Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Botulinum Toxin Type A Haemagglutinin Complex Next Generation (BTX-A-HAC NG) in Glabellar Lines

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: NCT02493946
Recruitment Status : Completed
First Posted : July 10, 2015
Results First Posted : May 27, 2019
Last Update Posted : May 27, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Glabellar Lines
Interventions Drug: Clostridium Botulinum Toxin Type A
Drug: Placebo
Enrollment 600
Recruitment Details Subjects with moderate or severe glabellar lines were enrolled in 24 sites in France, Germany and the United Kingdom from 23 April 2015. The study was completed in December 2016.
Pre-assignment Details 605 subjects were screened. 192 were screened for the double blind (DB) period; 2 were screen failures and 190 were randomised to treatment or placebo. 413 additional subjects were screened for the open label (OL) period referred to as de novo subjects; 3 were screen failures and 410 received at least one treatment cycle.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period BTX-A-HAC Solution 50 U - Long Term (LT) Analyses
Hide Arm/Group Description

During the DB period, subjects were randomised to receive a single treatment of Clostridium botulinum toxin type A haemagglutinin complex (BTX-A-HAC) solution 50 Units (U).

50 U (0.25 millilitres [mL]) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Period Title: DB Period
Started 126 64 0
Completed 118 59 0
Not Completed 8 5 0
Reason Not Completed
Withdrawal by Subject             8             5             0
Period Title: Open Label Period
Started 0 [1] 0 [1] 595 [2]
Completed 0 0 509
Not Completed 0 0 86
Reason Not Completed
Withdrawal by Subject             0             0             74
Adverse Event             0             0             4
Lost to Follow-up             0             0             1
Investigator decision, non-compliance             0             0             2
Investigator decision, non-availability             0             0             1
Pregnancy             0             0             3
Site error             0             0             1
[1]
Only the BTX-A-HAC Solution 50 U - LT Analyses arm is applicable for this period.
[2]
The previous period relates to DB period only, this period relates to OL treatment only.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo -DB Period BTX-A-HAC Solution 50 U - LT Analyses de Novo Subjects Total
Hide Arm/Group Description

