A Non-inferiority Clinical Trial to Compare Efficacy and Safety of Abobotulinumtoxin A (Espad Pharmed) Versus AbobotulinumtoxinA (Dysport®, Ipsen Co.) for Correction of Moderate to Severe Glabellar Lines

A Phase I/III, Randomized, Two-armed, Double-blinded, Parallel, Active-controlled, Non-inferiority Clinical Trial to Compare Efficacy and Safety of AbobotulinumtoxinA (Espad Pharmed) Versus AbobotulinumtoxinA (Dysport®, Ipsen Co.) for Correction of Moderate to Severe Glabellar Lines

The aim of this study is to evaluate the efficacy and safety of AbobotulinumtoxinA (produced by Espad Pharmed Darou Co.) for correction of moderate to severe glabellar lines.

Hypothesis: AbobotulinumtoxinA (produced by Espad Pharmed Darou Co.) has acceptable efficacy and safety profile for correction of moderate to severe glabellar lines.

Primary Outcome: To verify the non-inferiority of the efficacy of AbobotulinumtoxinA (produced by Espad Pharmed Darou Co.) compared with AbobotulinumtoxinA (Dysport®, produced by Ipsen Co.) by percentage of responders at maximum frown at day 30 after treatment.

Researchers will compare the efficacy and safety profile of AbobotulinumtoxinA (produced by Espad Pharmed Darou Co.) with AbobotulinumtoxinA (Dysport®, produced by Ipsen Co.).

The study is designed as phase III, randomized, two armed, double-blind, parallel, active controlled, non-inferiority clinical trial.

Participants received a total dose of 40-60 units into 3 to 5 sites. After two weeks, a touch-up intervention could be done based on physician's assessment.

Study Overview

• Status: Completed
• Conditions: Glabellar Frown Lines; Glabellar Lines
• Intervention / Treatment: Drug: Abobotulinumtoxin A (Espad Pharmed Darou Co.); Drug: Abobotulinumtoxin A (Ipsen Co.)

Detailed Description

The study schedule includes Visit 0 (Screening), Visit 1 (Intervention, Day 0), and Follow-up Visits 2 (Day 14), 3 (Day 30), 4 (Day 90), and 5 (Day 120). At Visit 0, informed consent is obtained, and eligibility is assessed through initial evaluations and review of inclusion and exclusion criteria. At Visit 1, subjects are randomized (1:1) and receive the investigational treatment. Full-face photographs are obtained at Visit 1 (Before receiving the investigational treatment), and at Follow-up Visits 2, 3, 4, and 5, in both resting state and maximum frown. Efficacy is evaluated at Visits 3, 4, and 5. All adverse events are Recorded at all visits.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Center for Research and Training in Skin Diseases and Leprosy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥18 to ≤65 years of age
2. Willingness for signing and having signed the informed consent form
3. Moderate to severe glabellar wrinkle at maximum frown based on glabellar lines severity scale (GLSS)
4. be able to participate in the visit schedules and the study procedures.

Exclusion Criteria:

