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CompletedNCT02493946Updated Sep 28, 2022Results posted

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

A Phase 3 interventional study of Botulinum toxin type A and Placebo in Glabellar Lines, sponsored by Ipsen. Completed at 24 sites in 3 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-09-28.

Sponsored by Ipsen · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
600
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The purpose of the protocol is to demonstrate the safety and the efficacy of a single injection of a new formulation of Clostridium Botulinum toxin type A haemagglutinin complex (BTX A HAC NG) to improve the appearance of moderate to severe glabellar lines (the lines between the eyebrows) and to assess the long term efficacy and safety of BTX-A-HAC NG after repeated injections.

Read the detailed description

This is a multicentre study conducted in two periods. Subjects will first be enrolled to enter the double blind (DB) period Cycle 1. Subjects who are eligible for retreatment will then be offered to enter open label (OL) Cycles 2 to 5 as DB roll-over subjects. Once recruitment of the DB period is complete, the study will enrol additional BTX-naïve subjects (hereafter referred to as OL de novo subjects) into the OL period Cycle 1. All OL de novo subjects who are eligible for retreatment will also be offered to enter OL Cycles 2 to 5. A total of 580 subjects (180 subjects randomised in the DB period and an additional 400 de novo subjects in the OL period) are planned to complete the study.

02

Conditions studied

  • Glabellar Lines
03

In context

Lead sponsor

Ipsen is the lead sponsor of 282 studies on the registry; 16 are open to participants now.

Of its 24 completed or terminated interventional studies of FDA-regulated products, 19 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Provision of written informed consent prior to any study related procedures.
  • Male or female subjects between 18 and 65 years of age.
  • Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at Baseline (Day 1), as assessed by the ILA using a validated 4- point photographic scale.
  • Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at Baseline (Day 1), as assessed by the SSA using a validated 4-point categorical scale.
  • Are dissatisfied or very dissatisfied (Grade 2 or 3) with their glabellar lines at Baseline (Day 1), as assessed by the subject's level of satisfaction.
  • Have a negative pregnancy test (for females of childbearing potential only). No childbearing potential is defined as post-menopausal for at least 1 year, surgical sterilisation at least 3 months before entering the study, or hysterectomy.
  • Have both the time and the ability to complete the study and comply with study instructions.

Exclusion criteria

Exclusion Criteria:

  • Previous treatment with any serotype of BTX.
  • Any prior treatment with permanent fillers in the upper face including the glabellar lines area.
  • Any prior treatment with any dermal fillers in the upper face including the glabellar lines area within the past 3 years and/or skin abrasions/resurfacing (whatever the interventional technic used) within the past 5 years, or photo rejuvenation or skin/vascular laser intervention within the past 12 months.
  • Any planned facial cosmetic surgery during the study.
  • A history of eyelid blepharoplasty or brow lifts within the past 5 years.
  • An inability to substantially reduce glabellar lines by physically spreading them apart or lack of capacity to frown.
  • An active infection or other skin problems in the upper face including the glabellar lines area (e.g. acute acne lesions or ulcers).
  • Use of concomitant therapy, which in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the investigational medicinal product (IMP), including medications affecting bleeding disorders (antiplatelet agents and/or anticoagulants given for treatment or prevention of cardio/cerebro vascular diseases).
  • Pregnant women, nursing mothers, or women who are planning a pregnancy during the study, or believe they may be pregnant at the start of the study. Throughout the course of the study, women of childbearing potential must use a reliable form of contraception (e.g. oral contraceptives for more than 12 consecutive weeks, or spermicide and condoms).
  • Treatment with an experimental drug or use of any experimental device within 30 days prior to the start of the study and during the conduct of the study.
  • Known allergy or hypersensitivity to any component of BTX-A-HAC NG.
  • Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the subject's participation in the study.
  • Use of medications that affect neuromuscular transmission, such as curare-like non depolarising agents, lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within the past 30 days.
  • A history of facial nerve palsy.
  • Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.
  • The presence of any other condition (e.g. neuromuscular disorder or other disorder that could interfere with neuromuscular function), laboratory finding or circumstance that, in the judgement of the investigator, might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
600 participants (actual)

Study arms

  • Experimental
    BTX-A-HAC NG

    Clostridium Botulinum Toxin Type A (BTX A HAC NG), total treatment volume 0.25mL will be divided into 5 injections (0.05mL per injections) injected in 5 pre-defined sites across the glabellar region. A total of 50 Units of BTX-A-HAC NG will be injected/ cycle.

