Glabellar Lines
Conditions
Brief summary
The objective of this study is to demonstrate the efficacy of Dysport for the improvement in appearance of moderate to severe glabellar lines and to assess the short term and long term safety of Dysport, used for the improvement in appearance of moderate to severe glabellar lines in Chinese subjects.
Detailed description
The first treatment cycle will be double blind and subjects will be randomised to receive Dysport, Botox or placebo. After the first treatment cycle, all subjects will receive a maximum of four treatment cycles with Dysport, occurring at intervals of no less than 84 Days (12 weeks) between each treatment cycle, depending upon individual duration of response to Dysport treatment.
Interventions
BIOLOGICALBotulinum toxin type A
DRUGPlacebo
50 Units
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent * Male or female Chinese subjects who are between 18 to 65 years of age inclusive. * Have moderate or severe wrinkles of vertical glabellar lines (Grade 2 or 3) at maximum frown at baseline (Day 1), as assessed by the subject using SSA. * Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at baseline (Day 1), as assessed by the Investigator using ILA. * Be Botulinum Toxin (BTX) naïve or have received their most recent BTX-A treatment more than 1 year prior to screening. * Have a negative pregnancy test * Have an understanding of the study
Exclusion criteria
* Any prior surgery affecting corrugator supercilii, prior blepharoplasty or brow lift, dermal resurfacing, or any prior cosmetic procedures or scars within 36 months. * Any prior treatment with permanent fillers in the upper face. * Any prior treatment with nonpermanent dermal fillers in the upper face within the past 3 years and/or skin abrasions/resurfacing, photorejuvenation or skin/vascular laser intervention within the past 12 months. * Any planned facial cosmetic surgery or procedures during the study period. * Lack of capacity to frown. * Facial conditions that could affect safety or efficacy results. * History of facial nerve palsy. * Marked asymmetry; ptosis; excessive dermatochalasis; deep dermal scarring; thick sebaceous skin; photodamage etc. * Presence of any condition that could affect the safety, conduct or outcome of the study. * Any subjects who have any psychiatric illness or are taking antidepressant, anxiolytic or antipsychotic medication. * Pregnant and/or lactating female subjects. * Female subjects of childbearing potential not willing to use contraceptive measures throughout the course of the study. * History of drug or alcohol abuse. * Treatment with an experimental drug or device within 30 days prior to screening for this study and during the conduct of this study. * Requirement for BTX injection to site(s) for disorders other than glabellar lines. * Known allergy or hypersensitivity to BTX. * Any medical condition or laboratory finding from central laboratory results. * The subject is unable and/or unwilling to comply fully with the protocol and the study. * Mental incapacity, unwillingness or language barriers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | At Cycle 1, Day 29. | At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. |
| Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period). | At Cycle 1, Day 29. | At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. |
| Non-Inferiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | At Cycle 1, Day 29. | At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Non Inferiority analysis of Dysport® versus Botox was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period). | At Cycle 1, Day 29. | Photographs of the glabellar region of subjects were taken at maximum frown at baseline (Cycle 1, Day 1) and at Cycle 1, Day 29. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity which rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of three readings by three independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment to placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. |
| Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period). | At Cycle 1, Day 29. | On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score at Cycle 1, Day 29 is presented. |
| The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period). | At Cycle 1, Day 29. | On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Up to Cycle 1, Day 85. | At baseline (Cycle 1, Day 1) and all subsequent study visits in Cycle 1, subjects were asked to evaluate their age over the past 7 days at the time of assessment, using the following categories: * I look like my current age; * I look \_ years younger; * I look \_ years older. The LS mean change from baseline in subject's self-perception of age at all study visits in the DB Period was calculated. A negative LS mean change from baseline in the subject's self-perception of age indicates that the subject's self-perception was to look younger compared with baseline. |
| The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period). | At Cycle 1, Day 8. | Subjects were given the diary card at baseline (Cycle 1, Day 1 ) and asked to record their assessment of study treatment response for the first 7 days post-treatment (Days 2 to 8). They were asked to respond 'yes' or 'no' to the following question: 'Since being injected have you noticed an improvement in the appearance of your glabellar lines (lines between your eyebrows)?' Subjects with no treatment response were censored at the date of last assessment of treatment response recorded in the diary card. The 50th percentile of Kaplan-Meier estimates was used to estimate the median time to onset of treatment response for each treatment group. |
