Glabellar Frown Lines
Conditions
Keywords
Glabellar Frown Lines, Frown Lines, Facial Wrinkles
Brief summary
The purpose of this study is to show that two FDA-approved botulinum toxin drugs called Xeomin® and Botox® can reduce the severity of vertical lines (wrinkles) that appear between the eyebrows (glabellar frown lines).
Detailed description
This is a prospective, multicenter, randomized, double-blind, parallel group clinical study to investigate the equivalence of incobotulinumtoxinA (Xeomin®) to onabotulinumtoxinA (Botox®) in the treatment of glabellar frown lines.
Interventions
20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
DRUGOnabotulinumtoxinA
20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Sponsors
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Outpatient females 18 to 50 years of age * Moderate to severe glabellar frown lines
Exclusion criteria
* Glabellar Frown Lines at rest rating 3 on the 4-point Facial Wrinkle Scale * Previous treatment with botulinum toxin * Previous treatment with biodegradable fillers in glabellar area within last 12 months * Any severe or uncontrolled systemic disease, malignant tumor, or medical history of HIV infection * Known hypersensitivity to incobotulinumtoxinA or onabotulinumtoxinA or to any of their excipients * Intake of any of the forbidden concomitant medication or other agents that might interfere with neuromuscular function or might interfere with the action of botulinum toxin type within 14 days prior to injection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy, Measured as the Percentage of Participants Who Responded to Treatment | 1 Month from baseline | Response defined as ≥ 1 point improvement from baseline (prior to treatment) on the Facial Wrinkle Scale at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 1 month from treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response at Maximum Frown Rated by Independent Rater | 2 months from baseline | Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 2 months from baseline. |
| Response at Maximum Frown Rated by Treating Physician | 1 month from baseline | Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 1 month from treatment. |
| Subject Satisfaction | 1 month from baseline | Assessment of subject treatment satisfaction by subject questionnaire and diary at 1 month from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as Satisfaction and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as Dissatisfaction. Subjects with missing data were categorized as Missing. |
| Subject Perception of Treatment Onset | Open-ended time frame for the 4 month study duration. Data for onset and peak effect is recorded in the subject diary. | Assessment of subject perception of date of treatment onset using a take-home diary |
| Subject Perception of Treatment Peak Effect | Open-ended time frame for the 4 month study duration. Data for onset and peak effect is recorded in the subject diary. | Assessment of subject perception of date of treatment peak effect using a take-home diary |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IncobotulinumtoxinA 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points.
IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection | 122 |
| OnabotulinumtoxinA 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points.
OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection | 128 |
| Total | 250 |
Baseline characteristics
| Characteristic | OnabotulinumtoxinA | Total | IncobotulinumtoxinA |
|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 7.8 | 39.3 years STANDARD_DEVIATION 7.6 | 39.3 years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 58 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 192 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 27 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 107 Participants | 211 Participants | 104 Participants |
| Sex: Female, Male Female | 128 Participants | 250 Participants | 122 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 | 9 / 122 | 8 / 128 |
| serious Total, serious adverse events | 1 / 122 | 1 / 128 |
Outcome results
Primary
Efficacy, Measured as the Percentage of Participants Who Responded to Treatment
Response defined as ≥ 1 point improvement from baseline (prior to treatment) on the Facial Wrinkle Scale at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 1 month from treatment.
Time frame: 1 Month from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Efficacy, Measured as the Percentage of Participants Who Responded to Treatment | 95.7 percentage of participants |
| OnabotulinumtoxinA | Efficacy, Measured as the Percentage of Participants Who Responded to Treatment | 99.2 percentage of participants |
Comparison: With assumptions of an alpha of 5%, an equivalence margin of 15% for each side, the real response rate expected as 90% for incobotulinumtoxinA and onabotulinumtoxinA at day 30 and a 1:1 allocation ratio, a total of 225 subjects were needed to achieve a statistical power of 90% in order to make an equivalence conclusion at day 30. Results are based on the Newcombe-Wilson confidence interval. To account for exclusions from the PPS of about 10%, approximately 250 subjects were enrolled.95% CI: [-7.5, 0.6]
Secondary
Response at Maximum Frown Rated by Independent Rater
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 2 months from baseline.
Time frame: 2 months from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Independent Rater | 89.7 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Independent Rater | 95.0 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-12.1, 1.5]
Secondary
Response at Maximum Frown Rated by Independent Rater
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 3 months from baseline.
Time frame: 3 months from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Independent Rater | 80.2 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Independent Rater | 80.7 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-10.6, 9.6]
Secondary
Response at Maximum Frown Rated by Independent Rater
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 4 months from baseline.
