.05 score on a scale
Interval -0.08 to 0.18
|
2.43 score on a scale
Interval 2.34 to 2.53
|
1.99 score on a scale
Interval 1.86 to 2.12
|
SECONDARY outcome
Timeframe: Up to 22 WeeksPopulation: The Safety Evaluation Set (SES) included all subjects treated.
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.
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=91 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=179 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs)
|
2 Participants
|
11 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to 39 WeeksPopulation: SES.
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.
Outcome measures
| Measure |
Main Period: Placebo (Group P)
n=86 Participants
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=144 Participants
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=73 Participants
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
|---|---|---|---|
|
OLEX Period: Number of Subjects With Related TEAEs
|
10 Participants
|
6 Participants
|
3 Participants
|
Adverse Events
Main Period: Placebo (Group P)
Main Period: NT 201 (Group U)
Main Period: NT 201 and Placebo (Group G and H)
OLEX: NT 201 (Main Period: Group P)
OLEX: NT 201 (Main Period: Group U)
OLEX: NT 201 (Main Period: Group G and H)
Serious adverse events
| Measure |
Main Period: Placebo (Group P)
n=91 participants at risk
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=179 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 participants at risk
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
OLEX: NT 201 (Main Period: Group P)
n=86 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group U)
n=144 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group G and H)
n=73 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
|---|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
1.1%
1/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.69%
1/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion
|
1.1%
1/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
1.2%
1/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.69%
1/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
Other adverse events
| Measure |
Main Period: Placebo (Group P)
n=91 participants at risk
Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period.
|
Main Period: NT 201 (Group U)
n=179 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period.
|
Main Period: NT 201 and Placebo (Group G and H)
n=92 participants at risk
Subjects received a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period.
|
OLEX: NT 201 (Main Period: Group P)
n=86 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group U)
n=144 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
OLEX: NT 201 (Main Period: Group G and H)
n=73 participants at risk
Subjects received a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period.
|
|---|---|---|---|---|---|---|
|
Infections and infestations
COVID-19
|
3.3%
3/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
4.5%
8/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
2.2%
2/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
7.0%
6/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
3.5%
5/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
2.7%
2/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
|
Investigations
Blood pressure increased
|
5.5%
5/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
3.4%
6/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
2.2%
2/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
5.8%
5/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
5.6%
8/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
0.00%
0/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
|
General disorders
Injection site bruising
|
2.2%
2/91 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
2.2%
4/179 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
4.3%
4/92 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
8.1%
7/86 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
2.8%
4/144 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
4.1%
3/73 • Main Period: Up to 22 weeks; OLEX Period: Up to 39 weeks
SES. The investigator reported AEs systematically at each visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
- Publication restrictions are in place
Restriction type: OTHER