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

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)

Population: 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.

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.

Population: 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.

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).

Population: 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.

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).

Population: 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.

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.

Population: 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.

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).

Population: 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.

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.

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.

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).

Population: 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.