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Total of all reporting groups
Overall Number of Baseline Participants 126 64 410 600
Hide Baseline Analysis Population Description
Baseline characteristics are presented for subjects randomised in the DB period and de novo subjects enrolled in the OL period.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 64 participants 410 participants 600 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
123
  97.6%
64
 100.0%
401
  97.8%
588
  98.0%
>=65 years
3
   2.4%
0
   0.0%
9
   2.2%
12
   2.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 64 participants 410 participants 600 participants
Female
115
  91.3%
58
  90.6%
360
  87.8%
533
  88.8%
Male
11
   8.7%
6
   9.4%
50
  12.2%
67
  11.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 64 participants 410 participants 600 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.2%
Asian
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.8%
0
   0.0%
0
   0.0%
1
   0.2%
White
125
  99.2%
64
 100.0%
405
  98.8%
594
  99.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
3
   0.7%
3
   0.5%
1.Primary Outcome
Title The Percentage of Responders at Day 29 Cycle 1 as Measured by Investigator's Live Assessment (ILA) of Glabellar Lines at Maximum Frown: DB Period
Hide Description The appearance of glabellar lines at maximum frown was assessed in the DB period at the Day 29 follow-up visit using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline (Day 1 Cycle 1). The adjusted percentage of responders (determined by multivariate logistic regression analysis) at Day 29 of Cycle 1 is presented.
Time Frame Day 29 (Cycle 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 124 61
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Adjusted Percentage of Responders
81.6
(61.3 to 92.5)
0.8
(0.1 to 4.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 80.8
Confidence Interval (2-Sided) 95%
73.7 to 88.0
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit (Except Day 29 Cycle 1) as Measured by the ILA at Maximum Frown: DB Period
Hide Description The appearance of glabellar lines at maximum frown was assessed in the DB period at post treatment follow-up visits using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline (Day 1 Cycle 1). The adjusted percentage of responders (determined by multivariate logistic regression analysis) at Days 8, 57 and 85 of Cycle 1 is presented.
Time Frame Days 8, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Adjusted Percentage of Responders
Day 8 Number Analyzed 125 participants 63 participants
75.9
(56.7 to 88.3)
0.9
(0.1 to 5.5)
Day 57 Number Analyzed 122 participants 60 participants
74.7
(51.4 to 89.2)
0.6
(0.1 to 4.0)
Day 85 Number Analyzed 123 participants 59 participants
55.5
(35.8 to 73.5)
1.8
(0.4 to 8.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 75.0
Confidence Interval (2-Sided) 95%
67.1 to 82.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 74.1
Confidence Interval (2-Sided) 95%
66.2 to 82.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 53.6
Confidence Interval (2-Sided) 95%
44.2 to 63.1
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Percentage of Responders on Day 29 Cycle 1 Who Remained Responders on Days 57 and 85 as Measured by the ILA at Maximum Frown: DB Period
Hide Description The appearance of glabellar lines at maximum frown was assessed in the DB period at post treatment follow-up visits using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline (Day 1 Cycle 1). The percentage of responders (unadjusted) at Day 29 of Cycle 1 who still fulfilled the criteria for a responder at Days 57 and 85 is presented.
Time Frame Days 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only responders on Day 29 (n=107,1) and those with data available at the timepoints of testing were included in the analysis.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 107 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Responders
Day 57 Number Analyzed 106 participants 1 participants
87.7
(81.5 to 94.0)
100.0
(100.0 to 100.0)
Day 85 Number Analyzed 106 participants 1 participants
63.2
(54.0 to 72.4)
0
(0 to 0)
4.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest: DB Period
Hide Description The appearance of glabellar lines at rest was assessed in the DB period at post treatment follow-up visits using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline (Day 1 Cycle 1). The adjusted percentage of responders (determined by multivariate logistic regression analysis) at Days 8, 29, 57 and 85 of Cycle 1 is presented.
Time Frame Days 8, 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Adjusted Percentage of Responders
Day 8 Number Analyzed 90 participants 42 participants
69.4
(49.2 to 84.2)
11.4
(3.9 to 29.0)
Day 29 Number Analyzed 89 participants 41 participants
62.2
(39.0 to 80.9)
5.4
(1.4 to 18.5)
Day 57 Number Analyzed 87 participants 40 participants
63.1
(35.2 to 84.4)
0.6
(0.0 to 8.2)
Day 85 Number Analyzed 88 participants 39 participants
49.5
(29.0 to 70.1)
6.8
(1.9 to 22.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 58.0
Confidence Interval (2-Sided) 95%
44.5 to 71.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 29 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 56.8
Confidence Interval (2-Sided) 95%
44.5 to 69.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 62.5
Confidence Interval (2-Sided) 95%
52.1 to 72.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 42.6
Confidence Interval (2-Sided) 95%
29.5 to 55.7
Estimation Comments [Not Specified]
5.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject's Self-Assessment (SSA) at Maximum Frown: DB Period
Hide Description The appearance of glabellar lines at maximum frown was assessed using the SSA, a validated 4-point categorical scale of glabellar line severity, in the DB period at post-treatment follow-up visits. A responder was defined as having a severity grade of no wrinkles (Grade 0) or mild wrinkles (Grade 1) at maximum frown at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) wrinkles at baseline (Day 1 Cycle 1). The adjusted percentage of responders (determined by multivariate logistic regression analysis) at Days 8, 29, 57 and 85 of Cycle 1 is presented.
Time Frame Days 8, 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Adjusted Percentage of Responders
Day 8 Number Analyzed 125 participants 63 participants
63.5
(44.0 to 79.3)
2.3
(0.6 to 9.1)
Day 29 Number Analyzed 124 participants 61 participants
68.1
(48.4 to 82.9)
2.3
(0.6 to 8.5)
Day 57 Number Analyzed 122 participants 60 participants
71.2
(51.2 to 85.3)
0.7
(0.1 to 6.8)
Day 85 Number Analyzed 123 participants 60 participants
34.7
(18.5 to 55.4)
1.7
(0.3 to 8.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 61.1
Confidence Interval (2-Sided) 95%
51.9 to 70.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 29 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 65.8
Confidence Interval (2-Sided) 95%
56.8 to 74.8
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 70.5
Confidence Interval (2-Sided) 95%
62.2 to 78.8
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 33.0
Confidence Interval (2-Sided) 95%
24.0 to 42.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject’s Level of Satisfaction With the Appearance of Their Glabellar Lines: DB Period
