Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AbobotulinumtoxinA | Experimental | Dysport, 50 Units, divided into five injections into the glabellar area. Administered in double blind fashion at cycle 1 followed by up to 4 cycles Dysport, 50 Units administered with an interval period depending on response, no less than 12 weeks between each treatment cycle. |
|
| OnabotulinumtoxinA | Active Comparator | Botox will be administered in treatment cycle 1 only. On Day 1, 20 Units, divided into five injections into the glabellar area. |
|
| AbobotulinumtoxinA Placebo | Placebo Comparator | Dysport placebo will be administered in treatment cycle 1 only. On Day 1, 50 Units, divided into five injections into the glabellar area. |
|
| OnabotulinumtoxinA Placebo | Placebo Comparator | Botox placebo will be administered in treatment cycle 1 only. On Day 1, 20 Units, divided into five injections into the glabellar area. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Botulinum toxin type A | Biological |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 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 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. | At 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 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ipsen Study Director, M.D. | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University First Hospital | Beijing | 100034 | China | |||
| Air Force General Hospital, PLA |
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Dysport® 50 Units (U) - DB Period | Subjects randomised to the Dysport® treatment group in Cycle 1 received on Day 1, 50 U (0.25 millilitres [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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | Dysport® 50 U - OL Period (Cycles 2-5) | After the first treatment cycle, all eligible subjects entered the OL period and received Dysport® 50 U (0.25 mL), injected into five predefined sites across the glabellar region. 10 U (0.05 mL) of Dysport® was administered intramuscularly, at right angles to the skin into each of the five injection sites per treatment cycle. Subjects received a maximum of four treatment cycles (Cycles 2 to 5) with Dysport®. These cycles occurred at intervals of no less than 84 days (12 weeks) between each cycle, depending upon individual duration of response to Dysport® treatment. 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DB Period (Cycle 1) |
|
| |||||||||||||||||||||
| OL Period (Cycles 2-5) |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | At Cycle 1, Day 29. |
Treatment emergent adverse events (TEAEs) were defined as any adverse event with start date on or after the first injection of study treatment or with start date prior to the first injection of study treatment but the intensity increased after the first injection of study treatment. TEAEs were collected until the end of Cycle 5 of the OL period, over a total timeframe of up to approximately 29 months.
The safety population consisted of all randomised subjects who received at least one injection of study treatment into at least one injection site. The safety population was analysed based on the treatment the subject actually received rather than the treatment to which the subject was randomised. The 1 subject who was randomised to Botox placebo group but received treatment of Dysport® 50 U in Cycle 1 was included in the Dysport® 50 U group and excluded from the Botox placebo group.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eyelid oedema | Eye disorders | MedDRA (20.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen | clinical.trials@ipsen.com |
Not provided
| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| C542869 | abobotulinumtoxinA |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Botulinum toxin type A |
| Biological |
|
|
| Placebo | Drug | 50 Units |
|
| Placebo | Drug | 20 Units |
|
| At Cycle 1, Day 29. |
| At Cycle 1, Day 29. |
| 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. | At Cycle 1, Day 29. |
| 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. | At Cycle 1, Day 29. |
| Up to Cycle 1, Day 85. |
| 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). | Up to Cycle 1, Day 85. |
| 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). | Up to Cycle 1, Day 85. |
| 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 . | At Cycle 1, Day 85. |
| 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). | Up to Cycle 1, Day 85. |
| 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). | Up to Cycle 1, Day 85. |
| 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:
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. | Up to Cycle 1, Day 85. |
| 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. | At Cycle 1, Day 8. |
| 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. | Up to Cycle 5, Day 85. |
| 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. | Up to Cycle 5, Day 85. |
| 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. | Up to Cycle 5, Day 85. |
| 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. | Up to Cycle 5, Day 85. |
| 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. | Up to Cycle 5, Day 85. |
| 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:
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. | Up to Cycle 5, Day 29. |
| Beijing |
| 100142 |
| China |
| Peking Union Medical College Hospital | Beijing | 100730 | China |
| Chinese PLA General Hospital | Beijing | 100853 | China |
| The Third Xiangya Hospital of Central South University | Changsha | 410013 | China |
| West China Hospital, Sichuan University | Chengdu | 610041 | China |
| The Third Affiliated Hospital of Sun Yat-sen University | Guanzhou | 510630 | China |
| Dermatology Hospital of the Chinese Academy of Medical Sciences | Nanjing | 210042 | China |
| Tianjin Medical University General Hospital | Tianjing | 300052 | China |
| Union Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan | 430022 | China |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| Safety Population |