| The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Up to Cycle 5, Day 85. | At baseline (Cycle 1, Day 1) and all subsequent study visits (per treatment cycle) in the OL period, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at each study visit, and a severity grade of 2 or 3 at baseline. The proportion (percentage) of responders measured by ILA at all study visits in each treatment cycle, is presented. |
| The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Up to Cycle 5, Day 85. | At baseline (Cycle 1, Day 1) and all subsequent study visits per treatment cycle in the OL period, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of no wrinkles (0) or mild wrinkles (1) at maximum frown at a given visit and a severity grade of moderate wrinkles (2) or severe wrinkles (3) at maximum frown at baseline. The proportion (percentage) of responders measured by SSA at all study visits in Cycle 2 to 5 is presented. |
| The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Up to Cycle 1, Day 85. | At baseline (Cycle 1, Day 1) and at all subsequent study visits, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point photographic scale of glabellar line severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at any given visit, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29). |
| Mean SGA Score at All Other Study Visits (OL Period). | Up to Cycle 5, Day 85. | On each study visit per treatment cycle in the OL period, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score for study visits on Day 8 to Day 85 in the OL period is presented. |
| The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Up to Cycle 5, Day 85. | On each study visit per treatment cycle in the OL period, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). The proportion (percentage) of responders at each study visit on Day 8 to Day 85 in the OL period is presented. |
| Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period) | Up to Cycle 5, Day 29. | At cycle baseline (Day 1 of each treatment cycle) and Day 29 of each cycle in the OL period, subjects were asked to evaluate their age over the past 7 days at the time of assessment, using the following categories: * I look like my current age; * I look \_ years younger; * I look \_ years older. The mean change from cycle baseline in subject's self-perception of age at Day 29 of each cycle of the OL Period was calculated. A negative mean change from baseline in the subject's self-perception of age indicates that the subject's self-perception was to look younger compared with baseline. |
| The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Up to Cycle 5, Day 85. | At baseline (Cycle 1, Day 1) and all subsequent study visits per treatment cycle in the OL period, the Investigator assessed the appearance of the glabellar lines at rest using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at a given visit, and a severity grade of 2 or 3 at baseline. Subjects with a baseline score of 0 or 1 were excluded from the analysis of responders. The proportion (percentage) of responders measured by ILA at all study visits per treatment cycle in in the OL period is presented. |
| The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Up to Cycle 1, Day 85. | At baseline (Cycle 1, Day 1) and all subsequent study visits, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at any given visit, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29). |
| The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Up to Cycle 1, Day 85. | At baseline (Cycle 1, Day 1) and at all subsequent study visits, the Investigator assessed the appearance of the glabellar lines at rest using a validated 4-point photographic scale of glabellar line severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at rest at any given visit, and a severity grade of 2 or 3 at rest at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29). |
| The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period). | At Cycle 1, Day 85. | Photographs of the glabellar region of subjects were taken at baseline and at maximum frown at Cycle 1, Day 85. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of 3 readings by 3 independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 85, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 85 . |
| Mean SGA Score at Cycle 1 Study Visits (DB Period). | Up to Cycle 1, Day 85. | On all study visits, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score for study visits on Day 8 to Day 85 in the DB period is presented (except Cycle 1, Day 29). |
| The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Up to Cycle 1, Day 85. | On all study visits, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29). |
Countries
China
Participant flow
Recruitment details
This was a multicentre, phase III, randomised, double-blind (DB) then open-label (OL) study. The 12 month recruitment period began in April 2015. A total of 555 subjects were screened across the 10 study centres in China and 520 subjects were randomised into the study.
Pre-assignment details
The 35 screen failures were due to 17 subjects not meeting the eligibility criteria, 17 subjects withdrawing consent, and one subject reporting an adverse event.
Participants by arm
| Arm | Count |
|---|---|
| Dysport® 50 U - DB Period Subjects randomised to the Dysport® treatment group in Cycle 1 received on Day 1, 50 U (0.25 mL), divided into five injections into the glabellar area. 10 U (0.05 mL) of Dysport® was administered intramuscularly, at right angles to the skin into each of the five injection sites. The Investigator was blinded with respect to treatment injection.
Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57 and 85 of Cycle 1. On Day 85, subjects were assessed for their eligibility to enter the OL period (Cycles 2 to 5). Any subjects not eligible for retreatment were evaluated every 28 days at additional follow-up visits until they were eligible for retreatment or had completed the study. A subject was considered to have completed the study in Cycle 1 if they were not eligible for retreatment and had completed a total of 15 months follow-up following study treatment administration on Day 1. | 325 |
| Dysport® Placebo - DB Period Subjects randomised to the Dysport® placebo group in Cycle 1 received on Day 1, 0.25 mL, divided into five injections into the glabellar area. 0.05 mL of Dysport® placebo was administered intramuscularly, at right angles to the skin into each of the five injection sites. The Investigator was blinded with respect to treatment injection.
Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57 and 85 of Cycle 1. On Day 85, subjects were assessed for their eligibility to enter the OL period (Cycles 2 to 5). Any subjects not eligible for retreatment were evaluated every 28 days at additional follow-up visits until they were eligible for retreatment or had completed the study. A subject was considered to have completed the study in Cycle 1 if they were not eligible for retreatment and had completed a total of 15 months follow-up following study treatment administration on Day 1. | 66 |
| Botox 20 U - DB Period Subjects randomised to the Botox treatment group in Cycle 1 received on Day 1, 20 U (0.5 mL), divided into five injections into the glabellar area. 4 U (0.1 mL) of Botox was administered intramuscularly, at right angles to the skin into each of the five injection sites. The Investigator was blinded with respect to treatment injection.
Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57 and 85 of Cycle 1. On Day 85, subjects were assessed for their eligibility to enter the OL period (Cycles 2 to 5). Any subjects not eligible for retreatment were evaluated every 28 days at additional follow-up visits until they were eligible for retreatment or had completed the study. A subject was considered to have completed the study in Cycle 1 if they were not eligible for retreatment and had completed a total of 15 months follow-up following study treatment administration on Day 1. | 107 |
| Botox Placebo - DB Period Subjects randomised to the Botox placebo group in Cycle 1 received on Day 1, 0. 5 mL, divided into five injections into the glabellar area. 0.1 mL of Botox placebo was administered intramuscularly, at right angles to the skin into each of the five injection sites. The Investigator was blinded with respect to treatment injection.
Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57 and 85 of Cycle 1. On Day 85, subjects were assessed for their eligibility to enter the OL period (Cycles 2 to 5). Any subjects not eligible for retreatment were evaluated every 28 days at additional follow-up visits until they were eligible for retreatment or had completed the study. A subject was considered to have completed the study in Cycle 1 if they were not eligible for retreatment and had completed a total of 15 months follow-up following study treatment administration on Day 1. | 22 |
| Total | 520 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| DB Period (Cycle 1) | Adverse Event | 0 | 0 | 2 | 0 | 0 |
| DB Period (Cycle 1) | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| DB Period (Cycle 1) | Protocol Violation | 2 | 0 | 0 | 1 | 0 |
| DB Period (Cycle 1) | Withdrawal by Subject | 28 | 3 | 8 | 1 | 0 |
| OL Period (Cycles 2-5) | Adverse Event | 0 | 0 | 0 | 0 | 2 |
| OL Period (Cycles 2-5) | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 |
| OL Period (Cycles 2-5) | Protocol Violation | 0 | 0 | 0 | 0 | 7 |
| OL Period (Cycles 2-5) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 31 |
Baseline characteristics
| Characteristic | Dysport® 50 U - DB Period | Dysport® Placebo - DB Period | Botox 20 U - DB Period | Botox Placebo - DB Period | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 325 Participants | 66 Participants | 107 Participants | 22 Participants | 520 Participants |
| Age, Continuous | 45.6 years STANDARD_DEVIATION 9.4 | 44.3 years STANDARD_DEVIATION 9.5 | 44.9 years STANDARD_DEVIATION 8.2 | 42.8 years STANDARD_DEVIATION 9.8 | 45.1 years STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 325 Participants | 66 Participants | 107 Participants | 22 Participants | 520 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 282 Participants | 57 Participants | 94 Participants | 19 Participants | 452 Participants |
| Sex: Female, Male Male | 43 Participants | 9 Participants | 13 Participants | 3 Participants | 68 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 326 | 0 / 66 | 0 / 107 | 0 / 21 | 0 / 465 |
| other Total, other adverse events | 83 / 326 | 9 / 66 | 23 / 107 | 4 / 21 | 142 / 465 |
| serious Total, serious adverse events | 5 / 326 | 2 / 66 | 2 / 107 | 0 / 21 | 28 / 465 |
Outcome results
Primary
Non-Inferiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period).
