Crow's Feet Lines, Facial Rhytides, Glabellar Lines
Conditions
Brief summary
This study will evaluate the safety and efficacy of botulinum toxin Type A compared to placebo for the treatment of Crow's Feet Lines and Frown Lines (Facial Rhytides)
Interventions
BIOLOGICALonabotulinumtoxinA 24 U
24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients will receive two treatments 4 months apart.
BIOLOGICALonabotulinumtoxinA 44 U
44 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients will receive two treatments 4 months apart
DRUGnormal saline
Normal Saline injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients will receive two treatments 4 months apart.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate to severe Crow's Feet Lines and Frown Lines * Have adequate vision without the use of eyeglasses to assess facial wrinkles in the mirror (contact lenses OK)
Exclusion criteria
* Current or previous botulinum toxin treatment of any serotype * Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis * Prior facial cosmetic surgery (e.g., prior periorbital surgery, facial lift, brow lift, eyelid lift or eyebrow surgery) * Facial laser or light treatment, microdermabrasion, or superficial peels within 3 months * Oral retinoid therapy within one year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile | Baseline, Day 30 | The composite facial wrinkle scale assessment is based on both the Investigator and Subject Facial Wrinkle scales at Day 30. The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe and the patient assessed the severity of their Crow's Feet Lines at maximum smile using the same 4-point Facial Wrinkle Scale. A responder is defined as a participant with a ≥ 2-grade improvement from Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile | Baseline, Day 30 | The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported. |
| Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest | Baseline, Day 30 | The Investigator assessed the severity of the patient's Crow's Feet Lines at rest using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported. |
| Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score | Day 30 | Patients rated the change in their Crow's Feet Lines using the SGA-CFL 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse or 7=very much worse at Day 30. Lower scores indicate improvement. |
| Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines | Day 30 | The Investigator assessed the severity of the patient's Crow's Feet lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a score of none or mild at Day 30 is reported. |
| Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30 | Baseline, Day 30 | The percentage of FLO-11 Item #2 responders, defined as participants with a ≥ 2-point improvement in FLO-11 score from Baseline for FLO-11 Question #2: When I look in the mirror, my facial lines make me look older than I want to look. The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much). |
| Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30 | Baseline, Day 30 | The percentage of FLO-11 Item #5 responders, defined as participants with a ≥ 2-point improvement in FLO-11 score from Baseline for FLO-11 Question #5: My facial lines make me look less attractive than I want to look. The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much). |
| Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30 | Baseline, Day 30 | The percentage of FLO-11 Item #8 responders, defined as participants with a ≥ 3-point improvement in FLO-11 score from Baseline for FLO-11 Question #8: My facial lines make me look tired. The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much). |
| Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline | Baseline, Day 30 | Participants were considered to judge themselves as looking younger if the category change was from look my current age at Baseline to look younger at Day 30 or from look older at Baseline to look my current age/younger at Day 30. |
Countries
Canada, France, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| onabotulinumtoxinA 44U 44 units (U) onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients received two treatments 4 months apart. | 305 |
| onabotulinumtoxinA 24U 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose and placebo (normal saline) injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients received two treatments 4 months apart. | 306 |
| Placebo (Normal Saline) Normal Saline injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients received two treatments 4 months apart. | 306 |
| Total | 917 |
Baseline characteristics
| Characteristic | onabotulinumtoxinA 44U | onabotulinumtoxinA 24U | Placebo (Normal Saline) | Total |
|---|---|---|---|---|
| Age, Customized 45 to 65 Years | 204 Participants | 200 Participants | 194 Participants | 598 Participants |
| Age, Customized <45 Years | 87 Participants | 89 Participants | 100 Participants | 276 Participants |
| Age, Customized >65 Years | 14 Participants | 17 Participants | 12 Participants | 43 Participants |
| CFL Severity as Assessed by the Investigator Moderate | 109 Participants | 115 Participants | 113 Participants | 337 Participants |
| CFL Severity as Assessed by the Investigator Severe | 196 Participants | 191 Participants | 193 Participants | 580 Participants |
| Sex: Female, Male Female | 267 Participants | 273 Participants | 263 Participants | 803 Participants |
| Sex: Female, Male Male | 38 Participants | 33 Participants | 43 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 305 | 51 / 306 | 38 / 306 |
| serious Total, serious adverse events | 5 / 305 | 8 / 306 | 6 / 306 |
Outcome results
Primary
Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile
The composite facial wrinkle scale assessment is based on both the Investigator and Subject Facial Wrinkle scales at Day 30. The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe and the patient assessed the severity of their Crow's Feet Lines at maximum smile using the same 4-point Facial Wrinkle Scale. A responder is defined as a participant with a ≥ 2-grade improvement from Baseline.
