Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dysport in the Treatment of Glabellar Lines in Chinese Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02450526
Recruitment Status : Completed
First Posted : May 21, 2015
Results First Posted : June 6, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Glabellar Lines
Interventions Biological: Botulinum toxin type A
Drug: Placebo
Enrollment 520
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.
Arm/Group Title Dysport® 50 Units (U) - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period Dysport® 50 U - OL Period (Cycles 2-5)
Hide Arm/Group Description

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.

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.

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.

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.

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.

Period Title: DB Period (Cycle 1)
Started [1] 325 66 107 22 0 [2]
Safety Population [3] 326 66 107 21 0
Completed 294 63 97 20 0 [2]
Not Completed 31 3 10 2 0
Reason Not Completed
Adverse Event             0             0             2             0             0
Withdrawal by Subject             28             3             8             1             0
Lost to Follow-up             1             0             0             0             0
Protocol Violation             2             0             0             1             0
[1]
Subjects randomised to each treatment group.
[2]
This arm was not included in DB Period (Cycle 1).
[3]
1 subject was randomised to Botox placebo group but received treatment of Dysport® 50 U in Cycle 1.
Period Title: OL Period (Cycles 2-5)
Started 0 [1] 0 [1] 0 [1] 0 [1] 465 [2]
Safety Population 0 0 0 0 465
Discontinued During Cycle 2 0 0 0 0 28
Discontinued During Cycle 3 0 0 0 0 11
Discontinued During Cycle 4 0 0 0 0 2
Discontinued During Cycle 5 0 0 0 0 0
Completed 0 0 0 0 424
Not Completed 0 0 0 0 41
Reason Not Completed
Adverse Event             0             0             0             0             2
Withdrawal by Subject             0             0             0             0             31
Lack of Efficacy             0             0             0             0             1
Protocol Violation             0             0             0             0             7
[1]
This arm was not included in OL Period (Cycles 2-5).
[2]
Nine subjects completed the DB Period but were not eligible for retreatment in the OL Period.
Arm/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period Total
Hide Arm/Group Description

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.

