Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Crow's Feet Lines and Frown Lines

Study Overview
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Brief Summary
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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)

Conditions
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Facial Rhytides, Crow's Feet Lines, Glabellar Lines

Intervention / Treatment
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* Biological: onabotulinumtoxinA 24 U
* Biological: onabotulinumtoxinA 44 U
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: onabotulinumtoxinA 44U<br>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. | Biological: onabotulinumtoxinA 44 U<br>* 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<br>* Other names: onabotulinumtoxinA;|
| Other: onabotulinumtoxinA 24U<br>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. | Biological: onabotulinumtoxinA 24 U<br>* 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.<br>* Other names: onabotulinumtoxinA;Drug: normal saline<br>* Normal Saline injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients will receive two treatments 4 months apart.<br>|
| Placebo Comparator: placebo (normal saline)<br>Normal Saline injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients received two treatments 4 months apart. | Drug: normal saline<br>* Normal Saline injected into bilateral Crow's Feet Line and Frown Line areas per treatment. Patients will receive two treatments 4 months apart.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 30 | 
| 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. | Baseline, Day 30 | 
| 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. | Baseline, Day 30 | 
| 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. | Day 30 | 
| 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. | Baseline, Day 30 | 
| 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). | Baseline, Day 30 | 
| 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). | Baseline, Day 30 | 
| 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). | Baseline, Day 30 |