Glabellar Frown Lines
Conditions
Brief summary
The primary objective is to demonstrate the safety and efficacy of DWP-450 (Botulinum purified neurotoxin, Type A) Injection in the treatment of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult subjects
Detailed description
Three hundred and twenty-four eligible subjects will be randomly assigned 3:1 to receive DWP-450 or placebo. Safety and efficacy will be assessed on Days 2, 7, 14, 30, 90, 120 and 150. The primary efficacy end point assesses the effectiveness of the DWP-450 against placebo on Day 30 in a superiority design.
Interventions
BIOLOGICALBotulinum toxin, Type A
Botulinum toxin, Type A
Placebo Comparator Arm
Sponsors
PPD Development, LP
Evolus, Inc.
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
Yes
Inclusion criteria
* Subjects is an adult, of at least 18 years of age * Subject is able to provide informed consent and comply with study instructions * Subject has moderate to severe glabellar lines at maximum frown as assessed by the investigator using the GLS * Subject has moderate to severe glabellar lines at maximum frown as assessed by the subject using the GLS * Subject is willing and able to complete the entire course of the study
Exclusion criteria
* Previous treatment with botulinum toxin of any serotype in any area within the last 6 months * Previous treatment with any facial aesthetic procedure (e.g. injection with fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 months * Previous insertion of permanent material in the glabellar area * Planned treatment with botulinum toxin of any serotype in any other body region during the study period * 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 eye brow) * Energy-based or cryo-therapy 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 (subjects can continue with their usual skin care routine) * Subjects who may not respond to 20 Units of botulinum toxin (e.g., inability to substantially lessen glabellar frown lines even by physically spreading them apart) * Marked facial asymmetry * 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 * Any active infection in the area of the injection sites * Medical condition that may affect neuromuscular function (e.g., myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis) * Evidence of recent alcohol or drug abuse * 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 * Pregnant or sexually active female subjects who are of childbearing potential and who are not willing to use an acceptable form of contraception * Known allergy or hypersensitivity to botulinum toxin preparation * Participation in another interventional clinical study within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | Day 30 | The primary efficacy end point assesses the effectiveness of DWP-450 against placebo on Day 30. The primary efficacy measure is a composite end point. Using the GLS scale, investigators and subjects will assess the glabellar lines at Day 0 and Day 30. A subject is a responder only if both the investigator and subject independently agree that a ≥2 improvement has occurred from Day 0 to Day 30. GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 90 Days | Secondary endpoint was the proportion of subjects classified as responders on Day 90. This was a composite endpoint based on both the Investigator and subject assessments of glabellar lines at maximum frown on the GLS; a subject was a responder only if both the Investigator and subject independently agreed that a ≥2 point improvement had occurred from Day 0 to 90 Day. GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin, Type A Botulinum toxin, Type A
Botulinum toxin, Type A: Botulinum toxin, Type A | 246 |
| Placebo 0.9% sterile, unpreserved saline
0.9% sterile, unpreserved saline: Placebo Comparator Arm | 78 |
| Total | 324 |
Baseline characteristics
| Characteristic | Botulinum Toxin, Type A | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 6 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 219 Participants | 72 Participants | 291 Participants |
| Age, Continuous | 51.5 years STANDARD_DEVIATION 11.54 | 50.4 years STANDARD_DEVIATION 10.14 | 51.2 years STANDARD_DEVIATION 11.21 |
| Sex: Female, Male Female | 220 Participants | 70 Participants | 290 Participants |
| Sex: Female, Male Male | 26 Participants | 8 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 246 | 21 / 78 |
| serious Total, serious adverse events | 4 / 246 | 0 / 78 |
Outcome results
Primary
Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject
The primary efficacy end point assesses the effectiveness of DWP-450 against placebo on Day 30. The primary efficacy measure is a composite end point. Using the GLS scale, investigators and subjects will assess the glabellar lines at Day 0 and Day 30. A subject is a responder only if both the investigator and subject independently agree that a ≥2 improvement has occurred from Day 0 to Day 30. GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe.
Time frame: Day 30
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Botulinum Toxin, Type A | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 70.4 percentage of responders |
| Placebo | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 1.3 percentage of responders |
Secondary
Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject
Secondary endpoint was the proportion of subjects classified as responders on Day 90. This was a composite endpoint based on both the Investigator and subject assessments of glabellar lines at maximum frown on the GLS; a subject was a responder only if both the Investigator and subject independently agreed that a ≥2 point improvement had occurred from Day 0 to 90 Day. GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe.
Time frame: 90 Days
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Botulinum Toxin, Type A | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 25.8 percentage of responders |
| Placebo | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 0.0 percentage of responders |
Secondary
Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject
Secondary endpoint was the proportion of subjects classified as responders on Day 120. This was a composite endpoint based on both the Investigator and subject assessments of glabellar lines at maximum frown on the GLS; a subject was a responder only if both the Investigator and subject independently agreed that a ≥2 point improvement had occurred from Day 0 to 120 Day GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe.
Time frame: Day 120
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Botulinum Toxin, Type A | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 12.4 percentage of responders |
| Placebo | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 0.0 percentage of responders |
Secondary
Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject
Secondary endpoint was the proportion of subjects classified as responders on Day 150. This was a composite endpoint based on both the Investigator and subject assessments of glabellar lines at maximum frown on the GLS; a subject was a responder only if both the Investigator and subject independently agreed that a ≥2 point improvement had occurred from Day 0 to 150 Day GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe.
Time frame: Day 150
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Botulinum Toxin, Type A | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 4.6 percentage of responders |
| Placebo | Percentage of Participants With a ≥2 Point Improvement in Glabellar Line Scale (GLS) as Independently Assessed by Investigator and and Subject | 0.0 percentage of responders |