    Biological: Botulinum toxin type A

  • Placebo comparator
    Placebo

    The total placebo volume 0.25mL will be divided into 5 injections (0.05mL per injections) injected in 5 pre-defined sites across the glabellar region. Administered in Cycle 1 of the double blind phase only.

    Drug: Placebo

Interventions

  • BiologicalBotulinum toxin type A

    Also known as: BTX-A-HAC NG

  • DrugPlacebo
06

What researchers measure

Primary outcomes

  1. 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

    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)

Secondary outcomes

  1. The Percentage of Responders at Each Post-treatment Visit (Except Day 29 Cycle 1) as Measured by the ILA at Maximum Frown: DB Period

    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).

  2. 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

    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).

  3. The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest: DB Period

    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).

  4. 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

    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).

  5. 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

    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).

  6. The Median Time to Onset of Treatment Response Based on the Subject's Diary Card: DB Period

    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).

  7. Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: DB Period

    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).

  8. Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: DB Period

    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).

  9. Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal Visual Analogue Scale (VAS): DB Period

    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).

  10. The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Maximum Frown: LT Analyses

    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).

  11. The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Rest: LT Analyses

    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).

  12. The Percentage of Responders at Each Post-treatment Visit as Measured by the SSA at Maximum Frown: LT Analyses

    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).

  13. 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

    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).

  14. Median Time to Retreatment in LT Analysis

    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).

  15. Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: LT Analyses

    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.

  16. Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: LT Analyses

    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.

  17. Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal VAS: LT Analyses

    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.

07

Results

Posted May 28, 2019

Participant flow

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.

DB Period
Participant flow — DB Period
MilestoneBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB PeriodBTX-A-HAC Solution 50 U - Long Term (LT) Analyses
Started126640
Completed118590
Not completed850
Withdrew: Withdrawal by subject850
Open Label Period
Participant flow — Open Label Period
MilestoneBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB PeriodBTX-A-HAC Solution 50 U - Long Term (LT) Analyses
Started00595
Completed00509
Not completed0086
Withdrew: Withdrawal by subject0074
Withdrew: Adverse event004
Withdrew: Lost to follow-up001
Withdrew: Investigator decision, non-compliance002
Withdrew: Investigator decision, non-availability001
Withdrew: Pregnancy003
Withdrew: Site error001

Outcome measures

PrimaryThe Percentage of Responders at Day 29 Cycle 1 as Measured by Investigator's Live Assessment (ILA) of Glabellar Lines at Maximum Frown: DB Period

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)
Reported as:
Number · Adjusted Percentage of Responders
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
Adjusted Percentage of RespondersBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
The Percentage of Responders at Day 29 Cycle 1 as Measured by Investigator's Live Assessment (ILA) of Glabellar Lines at Maximum Frown: DB Period81.6 (61.3 to 92.5)0.8 (0.1 to 4.8)
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 80.8 · 95% CI 73.7 to 88.0
SecondaryThe Percentage of Responders at Each Post-treatment Visit (Except Day 29 Cycle 1) as Measured by the ILA at Maximum Frown: DB Period

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).
Reported as:
Number · Adjusted Percentage of Responders
The Percentage of Responders at Each Post-treatment Visit (Except Day 29 Cycle 1) as Measured by the ILA at Maximum Frown: DB Period
Adjusted Percentage of RespondersBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 875.9 (56.7 to 88.3)0.9 (0.1 to 5.5)
Day 5774.7 (51.4 to 89.2)0.6 (0.1 to 4.0)
Day 8555.5 (35.8 to 73.5)1.8 (0.4 to 8.9)
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 75.0 · 95% CI 67.1 to 82.8
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 74.1 · 95% CI 66.2 to 82.1
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 53.6 · 95% CI 44.2 to 63.1
SecondaryThe 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