Hide Description The subject’s level of satisfaction with the appearance of their glabellar lines was assessed in the DB period at post-treatment follow-up visits using a 4-point categorical scale. A responder was defined as having a satisfaction rating of very satisfied (Grade 0) or satisfied (Grade 1) at a given visit and a satisfaction rating of dissatisfied (Grade 2) or very dissatisfied (Grade 3) at baseline (Day 1 Cycle 1). The adjusted percentage of responders (determined by multivariate logistic regression analysis) at Days 8, 29, 57 and 85 of Cycle 1 is presented.
Time Frame Days 8, 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Adjusted Percentage of Responders
Day 8 Number Analyzed 125 participants 63 participants
76.3
(59.3 to 87.6)
8.1
(3.0 to 19.7)
Day 29 Number Analyzed 124 participants 61 participants
83.1
(67.3 to 92.1)
5.7
(1.9 to 15.7)
Day 57 Number Analyzed 122 participants 60 participants
77.9
(60.0 to 89.2)
3.5
(1.0 to 11.9)
Day 85 Number Analyzed 123 participants 60 participants
51.3
(30.7 to 71.4)
0.3
(0.0 to 4.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 68.2
Confidence Interval (2-Sided) 95%
58.2 to 78.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 29 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 77.4
Confidence Interval (2-Sided) 95%
68.6 to 86.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 74.4
Confidence Interval (2-Sided) 95%
65.7 to 83.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference against placebo in the adjusted percentage of responders at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The treatment difference and p-value were obtained from a logistic regression on responders with treatment group, gender, baseline severity score on ILA at maximum frown and centre as fixed variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 51.0
Confidence Interval (2-Sided) 95%
42.0 to 59.9
Estimation Comments [Not Specified]
7.Secondary Outcome
Title The Median Time to Onset of Treatment Response Based on the Subject’s Diary Card: DB Period
Hide Description Subjects were asked to record their assessment of study treatment response on a diary card on Days 1 to 7 at approximately the same time each day. Subjects 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)?’ The time to onset of response was defined as the first day the subject responded 'yes' to this question.
Time Frame Days 1 to 7 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Median (95% Confidence Interval)
Unit of Measure: Days
2.0
(2.0 to 3.0)
NA [1] 
(NA to NA)
[1]
The median was not calculable due to the small number of responders.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference in median time to onset of treatment response.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox proportional hazard model
Comments The cox proportional hazard model used centre, gender and ILA baseline severity score as covariates.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 15.296
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: DB Period
Hide Description FACE-Q is a subject-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the subject's perspective. One of three scales that was selected for this study was the satisfaction with facial appearance overall scale. This consisted of 10 items with 4 possible answers for each: 1 (Very Dissatisfied), 2 (Somewhat Dissatisfied), 3 (Somewhat Satisfied) and 4 (Very Satisfied). The least squares mean change from baseline at post-treatment visits of Rasch transformed scores is presented. The Rasch transformed score was calculated by adding the 10 items (scored from 1 to 4) and converting the score to a scale from 0 (most dissatisfied) to 100 (most satisfied) using a conversion table.
Time Frame Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a Scale
Day 8 Number Analyzed 123 participants 62 participants
9.4  (1.72) 0.8  (1.93)
Day 29 Number Analyzed 123 participants 60 participants
8.1  (1.90) -3.0  (2.12)
Day 57 Number Analyzed 121 participants 59 participants
11.2  (1.83) 0.7  (2.03)
Day 85 Number Analyzed 122 participants 59 participants
4.7  (1.91) -5.0  (2.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference ( BTX-A-HAC Solution – Placebo) at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariates.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 8.6
Confidence Interval (2-Sided) 95%
5.2 to 12.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 29 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariates.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 11.1
Confidence Interval (2-Sided) 95%
7.4 to 14.8
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariates.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
6.8 to 14.0
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariates.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 9.6
Confidence Interval (2-Sided) 95%
5.9 to 13.3
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: DB Period
Hide Description FACE-Q is a subject-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the subject's perspective. One of three scales that was selected for this study was the psychological well-being scale. This consisted of 10 items with 4 possible answers for each: 1 (Definitely disagree), 2 (Somewhat disagree), 3 (Somewhat agree) and 4 (Definitely agree). The least squares mean change from baseline at post-treatment visits of Rasch transformed scores is presented. The Rasch transformed score was calculated by adding the 10 items (scored from 1 to 4) and converting the score to a scale from 0 (worst) to 100 (best) using a conversion table.
Time Frame Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a Scale
Day 8 Number Analyzed 124 participants 62 participants
6.6  (2.19) -2.7  (2.46)
Day 29 Number Analyzed 123 participants 60 participants
4.5  (2.39) -6.9  (2.66)
Day 57 Number Analyzed 121 participants 59 participants
6.1  (2.41) -5.1  (2.69)
Day 85 Number Analyzed 122 participants 59 participants
0.7  (2.28) -7.5  (2.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 9.3
Confidence Interval (2-Sided) 95%
5.0 to 13.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 29 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
6.7 to 16.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 11.2
Confidence Interval (2-Sided) 95%
6.4 to 15.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 8.1
Confidence Interval (2-Sided) 95%
3.7 to 12.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal Visual Analogue Scale (VAS): DB Period
Hide Description FACE-Q is a subject-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the subject's perspective. One of three scales that was selected for this study was the aging appearance appraisal VAS. The VAS ranged from -15 ('I look 15 years younger') to +15 ('I look 15 years older'), with 0 indicating 'I look my age'. Subjects were asked to circle one number on the VAS indicating how many years younger or older they thought they looked compared to their actual age, with lower scores indicating a better outcome and higher scores a worse outcome. The least squares mean change from baseline at post-treatment visits is presented.
Time Frame Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population which consisted of all subjects who were randomised, received study treatment (BTX-A-HAC solution or placebo) and completed one post-treatment assessment of the ILA of glabellar lines at maximum frown. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period
Hide Arm/Group Description:

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Overall Number of Participants Analyzed 125 63
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a Scale
Day 8 Number Analyzed 123 participants 62 participants
-0.8  (0.25) -0.2  (0.28)
Day 29 Number Analyzed 122 participants 60 participants
-0.8  (0.28) 0.3  (0.32)
Day 57 Number Analyzed 121 participants 59 participants
-0.6  (0.34) 0.7  (0.39)
Day 85 Number Analyzed 122 participants 59 participants
-0.4  (0.31) 1.1  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 8 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0174
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.1 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 29 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-1.7 to -0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 57 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.0 to -0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BTX-A-HAC Solution 50 U - DB Period, Placebo - DB Period
Comments Treatment difference (BTX-A-HAC Solution – Placebo) at Day 85 Cycle 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The general linear model included mean change from baseline as a dependent variable and treatment group, gender and centre as fixed effects, and baseline severity score on ILA at maximum frown as covariate.
Method General linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.1 to -0.8
Estimation Comments [Not Specified]
11.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Maximum Frown: LT Analyses
Hide Description The appearance of glabellar lines at maximum frown was assessed in the OL period at post-treatment follow-up visits using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline. The cycle baseline was defined as the last measurement collected prior to the study treatment injection of the corresponding cycle. The percentage of responders (unadjusted) at each post-treatment visit for Cycles 1 to 5 is presented. Cycle 1 corresponds to the first administration of BTX-A-HAC solution and includes the DB Cycle 1 of subjects who were treated with BTX-A-HAC solution, the Cycle 1 of de novo subjects and Cycle 2 of subjects who were randomised to receive placebo in the DB period.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Responders
Cycle 1: Day 8 Number Analyzed 589 participants
75.7
(72.3 to 79.2)
Cycle 1: Day 29 Number Analyzed 585 participants
82.2
(79.1 to 85.3)
Cycle 1: Day 57 Number Analyzed 575 participants
69.9
(66.2 to 73.7)
Cycle 1: Day 85 Number Analyzed 579 participants
53.0
(49.0 to 57.1)
Cycle 2: Day 8 Number Analyzed 553 participants
80.8
(77.6 to 84.1)
Cycle 2: Day 29 Number Analyzed 547 participants
84.5
(81.4 to 87.5)
Cycle 2: Day 57 Number Analyzed 544 participants
74.3
(70.6 to 77.9)
Cycle 2: Day 85 Number Analyzed 544 participants
53.7
(49.5 to 57.9)
Cycle 3: Day 8 Number Analyzed 483 participants
86.5
(83.5 to 89.6)
Cycle 3: Day 29 Number Analyzed 476 participants
87.8
(84.9 to 90.8)
Cycle 3: Day 57 Number Analyzed 472 participants
78.6
(74.9 to 82.3)
Cycle 3: Day 85 Number Analyzed 472 participants
56.8
(52.3 to 61.2)
Cycle 4: Day 8 Number Analyzed 312 participants
84.3
(80.3 to 88.3)
Cycle 4: Day 29 Number Analyzed 310 participants
86.1
(82.3 to 90.0)
Cycle 4: Day 57 Number Analyzed 306 participants
76.1
(71.4 to 80.9)
Cycle 4: Day 85 Number Analyzed 302 participants
50.7
(45.0 to 56.3)
Cycle 5: Day 8 Number Analyzed 88 participants
84.1
(76.4 to 91.7)
Cycle 5: Day 29 Number Analyzed 87 participants
82.8
(74.8 to 90.7)
Cycle 5: Day 57 Number Analyzed 86 participants
55.8
(45.3 to 66.3)
Cycle 5: Day 85 Number Analyzed 86 participants
45.3
(34.8 to 55.9)
12.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Rest: LT Analyses
Hide Description The appearance of glabellar lines at rest was assessed in the OL period at post-treatment follow-up visits using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline. The cycle baseline was defined as the last measurement collected prior to the study treatment injection of the corresponding cycle. The percentage of responders (unadjusted) at each post-treatment visit for Cycles 1 to 5 is presented. Cycle 1 corresponds to the first administration of BTX-A-HAC solution and includes the DB Cycle 1 of subjects who were treated with BTX-A-HAC solution, the Cycle 1 of de novo subjects and Cycle 2 of subjects who were randomised to receive placebo in the DB period.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Responders
Cycle 1: Day 8 Number Analyzed 375 participants
74.1
(69.7 to 78.6)
Cycle 1: Day 29 Number Analyzed 372 participants
81.7
(77.8 to 85.6)
Cycle 1: Day 57 Number Analyzed 365 participants
77.3
(73.0 to 81.6)
Cycle 1: Day 85 Number Analyzed 368 participants
61.1
(56.2 to 66.1)
Cycle 2: Day 8 Number Analyzed 239 participants
74.5
(68.9 to 80.0)
Cycle 2: Day 29 Number Analyzed 236 participants
78.4
(73.1 to 83.6)
Cycle 2: Day 57 Number Analyzed 234 participants
71.4
(65.6 to 77.2)
Cycle 2: Day 85 Number Analyzed 234 participants
47.9
(41.5 to 54.3)
Cycle 3: Day 8 Number Analyzed 202 participants
82.2
(76.9 to 87.5)
Cycle 3: Day 29 Number Analyzed 196 participants
84.2
(79.1 to 89.3)
Cycle 3: Day 57 Number Analyzed 195 participants
80.0
(74.4 to 85.6)
Cycle 3: Day 85 Number Analyzed 196 participants
58.7
(51.8 to 65.6)
Cycle 4: Day 8 Number Analyzed 134 participants
77.6
(70.6 to 84.7)
Cycle 4: Day 29 Number Analyzed 134 participants
81.3
(74.7 to 87.9)
Cycle 4: Day 57 Number Analyzed 133 participants
