Glabellar Lines
Conditions
Keywords
OnabotulinumtoxinA X, BOTOX, Glabellar Lines
Brief summary
This is a Phase 2, dose ranging study to evaluate the safety of OnabotulinumtoxinA X and to compare the efficacy of OnabotulinumtoxinA X and placebo for the treatment of Glabellar Lines in adult participants with moderate to severe GL.
Interventions
Injection
DRUGPlacebo
Injection
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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, in the opinion of the investigator. * Participant has moderate or severe GL at maximum frown.
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. * Facial nerve palsy. * Infection or dermatological condition at the site of study drug injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale. | Day 1 to Day 30 | The Clinician Glabellar Lines Scale is a four point scale used to assess the severity of Glabellar Lines at maximum contraction ranging from 0 - None to 3 - Severe |
| Percentage of Participants With Adverse Events (AEs) | Day 1 to Day 270 | 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 causal relationship with this treatment. The investigator assesses the relationship of each event to the use of 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. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale. | Day 1 to Day 30 | The Clinician Glabellar Lines Scale is a four point scale used to assess the severity of Glabellar Lines at maximum contraction ranging from 0 - None to 3 - Severe |
| Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater. | Day 1 to Day 30 | The Facial Line Satisfaction Questionnaire assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the subject perspective. Domain scores are calculated as the mean of transformed item scores on a 0 (low impact) to 100 (highest negative impact) scale. |
| Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5. | Day 1 to Day 60 | The Facial Line Satisfaction Questionnaire assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the subject perspective. A score of 100 represents the best score (very satisfied) and a score of 0 represent the worst score (very dissatisfied) on the satisfaction domain or satisfaction single items. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was injected into the Glabellar Complex on Day 1. | 45 |
| OnabotulinumtoxinA X Dose A OnabotulinumtoxinA X Dose A was injected into the Glabellar Complex on Day 1. | 90 |
| OnabotulinumtoxinA X Dose B OnabotulinumtoxinA X Dose B was injected into the Glabellar Complex on Day 1. | 92 |
| OnabotulinumtoxinA X Dose C OnabotulinumtoxinA X Dose C was injected into the Glabellar Complex on Day 1. | 101 |
| Total | 328 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 8 | 3 | 6 |
| Overall Study | Other | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 9 | 7 |
Baseline characteristics
| Characteristic | OnabotulinumtoxinA X Dose A | OnabotulinumtoxinA X Dose B | Placebo | OnabotulinumtoxinA X Dose C | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 12.19 | 46.9 years STANDARD_DEVIATION 11.35 | 48.1 years STANDARD_DEVIATION 12.16 | 50.4 years STANDARD_DEVIATION 13.34 | 48.8 years STANDARD_DEVIATION 12.35 |
| Age, Customized 18-25 years | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants |
| Age, Customized 26-40 years | 21 Participants | 30 Participants | 9 Participants | 19 Participants | 79 Participants |
| Age, Customized 41-55 years | 42 Participants | 43 Participants | 25 Participants | 43 Participants | 153 Participants |
| Age, Customized 56-64 years | 12 Participants | 11 Participants | 6 Participants | 21 Participants | 50 Participants |
| Age, Customized ≥65 years | 14 Participants | 7 Participants | 4 Participants | 15 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 11 Participants | 15 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 77 Participants | 34 Participants | 86 Participants | 270 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 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 2 Participants | 2 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 2 Participants | 8 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 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 | 77 Participants | 84 Participants | 41 Participants | 88 Participants | 290 Participants |
| Sex: Female, Male Female | 77 Participants | 75 Participants | 40 Participants | 90 Participants | 282 Participants |
| Sex: Female, Male Male | 13 Participants | 17 Participants | 5 Participants | 11 Participants | 46 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 / 45 | 0 / 90 | 0 / 91 | 0 / 99 |
| other Total, other adverse events | 11 / 45 | 15 / 90 | 14 / 91 | 22 / 99 |
| serious Total, serious adverse events | 1 / 45 | 1 / 90 | 0 / 91 | 2 / 99 |
Outcome results
Primary
Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale.
The Clinician Glabellar Lines Scale is a four point scale used to assess the severity of Glabellar Lines at maximum contraction ranging from 0 - None to 3 - Severe
Time frame: Day 1 to Day 30
Population: Multiple Imputation - Intent-to-Treat Population~Estimated responder is the average number of responders across 5 imputed datasets.~Confidence interval for responder rate is calculated using normal approximation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 17.8 percentage of participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 95.6 percentage of participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 98.9 percentage of participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 98.0 percentage of participants |
Primary
Percentage of Participants With Adverse Events (AEs)
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 causal relationship with this treatment. The investigator assesses the relationship of each event to the use of 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. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Time frame: Day 1 to Day 270
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Percentage of Participants With Adverse Events (AEs) | Treatment-Emergent Adverse Events (TEAE) | 23 Participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Treatment | 7 Participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Drug | 7 Participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Procedure | 7 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Adverse Events (AEs) | Treatment-Emergent Adverse Events (TEAE) | 34 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Drug | 13 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Treatment | 13 Participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Procedure | 10 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Adverse Events (AEs) | Treatment-Emergent Adverse Events (TEAE) | 30 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Drug | 10 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Procedure | 10 Participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Treatment | 10 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Drug | 15 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Adverse Events (AEs) | Treatment-Emergent Adverse Events (TEAE) | 44 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Procedure | 14 Participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Adverse Events (AEs) | TEAE Related to Study Treatment | 15 Participants |
Secondary
Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater.
The Facial Line Satisfaction Questionnaire assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the subject perspective. Domain scores are calculated as the mean of transformed item scores on a 0 (low impact) to 100 (highest negative impact) scale.
Time frame: Day 1 to Day 30
Population: Multiple Imputation - Intent-to-Treat Population~Estimated responder is the average number of responders across 5 imputed datasets.~Confidence interval for responder rate is calculated using normal approximation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater. | 42.2 percentage of participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater. | 65.6 percentage of participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater. | 71.7 percentage of participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater. | 73.3 percentage of participants |
Secondary
Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale.
The Clinician Glabellar Lines Scale is a four point scale used to assess the severity of Glabellar Lines at maximum contraction ranging from 0 - None to 3 - Severe
Time frame: Day 1 to Day 30
Population: Multiple Imputation - Intent-to-Treat Population~Estimated responder is the average number of responders across 5 imputed datasets.~Confidence interval for responder rate is calculated using normal approximation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 6.7 percentage of participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 90.0 percentage of participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 93.5 percentage of participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale. | 95.0 percentage of participants |
Secondary
Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5.
The Facial Line Satisfaction Questionnaire assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the subject perspective. A score of 100 represents the best score (very satisfied) and a score of 0 represent the worst score (very dissatisfied) on the satisfaction domain or satisfaction single items.
Time frame: Day 1 to Day 60
Population: Multiple Imputation - Intent-to-Treat Population~Estimated responder is the average number of responders across 5 imputed datasets.~Confidence interval for responder rate is calculated using normal approximation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5. | 4.4 percentage of participants |
| OnabotulinumtoxinA X Dose A | Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5. | 80.0 percentage of participants |
| OnabotulinumtoxinA X Dose B | Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5. | 78.3 percentage of participants |
| OnabotulinumtoxinA X Dose C | Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5. | 87.1 percentage of participants |