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants. Participants with missing values are considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile | 21.3 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile | 20.6 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile | 0.0 Percentage of participants |
Secondary
Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines
The Investigator assessed the severity of the patient's Crow's Feet lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a score of none or mild at Day 30 is reported.
Time frame: Day 30
Population: Intent-to-treat population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines | 59.0 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines | 54.9 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines | 3.3 Percentage of participants |
Secondary
Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline
Participants were considered to judge themselves as looking younger if the category change was from look my current age at Baseline to look younger at Day 30 or from look older at Baseline to look my current age/younger at Day 30.
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants. Only those participants who rated themselves as look my current age or look older at Baseline are included in the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline | 50.6 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline | 33.6 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline | 9.1 Percentage of participants |
Secondary
Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile
The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported.
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile | 87.9 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile | 78.1 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile | 10.1 Percentage of participants |
Secondary
Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest
The Investigator assessed the severity of the patient's Crow's Feet Lines at rest using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported.
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants. Only those participants who were rated at least mild at Baseline are included in the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest | 75.1 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest | 61.3 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest | 13.4 Percentage of participants |
Secondary
Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30
The percentage of FLO-11 Item #2 responders, defined as participants with a ≥ 2-point improvement in FLO-11 score from Baseline for FLO-11 Question #2: When I look in the mirror, my facial lines make me look older than I want to look. The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much).
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants. Only participants with a Baseline score ≥ 2 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30 | 69.9 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30 | 54.4 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30 | 24.6 Percentage of participants |
Secondary
Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30
The percentage of FLO-11 Item #5 responders, defined as participants with a ≥ 2-point improvement in FLO-11 score from Baseline for FLO-11 Question #5: My facial lines make me look less attractive than I want to look. The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much).
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants. Only participants with a Baseline score ≥ 2 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30 | 61.7 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30 | 48.6 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30 | 18.6 Percentage of participants |
Secondary
Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30
The percentage of FLO-11 Item #8 responders, defined as participants with a ≥ 3-point improvement in FLO-11 score from Baseline for FLO-11 Question #8: My facial lines make me look tired. The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much).
Time frame: Baseline, Day 30
Population: Intent-to-treat population included all randomized participants. Only participants with a Baseline score ≥ 3 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| onabotulinumtoxinA 44U | Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30 | 58.1 Percentage of participants |
| onabotulinumtoxinA 24U | Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30 | 40.7 Percentage of participants |
| Placebo (Normal Saline) | Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30 | 14.9 Percentage of participants |
Secondary
Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score
Patients rated the change in their Crow's Feet Lines using the SGA-CFL 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse or 7=very much worse at Day 30. Lower scores indicate improvement.
Time frame: Day 30
Population: Intent-to-treat population included all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| onabotulinumtoxinA 44U | Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score | 2.3 Score on a scale | Standard Deviation 0.96 |
| onabotulinumtoxinA 24U | Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score | 2.5 Score on a scale | Standard Deviation 1.05 |
| Placebo (Normal Saline) | Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score | 3.8 Score on a scale | Standard Deviation 0.54 |