Forehead Rhytides, Glabellar Rhytides
Conditions
Brief summary
This is a safety and efficacy study of onabotulinumtoxinA in subjects with forehead and glabellar facial rhytides (frown lines).
Interventions
BIOLOGICALOnabotulinumtoxinA
OnabotulinumtoxinA injected into the protocol-specified areas. Subjects will receive at least 1 and up to 3 treatments.
DRUGNormal Saline
Placebo (normal saline) injected into the protocol-specified areas on Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate to severe forehead and glabellar lines * Willing to have facial photos taken
Exclusion criteria
* Prior exposure to botulinum toxin of any serotype for any indication * Anticipated need for treatment with botulinum toxin of any serotype for any indication during the study, other than study treatment * Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis * Any facial resurfacing laser or light treatment, microdermabrasion, or superficial peels in the past 3 months * Any medium depth or deep depth facial chemical peels; facial skin resurfacing; or permanent facial make-up in the past 6 months * Any nonpermanent soft tissue fillers, or treatment with oral retinoids in the past year * Prior face lift, thread lift, eyebrow lift, or related procedures (eg, eyelid and/or eyebrow surgery) * Prior facial treatment with permanent soft tissue fillers, synthetic implants (eg, Gore-Tex®), and/or fat transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation | Baseline, Day 30 | The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest | Baseline, Day 30 | The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported. |
| Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5 | Day 60 | The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks How satisfied are you with the effect your treatment had on your facial lines? Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported. |
| Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation | Day 30 | The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of none and mild are reported. |
| Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire© | Baseline, Day 30 | The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is I look older than my actual age because of my facial lines with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis. |
| Time to Retreatment Eligibility | 12 Months | Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis. |
| Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points | Baseline, Day 30 | The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis. |
Countries
Canada, Ireland, United States
Participant flow
Recruitment details
A total of 421 subjects were enrolled in the study, of these, 30 subjects were excluded from the data analyses at one site. The participant flow reflects all subjects included in the data analyses.
Pre-assignment details
Subjects were randomized to either placebo or onabotulinumtoxinA in Period 1. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are also included in the onabotulinumtoxinA group for the Safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas. | 101 |
| OnabotulinumtoxinA OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments. | 290 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Enrolled in Error | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 13 |
| Overall Study | Personal Reasons | 17 | 22 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Followed by OnabotulinumtoxinA in Period 2 | OnabotulinumtoxinA | Total |
|---|---|---|---|
| Age, Customized <65 years | 101 Participants | 281 Participants | 382 Participants |
| Age, Customized >=65 years | 0 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Female | 87 Participants | 249 Participants | 336 Participants |
| Sex: Female, Male Male | 14 Participants | 41 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 100 | 92 / 374 |
| serious Total, serious adverse events | 0 / 100 | 5 / 374 |
Outcome results
Primary
Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation
The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.
Time frame: Baseline, Day 30
Population: Intent-to-Treat: all randomized subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 | Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation | 0.0 Percentage of Subjects |
| OnabotulinumtoxinA | Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation | 61.4 Percentage of Subjects |
Secondary
Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5
The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks How satisfied are you with the effect your treatment had on your facial lines? Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.
Time frame: Day 60
Population: Intent-to-Treat: all randomized subjects with data reported at this time point
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 | Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5 | 1.0 Percentage of Subjects |
| OnabotulinumtoxinA | Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5 | 90.3 Percentage of Subjects |
Secondary
Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest
The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.
Time frame: Baseline, Day 30
Population: Intent-to-Treat: all randomized subjects with at least a 1-grade improvement assessed by the Investigator on the FWS at rest
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 | Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest | 19.8 Percentage of Subjects |
| OnabotulinumtoxinA | Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest | 85.6 Percentage of Subjects |
Secondary
Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points
The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.
Time frame: Baseline, Day 30
Population: Intent-to-Treat: all randomized subjects with baseline scores ≥ 20 on the Impact Domain of the FLSQ
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 | Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points | 18.9 Percentage of Subjects |
| OnabotulinumtoxinA | Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points | 73.9 Percentage of Subjects |
Secondary
Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©
The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is I look older than my actual age because of my facial lines with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.
Time frame: Baseline, Day 30
Population: Intent-to-Treat: all randomized subjects with baseline scores ≥ 3 on Item 4 of the FLO-11
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 | Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire© | 11.2 Percentage of Subjects |
| OnabotulinumtoxinA | Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire© | 77.2 Percentage of Subjects |
Secondary
Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation
The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of none and mild are reported.
Time frame: Day 30
Population: Intent-to-Treat: all randomized subjects with a score of none and mild on the FWS at maximum eyebrow elevation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Followed by OnabotulinumtoxinA in Period 2 | Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation | 2.0 Percentage of Subjects |
| OnabotulinumtoxinA | Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation | 94.1 Percentage of Subjects |
Secondary
Time to Retreatment Eligibility
Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.
Time frame: 12 Months
Population: Intent-to-Treat: all randomized subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| OnabotulinumtoxinA | Time to Retreatment Eligibility | 119 Days | Standard Deviation 52.9 |