The Efficacy and Safety Study of Protoxin Versus Botox® in Subjects With Moderate to Severe Glabellar Lines

Study Overview
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Brief Summary
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This study will be conducted in Phase Ⅲ clinical trials. In Phase Ⅲ, subjects with moderate to severe glabellar lines are enrolled and those who are judged to be eligible for this study will be injected with the PROTOXIN at a total of 20U(4U/0.1mL each) in five sites of the glabellar lines. The investigational product is administered once, maintaining double-blind for a total of 16 weeks of observation. Thereafter, efficacy and safety are assessed by comparing with BOTOX® after regular visits conducted at 4,8,12 and 16 weeks.

Official Title
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A Multicenter, Double-blind, Randomized, Parallel, Active-controlled, Phase III Clinical Trial to Compare the Efficacy and Safety of Protoxin Versus Botox® in Subjects With Moderate to Severe Glabellar Lines

Conditions
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Glabellar Frown Lines

Intervention / Treatment
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* Biological: PROTOXIN
* Biological: Botox®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged between 19 to 65 years old Subjects attaining ≥grade 2 (moderate) in the investigator's rating of the severity of glabella lines at maximum frown Those who understand and comply with clinical trial procedures and visit schedules Subjects who voluntarily decides to participate and signs the consent form after hearing the explanation of this clinical trial. Exclusion Criteria Those with or accompanied by the following diseases at the time of screening Subjects with Neuromuscular Junction Disorder that may affect neuromuscular action Subjects with previous history of weakness or paralysis in the forehead area Subjects with infection, skin disorders, or scars at the glabellar region Subjects with wrinkles that physically prevent wrinkles from spreading, such as when wrinkles are not spread out by hand Subjects who is administering a drug with muscle relaxation within four weeks of screening. Subjects who have taken Aspirin and NSAIDs within 7 days prior to administration of the investigational drug Subjects with surgical history who may affect wrinkles around the forehead or glabellar region Subjects who have planned facial cosmetic procedure during the clinical trial Subjects who have been administered similar drugs within 12 weeks (Botulinum toxin type A) or within 16 weeks (Botulinum toxin type B) before screening Subjects who are expected to administer botulinum toxin preparations other than Investigational product during the clinical trial period Subjects with allergy or hypersensitivity to the botulinum toxin or their components A history of drug or alcohol abuse Anxiety disorders or other significant mental disorders based on the judgment of an investigator Fertile women and men who have plans to conceive during pregnancy, breastfeeding and clinical trials or who do not agree to appropriate contraception Pregnant or lactating women Subjects with severe comorbidities or acute diseases that does not suitable for participation in clinical trials Those who participated in other clinical trials/clinical medical device trials within 30 days prior to screening and who received Investigational product/medical devices/procedures, or those who had less than 5 times the half-life of the Investigational product Subjects who are not eligible for this study based on the judgment of an investigator

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PROTOXIN(Phase Ⅲ)<br>PROTOXIN will be injected to 5 glabellar lines (Each 4U/0.1mL, Total 20U/0.5mL) | Biological: PROTOXIN<br>* Botulinum toxin Type A<br>|
| Active Comparator: Botox® (Phase Ⅲ)<br>Botox® will be injected to 5 glabellar lines (Each 4U/0.1mL, Total 20U/0.5mL). | Biological: Botox®<br>* Botulinum toxin Type A<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving at least a 2-grade improvement from baseline on the facial wrinkle scale of GL at maximum frown at Week 4 | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | 4 weeks post injection compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-rated improvement rate of glabellar lines at maximum frown | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | Week 8, 12, 16 | 
| Participant-rated improvement rate of glabellar lines at maximum frown | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | Week 4, 8, 12, 16 | 
| Investigator-rated improvement rate of glabellar lines at rest | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | Week 4, 8, 12, 16 | 
| Participant-rated improvement rate of glabellar lines at rest | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | Week 4, 8, 12, 16 | 
| Independent photo evaluator-rated improvement rate of glabellar lines at frown | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | Week 4, 8, 12, 16 | 
| Independent photo evaluator-rated improvement rate of glabellar lines at rest | The investigator and participant evaluate the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe | Week 4, 8, 12, 16 | 
| Participant-rated satisfaction after treatment | Participant evaluate the level of satisfaction by Patient Satisfaction(PS) 7-grade score(1 to 7) where 1 = very dissatisfied and 7 = very satisfied | Week 4, 8, 12, 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glabellar Lines, Botulinum toxin, Botulinum toxin type A