Moderate to Severe Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)
Conditions
Brief 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.
Interventions
DRUGNT 201
Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% NaCl.
DRUGPlacebo
Solution for injection prepared by reconstitution of powder with percent (%) Sodium Chloride (NaCl).
Sponsors
Merz Pharmaceuticals GmbH
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main Period: Percentage of Glabellar Frown Line (GFL) Responders at Day 30 | 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. |
| Main Period: Percentage of Horizontal Forehead Lines (HFL) Responders at Day 30 | 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. |
| Main Period: Percentage of Lateral Canthal Lines (LCL) Responders at Day 30 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Subjects | Day 30 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator | Day 30 | 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. |
| Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs) | Up to 22 Weeks | 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. |
| OLEX Period: Number of Subjects With Related TEAEs | Up to 39 Weeks | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at 12 investigational sites in the United States.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Main Period: Placebo (Group P) Subjects received placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period. | 91 |
| Main Period: NT 201 (Group U) 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. | 179 |
| 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. | 92 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Main Period (Up to 22 Weeks) | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 |
| Main Period (Up to 22 Weeks) | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Main Period (Up to 22 Weeks) | Withdrawal by Subject | 2 | 6 | 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) | No need for re-injection | 0 | 0 | 0 | 7 | 22 | 5 |
| OLEX Period (Up to 39 Weeks) | Other | 0 | 0 | 0 | 1 | 3 | 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) | Pregnancy | 0 | 0 | 0 | 0 | 0 | 1 |
| 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 |
Baseline characteristics
| Characteristic | Main Period: Placebo (Group P) | Main Period: NT 201 (Group U) | Main Period: NT 201 and Placebo (Group G and H) | Total |
|---|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 12.99 | 47.2 years STANDARD_DEVIATION 13.21 | 47.8 years STANDARD_DEVIATION 13.47 | 47.4 years STANDARD_DEVIATION 13.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 49 Participants | 29 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 130 Participants | 63 Participants | 256 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 3 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 20 Participants | 7 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 79 Participants | 150 Participants | 80 Participants | 309 Participants |
| Sex: Female, Male Female | 79 Participants | 154 Participants | 75 Participants | 308 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 17 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 91 | 0 / 179 | 0 / 92 | 0 / 86 | 0 / 144 | 0 / 73 |
| other Total, other adverse events | 10 / 91 | 18 / 179 | 7 / 92 | 16 / 86 | 15 / 144 | 5 / 73 |
| serious Total, serious adverse events | 1 / 91 | 0 / 179 | 1 / 92 | 1 / 86 | 2 / 144 | 0 / 73 |
Outcome results
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | Main Period: Percentage of Glabellar Frown Line (GFL) Responders at Day 30 | 0 percentage of subjects |
| Main Period: NT 201 (Group U) | Main Period: Percentage of Glabellar Frown Line (GFL) Responders at Day 30 | 52.3 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | Main Period: Percentage of Horizontal Forehead Lines (HFL) Responders at Day 30 | 0 percentage of subjects |
| Main Period: NT 201 (Group U) | Main Period: Percentage of Horizontal Forehead Lines (HFL) Responders at Day 30 | 66.5 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | Main Period: Percentage of Lateral Canthal Lines (LCL) Responders at Day 30 | 0 percentage of subjects |
| Main Period: NT 201 (Group U) | Main Period: Percentage of Lateral Canthal Lines (LCL) Responders at Day 30 | 51.7 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: FAS. Here overall number of subjects analyzed were subjects who had non-missing data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Main Period: Placebo (Group P) | Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator | 0.05 score on a scale |
| Main Period: NT 201 (Group U) | Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator | 2.43 score on a scale |
| Main Period: NT 201 and Placebo (Group G and H) | Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator | 1.99 score on a scale |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Main Period: Placebo (Group P) | Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Subjects | 0.08 score on a scale |
| Main Period: NT 201 (Group U) | Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Subjects | 2.24 score on a scale |
p-value: <0.0001ANCOVA
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.
Time frame: Up to 22 Weeks
Population: The Safety Evaluation Set (SES) included all subjects treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Period: Placebo (Group P) | Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| Main Period: NT 201 (Group U) | Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs) | 11 Participants |
| Main Period: NT 201 and Placebo (Group G and H) | Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 81.3 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 65.9 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 88.6 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 75.6 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 92.0 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 77.3 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: FAS. Here overall number of subjects analyzed were subjects who had non-missing data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 89.0 percentage of subjects |
| Main Period: NT 201 and Placebo (Group G and H) | 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 | 29.3 percentage of subjects |
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: FAS. Here overall number of subjects analyzed were subjects who had non-missing data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 96.5 percentage of subjects |
| Main Period: NT 201 and Placebo (Group G and H) | 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 | 96.7 percentage of subjects |
p-value: <0.0001Mantel Haenszel
p-value: <0.0001Mantel Haenszel
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.
Time frame: Day 30
Population: FAS. Here overall number of subjects analyzed were subjects who had non-missing data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Period: Placebo (Group P) | 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 |
| Main Period: NT 201 (Group U) | 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 | 96.0 percentage of subjects |
| Main Period: NT 201 and Placebo (Group G and H) | 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 | 96.7 percentage of subjects |
p-value: <0.0001Mantel Haenszel
p-value: <0.0001Mantel Haenszel
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.
Time frame: Up to 39 Weeks
Population: SES.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Period: Placebo (Group P) | OLEX Period: Number of Subjects With Related TEAEs | 10 Participants |
| Main Period: NT 201 (Group U) | OLEX Period: Number of Subjects With Related TEAEs | 6 Participants |
| Main Period: NT 201 and Placebo (Group G and H) | OLEX Period: Number of Subjects With Related TEAEs | 3 Participants |