|
| Discontinued During Cycle 2 |
|
| Discontinued During Cycle 3 |
|
| Discontinued During Cycle 4 |
|
| Discontinued During Cycle 5 |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | At Cycle 1, Day 29. |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | At Cycle 1, Day 29. |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | At Cycle 1, Day 29. |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | units on the SGA scale | At Cycle 1, Day 29. |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | At Cycle 1, Day 29. |
|
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | Up to Cycle 1, Day 85. |
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | Up to Cycle 1, Day 85. |
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | Up to Cycle 1, Day 85. |
|
|
|
| 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 . | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | At Cycle 1, Day 85. |
|
|
|
| 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). | 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. | Posted | Mean | Standard Deviation | units on the SGA scale | Up to Cycle 1, Day 85. |
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | adjusted percentage of responders | Up to Cycle 1, Day 85. |
|
|
|
| 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:
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 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. | Posted | Least Squares Mean | Standard Error | years | Up to Cycle 1, Day 85. |
|
|
|
| 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. | 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. | Posted | Median | 95% Confidence Interval | days | At Cycle 1, Day 8. |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of responders | Up to Cycle 5, Day 85. |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of responders | Up to Cycle 5, Day 85. |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of responders | Up to Cycle 5, Day 85. |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | units on the SGA scale | Up to Cycle 5, Day 85. |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of responders | Up to Cycle 5, Day 85. |
|
|
|
| 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:
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 OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis is presented. | Posted | Mean | Standard Deviation | years | Up to Cycle 5, Day 29. |
|
|
|
| 0 |
| 326 |
| 5 |
| 326 |
| 83 |
| 326 |
| EG001 | 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. | 0 | 66 | 2 | 66 | 9 | 66 |
| EG002 | 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 | 0 | 107 | 2 | 107 | 23 | 107 |
| EG003 | 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. | 0 | 21 | 0 | 21 | 4 | 21 |
| EG004 | Dysport® 50 U - OL Period | After the first treatment cycle, all eligible subjects entered the OL period and received Dysport® 50 U (0.25 mL), injected into five predefined sites across the glabellar region. 10 U (0.05 mL) of Dysport® was administered intramuscularly, at right angles to the skin into each of the five injection sites per treatment cycle. Subjects received a maximum of four treatment cycles (Cycles 2 to 5) with Dysport®. These cycles occurred at intervals of no less than 84 days (12 weeks) between each cycle, depending upon individual duration of response to Dysport® treatment. 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 | 0 | 465 | 28 | 465 | 142 | 465 |
| Large intestine polyp | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Hyperplastic cholecystopathy | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Chronic tonsillitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Papillary thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Goitre | Endocrine disorders | MedDRA (20.0) | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Chronic sinusitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Pneumonia bacterial | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Ligament injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Breast neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Cervix carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Fibroadenoma of breast | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Invasive breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Squamous cell carcinoma of the cervix | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Post herpetic neuralgia | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (20.0) | Systematic Assessment |
|
| Cervical polyp | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Hydrosalpinx | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Uterine haemorrhage | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Uterine polyp | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Nasal septum deviation | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Abortion induced | Surgical and medical procedures | MedDRA (20.0) | Systematic Assessment |
|
| Lymphocele | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| Eyelid ptosis | Eye disorders | MedDRA (20.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Neurodermatitis | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
The disclosure restriction on the PI is that the sponsor must review all results communications prior to public release. The sponsor has the right to delay a publication by 60 days from the time submitted to the sponsor for review. Any factual amendments proposed by sponsor will be incorporated, provided that they do not alter the scientific value of the material.
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| Cycle 1, Day 57 |
|
| Cycle 1, Day 85 |
|
| Cycle 1, Day 57 |
|
| Cycle 1, Day 85 |
|
| Cycle 1, Day 57 |
|
| Cycle 1, Day 85 |
|
|
| Cycle 1, Day 57 |
|
|
| Cycle 1, Day 85 |
|
|
| Cycle 1, Day 57 |
|
| Cycle 1, Day 85 |
|
|
| Cycle 1, Day 29 |
|
|
| Cycle 1, Day 57 |
|
|
| Cycle 1, Day 85 |
|
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 29 |
|
| Day 57 |
|
| Day 85 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|