78.9
(72.0 to 85.9)
Cycle 4: Day 85 Number Analyzed 131 participants
59.5
(51.1 to 67.9)
Cycle 5: Day 8 Number Analyzed 42 participants
85.7
(75.1 to 96.3)
Cycle 5: Day 29 Number Analyzed 41 participants
78.0
(65.4 to 90.7)
Cycle 5: Day 57 Number Analyzed 41 participants
63.4
(48.7 to 78.2)
Cycle 5: Day 85 Number Analyzed 41 participants
56.1
(40.9 to 71.3)
13.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit as Measured by the SSA at Maximum Frown: LT Analyses
Hide Description The appearance of glabellar lines at maximum frown was assessed using the SSA, a validated 4-point categorical scale of glabellar line severity, in the OL period at post-treatment follow-up visits. A responder was defined as having a severity grade of no wrinkles (Grade 0) or mild wrinkles (Grade 1) at maximum frown at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) wrinkles at baseline. The cycle baseline was defined as the last measurement collected prior to the study treatment injection of the corresponding cycle. The percentage of responders (unadjusted) at each post-treatment visit for Cycles 1 to 5 is presented. Cycle 1 corresponds to the first administration of BTX-A-HAC solution and includes the DB Cycle 1 of subjects who were treated with BTX-A-HAC solution, the Cycle 1 of de novo subjects and Cycle 2 of subjects who were randomised to receive placebo in the DB period.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Responders
Cycle 1: Day 8 Number Analyzed 589 participants
62.8
(58.9 to 66.7)
Cycle 1: Day 29 Number Analyzed 585 participants
72.5
(68.9 to 76.1)
Cycle 1: Day 57 Number Analyzed 575 participants
64.3
(60.4 to 68.3)
Cycle 1: Day 85 Number Analyzed 578 participants
43.6
(39.6 to 47.6)
Cycle 2: Day 8 Number Analyzed 524 participants
74.8
(71.1 to 78.5)
Cycle 2: Day 29 Number Analyzed 522 participants
75.3
(71.6 to 79.0)
Cycle 2: Day 57 Number Analyzed 518 participants
69.3
(65.3 to 73.3)
Cycle 2: Day 85 Number Analyzed 517 participants
44.3
(40.0 to 48.6)
Cycle 3: Day 8 Number Analyzed 476 participants
78.8
(75.1 to 82.5)
Cycle 3: Day 29 Number Analyzed 469 participants
80.6
(77.0 to 84.2)
Cycle 3: Day 57 Number Analyzed 465 participants
67.1
(62.8 to 71.4)
Cycle 3: Day 85 Number Analyzed 465 participants
44.9
(40.4 to 49.5)
Cycle 4: Day 8 Number Analyzed 310 participants
80.3
(75.9 to 84.7)
Cycle 4: Day 29 Number Analyzed 307 participants
75.2
(70.4 to 80.1)
Cycle 4: Day 57 Number Analyzed 304 participants
66.1
(60.8 to 71.4)
Cycle 4: Day 85 Number Analyzed 300 participants
47.3
(41.7 to 53.0)
Cycle 5: Day 8 Number Analyzed 87 participants
66.7
(56.8 to 76.6)
Cycle 5: Day 29 Number Analyzed 86 participants
62.8
(52.6 to 73.0)
Cycle 5: Day 57 Number Analyzed 85 participants
49.4
(38.8 to 60.0)
Cycle 5: Day 85 Number Analyzed 85 participants
37.6
(27.3 to 47.9)
14.Secondary Outcome
Title The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject’s Level of Satisfaction With the Appearance of Their Glabellar Lines: LT Analyses
Hide Description The subject's level of satisfaction with the appearance of their glabellar lines was assessed in the OL period at post-treatment follow-up visits of each treatment cycle using a 4-point categorical scale. A responder was defined as having a satisfaction rating of very satisfied (Grade 0) or satisfied (Grade 1) at a given visit and a satisfaction rating of dissatisfied (Grade 2) or very dissatisfied (Grade 3) at baseline. The cycle baseline was defined as the last measurement collected prior to the study treatment injection of the corresponding cycle. The percentage of responders (unadjusted) at each post-treatment visit for Cycles 1 to 5 is presented. Cycle 1 corresponds to the first administration of BTX-A-HAC solution and includes the DB Cycle 1 of subjects who were treated with BTX-A-HAC solution, the Cycle 1 of de novo subjects and Cycle 2 of subjects who were randomised to receive placebo in the DB period.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Responders
Cycle 1: Day 8 Number Analyzed 589 participants
78.8
(75.5 to 82.1)
Cycle 1: Day 29 Number Analyzed 585 participants
86.0
(83.2 to 88.8)
Cycle 1: Day 57 Number Analyzed 575 participants
75.8
(72.3 to 79.3)
Cycle 1: Day 85 Number Analyzed 579 participants
56.3
(52.3 to 60.3)
Cycle 2: Day 8 Number Analyzed 448 participants
80.8
(77.2 to 84.5)
Cycle 2: Day 29 Number Analyzed 446 participants
85.2
(81.9 to 88.5)
Cycle 2: Day 57 Number Analyzed 442 participants
79.0
(75.2 to 82.8)
Cycle 2: Day 85 Number Analyzed 444 participants
51.8
(47.2 to 56.4)
Cycle 3: Day 8 Number Analyzed 401 participants
88.3
(85.1 to 91.4)
Cycle 3: Day 29 Number Analyzed 395 participants
87.8
(84.6 to 91.1)
Cycle 3: Day 57 Number Analyzed 391 participants
80.6
(76.6 to 84.5)
Cycle 3: Day 85 Number Analyzed 392 participants
54.6
(49.7 to 59.5)
Cycle 4: Day 8 Number Analyzed 263 participants
87.1
(83.0 to 91.1)
Cycle 4: Day 29 Number Analyzed 260 participants
87.3
(83.3 to 91.4)
Cycle 4: Day 57 Number Analyzed 257 participants
74.3
(69.0 to 79.7)
Cycle 4: Day 85 Number Analyzed 254 participants
58.3
(52.2 to 64.3)
Cycle 5: Day 8 Number Analyzed 73 participants
74.0
(63.9 to 84.0)
Cycle 5: Day 29 Number Analyzed 72 participants
72.2
(61.9 to 82.6)
Cycle 5: Day 57 Number Analyzed 71 participants
60.6
(49.2 to 71.9)
Cycle 5: Day 85 Number Analyzed 70 participants
44.3
(32.6 to 55.9)
15.Secondary Outcome
Title Median Time to Retreatment in LT Analysis
Hide Description

