BOTOX® (onabotulinumtoxinA) Treatment of Masseter Muscle... | NCT03861936

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BOTOX® 72U	Experimental	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72 units (U) total dose administered intramuscularly to the bilateral masseter muscles on Day 1.	Biological: OnabotulinumtoxinA
BOTOX® 48U	Experimental	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.	Biological: OnabotulinumtoxinA
Placebo	Placebo Comparator	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.	Drug: Normal saline

Interventions

Name	Type	Description	Arm Group Labels	Other Names
OnabotulinumtoxinA	Biological	OnabotulinumtoxinA (botulinum toxin Type A;BOTOX®) administered intramuscularly to the bilateral masseter muscles on Day 1.	BOTOX® 48U

Outcomes Module

Primary Outcomes

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.

Secondary Outcomes

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.

Eligibility Module

Eligibility Criteria

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:
1. Not a woman of childbearing potential (WOCBP) OR
2. 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.

Name	Affiliation	Role
Tanya Brandstetter	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Total Skin & Beauty Dermatology Center, PC		Birmingham	Alabama	35205	United States
Westside Aesthetics

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
FG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48 units (U) total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 12, 2019	Apr 2, 2021

ID	Title	Description
BG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
BG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
BG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00046 BG00153 BG00246 BG003145

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment.

Posted

Number

95% Confidence Interval

percentage of participants

Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Units	Counts
Participants	OG00046 OG00153 OG00246

Title

Denominators

Categories

Title	Measurements
	OG00021.7(9.8 to 33.7) OG00190.6(82.7 to 98.4) OG00291.3(83.2 to 99.4)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		<.0001	P-values for between-treatment comparisons are based on Cochran-Mantel-Haenszel (CMH) model stratified by baseline MMPS Grade (4 or 5).	Percentage Difference	68.8			2-Sided	95	54.5	83.1					Superiority
OG000 OG002		Cochran-Mantel-Haenszel

Primary

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.

Safety Population consisted of all participants who received at least 1 injection of study intervention.

Posted

Count of Participants

Participants

First dose (Day 1) to the End of Study (Up to Day 180)

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Primary

Change From Baseline in Systolic Blood Pressure

Safety Population consisted of all participants who received at least 1 injection of study intervention. Number analyzed is the number of participants with data available at the given time-point.

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

Baseline (Day 1) to the End of Study (Up to Day 180)

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Units	Counts
Participants

Primary

Change From Baseline in Diastolic Blood Pressure

Safety Population consisted of all participants who received at least 1 injection of study intervention. Number analyzed is the number of participants with data available at the given time-point.

Posted

Mean

Standard Deviation

mmHg

Baseline (Day 1) to the End of Study (Up to Day 180)

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Units	Counts
Participants

Primary

Change From Baseline in Respiratory Rate

Respiratory rate is calculated as number of breaths (inhalation and exhalation) in one minute.

Safety Population consisted of all participants who received at least 1 injection of study intervention. Number analyzed is the number of participants with data available at the given time-point.

Posted

Mean

Standard Deviation

breaths/minute

Baseline (Day 1) to the End of Study (Up to Day 180)

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Units	Counts

Primary

Change From Baseline in Pulse Rate

Pulse rate measures the number of times your heart beats per minute.

Safety Population consisted of all participants who received at least 1 injection of study intervention. Number analyzed is the number of participants with data available at the given time-point.

Posted

Mean

Standard Deviation

beats/minute

Baseline (Day 1) to the End of Study (Up to Day 180) ]

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Units	Counts

Secondary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment. Missing postbaseline data are imputed using last observation carried forward (LOCF).

Posted

Number

95% Confidence Interval

percentage of participants

Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Secondary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment. Missing postbaseline data are imputed using LOCF.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline (Day 1) to Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Secondary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment. Missing postbaseline data are imputed using LOCF.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline (Day 1) to Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Secondary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment. Missing postbaseline data are imputed using LOCF.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline (Day 1) to Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Secondary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment. Missing postbaseline data are imputed using LOCF.

Posted

Least Squares Mean

Standard Error

cubic centimeter (cm^3)

Baseline (Day 1) to Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U

Secondary

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.

mITT Population consisted of all randomized participants who received study treatment and had at least 1 postbaseline MMPS assessment. Missing postbaseline data are imputed using LOCF.

Posted

Least Squares Mean

Standard Error

cm^3

Baseline (Day 1) to Day 90

ID	Title	Description
OG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.
OG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.
OG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected48 at risk EG0010 affected53 at risk EG0020 affected49 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected48 at risk EG0010 affected53 at risk EG0020 affected49 at risk
Anxiety	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0011 affected53 at risk EG0020 affected49 at risk
Suicide attempt	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0011 affected53 at risk EG0020 affected49 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected53 at risk EG0021 affected49 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected53 at risk EG0020 affected49 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0010 affected53 at risk EG0023 affected49 at risk

ID	Term
D019274	Botulinum Toxins, Type A
D000077330	Saline Solution

ID	Term
D001905	Botulinum Toxins
D008666	Metalloendopeptidases
D010450	Endopeptidases
D010447	Peptide Hydrolases
D006867	Hydrolases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D045726	Metalloproteases
D001426	Bacterial Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D001427	Bacterial Toxins
D014118	Toxins, Biological
D001685	Biological Factors
D000077324	Crystalloid Solutions
D007552	Isotonic Solutions
D012996	Solutions
D004364	Pharmaceutical Preparations

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1.	48	1	48	0	48
EG001	BOTOX® 48U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.	53	1	53	6	53
EG002	BOTOX® 72U	OnabotulinumtoxinA (botulinum toxin Type A; BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1.	49	0	49	4	49