The purpose of this study was to demonstrate the safety and the efficacy of a single treatment of an injectable liquid form of Clostridium botulinum toxin type A haemagglutinin complex (BTX-A-HAC; hereafter referred to as BTX-A-HAC Next Generation (BTX-A-HAC NG)), used for the improvement in the appearance of moderate to severe glabellar lines (the lines between the eyebrows).
At the Baseline Visit (Day 1), subjects were randomised in a ratio of 2:1 to receive either BTX-A-HAC NG solution (50 U) or placebo. Randomisation was stratified according to gender and severity of glabellar lines at maximum frown (moderate to severe) at Baseline. A single dose of BTX-A-HAC NG solution 50 U or placebo was injected on Day 1. Subjects were then monitored at the study centre for 30 minutes. On Day 4, subjects were contacted by telephone for adverse event monitoring and to record concomitant medications and treatments. Subjects attended follow-up visits at the study centre on Days 8, 15, 29, 57, 85, 113, 148 and 183. The Day 183 follow-up visit was the end of study visit; all subjects who had completed the Day 183 Visit were considered to have completed the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
185
A solution containing 50 U in 0.25 mL (200 U/mL). Each vial contained 0.625 mL of deliverable volume of solution. A volume of 0.25 mL, containing 50 U of BTX-A-HAC NG (i.e. 10 U/0.05 mL) was withdrawn from the vial into a syringe for administration. The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection), each of which was to be administered into predefined sites across the glabellar region (two injections into each corrugator muscle and one injection into the procerus muscle).
A solution containing only the excipients of BTX-A-HAC NG (identical in appearance to the active product). Each vial contained 0.625 mL of deliverable volume of solution. A volume of 0.25 mL was withdrawn from the vial into a syringe for administration. The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection), each of which was to be administered into predefined sites across the glabellar region (two injections into each corrugator muscle and one injection into the procerus muscle).
Nouvelle Clinique Bel Air
Bordeaux, France
Cabinet Medical
Cannes, France
Mediti
Juan-les-Pins, France
Clinique IENA
Paris, France
The Proportion of Responders at Day 29 in the ILA of Glabellar Lines at Maximum Frown.
ILA 4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3. A responder at maximum frown was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at maximum frown on Day 29 and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1). The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 29
The Proportion of Responders at Each Post-treatment Visit to the Study Centre (Except Day 29) as Measured by the ILA at Maximum Frown.
ILA 4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3. A responder at maximum frown was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at maximum frown at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1). The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 8, 15, 57, 85, 113, 148 and 183
The Proportion of Responders on Day 29 Who Remained Responders on Days 57, 85, 113, 148 and 183 as Measured by the ILA at Maximum Frown.
ILA 4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3. A responder at maximum frown was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at maximum frown at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1). Subjects who were not responders at Day 29 were excluded from the analysis. The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 57, 85, 113, 148 and 183
The Proportion of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest.
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Rzany & Hund Privatpraxis für Dermatologie
Berlin, Germany
Medical Skin Center
Düsseldorf, Germany
University of Hamburg
Hamburg, Germany
Rote Kreuz Krankenhaus
Kassel, Germany
Hautzentrum am Starnberger See
Starnberg, Germany
ILA 4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3. A responder at rest was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at rest at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1). The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Proportion of Subjects With a Reduction of Two or More Grades in the Severity of Glabellar Lines at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Maximum Frown.
ILA 4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3. Adjusted proportion of subjects with a reduction of two or more grades in the severity of glabellar lines at each post-treatment visit compared with Baseline. The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Proportion of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject's Self-assessment (SSA) at Maximum Frown.
SSA 4-point photographic scale: No wrinkles - 0; Mild wrinkles - 1; Moderate wrinkles - 2; Severe wrinkles - 3. A responder at maximum frown 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 wrinkles (Grade 2) or severe wrinkles (Grade 3) at Baseline (Day 1). The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Proportion 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.
Adjusted proportion of responders at each post-treatment visit (measured by the subject's level of satisfaction with the appearance of their glabellar lines). 4-point categorical scale: Grade 0 - very satisfied; Grade 1 - satisfied; Grade 2 - dissatisfied; Grade 3 - very dissatisfied. 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). The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Time frame: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Time to Onset of Treatment Response Based on the Subject's Diary Card.
Median time to onset of treatment response: subjects asked to record their assessment of study treatment response in a diary card on Days 1 to 7. They responded '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)?'
Time frame: Day 1 to 7