A Study Comparing the Safety, Efficacy, and Diffusion of Letibotulinum Toxin A Versus Other Botulinum Toxin Products in Adults With Moderate-to-Severe Forehead Wrinkles

NCT07072806 | Completed Phase 4

• 1 other identifier: 4-2021-1097
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if letibotulinum toxin A is effective and safe for treating moderate-to-severe horizontal forehead wrinkles in adults. It will also compare its diffusion characteristics with two other botulinum toxin A products. The main questions it aims to answer are:

1. 1.Does letibotulinum toxin A reduce forehead wrinkles as effectively as other botulinum toxin A products?
2. 2.Does letibotulinum toxin A show more localized (smaller) diffusion after injection?
3. 3.Receive botulinum toxin A injections on each side of the forehead (split-face design)
4. 4.Undergo wrinkle assessments and sweat gland function testing using 3D imaging and iodine-starch tests
5. 5.Return to the clinic 2 weeks after treatment for follow-up evaluation

Conditions

Forehead Rhytides

Keywords

Diffusion; botulinum toxin; forehead wrinkle; split-face; controlled trial

Outcome Measures

Primary Outcomes (1)

• Area of Anhidrosis

  The area of anhidrosis (sweat suppression) at each injection site will be measured using the Minor iodine-starch test to evaluate diffusion characteristics of botulinum toxin A formulations. The test is conducted under controlled temperature and humidity. Image-based quantification will be used to calculate the diffusion area in cm².

  2 weeks post-injection

Secondary Outcomes (1)

• Wrinkle Improvement

  Baseline and 2 weeks post-treatment

Other Outcomes (1)

• Safety and Local Tolerability of Botulinum Toxin A Products

  From baseline to 2 weeks post-injection

Study Arms (2)

Treatment arm A

ACTIVE COMPARATOR

The first treatment group received letibotulinum toxin A (Botulax) on one randomly assigned side of their face and prabotulinum toxin A (Nabota) on the other side of their face.

Drug: Letibotulinum toxin A; Drug: Prabotulinum toxin A

Treatment arm B

ACTIVE COMPARATOR

The first treatment group received letibotulinum toxin A (Botulax) on one randomly assigned side of their face and onabotulinum toxin A (Botox) on the other side of their face.

Drug: Letibotulinum toxin A; Drug: Onabotulinum toxin A

Interventions

Letibotulinum toxin A DRUG

Letibotulinum toxin A (Botulax) is a botulinum toxin type A formulation developed for aesthetic indications. In this trial, it was administered as the test intervention. Each participant received 2 units injected at four forehead sites (total 8 units), diluted to 20 U/mL, on one side of the forehead. The diffusion characteristics and efficacy were compared with those of onabotulinum and prabotulinum toxin A in a double-blind, randomized, split-face design.

Also known as: Botulax

Treatment arm A; Treatment arm B

Prabotulinum toxin A DRUG

Prabotulinum toxin A (Nabota) is a botulinum toxin type A product approved for aesthetic use in South Korea and other countries. It was used as a comparator agent in this trial. Participants received subcutaneous injections at four forehead sites (2 units per site, 8 units total), diluted to 20 U/mL, on one side of the forehead in a randomized, split-face design.

Also known as: Nabota

Treatment arm A

Onabotulinum toxin A DRUG

Onabotulinum toxin A (Botox) is an FDA-approved botulinum neurotoxin type A formulation used for cosmetic treatment of glabellar lines and other facial wrinkles. In this study, it was injected subcutaneously into the forehead at four standardized sites at a dose of 2 units per site (8 units total), diluted to 20 U/mL, and used as a comparator in the split-face design.

Also known as: Botox

Treatment arm B

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants were eligible if they were aged ≥20 years with visible horizontal forehead wrinkles scored as moderate to severe on the Facial Wrinkle Scale using a photonumeric guide

Sponsors & Collaborators

• Yonsei University: lead
• Korea International Cooperation Agency (KOICA): collaborator

Study Sites (1)

Severance Hospital, Yonsei University College of Medicine

Seoul, 03722, South Korea

Location

MeSH Terms

Interventions

onabotulinum toxin A; Botulinum Toxins, Type A

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Masking Details: The allocation of treatment to the left or right side of the forehead was determined according to the randomization schedule and was concealed from both the investigators administering the treatment and the evaluators conducting outcome assessments, thereby maintaining a double-blind protocol throughout the study period.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: For each participant, the forehead was divided along the midline, with one side randomly assigned to receive the letibotulinum toxin A (Botulax®; intervention group) and the contralateral side assigned to receive one of two comparator botulinum toxin A formulations, prabotulinum toxin A (Nabota®) or onabotulinum toxin A (Botox®) (control groups 1 and 2, respectively)

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 18, 2025
• Study Start: June 14, 2022
• Primary Completion: August 26, 2022
• Study Completion: September 7, 2022
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)