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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 325 66 107 22 520
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 325 participants 66 participants 107 participants 22 participants 520 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
325
 100.0%
66
 100.0%
107
 100.0%
22
 100.0%
520
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 325 participants 66 participants 107 participants 22 participants 520 participants
45.6  (9.4) 44.3  (9.5) 44.9  (8.2) 42.8  (9.8) 45.1  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 325 participants 66 participants 107 participants 22 participants 520 participants
Female
282
  86.8%
57
  86.4%
94
  87.9%
19
  86.4%
452
  86.9%
Male
43
  13.2%
9
  13.6%
13
  12.1%
3
  13.6%
68
  13.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 325 participants 66 participants 107 participants 22 participants 520 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
325
 100.0%
66
 100.0%
107
 100.0%
22
 100.0%
520
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title 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).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
95.2
(91.2 to 97.4)
0.9
(0.1 to 7.0)
94.0
(85.2 to 97.7)
4.3
(0.5 to 26.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 50 U - DB Period, Dysport® Placebo - DB Period
Comments Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.
Type of Statistical Test Superiority
Comments The model includes treatment group, stratification factors, gender and baseline severity score of glabellar lines at maximum frown measured by the ILA, and centre as explanatory variables and responder (Yes or No) as response variable.
Statistical Test of Hypothesis P-Value <0.0001
Comments The test is two-sided at the significance level of 0.025.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 94.3
Confidence Interval (2-Sided) 95%
90.8 to 97.7
Estimation Comments [Not Specified]
2.Primary Outcome
Title Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
89.4
(84.4 to 93.0)
1.9
(0.4 to 8.4)
89.3
(79.2 to 94.9)
1.5
(0.1 to 21.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 50 U - DB Period, Dysport® Placebo - DB Period
Comments Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.
Type of Statistical Test Superiority
Comments The model includes treatment group, stratification factors, gender and baseline severity score of glabellar lines at maximum frown measured by the ILA, and centre as explanatory variables and responder (Yes or No) as response variable.
Statistical Test of Hypothesis P-Value <0.0001
Comments The test is two-sided at the significance level of 0.025.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 87.5
Confidence Interval (2-Sided) 95%
82.5 to 92.4
Estimation Comments [Not Specified]
3.Primary Outcome
Title 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).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Botox 20 U - DB Period
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 294 94
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
94.7
(90.8 to 96.9)
97.0
(92.0 to 98.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 50 U - DB Period, Botox 20 U - DB Period
Comments The non-inferiority of Dysport® to Botox on the ILA at maximum frown was tested using a multivariate logistic regression model
Type of Statistical Test Non-Inferiority
Comments The model includes treatment group, stratification factors, gender and baseline severity score of glabellar lines at maximum frown measured by the ILA, and centre as explanatory variables and responder (Yes or No) as response variable.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-6.7 to 1.9
Estimation Comments [Not Specified]
4.Secondary Outcome
Title 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).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 194 34 60 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
99.1
(95.0 to 99.8)
25.3
(11.6 to 46.7)
94.4
(85.0 to 98.1)
31.5
(9.4 to 67.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 50 U - DB Period, Dysport® Placebo - DB Period
Comments Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.
Type of Statistical Test Superiority
Comments The model includes treatment group, stratification factors, gender and baseline severity score of glabellar lines at maximum frown measured by the ILA and centre as explanatory variables and responder (Yes or No) as response variable.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 73.8
Confidence Interval (2-Sided) 95%
59.1 to 88.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Subject’s Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Mean (Standard Deviation)
Unit of Measure: units on the SGA scale
2.6  (1.1) 0.1  (0.4) 2.7  (1.1) 0.1  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 50 U - DB Period, Dysport® Placebo - DB Period
Comments Superiority analysis of Dysport® to placebo was tested using a linear mixed model.
Type of Statistical Test Superiority
Comments The comparison between mean scores of SGA at Treatment Cycle 1, Day 29 is based on 2 separate linear mixed models, adjusting on the two stratification parameters, gender and baseline ILA severity score, and the centre.
Statistical Test of Hypothesis P-Value <0.0001
Comments The test was two-sided at the significance level of 0.05
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 2.603
Confidence Interval (2-Sided) 95%
2.327 to 2.878
Estimation Comments [Not Specified]
6.Secondary Outcome
Title The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
85.1
(80.2 to 88.9)
1.3
(0.2 to 9.0)
85.2
(74.4 to 91.9)
2.4
(0.2 to 23.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 50 U - DB Period, Dysport® Placebo - DB Period
Comments Superiority analysis of Dysport® to placebo was tested using a multivariate logistic regression model.
Type of Statistical Test Superiority
Comments The model includes treatment group, stratification factors, gender and baseline severity score of glabellar lines at maximum frown measured by the ILA, and centre as explanatory variables and responder (Yes or No) as response variable.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 83.7
Confidence Interval (2-Sided) 95%
78.7 to 88.7
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
Cycle 1, Day 8
86.3
(81.0 to 90.3)
1.0
(0.1 to 6.9)
87.3
(76.1 to 93.7)
1.1
(0.1 to 18.4)
Cycle 1, Day 57
87.7
(82.7 to 91.4)
2.9
(0.8 to 9.7)
92.6
(79.4 to 97.6)
1.0
(0.0 to 20.7)
Cycle 1, Day 85
80.3
(72.1 to 86.6)
0.1
(0.0 to 3.2)
76.4
(63.8 to 85.6)
1.1
(0.0 to 22.4)
8.Other Pre-specified Outcome
Title The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
Cycle 1, Day 8
78.6
(72.7 to 83.5)
2.0
(0.5 to 8.5)
77.3
(66.4 to 85.5)
7.4
(1.5 to 29.8)
Cycle 1, Day 57
84.9
(79.6 to 89.0)
2.1
(0.5 to 8.7)
88.1
(76.8 to 94.4)
2.6
(0.2 to 23.5)
Cycle 1, Day 85
68.2
(61.5 to 74.2)
1.7
(0.4 to 7.1)
72.2
(59.4 to 82.3)
1.0
(0.0 to 21.5)
9.Other Pre-specified Outcome
Title The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 123 17 33 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
Cycle 1, Day 8
54.2
(44.4 to 63.6)
12.2
(2.8 to 39.6)
65.4
(44.4 to 81.7)
8.4
(0.2 to 82.2)
Cycle 1, Day 57
66.5
(55.6 to 75.9)
13.1
(3.2 to 40.5)
68.2
(47.3 to 83.7)
24.9
(1.5 to 87.7)
Cycle 1, Day 85
61.8
(51.1 to 71.4)
22.1
(7.4 to 50.1)
71.8
(49.3 to 87.0)
5.8
(0.1 to 75.0)
10.Other Pre-specified Outcome
Title 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).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
93.3
(87.4 to 96.5)
13.5
(5.1 to 30.9)
89.0
(74.5 to 95.7)
22.0
(5.6 to 57.0)
11.Other Pre-specified Outcome
Title Mean SGA Score at Cycle 1 Study Visits (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Mean (Standard Deviation)
Unit of Measure: units on the SGA scale
Cycle 1, Day 8 Number Analyzed 294 participants 60 participants 94 participants 19 participants
2.3  (1.2) 0.1  (0.4) 2.3  (1.3) 0.2  (0.5)
Cycle 1, Day 57 Number Analyzed 293 participants 59 participants 94 participants 18 participants
2.4  (1.2) 0.1  (0.6) 2.4  (1.1) 0.1  (0.4)
Cycle 1, Day 85 Number Analyzed 294 participants 59 participants 94 participants 18 participants
1.9  (1.3) 0.1  (0.6) 1.8  (1.2) 0.1  (0.2)
12.Other Pre-specified Outcome
Title The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: adjusted percentage of responders
Cycle 1, Day 8
78.0
(72.3 to 82.7)
1.2
(0.2 to 8.5)
73.7
(62.5 to 82.5)
2.8
(0.3 to 22.8)
Cycle 1, Day 57
80.1
(74.4 to 84.7)
3.4
(1.0 to 10.7)
79.5
(67.8 to 87.8)
1.8
(0.1 to 22.2)
Cycle 1, Day 85
65.2
(59.1 to 70.9)
2.5
(0.6 to 9.7)
57.4
(46.5 to 67.5)
2.0
(0.1 to 23.5)
13.Other Pre-specified Outcome
Title Least Squares (LS) Mean Change From Baseline in Subject’s Self-perception of Age at Cycle 1 Study Visits (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 294 60 94 19
Least Squares Mean (Standard Error)
Unit of Measure: years
Cycle 1, Day 8 Number Analyzed 294 participants 60 participants 94 participants 19 participants
-2.083  (0.278) 0.344  (0.471) -1.442  (0.422) -0.266  (0.710)
Cycle 1, Day 29 Number Analyzed 294 participants 60 participants 94 participants 19 participants
-2.566  (0.296) 0.478  (0.524) -2.421  (0.437) -0.003  (0.754)
Cycle 1, Day 57 Number Analyzed 293 participants 59 participants 94 participants 18 participants
-2.483  (0.293) 0.698  (0.515) -1.857  (0.420) -0.453  (0.711)
Cycle 1, Day 85 Number Analyzed 290 participants 58 participants 93 participants 18 participants
-2.035  (0.281) 0.581  (0.481) -1.374  (0.452) -0.208  (0.802)
14.Other Pre-specified Outcome
Title The Time to Onset of Treatment Response Based on the Subject’s Diary Card (DB Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period
Hide Arm/Group Description:
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.
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.