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).
Reported as:
Number · Percentage of Responders
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
Percentage of RespondersBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 5787.7 (81.5 to 94.0)100.0 (100.0 to 100.0)
Day 8563.2 (54.0 to 72.4)0 (0 to 0)
SecondaryThe Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest: DB Period

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).
Reported as:
Number · Adjusted Percentage of Responders
The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest: DB Period
Adjusted Percentage of RespondersBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 869.4 (49.2 to 84.2)11.4 (3.9 to 29.0)
Day 2962.2 (39.0 to 80.9)5.4 (1.4 to 18.5)
Day 5763.1 (35.2 to 84.4)0.6 (0.0 to 8.2)
Day 8549.5 (29.0 to 70.1)6.8 (1.9 to 22.0)
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 58.0 · 95% CI 44.5 to 71.6
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 56.8 · 95% CI 44.5 to 69.0
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 62.5 · 95% CI 52.1 to 72.9
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 42.6 · 95% CI 29.5 to 55.7
SecondaryThe 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

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).
Reported as:
Number · Adjusted Percentage of Responders
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
Adjusted Percentage of RespondersBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 863.5 (44.0 to 79.3)2.3 (0.6 to 9.1)
Day 2968.1 (48.4 to 82.9)2.3 (0.6 to 8.5)
Day 5771.2 (51.2 to 85.3)0.7 (0.1 to 6.8)
Day 8534.7 (18.5 to 55.4)1.7 (0.3 to 8.0)
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 61.1 · 95% CI 51.9 to 70.3
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 65.8 · 95% CI 56.8 to 74.8
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 70.5 · 95% CI 62.2 to 78.8
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 33.0 · 95% CI 24.0 to 42.0
SecondaryThe 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

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).
Reported as:
Number · Adjusted Percentage of Responders
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
Adjusted Percentage of RespondersBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 876.3 (59.3 to 87.6)8.1 (3.0 to 19.7)
Day 2983.1 (67.3 to 92.1)5.7 (1.9 to 15.7)
Day 5777.9 (60.0 to 89.2)3.5 (1.0 to 11.9)
Day 8551.3 (30.7 to 71.4)0.3 (0.0 to 4.2)
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Linear · p = <0.0001 (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.) · Treatment difference: 68.2 · 95% CI 58.2 to 78.3
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 77.4 · 95% CI 68.6 to 86.2
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 74.4 · 95% CI 65.7 to 83.1
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Regression, Logistic · p = <0.0001 (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.) · Treatment difference: 51.0 · 95% CI 42.0 to 59.9
SecondaryThe Median Time to Onset of Treatment Response Based on the Subject's Diary Card: DB Period

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).
Reported as:
Median · Days
The Median Time to Onset of Treatment Response Based on the Subject's Diary Card: DB Period
DaysBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
The Median Time to Onset of Treatment Response Based on the Subject's Diary Card: DB Period2.0 (2.0 to 3.0)NA (NA to NA)
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · Cox proportional hazard model · p = <0.0001 · Hazard ratio (hr): 15.296The cox proportional hazard model used centre, gender and ILA baseline severity score as covariates.
SecondaryChange From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: DB Period

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).
Reported as:
Least squares mean · Scores on a Scale
Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: DB Period
Scores on a ScaleBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 89.4 ± 1.720.8 ± 1.93
Day 298.1 ± 1.90-3.0 ± 2.12
Day 5711.2 ± 1.830.7 ± 2.03
Day 854.7 ± 1.91-5.0 ± 2.15
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 8.6 · 95% CI 5.2 to 12.0
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 11.1 · 95% CI 7.4 to 14.8
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 10.4 · 95% CI 6.8 to 14.0
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 9.6 · 95% CI 5.9 to 13.3
SecondaryChange From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: DB Period

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).
Reported as:
Least squares mean · Scores on a Scale
Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: DB Period
Scores on a ScaleBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 86.6 ± 2.19-2.7 ± 2.46
Day 294.5 ± 2.39-6.9 ± 2.66
Day 576.1 ± 2.41-5.1 ± 2.69
Day 850.7 ± 2.28-7.5 ± 2.57
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 9.3 · 95% CI 5.0 to 13.6
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 11.4 · 95% CI 6.7 to 16.0
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: 11.2 · 95% CI 6.4 to 15.9
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = 0.0004 (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.) · Treatment difference: 8.1 · 95% CI 3.7 to 12.6
SecondaryChange From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal Visual Analogue Scale (VAS): DB Period

