Glabellar Frown Lines
Conditions
Keywords
Botulinum toxin type A
Brief summary
The purpose of this study is to demonstrate the safety and duration of effect of 40 Units of prabotulinumtoxinA-xvfs (Jeuveau®) in providing temporary improvement in the appearance of moderate to severe glabellar lines (frown lines, which are the vertical lines that develop between the eyebrows) in adult participants. It will also determine if the duration of effect of 40 Units of Jeuveau® is greater than that of 20 Units of Jeuveau® and 20 Units of Botox® Cosmetic.
Detailed description
This is a multicenter, prospective, randomized, double-blind, active-controlled, single-treatment, increasing dose design. Up to one hundred and fifty subjects will be randomized 1:1:1, to either 20 Units onabotulinumtoxinA (Botox® Cosmetic), 20 Units prabotulinumtoxinA-xvfs (Jeuveau®), or 40 Units prabotulinumtoxinA-xvfs (Jeuveau®).
Interventions
One treatment of 40 units
DRUGOnabotulinumtoxinA
One treatment of 20 units
Sponsors
ethica Clinical Research Inc.
Evolus, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Outpatient, male or female of any race, 18 years of age or older. * Female subjects of childbearing potential must have a negative urine pregnancy test during Visits 1 (Screening) and Visit 2 (if applicable) and practice a reliable method of contraception for the duration of the study. * Moderate to severe glabellar lines (i.e., score of 2 or 3) on maximum frown as assessed by the investigator using the Glabellar Line Scale (GLS). * Subject has moderate to severe glabellar lines (i.e., score of 2 or 3) at maximum frown as assessed by the subject using the GLS. * Able to follow study instructions and likely to complete all required visits. * Sign the Institutional Review Board (IRB) -approved Informed Consent Form (ICF) prior to any study-related procedures being performed.
Exclusion criteria
* Female subjects who are pregnant, breast-feeding, or of childbearing potential and not practicing reliable birth control. * Known hypersensitivity or previous allergic reaction to any constituent of the Investigational Product (IP) or control. * Any active infection in the area of the injection sites. * Inability to substantially lessen glabellar frown lines even by physically spreading them apart. * Marked facial asymmetry (Investigator discretion). * Ptosis of eyelid and/or eyebrow, or history of eyelid and/or eyebrow ptosis. * History of facial nerve palsy. * Excessive dermatochalasis, deep dermal scarring, thick sebaceous skin (Investigator discretion). * Medical condition that may affect neuromuscular function (e.g., myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis). * Previous treatment with botulinum toxin of any serotype above the level of the lateral canthus within the last 6 months. * Planned treatment with botulinum toxin of any serotype below the level of the lateral canthus during the study period. * Previous treatment with any facial aesthetic procedure (e.g., injection with biodegradable fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 months. * Previous insertion of permanent material in the glabellar area. * Any previous energy based or cryotherapy-based treatment of facial muscles superior to the lateral canthus. * Any other planned facial aesthetic procedure during the trial period, superior to the level of the lateral canthus (can continue with their usual skin care routine). * Any surgery in the glabellar area including surgical removal of the corrugator, procerus, or depressor supercilii muscles, or a combination of these, or scars in the glabellar area and the surrounding areas (including eyebrow). * Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study. * Evidence of recent alcohol or drug abuse (Investigator discretion). * History of poor cooperation or unreliability. * Planning to move out of the area prior to study completion. * Subjects who are investigational site staff members or family members of such employees. * Exposure to any other investigational drug/device within 30 days prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Effect Described by Kaplan-Meier Analysis | Duration of effect for each subject will be based on number of days from baseline to the day that Glabellar Line Scale severity (Investigator Assessment) returns to baseline value, assessed every 30 days up to 365 days. | Effectiveness of prabotulinumtoxinA 40 Units compared to prabotulinumtoxinA 20 Units will be assessed for each subject based on the number of days from baseline to the day that the Glabellar Line Scale (GLS) severity, by Investigator Assessment, returns to the baseline value. The treatment will be considered to remain effective for the amount of time during which the GLS severity at maximum frown has not returned to baseline severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Drug 40U of PrabotulinumtoxinA-xvfs
PrabotulinumtoxinA-Xvfs: One treatment of 40 units | 51 |
| OnabotulinumtoxinA 20U of OnabotulinumtoxinA
OnabotulinumtoxinA: One treatment of 20 units | 50 |
| PrabotulinumtoxinA-xvfs 20U of PrabotulinumtoxinA-xvfs
PrabotulinumtoxinA-Xvfs: One treatment of 20 units | 53 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not receive treatment | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Moved; too much driving | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Study Drug | OnabotulinumtoxinA | PrabotulinumtoxinA-xvfs | Total |
|---|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 11.3 | 47.0 years STANDARD_DEVIATION 11.1 | 46.8 years STANDARD_DEVIATION 12.9 | 47 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 16 Participants | 15 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 34 Participants | 37 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Glabellar Line Score of Moderate at Maximum Frown by Investigator Assessment | 15 Participants | 14 Participants | 18 Participants | 47 Participants |
| Glabellar Line Score of Moderate at Maximum Frown by Subject Assessment | 11 Participants | 7 Participants | 13 Participants | 31 Participants |
| Glabellar Line Score of Severe at Maximum Frown by Investigator Assessment | 36 Participants | 36 Participants | 35 Participants | 107 Participants |
| Glabellar Line Score of Severe at Maximum Frown by Subject Assessment | 40 Participants | 43 Participants | 40 Participants | 123 Participants |
| Participant Has a Prior history of botulinum toxin use | 26 Participants | 26 Participants | 19 Participants | 71 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 48 Participants | 47 Participants | 49 Participants | 144 Participants |
| Region of Enrollment United States | 51 participants | 50 participants | 53 participants | 154 participants |
| Sex: Female, Male Female | 48 Participants | 47 Participants | 50 Participants | 145 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 50 | 0 / 53 |
| other Total, other adverse events | 2 / 51 | 5 / 50 | 3 / 52 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 | 0 / 53 |
Outcome results
Primary
Duration of Effect Described by Kaplan-Meier Analysis
Effectiveness of prabotulinumtoxinA 40 Units compared to prabotulinumtoxinA 20 Units will be assessed for each subject based on the number of days from baseline to the day that the Glabellar Line Scale (GLS) severity, by Investigator Assessment, returns to the baseline value. The treatment will be considered to remain effective for the amount of time during which the GLS severity at maximum frown has not returned to baseline severity.
Time frame: Duration of effect for each subject will be based on number of days from baseline to the day that Glabellar Line Scale severity (Investigator Assessment) returns to baseline value, assessed every 30 days up to 365 days.
Population: 152 participants comprised the modified intent to treat population; all 152 participants had at least one post-treatment assessment for the primary efficacy endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Drug | Duration of Effect Described by Kaplan-Meier Analysis | 183 Days |
| OnabotulinumtoxinA | Duration of Effect Described by Kaplan-Meier Analysis | 148 Days |
| PrabotulinumtoxinA-xvfs | Duration of Effect Described by Kaplan-Meier Analysis | 149 Days |
Comparison: The primary effectiveness endpoint was a measure of duration of effect, described by Kaplan-Meier curves and the median times, with associated 2-sided 95% confidence intervals for each treatment group.p-value: 0.0109Log Rank