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.

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.

Overall Number of Participants Analyzed 268 8 82 5
Median (95% Confidence Interval)
Unit of Measure: days
2.0
(2.0 to 3.0)
NA [1] 
(NA to NA)
3.0
(2.0 to 3.0)
NA [1] 
(7.0 to NA)
[1]
Results were non-calculable due to censored data.
15.Other Pre-specified Outcome
Title The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U, Cycle 2 (OL Period) Dysport® 50 U, Cycle 3 (OL Period) Dysport® 50 U, Cycle 4 (OL Period) Dysport® 50 U, Cycle 5 (OL Period)
Hide Arm/Group Description:

All subjects who were eligible for retreatment following the DB period entered Cycle 2 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 2, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 2. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 2 entered Cycle 3 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 3 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 3. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 3 entered Cycle 4 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 4, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 4. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 4 entered Cycle 5 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 5, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 5. A subject was considered to have completed the study when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

Overall Number of Participants Analyzed 424 355 232 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Day 8 Number Analyzed 422 participants 350 participants 227 participants 96 participants
92.9
(90.1 to 95.2)
92.1
(88.8 to 94.7)
92.2
(88.0 to 95.3)
84.7
(76.0 to 91.2)
Day 29 Number Analyzed 410 participants 348 participants 226 participants 97 participants
92.7
(89.8 to 95.0)
93.5
(90.4 to 95.8)
90.1
(85.5 to 93.6)
84.7
(76.0 to 91.2)
Day 57 Number Analyzed 410 participants 349 participants 227 participants 97 participants
88.0
(84.5 to 90.9)
88.7
(85.0 to 91.8)
85.8
(80.6 to 90.0)
81.6
(72.5 to 88.7)
Day 85 Number Analyzed 407 participants 348 participants 231 participants 98 participants
71.7
(67.2 to 75.9)
73.8
(68.9 to 78.3)
68.1
(61.7 to 74.1)
61.2
(50.8 to 70.9)
16.Other Pre-specified Outcome
Title The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U, Cycle 2 (OL Period) Dysport® 50 U, Cycle 3 (OL Period) Dysport® 50 U, Cycle 4 (OL Period) Dysport® 50 U, Cycle 5 (OL Period)
Hide Arm/Group Description:

