Study to Compare 2 Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines

Study Overview
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Brief Summary
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The purpose of the study is to provide preliminary comparative data on BoNT/A-DP versus Botox Cosmetic. Subsequently the sample size is primarily based on clinical judgement and practical considerations.

Detailed Description
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This will be a multi-center, randomized, double-blind, comparator-controlled study. The study will take place in the EU, US and Canada. To allow all subjects to profit from treatment and to obtain adequate data for BoNT/A DP treatment, the study will be comprised of a double-blinded treatment comparing BoNT/A-DP with Botox Cosmetic (ratio 1:1). Primary and secondary endpoints will compare efficacy, safety and subject satisfaction after a single treatment of the investigational BoNT/A DP to an existing commercially available product (Botox Cosmetic). Two hundred subjects will be enrolled, which should allow for a precise estimate of response rate and for post-hoc sensitivity analyses. The duration of study participation for each subject will be up to 18 weeks, to include screening (maximum of 2 weeks; re-screening will not be permitted), and a single treatment (comprised of one injection at five injection points) of BoNT/A-DP (Group A) or Botox Cosmetic (Group B) followed by six efficacy and safety follow-up visits. A total of 200 subjects will be randomized 1:1 to Group A or Group B at Baseline. Both investigators and subjects will be blinded to treatment. Investigators and subjects will evaluate the severity of glabellar lines independently.

Official Title
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A Double-Blinded, Randomized, Controlled Study to Compare the Efficacy, Time to Onset, and Duration of Effect of Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines

Conditions
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Frown Lines

Intervention / Treatment
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* Biological: Botulinum toxin A BoNT/A-DP
* Biological: Botulinum toxin A Botox Cosmetics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:• Has moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on GLS-I/GLS-S) as determined by in clinic assessments by both the investigator and the subject (where: 0='none', 1='mild', 2='moderate', 3='severe'). Subject has a stable medical condition with no uncontrolled systemic disease. Female subjects of childbearing potential must test negative for pregnancy and agree to use highly effective birth control during the course of the study. Subjects who wear glasses must be able to adequately self-assess the severity of their glabellar lines (according to the GLS-S), without glasses obstructing the forehead area. Exclusion Criteria: Previous treatment with any serotype of botulinum toxin for any indication within the 12 months prior to Screening, or any planned treatment with botulinum toxin of any serotype for any reason during the study (other than the investigational treatment). Known hypersensitivity to either study medication or its excipients. Any medical condition that may place the subject at increased risk due to exposure to botulinum toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, profound atrophy or weakness in the target muscles, or any other condition (at the investigator's discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy. Facial laser or light treatment, microdermabrasion, superficial peels or retinoid therapy within the three months prior to Screening or planned during the study. o Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers, photo rejuvenation) within 12 months prior to Screening or planned during the study. Previous insertion of permanent material in the glabellar area, or planned insertion during the study. Any planned or history of surgery in the glabellar area and/or canthal line area, or scars in the glabellar and/or canthal line. Active skin disease/infection or irritation at the treatment area. Inability to substantially lessen glabellar frown lines and or lateral canthal lines even by physically spreading them apart. Use of a muscle relaxant within 2 weeks prior to Screening, or planned use during the study. Marked facial asymmetry or ptosis of eyelid and/or eyebrow, or current facial palsy or neuromuscular junction disorders as judged by the investigator. Pregnant, breastfeeding or planning to become pregnant during the study. Use of prohibited medication including anticholinergic drugs, or drugs which could interfere with neuromuscular function, including aminoglycoside antibiotics and curare-like compounds within 2 weeks prior to Screening or planned during the study. Planned surgery with general anesthetic (use of local anesthetic outside the glabellar area is permitted). Participation in another clinical study within one month of Screening and throughout the study. Previous participation in another botulinum toxin aesthetic study, which involved the treatment of glabellar, lines in combination with canthal lines and/or forehead lines in the previous 18 months. Chronic drug or alcohol abuse (as per investigator discretion).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: Multi-center, randomized, double-blind, comparator-controlled study. The study will take place in the EU, US and Canada. The benefit of participation in this study is the expected reduction in the severity of glabellar frown lines. All subjects will benefit from free medical screenings and follow up.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A (n=100): BoNT/A-DP (20 U, 0.5 mL)<br>The injection sites should be prepared according to standard clinical procedures.. A volume of 0.5 mL of the properly reconstituted BoNT/A-DP should be drawn into the sterile syringe and any air bubbles in the syringe barrel expelled. The needle used to reconstitute the product should be removed and replaced with a sterile insulin or tuberculin-type syringe of 1 mL volume with 0.01 mL graduation and with the gauge range of 30 to 33 G, which the investigator routinely uses for toxin administration. Each subject will receive a total of five i.m. injections of 4 U/0.1 mL (total of 20 U). | Biological: Botulinum toxin A BoNT/A-DP<br>* To assess the efficacy of treatment with BoNT/A-DP in reducing the severity of glabellar frown lines at maximum frown.<br>|
| Active Comparator: Group B (n=100): Botox Cosmetic (20 U, 0.5 mL)<br>The injection sites should be prepared according to standard clinical procedures. A volume of 0.5 mL of the properly reconstituted Botox Cosmetic should be drawn into the sterile syringe and any air bubbles in the syringe barrel expelled. The needle used to reconstitute the product should be removed and replaced with a sterile insulin or tuberculin-type syringe of 1 mL volume with 0.01 mL graduation and with the gauge range of 30 to 33 G, which the investigator routinely uses for toxin administration. Each subject will receive a total of five i.m. injections of 4 U/0.1 mL (total of 20 U). | Biological: Botulinum toxin A Botox Cosmetics<br>* To assess the efficacy of treatment with Botox Cosmetics in reducing the severity of glabellar frown lines at maximum frown.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To provide comparative efficacy data of BoNT/A DP versus Botox Cosmetic by comparing responder rates at week 4 based using the 5-point Facial Wrinkle Scale (FWS; where 0 means no glabellar lines and 4 means extreme glabellar lines). | To assess the efficacy of treatment with BoNT/A-DP as defined by the percentage of responders at Week 4 (Facial Wrinkle Scale [FWS] score of 0 or 1 and a ≥ 1 point reduction in FWS score) in reducing the severity of glabellar frown lines at maximum frown (the worst appearance of upper facial lines with maximum load on the muscle; eyebrows pushed together as far as they can go) compared to treatment with Botox Cosmetic, based on independent investigator assessment and subject assessment. | week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rates based on FWS Scores of 0 or 1 and a ≥ 1 point reduction in FWS score at maximum frown at weeks 1, 2, 8, 12 and 16 | To assess the percentage of responders (FWS score of 0 or 1 and a ≥ 1 point reduction in FWS score at maximum frown) after a single treatment with BoNT/A-DP compared to a single treatment of Botox Cosmetic at Weeks 1, 2, 8, 12 and 16, based on investigator and subject assessments. | Study weeks 1, 2, 8, 12 and 16 | 
| Responder rates based on FWS Scores of 0 or 1 and a ≥ 2 point reduction in FWS score at maximum frown at weeks 1, 2, 4, 8, 12 and 16 | To assess the percentage of responders (FWS score of 0 or 1 and a ≥ 2 point reduction in FWS score at maximum frown) after a single treatment with BoNT/A-DP compared to a single treatment of Botox Cosmetic at Weeks 1, 2, 4, 8, 12 and 16, based on independent investigator and subject assessments. | Study weeks 1, 2, 4, 8, 12 and 16 | 
| To assess treatment satisfaction at Weeks 4, 12, and 16 using FACE-Q Satisfaction with Outcome Scale. | To assess treatment satisfaction at Weeks 4, 12, and 16 using FACE-Q Satisfaction with Outcome Scale. | Study weeks 4, 12 and 16 | 
| To determine the safety of a single treatment of BoNT/A-DP compared to a single treatment of Botox Cosmetic in the treatment of glabellar lines. | Frequency, seriousness and severity of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs), as well as causal relationship to the study medication and the study procedure, during the entire study period. | through study completion, an average of 16 weeks |