Time frame: 4 months from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Independent Rater | 62.1 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Independent Rater | 67.2 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-17.4, 7.1]
Secondary
Response at Maximum Frown Rated by Treating Physician
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 4 months from treatment.
Time frame: 4 months from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 58.6 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 60.5 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-14.4, 10.7]
Secondary
Response at Maximum Frown Rated by Treating Physician
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 1 month from treatment.
Time frame: 1 month from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 93.1 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 95.8 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-8.5, 3.2]
Secondary
Response at Maximum Frown Rated by Treating Physician
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 2 months from treatment.
Time frame: 2 months from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 87.1 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 89.9 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-11, 5.3]
Secondary
Response at Maximum Frown Rated by Treating Physician
Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 3 months from treatment.
Time frame: 3 months from baseline
Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IncobotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 75.0 percentage of participants |
| OnabotulinumtoxinA | Response at Maximum Frown Rated by Treating Physician | 76.5 percentage of participants |
Comparison: The study was not powered for this secondary endpoint.95% CI: [-12.4, 9.5]
Secondary
Subject Perception of Treatment Onset
Assessment of subject perception of date of treatment onset using a take-home diary
Time frame: Open-ended time frame for the 4 month study duration. Data for onset and peak effect is recorded in the subject diary.
Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IncobotulinumtoxinA | Subject Perception of Treatment Onset | 3.0 days |
| OnabotulinumtoxinA | Subject Perception of Treatment Onset | 3.0 days |
Secondary
Subject Perception of Treatment Peak Effect
Assessment of subject perception of date of treatment peak effect using a take-home diary
Time frame: Open-ended time frame for the 4 month study duration. Data for onset and peak effect is recorded in the subject diary.
Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IncobotulinumtoxinA | Subject Perception of Treatment Peak Effect | Within 4 weeks | 108 participants |
| IncobotulinumtoxinA | Subject Perception of Treatment Peak Effect | Longer than 4 weeks | 7 participants |
| IncobotulinumtoxinA | Subject Perception of Treatment Peak Effect | Missing | 1 participants |
| OnabotulinumtoxinA | Subject Perception of Treatment Peak Effect | Longer than 4 weeks | 4 participants |
| OnabotulinumtoxinA | Subject Perception of Treatment Peak Effect | Within 4 weeks | 113 participants |
| OnabotulinumtoxinA | Subject Perception of Treatment Peak Effect | Missing | 2 participants |
Secondary
Subject Satisfaction
Assessment of subject treatment satisfaction by subject questionnaire and diary at 1 month from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as Satisfaction and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as Dissatisfaction. Subjects with missing data were categorized as Missing.
Time frame: 1 month from baseline
Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IncobotulinumtoxinA | Subject Satisfaction | Missing | 1 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Satisfaction | 112 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Dissatifaction | 3 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Missing | 0 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Satisfaction | 116 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Dissatifaction | 3 participants |
Secondary
Subject Satisfaction
Assessment of subject treatment satisfaction by subject questionnaire and diary at 2 months from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as Satisfaction and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as Dissatisfaction. Subjects with missing data were categorized as Missing.
Time frame: 2 months from baseline
Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IncobotulinumtoxinA | Subject Satisfaction | Satisfied | 110 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Dissatisfied | 5 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Missing | 1 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Satisfied | 113 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Dissatisfied | 6 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Missing | 0 participants |
Secondary
Subject Satisfaction
Assessment of subject treatment satisfaction by subject questionnaire and diary at 3 months from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as Satisfaction and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as Dissatisfaction. Subjects with missing data were categorized as Missing.
Time frame: 3 months from baseline
Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IncobotulinumtoxinA | Subject Satisfaction | Satisfaction | 108 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Missing | 1 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Dissatisfaction | 7 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Dissatisfaction | 10 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Missing | 1 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Satisfaction | 108 participants |
Secondary
Subject Satisfaction
Assessment of subject treatment satisfaction by subject questionnaire and diary at 4 months from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as Satisfaction and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as Dissatisfaction. Subjects with missing data were categorized as Missing.
Time frame: 4 months from baseline
Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IncobotulinumtoxinA | Subject Satisfaction | Missing | 1 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Satisfaction | 107 participants |
| IncobotulinumtoxinA | Subject Satisfaction | Dissatisfaction | 8 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Satisfaction | 104 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Dissatisfaction | 11 participants |
| OnabotulinumtoxinA | Subject Satisfaction | Missing | 4 participants |