A Safety and Efficacy Study of OnabotulinumtoxinA in Forehead and Glabellar Facial Rhytides

Study Overview
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Brief Summary
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This is a safety and efficacy study of onabotulinumtoxinA in subjects with forehead and glabellar facial rhytides (frown lines).

Official Title
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Evaluation of the Safety and Efficacy of Treatment With BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex for Subjects With Forehead and Glabellar Facial Rhytides

Conditions
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Forehead Rhytides, Glabellar Rhytides

Intervention / Treatment
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* Biological: OnabotulinumtoxinA
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe forehead and glabellar lines Willing to have facial photos taken Exclusion Criteria: Prior exposure to botulinum toxin of any serotype for any indication Anticipated need for treatment with botulinum toxin of any serotype for any indication during the study, other than study treatment Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis Any facial resurfacing laser or light treatment, microdermabrasion, or superficial peels in the past 3 months Any medium depth or deep depth facial chemical peels; facial skin resurfacing; or permanent facial make-up in the past 6 months Any nonpermanent soft tissue fillers, or treatment with oral retinoids in the past year Prior face lift, thread lift, eyebrow lift, or related procedures (eg, eyelid and/or eyebrow surgery) Prior facial treatment with permanent soft tissue fillers, synthetic implants (eg, Gore-Tex®), and/or fat transplantation

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<br>OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the protocol-specified areas. Subjects will receive at least 1 and up to 3 treatments.<br>* Other names: botulinum toxin Type A;|
| Placebo Comparator: Placebo followed by OnabotulinumtoxinA in Period 2<br>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas. | Drug: Normal Saline<br>* Placebo (normal saline) injected into the protocol-specified areas on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation | The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported. | Baseline, Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation | The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of none and mild are reported. | Day 30 | 
| Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest | The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported. | Baseline, Day 30 | 
| Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5 | The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks How satisfied are you with the effect your treatment had on your facial lines? Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported. | Day 60 | 
| Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points | The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis. | Baseline, Day 30 | 
| Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire© | The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is I look older than my actual age because of my facial lines with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis. | Baseline, Day 30 | 
| Time to Retreatment Eligibility | Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis. | 12 Months |