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).
Reported as:
Least squares mean · Scores on a Scale
Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal Visual Analogue Scale (VAS): DB Period
Scores on a ScaleBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB Period
Day 8-0.8 ± 0.25-0.2 ± 0.28
Day 29-0.8 ± 0.280.3 ± 0.32
Day 57-0.6 ± 0.340.7 ± 0.39
Day 85-0.4 ± 0.311.1 ± 0.36
Statistical analysis
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = 0.0174 (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.) · Treatment difference: -0.6 · 95% CI -1.1 to -0.1
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: -1.2 · 95% CI -1.7 to -0.6
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = 0.0001 (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.) · Treatment difference: -1.4 · 95% CI -2.0 to -0.7
  • BTX-A-HAC Solution 50 U - DB Period vs Placebo - DB Period · General linear model · p = <0.0001 (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.) · Treatment difference: -1.4 · 95% CI -2.1 to -0.8
SecondaryThe Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Maximum Frown: LT Analyses

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).
Reported as:
Number · Percentage of Responders
The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Maximum Frown: LT Analyses
Percentage of RespondersBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 875.7 (72.3 to 79.2)
Cycle 1: Day 2982.2 (79.1 to 85.3)
Cycle 1: Day 5769.9 (66.2 to 73.7)
Cycle 1: Day 8553.0 (49.0 to 57.1)
Cycle 2: Day 880.8 (77.6 to 84.1)
Cycle 2: Day 2984.5 (81.4 to 87.5)
Cycle 2: Day 5774.3 (70.6 to 77.9)
Cycle 2: Day 8553.7 (49.5 to 57.9)
Cycle 3: Day 886.5 (83.5 to 89.6)
Cycle 3: Day 2987.8 (84.9 to 90.8)
Cycle 3: Day 5778.6 (74.9 to 82.3)
Cycle 3: Day 8556.8 (52.3 to 61.2)
Cycle 4: Day 884.3 (80.3 to 88.3)
Cycle 4: Day 2986.1 (82.3 to 90.0)
Cycle 4: Day 5776.1 (71.4 to 80.9)
Cycle 4: Day 8550.7 (45.0 to 56.3)
Cycle 5: Day 884.1 (76.4 to 91.7)
Cycle 5: Day 2982.8 (74.8 to 90.7)
Cycle 5: Day 5755.8 (45.3 to 66.3)
Cycle 5: Day 8545.3 (34.8 to 55.9)
SecondaryThe Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Rest: LT Analyses

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).
Reported as:
Number · Percentage of Responders
The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Rest: LT Analyses
Percentage of RespondersBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 874.1 (69.7 to 78.6)
Cycle 1: Day 2981.7 (77.8 to 85.6)
Cycle 1: Day 5777.3 (73.0 to 81.6)
Cycle 1: Day 8561.1 (56.2 to 66.1)
Cycle 2: Day 874.5 (68.9 to 80.0)
Cycle 2: Day 2978.4 (73.1 to 83.6)
Cycle 2: Day 5771.4 (65.6 to 77.2)
Cycle 2: Day 8547.9 (41.5 to 54.3)
Cycle 3: Day 882.2 (76.9 to 87.5)
Cycle 3: Day 2984.2 (79.1 to 89.3)
Cycle 3: Day 5780.0 (74.4 to 85.6)
Cycle 3: Day 8558.7 (51.8 to 65.6)
Cycle 4: Day 877.6 (70.6 to 84.7)
Cycle 4: Day 2981.3 (74.7 to 87.9)
Cycle 4: Day 5778.9 (72.0 to 85.9)
Cycle 4: Day 8559.5 (51.1 to 67.9)
Cycle 5: Day 885.7 (75.1 to 96.3)
Cycle 5: Day 2978.0 (65.4 to 90.7)
Cycle 5: Day 5763.4 (48.7 to 78.2)
Cycle 5: Day 8556.1 (40.9 to 71.3)
SecondaryThe Percentage of Responders at Each Post-treatment Visit as Measured by the SSA at Maximum Frown: LT Analyses

