BOTOX® (onabotulinumtoxinA) Treatment of Masseter Muscle Prominence

Study Overview
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Brief Summary
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Based on the results of the Phase 2 Study 191622-130 [NCT02010775], the current Phase 2b study is designed to further evaluate the safety and efficacy of BOTOX® for the treatment of Masseter Muscle Prominence (MMP) in adults.

Official Title
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BOTOX® (onabotulinumtoxinA) Treatment of Masseter Muscle Prominence: A Phase 2b, Multicenter, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study

Conditions
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Masseter Muscle Prominence

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 Participant has bilateral MMP (identical grades for left and right masseter), as determined at the Day 1 visit by the investigator using the MMPS Participant has bilateral MMP, as determined at the Day 1 visit by the participant using the Masseter Muscle Prominence Scale-Participant (MMPS-P) Body mass index (BMI) ≤ 30 kilogram/square meter (kg/m^2) using the calculation: BMI = weight (kg) [height (m^2)] Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. A female participant is eligible to participate if she is not pregnant (has a negative urine pregnancy result prior to randomization), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the treatment and follow-up period Able, as assessed by the investigator, and willing to follow study instructions and likely to complete all required study visits. Exclusion Criteria Any medical condition that may put the participant at increased medical risk with exposure to BOTOX®, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function Any uncontrolled medical condition An anticipated need for surgery or overnight hospitalization during the study An anticipated need for treatment with botulinum toxin of any serotype for any indication during the study (other than study intervention) History of dental or surgical procedure for lower facial shaping or masseter muscle reduction Prior mid-facial and/or lower facial treatment with nonpermanent soft tissue fillers, synthetic implantations, autologous fat transplantation, fat-reducing injectables, and/or skin-tightening laser treatments within 6 months of entry into the study Current or planned dental or facial procedures during the study period (eg, braces, dental implants, and reconstructive or aesthetic surgery) that could interfere with MMPS, as determined by the investigator Facial hair or scarring (eg, acne) significant enough to interfere with the 3D clinical photography assessment Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study Prior exposure to botulinum toxin of any serotype to the masseter muscle or lower face at any time, or to any other part of the body within the 6 months prior to Day 1 Current intraoral infection, including infection of the mouth or gums, or facial skin infection requiring medical treatment in the opinion of the investigator History of or current Temporomandibular Joint Dysfunction (TMJD), or presence of signs/symptoms of possible TMJD, in the opinion of the investigator Weakness of the masseter, pterygoid, or temporalis muscles due to trauma, facial nerve injury, or other condition that could interfere with normal chewing and jaw clenching, as determined by the investigator Excess lower facial fat, loose or lax skin in lower face, or parotid gland prominence that could interfere with MMPS, as determined by the investigator Significant asymmetry of left and right sides of the face that could prevent identical MMPS grading on both sides of the face, as determined by the investigator Masseter prominence due to other etiologies (eg, parotid gland infection, parotiditis, malignancy) based upon findings from the oral examination.

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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Accepts Healthy Volunteers