At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Non Inferiority analysis of Dysport® versus Botox was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.
Time frame: At Cycle 1, Day 29.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport® 50 U - DB Period | Non-Inferiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | 94.7 adjusted percentage of responders |
| Dysport® Placebo - DB Period | Non-Inferiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | 97.0 adjusted percentage of responders |
Comparison: The non-inferiority of Dysport® to Botox on the ILA at maximum frown was tested using a multivariate logistic regression model95% CI: [-6.7, 1.9]
Primary
Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period).
At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.
Time frame: At Cycle 1, Day 29.
Population: The modified Intent-to-treat (mITT) population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and subjects' self assessment (SSA) of glabellar lines at maximum frown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport® 50 U - DB Period | Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | 95.2 adjusted percentage of responders |
| Dysport® Placebo - DB Period | Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | 0.9 adjusted percentage of responders |
| Botox 20 U - DB Period | Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | 94.0 adjusted percentage of responders |
| Botox Placebo - DB Period | Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period). | 4.3 adjusted percentage of responders |
Comparison: Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.p-value: <0.000195% CI: [90.8, 97.7]Regression, Logistic
Primary
Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period).
At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.
Time frame: At Cycle 1, Day 29.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport® 50 U - DB Period | Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period). | 89.4 adjusted percentage of responders |
| Dysport® Placebo - DB Period | Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period). | 1.9 adjusted percentage of responders |
| Botox 20 U - DB Period | Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period). | 89.3 adjusted percentage of responders |
| Botox Placebo - DB Period | Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period). | 1.5 adjusted percentage of responders |
Comparison: Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.p-value: <0.000195% CI: [82.5, 92.4]Regression, Logistic
Secondary
Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period).
On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score at Cycle 1, Day 29 is presented.
Time frame: At Cycle 1, Day 29.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® 50 U - DB Period | Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period). | 2.6 units on the SGA scale | Standard Deviation 1.1 |
| Dysport® Placebo - DB Period | Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period). | 0.1 units on the SGA scale | Standard Deviation 0.4 |
| Botox 20 U - DB Period | Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period). | 2.7 units on the SGA scale | Standard Deviation 1.1 |
| Botox Placebo - DB Period | Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period). | 0.1 units on the SGA scale | Standard Deviation 0.3 |
Comparison: Superiority analysis of Dysport® to placebo was tested using a linear mixed model.p-value: <0.000195% CI: [2.327, 2.878]Mixed Models Analysis
Secondary
The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period).
Photographs of the glabellar region of subjects were taken at maximum frown at baseline (Cycle 1, Day 1) and at Cycle 1, Day 29. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity which rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of three readings by three independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment to placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.
Time frame: At Cycle 1, Day 29.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Subjects with a baseline score of 0 or 1 are excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period). | 99.1 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period). | 25.3 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period). | 94.4 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period). | 31.5 adjusted percentage of responders |
Comparison: Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.p-value: <0.000195% CI: [59.1, 88.4]Regression, Logistic
Secondary
The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period).
On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.
Time frame: At Cycle 1, Day 29.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period). | 85.1 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period). | 1.3 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period). | 85.2 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period). | 2.4 adjusted percentage of responders |
Comparison: Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.p-value: <0.000195% CI: [78.7, 88.7]Regression, Logistic
Other Pre-specified
Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period).
At baseline (Cycle 1, Day 1) and all subsequent study visits in Cycle 1, subjects were asked to evaluate their age over the past 7 days at the time of assessment, using the following categories: * I look like my current age; * I look \_ years younger; * I look \_ years older. The LS mean change from baseline in subject's self-perception of age at all study visits in the DB Period was calculated. A negative LS mean change from baseline in the subject's self-perception of age indicates that the subject's self-perception was to look younger compared with baseline.