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).
Reported as:
Number · Percentage of Responders
The Percentage of Responders at Each Post-treatment Visit as Measured by the SSA at Maximum Frown: LT Analyses
Percentage of RespondersBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 862.8 (58.9 to 66.7)
Cycle 1: Day 2972.5 (68.9 to 76.1)
Cycle 1: Day 5764.3 (60.4 to 68.3)
Cycle 1: Day 8543.6 (39.6 to 47.6)
Cycle 2: Day 874.8 (71.1 to 78.5)
Cycle 2: Day 2975.3 (71.6 to 79.0)
Cycle 2: Day 5769.3 (65.3 to 73.3)
Cycle 2: Day 8544.3 (40.0 to 48.6)
Cycle 3: Day 878.8 (75.1 to 82.5)
Cycle 3: Day 2980.6 (77.0 to 84.2)
Cycle 3: Day 5767.1 (62.8 to 71.4)
Cycle 3: Day 8544.9 (40.4 to 49.5)
Cycle 4: Day 880.3 (75.9 to 84.7)
Cycle 4: Day 2975.2 (70.4 to 80.1)
Cycle 4: Day 5766.1 (60.8 to 71.4)
Cycle 4: Day 8547.3 (41.7 to 53.0)
Cycle 5: Day 866.7 (56.8 to 76.6)
Cycle 5: Day 2962.8 (52.6 to 73.0)
Cycle 5: Day 5749.4 (38.8 to 60.0)
Cycle 5: Day 8537.6 (27.3 to 47.9)
SecondaryThe 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

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).
Reported as:
Number · Percentage of Responders
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
Percentage of RespondersBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 878.8 (75.5 to 82.1)
Cycle 1: Day 2986.0 (83.2 to 88.8)
Cycle 1: Day 5775.8 (72.3 to 79.3)
Cycle 1: Day 8556.3 (52.3 to 60.3)
Cycle 2: Day 880.8 (77.2 to 84.5)
Cycle 2: Day 2985.2 (81.9 to 88.5)
Cycle 2: Day 5779.0 (75.2 to 82.8)
Cycle 2: Day 8551.8 (47.2 to 56.4)
Cycle 3: Day 888.3 (85.1 to 91.4)
Cycle 3: Day 2987.8 (84.6 to 91.1)
Cycle 3: Day 5780.6 (76.6 to 84.5)
Cycle 3: Day 8554.6 (49.7 to 59.5)
Cycle 4: Day 887.1 (83.0 to 91.1)
Cycle 4: Day 2987.3 (83.3 to 91.4)
Cycle 4: Day 5774.3 (69.0 to 79.7)
Cycle 4: Day 8558.3 (52.2 to 64.3)
Cycle 5: Day 874.0 (63.9 to 84.0)
Cycle 5: Day 2972.2 (61.9 to 82.6)
Cycle 5: Day 5760.6 (49.2 to 71.9)
Cycle 5: Day 8544.3 (32.6 to 55.9)
SecondaryMedian Time to Retreatment in LT Analysis

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).
Reported as:
Median · Days
Median Time to Retreatment in LT Analysis
DaysBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1113.0 (113.0 to 116.0)
Cycle 2114.0 (113.0 to 117.0)
Cycle 3110.0 (106.0 to 113.0)
Cycle 499.0 (92.0 to 110.0)
SecondaryChange From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: LT Analyses

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.
Reported as:
Mean · Scores on a Scale
Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: LT Analyses
Scores on a ScaleBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 89.2 ± 14.5
Cycle 1: Day 2910.9 ± 15.9
Cycle 1: Day 579.9 ± 15.4
Cycle 1: Day 856.6 ± 14.7
Cycle 2: Day 89.5 ± 14.6
Cycle 2: Day 299.7 ± 15.1
Cycle 2: Day 570.0 ± 0.0
Cycle 2: Day 854.8 ± 12.3
Cycle 3: Day 810.9 ± 15.0
Cycle 3: Day 299.9 ± 15.1
Cycle 3: Day 576.0 ± 4.6
Cycle 3: Day 855.0 ± 12.7
Cycle 4: Day 811.2 ± 14.3
Cycle 4: Day 299.9 ± 13.8
Cycle 4: Day 855.6 ± 11.8
Cycle 5: Day 812.0 ± 18.2
Cycle 5: Day 299.4 ± 17.5
Cycle 5: Day 855.3 ± 10.6
SecondaryChange From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: LT Analyses