The median time to onset of the next eligible treatment cycle is presented for Cycles 1 to 4.

Cycle 1 corresponds to the first administration of BTX-A-HAC solution and includes the DB Cycle 1 of subjects who were treated with BTX-A-HAC solution, the Cycle 1 of de novo subjects and Cycle 2 of subjects who were randomised to receive placebo in the DB period.

Subjects who were not subsequently retreated after a given cycle were excluded from the summary of time to retreatment at that cycle.

Time Frame Cycles 1 - 4 (up to 12 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Median (95% Confidence Interval)
Unit of Measure: Days
Cycle 1 Number Analyzed 595 participants
113.0
(113.0 to 116.0)
Cycle 2 Number Analyzed 558 participants
114.0
(113.0 to 117.0)
Cycle 3 Number Analyzed 486 participants
110.0
(106.0 to 113.0)
Cycle 4 Number Analyzed 305 participants
99.0
(92.0 to 110.0)
16.Secondary Outcome
Title Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: LT Analyses
Hide Description FACE-Q is a subject-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the subject's perspective. One of three scales that was selected for this study was the satisfaction with facial appearance overall scale. This consisted of 10 items with 4 possible answers for each: 1 (Very Dissatisfied), 2 (Somewhat Dissatisfied), 3 (Somewhat Satisfied) and 4 (Very Satisfied). The mean change from baseline at post-treatment visits of Rasch transformed scores is presented. The Rasch transformed score was calculated by adding the 10 items (scored from 1 to 4) and converting the score to a scale from 0 (most dissatisfied) to 100 (most satisfied) using a conversion table.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
Cycle 1: Day 8 Number Analyzed 586 participants
9.2  (14.5)
Cycle 1: Day 29 Number Analyzed 583 participants
10.9  (15.9)
Cycle 1: Day 57 Number Analyzed 517 participants
9.9  (15.4)
Cycle 1: Day 85 Number Analyzed 577 participants
6.6  (14.7)
Cycle 2: Day 8 Number Analyzed 553 participants
9.5  (14.6)
Cycle 2: Day 29 Number Analyzed 546 participants
9.7  (15.1)
Cycle 2: Day 57 Number Analyzed 1 participants
0.0  (0.0)
Cycle 2: Day 85 Number Analyzed 542 participants
4.8  (12.3)
Cycle 3: Day 8 Number Analyzed 484 participants
10.9  (15.0)
Cycle 3: Day 29 Number Analyzed 477 participants
9.9  (15.1)
Cycle 3: Day 57 Number Analyzed 3 participants
6.0  (4.6)
Cycle 3: Day 85 Number Analyzed 474 participants
5.0  (12.7)
Cycle 4: Day 8 Number Analyzed 314 participants
11.2  (14.3)
Cycle 4: Day 29 Number Analyzed 311 participants
9.9  (13.8)
Cycle 4: Day 85 Number Analyzed 308 participants
5.6  (11.8)
Cycle 5: Day 8 Number Analyzed 88 participants
12.0  (18.2)
Cycle 5: Day 29 Number Analyzed 87 participants
9.4  (17.5)
Cycle 5: Day 85 Number Analyzed 85 participants
5.3  (10.6)
17.Secondary Outcome
Title Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: LT Analyses
Hide Description FACE-Q is a subject-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the subject's perspective. One of three scales that was selected for this study was the psychological well-being scale. This consisted of 10 items with 4 possible answers for each: 1 (Definitely disagree), 2 (Somewhat disagree), 3 (Somewhat agree) and 4 (Definitely agree). The mean change from baseline at post-treatment visits of Rasch transformed scores is presented. The Rasch transformed score was calculated by adding the 10 items (scored from 1 to 4) and converting the score to a scale from 0 (worst) to 100 (best) using a conversion table.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
Cycle 1: Day 8 Number Analyzed 588 participants
6.7  (16.9)
Cycle 1: Day 29 Number Analyzed 584 participants
7.2  (19.2)
Cycle 1: Day 57 Number Analyzed 518 participants
5.5  (18.7)
Cycle 1: Day 85 Number Analyzed 578 participants
2.7  (16.9)
Cycle 2: Day 8 Number Analyzed 553 participants
7.8  (14.0)
Cycle 2: Day 29 Number Analyzed 546 participants
8.2  (15.6)
Cycle 2: Day 57 Number Analyzed 1 participants
0.0  (0.0)
Cycle 2: Day 85 Number Analyzed 541 participants
4.6  (13.6)
Cycle 3: Day 8 Number Analyzed 484 participants
8.8  (15.5)
Cycle 3: Day 29 Number Analyzed 477 participants
9.4  (15.3)
Cycle 3: Day 85 Number Analyzed 474 participants
4.4  (13.0)
Cycle 4: Day 8 Number Analyzed 314 participants
10.1  (16.0)
Cycle 4: Day 29 Number Analyzed 309 participants
8.8  (14.9)
Cycle 4: Day 85 Number Analyzed 307 participants
6.3  (13.7)
Cycle 5: Day 8 Number Analyzed 88 participants
10.1  (17.0)
Cycle 5: Day 29 Number Analyzed 87 participants
8.4  (14.4)
Cycle 5: Day 85 Number Analyzed 86 participants
7.0  (12.1)
18.Secondary Outcome
Title Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal VAS: LT Analyses
Hide Description FACE-Q is a subject-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the subject's perspective. One of three scales that was selected for this study was the aging appearance appraisal VAS. The VAS ranged from -15 ('I look 15 years younger') to +15 ('I look 15 years older'), with 0 indicating 'I look my age'. Subjects were asked to circle one number on the VAS indicating how many years younger or older they thought they looked compared to their actual age, with lower scores indicating a better outcome and higher scores a worse outcome. The mean change from baseline at post-treatment visits is presented.
Time Frame Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
The LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period. Only subjects with data available at the timepoints of testing are presented.
Arm/Group Title BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description:

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

Overall Number of Participants Analyzed 595
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
Cycle 1: Day 8 Number Analyzed 586 participants
-1.0  (2.2)
Cycle 1: Day 29 Number Analyzed 583 participants
-1.3  (2.5)
Cycle 1: Day 57 Number Analyzed 518 participants
-1.2  (2.6)
Cycle 1: Day 85 Number Analyzed 578 participants
-0.8  (2.5)
Cycle 2: Day 8 Number Analyzed 553 participants
-0.9  (1.8)
Cycle 2: Day 29 Number Analyzed 546 participants
-1.0  (1.9)
Cycle 2: Day 57 Number Analyzed 1 participants
0.0  (0.0)
Cycle 3: Day 8 Number Analyzed 484 participants
-1.0  (1.9)
Cycle 3: Day 29 Number Analyzed 477 participants
-1.0  (2.1)
Cycle 3: Day 57 Number Analyzed 3 participants
-0.3  (1.5)
Cycle 3: Day 85 Number Analyzed 474 participants
-0.5  (1.7)
Cycle 4: Day 8 Number Analyzed 314 participants
-1.1  (1.8)
Cycle 4: Day 29 Number Analyzed 311 participants
-0.9  (1.8)
Cycle 4: Day 85 Number Analyzed 307 participants
-0.5  (1.6)
Cycle 5: Day 8 Number Analyzed 88 participants
-1.3  (2.3)
Cycle 5: Day 29 Number Analyzed 87 participants
-1.1  (2.0)
Cycle 5: Day 85 Number Analyzed 86 participants
-0.7  (1.9)
Time Frame Treatment emergent adverse events were collected from baseline (Day 1 Cycle 1 of DB period or OL period, as applicable) up to end of DB period (for DB period arms) or up to end of Cycle 5 of the OL period (for LT Analyses arm), up to approximately 20 months.
Adverse Event Reporting Description

For the DB period arms, the safety population for the DB period consisted of all subjects who received at least one injection of study treatment into at least one injection site.

For the LT Analyses arm, the LTA population consisted of all subjects included in the DB period or as de novo subjects in the OL period who received at least one injection of BTX-A-HAC solution in the OL period.

 
Arm/Group Title BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period BTX-A-HAC Solution 50 U - LT Analyses
Hide Arm/Group Description

During the DB period, subjects were randomised to receive a single treatment of BTX-A-HAC solution 50 U.

50 U (0.25 mL) BTX-A-HAC was administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive further BTX-A-HAC treatment.

During the DB period, subjects were randomised to receive a single treatment of placebo. 0.25 mL placebo was administered as five injections of 0.05 mL each into one of five predefined sites across the glabellar region.

Subjects who completed the DB treatment (Cycle 1) were eligible to continue to the OL period to receive BTX-A-HAC treatment.

Eligible subjects who completed the DB Cycle 1 treatment were able to receive further treatment in the OL period (OL Cycles 2 to 5). Additional BTX-naïve (de novo) subjects were enrolled into the OL period to receive treatment with BTX-A-HAC during OL Cycle 1, and if eligible for retreatment de novo subjects received retreatment in OL Cycles 2 to 5.

Each treatment cycle included a single treatment with 50 U (0.25 mL) BTX-A-HAC administered as five injections of 10 U (0.05 mL) each into one of five predefined sites across the glabellar region, and treatments were separated by at least 12 weeks.