Time frame: Up to Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Only subjects with data available for analysis at each time point is presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport® 50 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | -2.083 years | Standard Error 0.278 |
| Dysport® 50 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 29 | -2.566 years | Standard Error 0.296 |
| Dysport® 50 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | -2.483 years | Standard Error 0.293 |
| Dysport® 50 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | -2.035 years | Standard Error 0.281 |
| Dysport® Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 29 | 0.478 years | Standard Error 0.524 |
| Dysport® Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 0.698 years | Standard Error 0.515 |
| Dysport® Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 0.581 years | Standard Error 0.481 |
| Dysport® Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 0.344 years | Standard Error 0.471 |
| Botox 20 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | -1.857 years | Standard Error 0.42 |
| Botox 20 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 29 | -2.421 years | Standard Error 0.437 |
| Botox 20 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | -1.374 years | Standard Error 0.452 |
| Botox 20 U - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | -1.442 years | Standard Error 0.422 |
| Botox Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | -0.208 years | Standard Error 0.802 |
| Botox Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 29 | -0.003 years | Standard Error 0.754 |
| Botox Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | -0.266 years | Standard Error 0.71 |
| Botox Placebo - DB Period | Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | -0.453 years | Standard Error 0.711 |
Other Pre-specified
Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period)
At cycle baseline (Day 1 of each treatment cycle) and Day 29 of each cycle in the OL period, subjects were asked to evaluate their age over the past 7 days at the time of assessment, using the following categories: * I look like my current age; * I look \_ years younger; * I look \_ years older. The mean change from cycle baseline in subject's self-perception of age at Day 29 of each cycle of the OL Period was calculated. A negative mean change from baseline in the subject's self-perception of age indicates that the subject's self-perception was to look younger compared with baseline.
Time frame: Up to Cycle 5, Day 29.
Population: The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis is presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® 50 U - DB Period | Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period) | -1.9 years | Standard Deviation 3 |
| Dysport® Placebo - DB Period | Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period) | -1.6 years | Standard Deviation 2.9 |
| Botox 20 U - DB Period | Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period) | -1.6 years | Standard Deviation 3 |
| Botox Placebo - DB Period | Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period) | -1.1 years | Standard Deviation 2.4 |
Other Pre-specified
Mean SGA Score at All Other Study Visits (OL Period).
On each study visit per treatment cycle in the OL period, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score for study visits on Day 8 to Day 85 in the OL period is presented.
Time frame: Up to Cycle 5, Day 85.
Population: The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport® 50 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 29 | 2.6 units on the SGA scale | Standard Deviation 1.1 |
| Dysport® 50 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 85 | 2.0 units on the SGA scale | Standard Deviation 1.2 |
| Dysport® 50 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 57 | 2.4 units on the SGA scale | Standard Deviation 1.1 |
| Dysport® 50 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 8 | 2.5 units on the SGA scale | Standard Deviation 1.1 |
| Dysport® Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 8 | 2.4 units on the SGA scale | Standard Deviation 1.1 |
| Dysport® Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 29 | 2.5 units on the SGA scale | Standard Deviation 1 |
| Dysport® Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 57 | 2.3 units on the SGA scale | Standard Deviation 1.2 |
| Dysport® Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 85 | 1.9 units on the SGA scale | Standard Deviation 1.2 |
| Botox 20 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 29 | 2.4 units on the SGA scale | Standard Deviation 1.1 |
| Botox 20 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 85 | 1.8 units on the SGA scale | Standard Deviation 1.2 |
| Botox 20 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 57 | 2.2 units on the SGA scale | Standard Deviation 1.1 |
| Botox 20 U - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 8 | 2.5 units on the SGA scale | Standard Deviation 1.2 |
| Botox Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 57 | 1.9 units on the SGA scale | Standard Deviation 1.1 |
| Botox Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 29 | 2.1 units on the SGA scale | Standard Deviation 1.2 |
| Botox Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 85 | 1.5 units on the SGA scale | Standard Deviation 1.2 |
| Botox Placebo - DB Period | Mean SGA Score at All Other Study Visits (OL Period). | Day 8 | 2.1 units on the SGA scale | Standard Deviation 1.1 |
Other Pre-specified
Mean SGA Score at Cycle 1 Study Visits (DB Period).
On all study visits, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening. The mean SGA score for study visits on Day 8 to Day 85 in the DB period is presented (except Cycle 1, Day 29).