1. Hypersensitivity to botulinum toxin or any other component of the formulation, as well as to injectable fillers in the facial region.
2. Previous treatment with botulinum toxin in facial areas within the past 6 months.
3. Previous treatment with dermal fillers, dermabrasion, or photo rejuvenation in the glabellar region within the past 12 months.
4. History of dermal filler injection in the forehead region within the past year.
5. History of eyebrow tattooing or any other procedure involving the eyebrow area within the past month.
6. Use of aminoglycosides, penicillamine, quinine, chloroquine, hydroxychloroquine, or calcium channel blockers within the past week.
7. Use of anticoagulants or aspirin within the past 10 days (participants are not required to discontinue their anticoagulant therapy to be enrolled in the study).
8. History of any cosmetic surgery (e.g., filler injections, chemical peels, or laser treatments) or use of products that induce skin remodeling or significantly affect the forehead area or its surroundings, including any aesthetic procedure involving the glabellar lines within the past 6 months.
9. History of any surgical procedure involving facial muscles or scarring in the forehead or surrounding areas (including the eyebrows).
10. Any planned aesthetic procedure involving the upper face during the course of the study.
11. Presence of disorders that may affect neuromuscular function (e.g., myasthenia gravis, amyotrophic lateral sclerosis [ALS], or Eaton-Lambert syndrome).
12. History of facial nerve paralysis.
13. Presence of clearly visible and defined facial asymmetry.
14. Ptosis of the eyelids or eyebrows due to facial muscle paralysis or a history thereof.
15. Presence of any active infection or acute dermatological condition in the injection areas.
16. Pregnancy (confirmed by urine test) or lactation.
17. Participation in other clinical studies within 30 days prior to randomization or intention to participate in other clinical trials.
18. Any other condition or circumstance that may pose a risk to the participant or interfere with the satisfactory completion of the clinical outcome.
19. History of participation in other clinical trials involving botulinum neurotoxin products or fillers within the past 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abobotulinumtoxin A (produced by Espad Pharmed Darou Co.); Vial of AbobotulinumtoxinA (produced by Espad Pharmed Darou Co.), administered via deep intramuscular injection into 3 to 5 sites in the glabellar area using a 1 ml syringe, with a total dose of 40 to 60 International Units (IU), administered in a single treatment session.	Drug: Abobotulinumtoxin A (Espad Pharmed Darou Co.); Vial of Abobotulinumtoxin A (produced by Espad Pharmed Darou Co.), administered via deep intramuscular injection
Active Comparator: Abobotulinumtoxin A (Dysport®, produced by Ipsen Co.); Vial of AbobotulinumtoxinA (Dysport®, produced by Ipsen Co.), administered via deep intramuscular injection into 3 to 5 sites in the glabellar area using a 1 ml syringe, with a total dose of 40 to 60 International Units (IU), administered in a single treatment session.	Drug: Abobotulinumtoxin A (Ipsen Co.); Vial of AbobotulinumtoxinA (Dysport®, produced by Ipsen Co.), administered via deep intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responders at maximum frown by investigator's assessment	Percentage of responders measured by the investigator's live assessment based on Glabellar Line Severity Scale (GLSS) at maximum frown at day 30 after treatment The Glabellar Line Severity Scale (GLSS) is a 4-grade scale defined as follows: 0 = no glabellar lines, 1 = mild lines, 2 = moderate lines, 3 = severe lines. Higher scores indicate more severe glabellar lines. Participants were considered responders if they showed a reduction of at least 2 points from baseline on the scale.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total injected dose (visit 1 and touch-up visit)		Day 14
Responders at rest by investigator's assessment	Percentage of responders measured by the investigator's live assessment based on Glabellar Line Severity Scale (GLSS) at rest at days 30, 90 and 120 after treatment The Glabellar Line Severity Scale (GLSS) is a 4-grade scale defined as follows: 0 = no glabellar lines, 1 = mild lines, 2 = moderate lines, 3 = severe lines. Higher scores indicate more severe glabellar lines. Participants were considered responders if they showed a reduction of at least 2 points from baseline on the scale.	Days 30, 90 and 120
Responders at maximum frown by subject's self-assessment	Percentage of responders measured by the subject's self-assessment (SSA) at maximum frown at days 30, 90 and 120 after treatment The 4-grade subject's self-assessment scale defined as follows: 0 = no glabellar lines, 1 = mild lines, 2 = moderate lines, 3 = severe lines. Higher scores indicate more severe glabellar lines. Responders are defined as those reporting a reduction of at least 2 points from baseline.	days 30, 90 and 120
Responders at rest by subject's self-assessment	Percentage of responders measured by the subject's self-assessment (SSA) at rest at days 30, 90 and 120 after treatment The 4-grade subject's self-assessment scale defined as follows: 0 = no glabellar lines, 1 = mild lines, 2 = moderate lines, 3 = severe lines. Higher scores indicate more severe glabellar lines. Responders are defined as those reporting a reduction of at least 2 points from baseline.	days 30, 90 and 120
Responders at maximum frown by investigator's assessment	Percentage of responders measured by the investigator's live assessment based on Glabellar Line Severity Scale (GLSS) at maximum frown at days 90 and 120 after treatment The Glabellar Line Severity Scale (GLSS) is a 4-grade scale defined as follows: 0 = no glabellar lines, 1 = mild lines, 2 = moderate lines, 3 = severe lines. Higher scores indicate more severe glabellar lines. Participants were considered responders if they showed a reduction of at least 2 points from baseline on the scale.	days 90 and 120
Onset of action measured by the subject's self-assessment (SSA) at rest	The participants were asked to record the date on which they first noticed the onset of the product's efficacy and to inform the investigator of this date during the visit on day 14.	Day 14
Onset of action measured by the subject's self-assessment (SSA) at maximum frown	The participants were asked to record the date on which they first noticed the onset of the product's efficacy and to inform the investigator of this date during the visit on day 14.	Day 14
Safety assessment by evaluation of adverse events (AEs)	Adverse events (AEs) were assessed at all visits. All reported events were classified as mild, moderate, or severe. Moreover, seriousness of Adverse events was assessed according to International Council for Harmonization (ICH-E2B) guidelines. The causality relation was assessed based on the World Health Organization (WHO) criteria.	Visit 0 (screening), visit 1 (Day 0), visit 2 (Day 14), visit 3 (Day 30), visit 4 (Day 90), visit 5 (Day 120)

Collaborators and Investigators

• Sponsor: Espad Pharmed
• Collaborators: Center for Research and Training in Skin Diseases and Leprosy
• Investigators: Principal Investigator: Alireza Firooz, Medical Doctor, Center for Research and Training in Skin Diseases and Leprosy, Tehran, Tehran 1416613675

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2024
• Primary Completion (Actual): February 18, 2025
• Study Completion (Actual): February 18, 2025

Study Registration Dates

• First Submitted: April 19, 2025
• First Submitted That Met QC Criteria: April 19, 2025
• First Posted (Actual): April 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 4, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: AbobotulinumtoxinA; glabellar lines
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Cholinergic Agents; Neuromuscular Agents; Acetylcholine Release Inhibitors; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: BOT.ESP.AF.III.02; IRCT20150101020514N23 (Registry Identifier: Iranian Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data produced in the present study are available upon reasonable request from the investigators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No