All-Cause Mortality
BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period BTX-A-HAC Solution 50 U - LT Analyses
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/126 (0.00%)      0/64 (0.00%)      0/595 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period BTX-A-HAC Solution 50 U - LT Analyses
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/126 (0.79%)      2/64 (3.13%)      34/595 (5.71%)    
Cardiac disorders       
Myocardial infarction  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Sinus tachycardia  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Endocrine disorders       
Goitre  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Eye disorders       
Holmes-Adie pupil  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Gastrointestinal disorders       
Abdominal discomfort  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Autoimmune pancreatitis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Crohn's disease  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Hiatus hernia  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Large intestine polyp  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
General disorders       
Catheter site extravasation  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Hepatobiliary disorders       
Cholelithiasis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Immune system disorders       
Drug hypersensitivity  1  0/126 (0.00%)  0 1/64 (1.56%)  1 1/595 (0.17%)  1
Anaphylactic reaction  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Hypersensitivity  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Infections and infestations       
Gastrointestinal infection  1  0/126 (0.00%)  0 1/64 (1.56%)  1 1/595 (0.17%)  1
Appendicitis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Cellulitis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Diverticulitis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Laryngitis bacterial  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Peritoneal abscess  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Peritonsillar abscess  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Salpingitis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Injury, poisoning and procedural complications       
Tendon rupture  1  0/126 (0.00%)  0 1/64 (1.56%)  1 1/595 (0.17%)  1
Post procedural haemorrhage  1  0/126 (0.00%)  0 0/64 (0.00%)  0 2/595 (0.34%)  2
Meniscus injury  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Upper limb fracture  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Metabolism and nutrition disorders       
Dehydration  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Hypokalaemia  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Musculoskeletal and connective tissue disorders       
Rotator cuff syndrome  1  0/126 (0.00%)  0 0/64 (0.00%)  0 2/595 (0.34%)  2
Intervertebral disc protrusion  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Myxofibrosarcoma  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Prostate cancer  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Small intestine carcinoma  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Nervous system disorders       
Sciatica  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Pregnancy, puerperium and perinatal conditions       
Ectopic pregnancy  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Psychiatric disorders       
Post-traumatic stress disorder  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Reproductive system and breast disorders       
Menorrhagia  1  1/126 (0.79%)  1 0/64 (0.00%)  0 1/595 (0.17%)  1
Endometriosis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
Postmenopausal haemorrhage  1  0/126 (0.00%)  0 0/64 (0.00%)  0 1/595 (0.17%)  1
1
Term from vocabulary, MedDRA (19.0)
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%
BTX-A-HAC Solution 50 U - DB Period Placebo - DB Period BTX-A-HAC Solution 50 U - LT Analyses
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/126 (27.78%)      13/64 (20.31%)      279/595 (46.89%)    
Ear and labyrinth disorders       
Vertigo  1  3/126 (2.38%)  3 0/64 (0.00%)  0 6/595 (1.01%)  6
Eye disorders       
Eyelid ptosis  1  0/126 (0.00%)  0 0/64 (0.00%)  0 15/595 (2.52%)  19
Eyelid oedema  1  2/126 (1.59%)  3 0/64 (0.00%)  0 14/595 (2.35%)  16
Infections and infestations       
Nasopharyngitis  1  13/126 (10.32%)  14 8/64 (12.50%)  10 168/595 (28.24%)  252
Pharyngitis  1  3/126 (2.38%)  3 0/64 (0.00%)  0 7/595 (1.18%)  7
Bronchitis  1  1/126 (0.79%)  1 0/64 (0.00%)  0 20/595 (3.36%)  21
Sinusitis  1  1/126 (0.79%)  1 1/64 (1.56%)  2 19/595 (3.19%)  22
Gastroenteritis  1  1/126 (0.79%)  1 0/64 (0.00%)  0 18/595 (3.03%)  19
Influenza  1  0/126 (0.00%)  0 0/64 (0.00%)  0 16/595 (2.69%)  17
Cystitis  1  1/126 (0.79%)  5 0/64 (0.00%)  0 15/595 (2.52%)  20
Musculoskeletal and connective tissue disorders       
Back pain  1  2/126 (1.59%)  2 1/64 (1.56%)  3 25/595 (4.20%)  29
Nervous system disorders       
Headache  1  13/126 (10.32%)  22 4/64 (6.25%)  4 117/595 (19.66%)  272
Migraine  1  2/126 (1.59%)  5 0/64 (0.00%)  0 13/595 (2.18%)  20
Vascular disorders       
Haematoma  1  5/126 (3.97%)  5 0/64 (0.00%)  0 15/595 (2.52%)  16
1
Term from vocabulary, MedDRA (19.0)
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.
Results Point of Contact
Name/Title: Medical Director, Neurology
Organization: Ipsen
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02493946     History of Changes
Other Study ID Numbers: Y-52-52120-214
2014-003841-86 ( EudraCT Number )
First Submitted: April 28, 2015
First Posted: July 10, 2015
Results First Submitted: July 18, 2018
Results First Posted: May 27, 2019
Last Update Posted: May 27, 2019