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.
Reported as:
Mean · Scores on a Scale
Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: LT Analyses
Scores on a ScaleBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 86.7 ± 16.9
Cycle 1: Day 297.2 ± 19.2
Cycle 1: Day 575.5 ± 18.7
Cycle 1: Day 852.7 ± 16.9
Cycle 2: Day 87.8 ± 14.0
Cycle 2: Day 298.2 ± 15.6
Cycle 2: Day 570.0 ± 0.0
Cycle 2: Day 854.6 ± 13.6
Cycle 3: Day 88.8 ± 15.5
Cycle 3: Day 299.4 ± 15.3
Cycle 3: Day 854.4 ± 13.0
Cycle 4: Day 810.1 ± 16.0
Cycle 4: Day 298.8 ± 14.9
Cycle 4: Day 856.3 ± 13.7
Cycle 5: Day 810.1 ± 17.0
Cycle 5: Day 298.4 ± 14.4
Cycle 5: Day 857.0 ± 12.1
SecondaryChange From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal VAS: LT Analyses

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.
Reported as:
Mean · Scores on a Scale
Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal VAS: LT Analyses
Scores on a ScaleBTX-A-HAC Solution 50 U - LT Analyses
Cycle 1: Day 8-1.0 ± 2.2
Cycle 1: Day 29-1.3 ± 2.5
Cycle 1: Day 57-1.2 ± 2.6
Cycle 1: Day 85-0.8 ± 2.5
Cycle 2: Day 8-0.9 ± 1.8
Cycle 2: Day 29-1.0 ± 1.9
Cycle 2: Day 570.0 ± 0.0
Cycle 3: Day 8-1.0 ± 1.9
Cycle 3: Day 29-1.0 ± 2.1
Cycle 3: Day 57-0.3 ± 1.5
Cycle 3: Day 85-0.5 ± 1.7
Cycle 4: Day 8-1.1 ± 1.8
Cycle 4: Day 29-0.9 ± 1.8
Cycle 4: Day 85-0.5 ± 1.6
Cycle 5: Day 8-1.3 ± 2.3
Cycle 5: Day 29-1.1 ± 2.0
Cycle 5: Day 85-0.7 ± 1.9

Adverse events

Collected over 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.. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BTX-A-HAC Solution 50 U - DB Period0/126 (0%)1/126 (0.8%)35/126 (27.8%)
Placebo - DB Period0/64 (0%)2/64 (3.1%)13/64 (20.3%)
BTX-A-HAC Solution 50 U - LT Analyses0/595 (0%)34/595 (5.7%)279/595 (46.9%)
Most frequent serious events
Showing 10 of 39
Most frequent serious events
EventBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB PeriodBTX-A-HAC Solution 50 U - LT Analyses
Drug hypersensitivityImmune system disorders0/1261/641/595
Gastrointestinal infectionInfections and infestations0/1261/641/595
Tendon ruptureInjury, poisoning and procedural complications0/1261/641/595
MenorrhagiaReproductive system and breast disorders1/1260/641/595
Post procedural haemorrhageInjury, poisoning and procedural complications0/1260/642/595
Rotator cuff syndromeMusculoskeletal and connective tissue disorders0/1260/642/595
AppendicitisInfections and infestations0/1260/641/595
CellulitisInfections and infestations0/1260/641/595
DiverticulitisInfections and infestations0/1260/641/595
Laryngitis bacterialInfections and infestations0/1260/641/595
Most frequent other events
Showing 10 of 14
Most frequent other events
EventBTX-A-HAC Solution 50 U - DB PeriodPlacebo - DB PeriodBTX-A-HAC Solution 50 U - LT Analyses
NasopharyngitisInfections and infestations13/1268/64168/595
HeadacheNervous system disorders13/1264/64117/595
Back painMusculoskeletal and connective tissue disorders2/1261/6425/595
HaematomaVascular disorders5/1260/6415/595
BronchitisInfections and infestations1/1260/6420/595
SinusitisInfections and infestations1/1261/6419/595
GastroenteritisInfections and infestations1/1260/6418/595
InfluenzaInfections and infestations0/1260/6416/595
CystitisInfections and infestations1/1260/6415/595
Eyelid ptosisEye disorders0/1260/6415/595

Baseline characteristics

Baseline characteristics are presented for subjects randomised in the DB period and de novo subjects enrolled in the OL period.