Time frame: Up to Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport® 50 U - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 2.3 units on the SGA scale | Standard Deviation 1.2 |
| Dysport® 50 U - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 1.9 units on the SGA scale | Standard Deviation 1.3 |
| Dysport® 50 U - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 2.4 units on the SGA scale | Standard Deviation 1.2 |
| Dysport® Placebo - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 0.1 units on the SGA scale | Standard Deviation 0.4 |
| Dysport® Placebo - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 0.1 units on the SGA scale | Standard Deviation 0.6 |
| Dysport® Placebo - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 0.1 units on the SGA scale | Standard Deviation 0.6 |
| Botox 20 U - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 2.4 units on the SGA scale | Standard Deviation 1.1 |
| Botox 20 U - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 2.3 units on the SGA scale | Standard Deviation 1.3 |
| Botox 20 U - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 1.8 units on the SGA scale | Standard Deviation 1.2 |
| Botox Placebo - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 0.2 units on the SGA scale | Standard Deviation 0.5 |
| Botox Placebo - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 0.1 units on the SGA scale | Standard Deviation 0.2 |
| Botox Placebo - DB Period | Mean SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 0.1 units on the SGA scale | Standard Deviation 0.4 |
Other Pre-specified
The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period).
At baseline (Cycle 1, Day 1) and all subsequent study visits (per treatment cycle) in the OL period, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at each study visit, and a severity grade of 2 or 3 at baseline. The proportion (percentage) of responders measured by ILA at all study visits in each treatment cycle, is presented.
Time frame: Up to Cycle 5, Day 85.
Population: The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 92.9 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 92.7 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 88.0 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 71.7 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 93.5 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 88.7 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 73.8 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 92.1 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 85.8 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 90.1 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 68.1 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 92.2 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 61.2 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 84.7 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 84.7 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 81.6 percentage of responders |
Other Pre-specified
The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period).
At baseline (Cycle 1, Day 1) and at all subsequent study visits, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point photographic scale of glabellar line severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at any given visit, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).
Time frame: Up to Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 86.3 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 80.3 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 87.7 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 1.0 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 0.1 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 2.9 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 92.6 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 87.3 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 76.4 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 1.1 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 1.1 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 1.0 adjusted percentage of responders |
Other Pre-specified
The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period).
At baseline (Cycle 1, Day 1) and all subsequent study visits per treatment cycle in the OL period, the Investigator assessed the appearance of the glabellar lines at rest using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at a given visit, and a severity grade of 2 or 3 at baseline. Subjects with a baseline score of 0 or 1 were excluded from the analysis of responders. The proportion (percentage) of responders measured by ILA at all study visits per treatment cycle in in the OL period is presented.
Time frame: Up to Cycle 5, Day 85.
Population: The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with a baseline score of 2 or 3 and with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 8 | 60.6 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 29 | 63.3 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 57 | 62.4 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 85 | 56.9 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 29 | 58.0 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 57 | 56.5 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 85 | 58.0 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 8 | 52.2 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 57 | 54.5 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 29 | 54.5 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 85 | 59.1 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 8 | 54.5 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 85 | 25.0 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 29 | 25.0 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 8 | 18.8 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period). | Day 57 | 25.0 percentage of responders |
Other Pre-specified
The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period).
At baseline (Cycle 1, Day 1) and at all subsequent study visits, the Investigator assessed the appearance of the glabellar lines at rest using a validated 4-point photographic scale of glabellar line severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at rest at any given visit, and a severity grade of 2 or 3 at rest at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).
Time frame: Up to Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Subjects with a baseline score of 0 or 1 were excluded from the analysis of responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 54.2 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 61.8 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 66.5 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 12.2 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 22.1 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 13.1 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 68.2 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 65.4 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 71.8 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 8.4 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 5.8 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 24.9 adjusted percentage of responders |
Other Pre-specified
The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period).
At baseline (Cycle 1, Day 1) and all subsequent study visits per treatment cycle in the OL period, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of no wrinkles (0) or mild wrinkles (1) at maximum frown at a given visit and a severity grade of moderate wrinkles (2) or severe wrinkles (3) at maximum frown at baseline. The proportion (percentage) of responders measured by SSA at all study visits in Cycle 2 to 5 is presented.