All subjects who were eligible for retreatment following the DB period entered Cycle 2 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 2, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 2. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 2 entered Cycle 3 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 3 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 3. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 3 entered Cycle 4 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 4, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 4. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 4 entered Cycle 5 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 5, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 5. A subject was considered to have completed the study when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

Overall Number of Participants Analyzed 424 355 232 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Day 8 Number Analyzed 422 participants 349 participants 227 participants 96 participants
85.3
(81.6 to 88.6)
89.0
(85.3 to 92.1)
87.5
(82.5 to 91.5)
77.6
(68.0 to 85.4)
Day 29 Number Analyzed 411 participants 348 participants 226 participants 97 participants
89.1
(85.8 to 91.9)
88.5
(84.7 to 91.6)
87.5
(82.5 to 91.5)
77.6
(68.0 to 85.4)
Day 57 Number Analyzed 410 participants 349 participants 227 participants 97 participants
85.1
(81.4 to 88.4)
83.9
(79.7 to 87.6)
82.8
(77.3 to 87.4)
71.4
(61.4 to 80.1)
Day 85 Number Analyzed 406 participants 348 participants 231 participants 98 participants
68.8
(64.1 to 73.2)
70.7
(65.7 to 75.4)
62.5
(55.9 to 68.7)
62.2
(51.9 to 71.8)
17.Other Pre-specified Outcome
Title The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period).
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U, Cycle 2 (OL Period) Dysport® 50 U, Cycle 3 (OL Period) Dysport® 50 U, Cycle 4 (OL Period) Dysport® 50 U, Cycle 5 (OL Period)
Hide Arm/Group Description:

All subjects who were eligible for retreatment following the DB period entered Cycle 2 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 2, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 2. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 2 entered Cycle 3 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 3 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 3. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 3 entered Cycle 4 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 4, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 4. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 4 entered Cycle 5 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 5, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 5. A subject was considered to have completed the study when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

Overall Number of Participants Analyzed 109 69 44 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Day 8
60.6
(50.7 to 69.8)
52.2
(39.8 to 64.4)
54.5
(38.8 to 69.6)
18.8
(4.0 to 45.6)
Day 29
63.3
(53.5 to 72.3)
58.0
(45.5 to 69.8)
54.5
(38.8 to 69.6)
25.0
(7.3 to 52.4)
Day 57
62.4
(52.6 to 71.5)
56.5
(44.0 to 68.4)
54.5
(38.8 to 69.6)
25.0
(7.3 to 52.4)
Day 85
56.9
(47.0 to 66.3)
58.0
(45.5 to 69.8)
59.1
(43.2 to 73.7)
25.0
(7.3 to 52.4)
18.Other Pre-specified Outcome
Title Mean SGA Score at All Other Study Visits (OL Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U, Cycle 2 (OL Period) Dysport® 50 U, Cycle 3 (OL Period) Dysport® 50 U, Cycle 4 (OL Period) Dysport® 50 U, Cycle 5 (OL Period)
Hide Arm/Group Description:

All subjects who were eligible for retreatment following the DB period entered Cycle 2 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 2, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 2. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 2 entered Cycle 3 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 3 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 3. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 3 entered Cycle 4 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 4, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 4. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 4 entered Cycle 5 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 5, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 5. A subject was considered to have completed the study when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

Overall Number of Participants Analyzed 424 355 232 98
Mean (Standard Deviation)
Unit of Measure: units on the SGA scale
Day 8 Number Analyzed 422 participants 350 participants 227 participants 98 participants
2.5  (1.1) 2.4  (1.1) 2.5  (1.2) 2.1  (1.1)
Day 29 Number Analyzed 410 participants 348 participants 226 participants 97 participants
2.6  (1.1) 2.5  (1.0) 2.4  (1.1) 2.1  (1.2)
Day 57 Number Analyzed 410 participants 349 participants 227 participants 97 participants
2.4  (1.1) 2.3  (1.2) 2.2  (1.1) 1.9  (1.1)
Day 85 Number Analyzed 406 participants 348 participants 231 participants 98 participants
2.0  (1.2) 1.9  (1.2) 1.8  (1.2) 1.5  (1.2)
19.Other Pre-specified Outcome
Title The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period).
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Dysport® 50 U, Cycle 2 (OL Period) Dysport® 50 U, Cycle 3 (OL Period) Dysport® 50 U, Cycle 4 (OL Period) Dysport® 50 U, Cycle 5 (OL Period)
Hide Arm/Group Description:

All subjects who were eligible for retreatment following the DB period entered Cycle 2 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 2, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 2. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 2 entered Cycle 3 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 3 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 3. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 3 entered Cycle 4 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 4, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 4. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 4 entered Cycle 5 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 5, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 5. A subject was considered to have completed the study when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

Overall Number of Participants Analyzed 424 355 232 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of responders
Day 8 Number Analyzed 422 participants 350 participants 227 participants 96 participants
81.4
(77.3 to 85.0)
75.5
(70.7 to 79.9)
76.3
(70.3 to 81.6)
62.2
(51.9 to 71.8)
Day 29 Number Analyzed 410 participants 348 participants 226 participants 97 participants
82.1
(78.1 to 85.6)
80.3
(75.8 to 84.3)
75.4
(69.4 to 80.8)
65.3
(55.0 to 74.6)
Day 57 Number Analyzed 410 participants 349 participants 227 participants 97 participants
77.4
(73.1 to 81.3)
74.4
(69.5 to 78.8)
70.3
(63.9 to 76.1)
66.3
(56.1 to 75.6)
Day 85 Number Analyzed 406 participants 348 participants 231 participants 98 participants
63.4
(58.7 to 68.0)
65.4
(60.1 to 70.3)
61.6
(55.0 to 67.9)
52.0
(41.7 to 62.2)
20.Other Pre-specified Outcome
Title Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period)
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
The OL population was all randomised subjects who received any dose of OL Dysport®. Only subjects with data available for analysis is presented.
Arm/Group Title Dysport® 50 U, Cycle 2 (OL Period) Dysport® 50 U, Cycle 3 (OL Period) Dysport® 50 U, Cycle 4 (OL Period) Dysport® 50 U, Cycle 5 (OL Period)
Hide Arm/Group Description:

All subjects who were eligible for retreatment following the DB period entered Cycle 2 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 2 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 2. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 2 entered Cycle 3 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 3 Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 3. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 3 entered Cycle 4 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 4, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 4. Subjects were assessed for the eligibility to receive the next treatment cycle from Day 85.

Any subjects who were 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 when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

All subjects who were eligible for retreatment following Cycle 4 entered Cycle 5 and received OL Dysport® 50 U. The total treatment dose was injected in 5 predefined sites across the glabellar region on Cycle 5, Day 1.

Following treatment administration, all subjects attended follow-up visits on Days 8, 29, 57, and 85 of Cycle 5. A subject was considered to have completed the study when they had either received a total of five study treatment injections or completed a total of 15 months follow-up in the study following the first study treatment administration and completed the Day 85 visit following the last injection.

Overall Number of Participants Analyzed 410 347 225 97
Mean (Standard Deviation)
Unit of Measure: years
-1.9  (3.0) -1.6  (2.9) -1.6  (3.0) -1.1  (2.4)
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period Dysport® 50 U - OL Period
Hide Arm/Group Description

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.

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.

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

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.

