Forehead Lines
Conditions
Keywords
Forehead Lines, OnabotulinumtoxinA X
Brief summary
Facial lines that develop from repeated facial expression, such as forehead lines (FHL), are typically treated by selectively weakening specific muscles with small quantities of botulinum toxin. OnabotulinumtoxinA X is being investigated as another form of treatment to treat FHL by inhibiting the release of the neurotransmitter that causes the overactivity of the muscles responsible for the severity of these facial lines. The purpose of this study is to evaluate the safety and change in condition of 3 doses of OnabotulinumtoxinA X for the treatment of moderate to severe forehead lines. Study doctors will determine if a subject is eligible for the study. If so, the subject will be randomized into 1 of the 4 groups, called treatment arms. There is a 1 in 4 chance that a participant will be assigned to placebo. Around 120 adult participants with FHL will be enrolled in the study in approximately 10 sites in the United States. Participants will receive either intramuscular injections of onabotulinumtoxinA X or placebo. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular monthly visits during the study at the study site.
Interventions
Intramuscular Injection
DRUGPlacebo
Intramuscular Injection
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has sufficient visual acuity without the use of eyeglasses (contact lens use is acceptable) to accurately assess their facial lines * Participant has moderate or severe Forehead Lines (FHL) at maximum eyebrow elevation
Exclusion criteria
* History of known immunization to any botulinum toxin serotype. * History of known hypersensitivity to any botulinum toxin serotype, or any other constituents of the study drug or its excipients, and/or other products in the same class. * Presence or history of any medical condition that may place the participant at increased risk following exposure to OnabotulinumtoxinA X or interfere with the study evaluation, including: Diagnosed myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function. * History of Facial nerve palsy. * Infection or dermatological condition at the site of study drug injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Day 1 to Day 180 | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a casual relationship with this treatment. The investigator assesses the relationship of each event to the use of the study. A serious adverse event (SAE) is an event that results in death, is life threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event, that based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. |
| Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Day 1 to Day 180 | Percentage of participants with potentially clinically significant vital sign measurements like systolic and diastolic blood pressure will be assessed. |
| Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline on the Investigator-rated Clinician Forehead Lines Scale at Maximum Contraction. | Day 1 to Day 30 | Facial Wrinkle Scale - Forehead Lines (FWS-FHL) at maximum contraction (also known as eyebrow elevation) The Clinician Forehead Lines Scale is a four point scale used to assess the severity of forehead lines at maximum contraction ranging from 0 - None to 3 - Severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo will be injected into the forehead on Day 1. | 30 |
| OnabotulinumtoxinA X Dose A OnabotulinumtoxinA X will be injected into the forehead on Day 1. | 35 |
| OnabotulinumtoxinA X Dose B OnabotulinumtoxinA X will be injected into the forehead on Day 1. | 31 |
| OnabotulinumtoxinA X Dose C OnabotulinumtoxinA X will be injected into the forehead on Day 1. | 28 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 1 |
| Overall Study | Other | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | OnabotulinumtoxinA X Dose A | OnabotulinumtoxinA X Dose B | Placebo | OnabotulinumtoxinA X Dose C | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.7 years STANDARD_DEVIATION 11.97 | 46.6 years STANDARD_DEVIATION 11.82 | 46.1 years STANDARD_DEVIATION 12.33 | 50.5 years STANDARD_DEVIATION 12.87 | 46.6 years STANDARD_DEVIATION 12.32 |
| Age, Customized 18-25 | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Age, Customized 26-40 | 11 Participants | 7 Participants | 9 Participants | 8 Participants | 35 Participants |
| Age, Customized 41-55 | 16 Participants | 13 Participants | 11 Participants | 9 Participants | 49 Participants |
| Age, Customized 56-64 | 5 Participants | 9 Participants | 8 Participants | 7 Participants | 29 Participants |
| Age, Customized >=65 | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 27 Participants | 24 Participants | 22 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 28 Participants | 30 Participants | 26 Participants | 118 Participants |
| Sex: Female, Male Female | 28 Participants | 28 Participants | 26 Participants | 26 Participants | 108 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 4 Participants | 2 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 35 | 0 / 31 | 0 / 28 |
| other Total, other adverse events | 4 / 30 | 5 / 35 | 10 / 31 | 9 / 28 |
| serious Total, serious adverse events | 1 / 30 | 0 / 35 | 0 / 31 | 0 / 28 |
Outcome results
Primary
Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a casual relationship with this treatment. The investigator assesses the relationship of each event to the use of the study. A serious adverse event (SAE) is an event that results in death, is life threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event, that based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: Day 1 to Day 180
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events | 10 Participants |
| OnabotulinumtoxinA X Dose A | Number of Participants With Adverse Events | 12 Participants |
| OnabotulinumtoxinA X Dose B | Number of Participants With Adverse Events | 18 Participants |
| OnabotulinumtoxinA X Dose C | Number of Participants With Adverse Events | 13 Participants |
Primary
Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline on the Investigator-rated Clinician Forehead Lines Scale at Maximum Contraction.
