Glabellar Frown Lines
Conditions
Brief summary
NT 201, also known as IncobotulinumtoxinA (Xeomin®/Bocouture®), is a Botulinum toxin type A preparation free of complexing proteins (150 kiloDalton). Injected into the muscle, NT201 causes a reversible local relaxation of the injected muscle. Botulinum toxin type A is used for aesthetic treatment of mimic wrinkles and in the therapy of neurologic diseases. This study will investigate the safety and efficacy (non-inferiority) of NT 201 in comparison with OnabotulinumtoxinA (Vistabel®) in the treatment of glabellar frown lines.
Interventions
DRUGNT 201 (IncobotulinumtoxinA (Xeomin®/Bocouture®))
NT201, also known as IncobotulinumtoxinA (Xeomin®/Bocouture®), active ingredient: Clostridium botulinum neurotoxin type A free from complexing proteins, powder for solution for injection dose, 24 units; one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl). Of the 0.6 mL total injection volume, an aliquot of 0.15 mL was administered in the procerus muscle, aliquots of 0.125 mL were administered in the medial part of the both corrugator muscles and aliquots of 0.1 mL were administered in the middle part of both corrugator muscles.
DRUGOnabotulinumtoxinA (Vistabel®)
OnabotulinumtoxinA (Vistabel®), active ingredient: Clostridium botulinum neurotoxin type A, powder for solution for injection dose, 24 units; one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl). Of the 0.6 mL total injection volume, an aliquot of 0.15 mL was administered in the procerus muscle, aliquots of 0.125 mL were administered in the medial part of the both corrugator muscles and aliquots of 0.1 mL were administered in the middle part of both corrugator muscles.
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: • Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on a 4-point facial wrinkle scale) as assessed by the investigator's rating: 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe'. Main
Exclusion criteria
* Marked facial asymmetry. * Ptosis of eyelid and/or eyebrow.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder by Independent Rater's Assessment at Maximum Frown at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at maximum frown. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder by Independent Rater's Assessment at Rest at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at rest. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Independent Rater's Assessment at Rest at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at rest. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Investigator's Assessment at Maximum Frown at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at maximum frown rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Investigator's Assessment at Maximum Frown at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at maximum frown rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Investigator's Assessment at Rest at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at rest rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Investigator's Assessment at Rest at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at rest rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Independent Rater's Assessment at Maximum Frown at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at maximum frown. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Patient's Assessment at Maximum Frown at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at maximum frown rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Patient's Assessment at Rest at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at rest rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Response by Patient's Assessment at Rest at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
| Responder by Patient's Global Assessment at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as a score of at least +2 (moderate improvement) on a 9-point scale (range from +4 complete improvement to -4 very marked worsening) 4 weeks after treatment rated by the patient. |
| Responder by Patient's Global Assessment at Week 12 | 12 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as a score of at least +2 (moderate improvement) on a 9-point scale (range from +4 complete improvement to -4 very marked worsening) 12 weeks after treatment rated by the patient. |
| Responder by Patient's Assessment at Maximum Frown at Week 4 | 4 weeks after injection | The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at maximum frown rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles. |
Countries
Austria, Germany, United Kingdom
Participant flow
Pre-assignment details
Subjects were randomized according to a ratio of 3:1 to be either treated with IncobotulinumtoxinA (Bocouture®) or with OnabotulinumtoxinA (Vistabel®).