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: BOTOX® 72U<br>OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72 units (U) total dose administered intramuscularly to the bilateral masseter muscles on Day 1. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA (botulinum toxin Type A;BOTOX®) administered intramuscularly to the bilateral masseter muscles on Day 1.<br>* Other names: botulinum toxin Type A;|
| Experimental: BOTOX® 48U<br>OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA (botulinum toxin Type A;BOTOX®) administered intramuscularly to the bilateral masseter muscles on Day 1.<br>* Other names: botulinum toxin Type A;|
| Placebo Comparator: Placebo<br>Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1. | Drug: Normal saline<br>* Normal saline (placebo) administered intramuscularly to the bilateral masseter muscles on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 at Day 90 as Assessed by the Investigator | The investigator assessed the severity of the participant's masseter muscle prominence (MMP) using the MMPS 5-point scale where: 1=minimal (best), 2=mild, 3=moderate, 4=marked, and 5=very marked (worst). The percentage of participants where the investigator selected 1=minimal, 2=mild, or 3=moderate are reported. | Day 90 | 
| Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. A TEAE is an AE that occurs or worsens after receiving study drug. | First dose (Day 1) to the End of Study (Up to Day 180) | 
| Change From Baseline in Systolic Blood Pressure |  | Baseline (Day 1) to the End of Study (Up to Day 180) | 
| Change From Baseline in Diastolic Blood Pressure |  | Baseline (Day 1) to the End of Study (Up to Day 180) | 
| Change From Baseline in Respiratory Rate | Respiratory rate is calculated as number of breaths (inhalation and exhalation) in one minute. | Baseline (Day 1) to the End of Study (Up to Day 180) | 
| Change From Baseline in Pulse Rate | Pulse rate measures the number of times your heart beats per minute. | Baseline (Day 1) to the End of Study (Up to Day 180) ] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Participant Masseter Muscle Prominence Scale-Participant (MMPS-P) Grade ≤ 3 at Day 90 as Assessed by the Participant | The participant assessed the severity of their MMP using the MMPS-P 5-point scale where: 1=not at all pronounced (best), 2=mildly pronounced, 3=moderately pronounced, 4=pronounced, and 5=very pronounced (worst). The percentage of participants who selected 1=not at all pronounced, 2=mildly pronounced, or 3=moderately pronounced are reported. | Day 90 | 
| Percentage of Participants Who Achieved ≥ 2-grade MMPS Improvement From Baseline at Day 90 as Assessed by the Investigator | The investigator assessed the severity of the participant's MMP using the MMPS 5-point scale where: 1=minimal (best), 2=mild, 3=moderate, 4=marked, and 5=very marked (worst). The percentage of participants who achieved a ≥ 2-grade improvement (decrease) from Baseline as assessed by the investigator are reported. | Baseline (Day 1) to Day 90 | 
| Percentage of Participants Who Achieved ≥ 2-grade MMPS-P Improvement From Baseline at Day 90 as Assessed by the Participant | The participant assessed the severity of their MMP using the MMPS-P 5-point scale where: 1=not at all pronounced (best), 2=mildly pronounced, 3=moderately pronounced, 4=pronounced, and 5=very pronounced (worst). The percentage of participants who achieved a ≥ 2-grade improvement (decrease) from Baseline as assessed by the participant are reported. | Baseline (Day 1) to Day 90 | 
| Percentage of Participants Who Achieved Participant Self-Assessment of Change (PSAC) in MMP Grade ≥ 2 (at Least Moderately Improved From Baseline) at Day 90 | The participants assessed the degree of change of their MMP using a single item composed of 7 grades (3 to -3) where: 3=much improved, 2=moderately improved, 1=minimally improved, 0=no change, -1=minimally worse, -2=moderately worse, and -3=much worse. The percentage of participants where the participant selected 2=moderately improved, or 3=much improved as compared to Baseline are reported. | Baseline (Day 1) to Day 90 | 
| Change From Baseline in Lower Facial Volume at Day 90 Using Landmark Area of Interest (AOI) Analysis | Lower facial volume was calculated from 3-dimensional (3D) surface images captured at Baseline and Day 90. The analysis region is defined using a series of anatomical landmarks placed on the baseline surface that are then projected mathematically to the posttreatment surface and verified by a technician. The difference in volume is measured between the select region of the baseline surface to the posttreatment surface. The lower facial volume is summed for both the left side and the right side of the face. An analysis of covariance (ANCOVA) model was used for analyses. | Baseline (Day 1) to Day 90 | 
| Change From Baseline in Lower Facial Volume at Day 90 Using Statistical MMP AOI Analysis | Lower facial volume was calculated from 3D surface models of the full area of the lower face captured at Baseline and Day 90. The statistical MMP AOI method is based on a statistical shape averaging of the area of change post masseter treatment from multiple facial models. The difference in volume is calculated between the two 3D surface models at Baseline and Day 90. An ANCOVA model was used for analyses. | Baseline (Day 1) to Day 90 |