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

All-Cause Mortality
Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period Dysport® 50 U - OL Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/326 (0.00%)      0/66 (0.00%)      0/107 (0.00%)      0/21 (0.00%)      0/465 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period Dysport® 50 U - OL Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/326 (1.53%)      2/66 (3.03%)      2/107 (1.87%)      0/21 (0.00%)      28/465 (6.02%)    
Endocrine disorders           
Goitre  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Eye disorders           
Cataract  1  0/326 (0.00%)  0 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 0/465 (0.00%)  0
Gastrointestinal disorders           
Large intestine polyp  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Intestinal obstruction  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Hepatobiliary disorders           
Hyperplastic cholecystopathy  1  0/326 (0.00%)  0 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 0/465 (0.00%)  0
Cholelithiasis  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 2/465 (0.43%)  2
Infections and infestations           
Appendicitis  1  0/326 (0.00%)  0 1/66 (1.52%)  1 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Chronic tonsillitis  1  0/326 (0.00%)  0 1/66 (1.52%)  1 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Herpes zoster  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Bronchitis  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Chronic sinusitis  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Pneumonia bacterial  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Urinary tract infection  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Injury, poisoning and procedural complications           
Ankle fracture  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Contusion  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Spinal compression fracture  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Ligament injury  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Ligament rupture  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  2
Radius fracture  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Musculoskeletal and connective tissue disorders           
Spinal osteoarthritis  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Intervertebral disc disorder  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Osteoarthritis  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Papillary thyroid cancer  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 0/465 (0.00%)  0
Breast neoplasm  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Cervix carcinoma  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Colon cancer  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Endometrial cancer  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Fibroadenoma of breast  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Invasive breast carcinoma  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Rectal cancer  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%) 
Squamous cell carcinoma of the cervix  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Uterine leiomyoma  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 2/465 (0.43%)  2
Nervous system disorders           
Post herpetic neuralgia  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Pregnancy, puerperium and perinatal conditions           
Ectopic pregnancy  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Reproductive system and breast disorders           
Cervical polyp  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Hydrosalpinx  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Uterine haemorrhage  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Uterine polyp  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Respiratory, thoracic and mediastinal disorders           
Nasal septum deviation  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Skin and subcutaneous tissue disorders           
Eczema  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Surgical and medical procedures           
Abortion induced  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
Vascular disorders           
Lymphocele  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 1/465 (0.22%)  1
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Dysport® 50 U - DB Period Dysport® Placebo - DB Period Botox 20 U - DB Period Botox Placebo - DB Period Dysport® 50 U - OL Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   83/326 (25.46%)      9/66 (13.64%)      23/107 (21.50%)      4/21 (19.05%)      142/465 (30.54%)    
Eye disorders           
Eyelid oedema  1  7/326 (2.15%)  7 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 6/465 (1.29%)  6
Eyelid ptosis  1  13/326 (3.99%)  13 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 15/465 (3.23%)  16
Gastrointestinal disorders           
Abdominal pain upper  1  1/326 (0.31%)  1 2/66 (3.03%)  2 0/107 (0.00%)  0 0/21 (0.00%)  0 3/465 (0.65%)  4
Dental caries  1  4/326 (1.23%)  4 0/66 (0.00%)  0 0/107 (0.00%)  0 0/21 (0.00%)  0 10/465 (2.15%)  10
Infections and infestations           
Upper respiratory tract infection  1  29/326 (8.90%)  35 4/66 (6.06%)  5 12/107 (11.21%)  13 0/21 (0.00%)  0 74/465 (15.91%)  94
Viral upper respiratory tract infection  1  15/326 (4.60%)  18 3/66 (4.55%)  3 4/107 (3.74%)  4 0/21 (0.00%)  0 25/465 (5.38%)  27
Metabolism and nutrition disorders           
Hyperlipidaemia  1  5/326 (1.53%)  5 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 12/465 (2.58%)  13
Musculoskeletal and connective tissue disorders           
Arthritis  1  2/326 (0.61%)  2 0/66 (0.00%)  0 1/107 (0.93%)  1 1/21 (4.76%)  1 1/465 (0.22%)  1
Nervous system disorders           
Headache  1  9/326 (2.76%)  10 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 9/465 (1.94%)  10
Respiratory, thoracic and mediastinal disorders           
Oropharyngeal pain  1  2/326 (0.61%)  2 1/66 (1.52%)  1 0/107 (0.00%)  0 1/21 (4.76%)  1 6/465 (1.29%)  6
Cough  1  4/326 (1.23%)  4 0/66 (0.00%)  0 1/107 (0.93%)  1 0/21 (0.00%)  0 12/465 (2.58%)  14
Skin and subcutaneous tissue disorders           
Dermatitis  1  3/326 (0.92%)  4 0/66 (0.00%)  0 3/107 (2.80%)  3 0/21 (0.00%)  0 2/465 (0.43%)  2
Dermatitis allergic  1  1/326 (0.31%)  1 0/66 (0.00%)  0 0/107 (0.00%)  0 1/21 (4.76%)  1 3/465 (0.65%)  3
Neurodermatitis  1  0/326 (0.00%)  0 0/66 (0.00%)  0 0/107 (0.00%)  0 1/21 (4.76%)  1 0/465 (0.00%)  0
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Ipsen
EMail: clinical.trials@ipsen.com
Layout table for additonal information
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02450526     History of Changes
Other Study ID Numbers: Y-52-52120-158
First Submitted: May 19, 2015
First Posted: May 21, 2015
Results First Submitted: September 6, 2018
Results First Posted: June 6, 2019
Last Update Posted: August 6, 2019