Participants by arm
| Arm | Count |
|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | 284 |
| OnabotulinumtoxinA (Vistabel®) | 97 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 12 | 5 |
| Overall Study | Non-compliance | 2 | 2 |
Baseline characteristics
| Characteristic | IncobotulinumtoxinA (Xeomin®/Bocouture®) | OnabotulinumtoxinA (Vistabel®) | Total |
|---|---|---|---|
| Age Continuous | 41.6 years STANDARD_DEVIATION 5.7 | 42.0 years STANDARD_DEVIATION 6 | 41.7 years STANDARD_DEVIATION 5.8 |
| Sex: Female, Male Female | 284 Participants | 97 Participants | 381 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 284 | 12 / 97 |
| serious Total, serious adverse events | 1 / 284 | 1 / 97 |
Outcome results
Primary
Responder by Independent Rater's Assessment at Maximum Frown at Week 4
The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at maximum frown. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Independent Rater's Assessment at Maximum Frown at Week 4 | 267 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Independent Rater's Assessment at Maximum Frown at Week 4 | 89 participants |
Comparison: Null Hypothesis: Response rate of IncobotulinumtoxinA (Xeomin®/Bocouture®) minus the response rate of OnabotulinumtoxinA (Vistabel®) is lower or equal -15% (non-inferiority margin).95% CI: [-3.2, 7.1]
Secondary
Responder by Independent Rater's Assessment at Maximum Frown at Week 12
The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at maximum frown. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Independent Rater's Assessment at Maximum Frown at Week 12 | 222 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Independent Rater's Assessment at Maximum Frown at Week 12 | 73 participants |
Secondary
Responder by Independent Rater's Assessment at Rest at Week 12
The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at rest. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Independent Rater's Assessment at Rest at Week 12 | 100 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Independent Rater's Assessment at Rest at Week 12 | 33 participants |
Secondary
Responder by Independent Rater's Assessment at Rest at Week 4
The Outcome Measure Data Table describes the number of responders. A subject is a responder if at least 2 out of 3 independent rater identified a response. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at rest. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Independent Rater's Assessment at Rest at Week 4 | 115 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Independent Rater's Assessment at Rest at Week 4 | 37 participants |
Secondary
Responder by Investigator's Assessment at Maximum Frown at Week 12
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at maximum frown rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Investigator's Assessment at Maximum Frown at Week 12 | 220 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Investigator's Assessment at Maximum Frown at Week 12 | 76 participants |
Secondary
Responder by Investigator's Assessment at Maximum Frown at Week 4
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at maximum frown rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Investigator's Assessment at Maximum Frown at Week 4 | 274 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Investigator's Assessment at Maximum Frown at Week 4 | 89 participants |
Secondary
Responder by Investigator's Assessment at Rest at Week 12
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at rest rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Investigator's Assessment at Rest at Week 12 | 166 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Investigator's Assessment at Rest at Week 12 | 51 participants |
Secondary
Responder by Investigator's Assessment at Rest at Week 4
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at rest rated by the investigator. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Investigator's Assessment at Rest at Week 4 | 210 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Investigator's Assessment at Rest at Week 4 | 66 participants |
Secondary
Responder by Patient's Assessment at Maximum Frown at Week 12
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter at maximum frown rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Patient's Assessment at Maximum Frown at Week 12 | 202 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Patient's Assessment at Maximum Frown at Week 12 | 71 participants |
Secondary
Responder by Patient's Assessment at Maximum Frown at Week 4
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at maximum frown rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Patient's Assessment at Maximum Frown at Week 4 | 260 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Patient's Assessment at Maximum Frown at Week 4 | 87 participants |
Secondary
Responder by Patient's Assessment at Rest at Week 4
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 4 weeks thereafter at rest rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Patient's Assessment at Rest at Week 4 | 193 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Patient's Assessment at Rest at Week 4 | 70 participants |
Secondary
Responder by Patient's Global Assessment at Week 12
The Outcome Measure Data Table describes the number of responders. A response is defined as a score of at least +2 (moderate improvement) on a 9-point scale (range from +4 complete improvement to -4 very marked worsening) 12 weeks after treatment rated by the patient.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Patient's Global Assessment at Week 12 | 229 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Patient's Global Assessment at Week 12 | 75 participants |
Secondary
Responder by Patient's Global Assessment at Week 4
The Outcome Measure Data Table describes the number of responders. A response is defined as a score of at least +2 (moderate improvement) on a 9-point scale (range from +4 complete improvement to -4 very marked worsening) 4 weeks after treatment rated by the patient.
Time frame: 4 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Responder by Patient's Global Assessment at Week 4 | 259 participants |
| OnabotulinumtoxinA (Vistabel®) | Responder by Patient's Global Assessment at Week 4 | 86 participants |
Secondary
Response by Patient's Assessment at Rest at Week 12
The Outcome Measure Data Table describes the number of responders. A response is defined as an improvement of at least one point on a 4-point facial wrinkle scale from baseline to 12 weeks thereafter rated by the patient. The scale comprises the items 0 = 'none', 1 = 'mild', 2 = 'moderate', 3 = 'severe' wrinkles.
Time frame: 12 weeks after injection
Population: Analysis per protocol: All subjects who received study medication, for whom a facial wrinkle score at maximum frown was observed at baseline and who had no major protocol deviations. Missing facial wrinkle scores were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA (Xeomin®/Bocouture®) | Response by Patient's Assessment at Rest at Week 12 | 152 participants |
| OnabotulinumtoxinA (Vistabel®) | Response by Patient's Assessment at Rest at Week 12 | 53 participants |