Age, Categorical
Age, Categorical(Participants)BTX-A-HAC Solution 50 U - DB PeriodPlacebo -DB PeriodBTX-A-HAC Solution 50 U - LT Analyses de Novo SubjectsTotal
<=18 years0000
Between 18 and 65 years12364401588
>=65 years30912
Sex: Female, Male
Sex: Female, Male(Participants)BTX-A-HAC Solution 50 U - DB PeriodPlacebo -DB PeriodBTX-A-HAC Solution 50 U - LT Analyses de Novo SubjectsTotal
Female11558360533
Male1165067
Race (NIH/OMB)
Race (NIH/OMB)(Participants)BTX-A-HAC Solution 50 U - DB PeriodPlacebo -DB PeriodBTX-A-HAC Solution 50 U - LT Analyses de Novo SubjectsTotal
American Indian or Alaska Native0011
Asian0011
Native Hawaiian or Other Pacific Islander0000
Black or African American1001
White12564405594
More than one race0000
Unknown or Not Reported0033
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Study locations

24 sites
  • Centre Médical Saint-Jean
    Arras, 62000, France
  • CHRU Hôpital
    Besançon cedex, 25000, France
  • Cabinet Médical
    Cannes, 06400, France
  • MEDITI/ Clinique Science et Beauté, Villa Sylvana
    Juan les Pins, 06160, France
  • Palais de Flore
    Lyon, 69006, France
  • Clinique Iéna
    Paris, 75116, France
  • Dermatologisches Studienzentrum
    Berlin, Germany
  • Privatpraxis für Dermatologie und ästhetische Medizin
    Berlin, Germany
  • Klinik
    Darmstadt, Germany
  • Rosenpark Research
    Darmstadt, Germany
  • Medical Skin Center
    Düsseldorf, Germany
  • Klinik für Dermatologie
    Frankfurt, Germany
  • Abteilung Biochemie und Molekularbiologie Fachrichtung Kosmetikwissenschaft
    Kassel, Germany
  • Rote Kreuz Krankenhaus
    Kassel, Germany
  • Klinik
    Ludwigshafen, Germany
  • Hautarztpraxis Mahlow
    Mahlow, Germany
  • Universitäts-Hautklinik der Gutenberg Universität Mainz
    Mainz, Germany
  • Privatpraxis für Dermatologie und Ästhetik
    München, Germany
  • Praxisklinik
    Münster, Germany
  • Klinische Forschung Osnabrück
    Osnabrück, Germany
  • Hautzentrum am Starnberger See
    Starnberg, Germany
  • Praxis für Dermatologie und Venerologie
    Wuppertal, Germany
  • London Bridge Plastic Surgery
    London, United Kingdom
  • PHI clinic
    London, United Kingdom
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References and documents

Publications

  • Hilton S, Kestemont P, Sattler G, Volteau M, Thompson C, Andriopoulos B, Prygova I, Berg AK, Ascher B. Liquid AbobotulinumtoxinA: Pooled Data From Two Double-Blind, Randomized, Placebo-Controlled Phase III Studies of Glabellar Line Treatment. Dermatol Surg. 2022 Nov 1;48(11):1198-1202. doi: 10.1097/DSS.0000000000003594. Epub 2022 Oct 7. PubMed 36206385 ↗

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board. .

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 28, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02493946
Lead sponsor
Ipsen
Responsible party
Sponsor
First posted
Jul 10, 2015
Start date
Apr 2015
Primary completion
Oct 2015
Completion
Dec 2016
Results posted
May 28, 2019
Last update
Sep 28, 2022

Study contacts

Ipsen Study Director
study director · Ipsen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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