Masseter Muscle Hypertrophy
Conditions
Brief summary
This study will evaluate the safety and efficacy of a range of doses of botulinum toxin Type A (BOTOX®) for the treatment of patients with bilateral Masseter Muscle Hypertrophy (MMH).
Interventions
BIOLOGICALbotulinum toxin Type A
Botulinum toxin Type A (BOTOX®) administered intramuscularly to the bilateral masseter muscles on Day 1 and retreatment at Day 180 if applicable.
DRUGNormal saline
Normal saline (placebo) administered intramuscularly to the bilateral masseter muscles.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
-Participants with Masseter Muscle Hypertrophy
Exclusion criteria
* Diagnosis of Myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function * Prior botulinum toxin treatment of any serotype to the masseter muscle or lower face * History of dental or surgical procedure for lower facial shaping or masseter muscle reduction * History of or current temporomandibular joint disorder (TMJD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lower Facial Volume Using VECTRA 3D Images | Baseline (Day 1) to Day 90 of Treatment Cycle 1 | Lower facial volume was calculated from 3-dimensional (3D) images captured with the VECTRA M3 3D Stereophotogrammetry imaging system and was analyzed using computer assisted systems and predetermined facial landmarks. The difference in volume was measured between the select region of the baseline surface 3D model and the select region of the posttreatment surface 3D model. A negative change from Baseline (decrease in volume) indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator | Day 90 of Treatment Cycle 1 | The investigator used visual inspection and palpation to grade the prominence of the participant's masseter muscle on the left and right sides of the face using the MMPS where: 1=minimal prominence (best), 2=mild prominence, 3=moderate prominence, 4=marked prominence, 5=very marked prominence (worst). The percentage of participants with grade 3 or less is reported. |
Countries
Australia, Canada, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BOTOX® 96U Botulinum Toxin Type A (BOTOX®) 96U total dose administered intramuscularly to the bilateral masseter muscles on Day 1 and retreatment at Day 180 if applicable. | 38 |
| BOTOX® 72U Botulinum Toxin Type A (BOTOX®) 72U total dose administered intramuscularly to the bilateral masseter muscles on Day 1 and retreatment at Day 180 if applicable. | 38 |
| BOTOX® 48U Botulinum Toxin Type A (BOTOX®) 48U total dose administered intramuscularly to the bilateral masseter muscles on Day 1 and retreatment at Day 180 if applicable. | 37 |
| BOTOX® 24U Botulinum Toxin Type A (BOTOX®) 24U total dose administered intramuscularly to the bilateral masseter muscles on Day 1 and retreatment at Day 180 if applicable. | 37 |
| Placebo Placebo (Normal saline) administered intramuscularly to the bilateral masseter muscles on Day 1 and retreatment at Day 180 if applicable. | 37 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 | 1 | 1 |
| Overall Study | Personal Reasons | 3 | 3 | 1 | 2 | 4 |
| Overall Study | Pregnancy | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | BOTOX® 96U | BOTOX® 72U | BOTOX® 48U | BOTOX® 24U | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 35.3 Years STANDARD_DEVIATION 9.1 | 34.9 Years STANDARD_DEVIATION 8.35 | 37.2 Years STANDARD_DEVIATION 7.69 | 34.0 Years STANDARD_DEVIATION 9.08 | 35.4 Years STANDARD_DEVIATION 8.08 | 35.4 Years STANDARD_DEVIATION 8.45 |
| Race/Ethnicity, Customized Asian | 30 Participants | 30 Participants | 30 Participants | 32 Participants | 27 Participants | 149 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants | 7 Participants | 7 Participants | 5 Participants | 10 Participants | 36 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other Race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 30 Participants | 28 Participants | 31 Participants | 32 Participants | 32 Participants | 153 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 6 Participants | 5 Participants | 5 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 38 | 0 / 37 | 0 / 37 | 0 / 37 |
| other Total, other adverse events | 13 / 38 | 10 / 38 | 12 / 37 | 16 / 37 | 10 / 37 |
| serious Total, serious adverse events | 1 / 38 | 0 / 38 | 0 / 37 | 2 / 37 | 3 / 37 |
Outcome results
Primary
Change From Baseline in Lower Facial Volume Using VECTRA 3D Images
Lower facial volume was calculated from 3-dimensional (3D) images captured with the VECTRA M3 3D Stereophotogrammetry imaging system and was analyzed using computer assisted systems and predetermined facial landmarks. The difference in volume was measured between the select region of the baseline surface 3D model and the select region of the posttreatment surface 3D model. A negative change from Baseline (decrease in volume) indicates improvement.
Time frame: Baseline (Day 1) to Day 90 of Treatment Cycle 1
Population: Participants from the mITT population, all randomized participants who received at least 1 injection of study treatment and had at least 1 follow-up visit, with data available for analysis at Day 90. Change in lower facial volume was quantified in cm\^3 using image subtraction techniques; as the Baseline is an image, no Baseline data are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BOTOX® 96U | Change From Baseline in Lower Facial Volume Using VECTRA 3D Images | -8.20 cubic centimeter (cm^3) |
| BOTOX® 72U | Change From Baseline in Lower Facial Volume Using VECTRA 3D Images | -7.41 cubic centimeter (cm^3) |
| BOTOX® 48U | Change From Baseline in Lower Facial Volume Using VECTRA 3D Images | -6.84 cubic centimeter (cm^3) |
| BOTOX® 24U | Change From Baseline in Lower Facial Volume Using VECTRA 3D Images | -4.40 cubic centimeter (cm^3) |
| Placebo | Change From Baseline in Lower Facial Volume Using VECTRA 3D Images | -0.52 cubic centimeter (cm^3) |
p-value: <0.00195% CI: [-5.58, -2.19]ANOVA
p-value: <0.00195% CI: [-8.02, -4.62]ANOVA
p-value: <0.00195% CI: [-8.56, -5.22]ANOVA
p-value: <0.00195% CI: [-9.35, -6]ANOVA
Secondary
Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator
The investigator used visual inspection and palpation to grade the prominence of the participant's masseter muscle on the left and right sides of the face using the MMPS where: 1=minimal prominence (best), 2=mild prominence, 3=moderate prominence, 4=marked prominence, 5=very marked prominence (worst). The percentage of participants with grade 3 or less is reported.
Time frame: Day 90 of Treatment Cycle 1
Population: Participants from the mITT population, all randomized participants who received at least 1 injection of study treatment and had at least 1 follow-up visit, with data available for analysis at Day 90. Missing data was imputed using last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX® 96U | Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator | 89.5 Percentage of participants |
| BOTOX® 72U | Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator | 89.5 Percentage of participants |
| BOTOX® 48U | Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator | 83.3 Percentage of participants |
| BOTOX® 24U | Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator | 66.7 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved a Masseter Muscle Prominence Scale (MMPS) Grade ≤ 3 as Assessed by the Investigator | 35.1 Percentage of participants |
p-value: 0.00895% CI: [9.8, 53.3]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [28.6, 67.8]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [36.1, 72.6]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [36.1, 72.6]Cochran-Mantel-Haenszel