Time frame: Up to Cycle 5, Day 85.
Population: The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 85.3 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 89.1 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 85.1 percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 68.8 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 70.7 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 83.9 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 88.5 percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 89.0 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 82.8 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 62.5 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 87.5 percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 87.5 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 29 | 77.6 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 8 | 77.6 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 85 | 62.2 percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period). | Day 57 | 71.4 percentage of responders |
Other Pre-specified
The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period).
At baseline (Cycle 1, Day 1) and all subsequent study visits, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at any given visit, and a severity grade of 2 or 3 at maximum frown at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).
Time frame: Up to Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 78.6 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 68.2 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 84.9 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 2.0 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 1.7 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 2.1 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 88.1 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 77.3 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 72.2 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 7.4 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 1.0 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 2.6 adjusted percentage of responders |
Other Pre-specified
The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period).
Photographs of the glabellar region of subjects were taken at baseline and at maximum frown at Cycle 1, Day 85. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of 3 readings by 3 independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 85, and a severity grade of 2 or 3 at baseline. Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 85 .
Time frame: At Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Subjects with a baseline score of 0 or 1 were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period). | 93.3 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period). | 13.5 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period). | 89.0 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period). | 22.0 adjusted percentage of responders |
Other Pre-specified
The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period).
On all study visits, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).
Time frame: Up to Cycle 1, Day 85.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 65.2 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 80.1 adjusted percentage of responders |
| Dysport® 50 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 78.0 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 2.5 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 3.4 adjusted percentage of responders |
| Dysport® Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 1.2 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 73.7 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 57.4 adjusted percentage of responders |
| Botox 20 U - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 79.5 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 85 | 2.0 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 57 | 1.8 adjusted percentage of responders |
| Botox Placebo - DB Period | The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period). | Cycle 1, Day 8 | 2.8 adjusted percentage of responders |
Other Pre-specified
The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period).
On each study visit per treatment cycle in the OL period, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). The proportion (percentage) of responders at each study visit on Day 8 to Day 85 in the OL period is presented.
Time frame: Up to Cycle 5, Day 85.
Population: The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis at each time point are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® 50 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 8 | 81.4 percentage of responders |
| Dysport® 50 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 29 | 82.1 percentage of responders |
| Dysport® 50 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 57 | 77.4 percentage of responders |
| Dysport® 50 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 85 | 63.4 percentage of responders |
| Dysport® Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 29 | 80.3 percentage of responders |
| Dysport® Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 57 | 74.4 percentage of responders |
| Dysport® Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 85 | 65.4 percentage of responders |
| Dysport® Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 8 | 75.5 percentage of responders |
| Botox 20 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 57 | 70.3 percentage of responders |
| Botox 20 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 29 | 75.4 percentage of responders |
| Botox 20 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 85 | 61.6 percentage of responders |
| Botox 20 U - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 8 | 76.3 percentage of responders |
| Botox Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 85 | 52.0 percentage of responders |
| Botox Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 29 | 65.3 percentage of responders |
| Botox Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 8 | 62.2 percentage of responders |
| Botox Placebo - DB Period | The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period). | Day 57 | 66.3 percentage of responders |
Other Pre-specified
The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period).
Subjects were given the diary card at baseline (Cycle 1, Day 1 ) and asked to record their assessment of study treatment response for the first 7 days post-treatment (Days 2 to 8). They were asked to respond 'yes' or 'no' to the following question: 'Since being injected have you noticed an improvement in the appearance of your glabellar lines (lines between your eyebrows)?' Subjects with no treatment response were censored at the date of last assessment of treatment response recorded in the diary card. The 50th percentile of Kaplan-Meier estimates was used to estimate the median time to onset of treatment response for each treatment group.
Time frame: At Cycle 1, Day 8.
Population: The mITT population was all randomised subjects who received study treatment in at least one injection site regardless of the amount administered and had both the baseline and Cycle 1, Day 29 assessments, for the ILA and SSA of glabellar lines at maximum frown. Only subjects with treatment response on Cycle 1, Day 8 were analysed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dysport® 50 U - DB Period | The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period). | 2.0 days |
| Dysport® Placebo - DB Period | The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period). | NA days |
| Botox 20 U - DB Period | The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period). | 3.0 days |
| Botox Placebo - DB Period | The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period). | NA days |