Facial Wrinkle Scale - Forehead Lines (FWS-FHL) at maximum contraction (also known as eyebrow elevation) The Clinician Forehead Lines Scale is a four point scale used to assess the severity of forehead lines at maximum contraction ranging from 0 - None to 3 - Severe.
Time frame: Day 1 to Day 30
Population: Intent-to-Treat Population~Overall Number of Participants Analyzed = Number of subjects with data at baseline and the visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline on the Investigator-rated Clinician Forehead Lines Scale at Maximum Contraction. | 58.6 percentage of participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline on the Investigator-rated Clinician Forehead Lines Scale at Maximum Contraction. | 100 percentage of participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline on the Investigator-rated Clinician Forehead Lines Scale at Maximum Contraction. | 96.8 percentage of participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline on the Investigator-rated Clinician Forehead Lines Scale at Maximum Contraction. | 100 percentage of participants |
Comparison: Confidence interval for responder rate is calculated using normal approximation.p-value: <0.00195% CI: [23.5, 59.3]Cochran-Mantel-Haenszel
Comparison: Confidence interval for responder rate is calculated using normal approximation.p-value: <0.00195% CI: [19.2, 57.1]Cochran-Mantel-Haenszel
Comparison: Confidence interval for responder rate is calculated using normal approximation.p-value: <0.00195% CI: [23.5, 59.3]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters
Percentage of participants with potentially clinically significant vital sign measurements like systolic and diastolic blood pressure will be assessed.
Time frame: Day 1 to Day 180
Population: Safety population~Overall Number of Participants Analyzed = Except for Temperature, number of subjects with an available baseline value and at least 1 postbaseline assessment; for Temperature, number of subjects with at least 1 postbaseline assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≥ 160 and Increase of ≥ 20 | 0 Participants |
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≥ 110 and Increase of ≥ 15 | 0 Participants |
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 0 Participants |
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Temperature (C): ≥ 38.3 | 0 Participants |
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≥ 100 and Increase of ≥ 15 | 1 Participants |
| Placebo | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≥ 100 and Increase of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≥ 110 and Increase of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Temperature (C): ≥ 38.3 | 0 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 1 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≥ 160 and Increase of ≥ 20 | 1 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≥ 160 and Increase of ≥ 20 | 1 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 1 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≥ 100 and Increase of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≥ 110 and Increase of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Temperature (C): ≥ 38.3 | 0 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≥ 100 and Increase of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Temperature (C): ≥ 38.3 | 0 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≤ 50 and Decrease of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 0 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Systolic Blood Pressure (mmHg): ≥ 160 and Increase of ≥ 20 | 1 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Heart Rate (beats/min): ≥ 110 and Increase of ≥ 15 | 0 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Potentially Clinically Significant Vital Sign Parameters | Diastolic Blood Pressure (mmHg): ≤ 50 and Decrease of ≥ 15 | 0 Participants |