Forehead RhytidesPhase 4NCT07072806
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
A Phase 4 study testing Letibotulinum toxin A, Prabotulinum toxin A and Onabotulinum toxin A in people with Forehead Rhytides, run by Yonsei University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Forehead Rhytides
- What is being tested?
- Letibotulinum toxin A, Prabotulinum toxin A and Onabotulinum toxin A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Korea
- Study dates
- 14 Jun 2022to 7 Sep 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Exclusion criteria included a history of BoNT-A injection or cosmetic procedures near the fore-head/orbital area within the past year; signs of infection or inflammation at the injection site; compen-satory frontal hyperactivity; neuromuscular disorders including myasthenia gravis or amyotrophic lateral sclerosis; use of anticoagulants, aminoglycosides, curare-like agents, or neuromuscular inhibitors (stable doses of muscle relaxants or benzodiazepines are permitted); and hypersensitivity to the inves-tigational product or iodine.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Severance Hospital, Yonsei University College of Medicine
Seoul, 03722
About this study
Official title: Diffusion Characteristics and Efficacy of Letibotulinum Toxin A in Forehead Wrinkle Treatment
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:
- Does letibotulinum toxin A reduce forehead wrinkles as effectively as other botulinum toxin A products?
- Does letibotulinum toxin A show more localized (smaller) diffusion after injection?
Read more
Researchers will compare letibotulinum toxin A with prabotulinum toxin A and onabotulinum toxin A (Botox®) to evaluate their diffusion profiles and wrinkle-reduction effects.
Participants will:
- Receive botulinum toxin A injections on each side of the forehead (split-face design)
- Undergo wrinkle assessments and sweat gland function testing using 3D imaging and iodine-starch tests
- Return to the clinic 2 weeks after treatment for follow-up evaluation
- Conditions
- Forehead Rhytides
- Being tested
- Letibotulinum toxin A, Prabotulinum toxin A, Onabotulinum toxin A
- Keywords
- Diffusion, botulinum toxin, forehead wrinkle, split-face, controlled trial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letibotulinum toxin ADrug
Also called Botulax
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.
Prabotulinum toxin ADrug
Also called Nabota
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.
Onabotulinum toxin ADrug
Also called Botox
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Letibotulinum toxin A; Drug: Onabotulinum toxin A |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 weeks post-injection
Secondary outcomes (1)
Wrinkle Improvement
Wrinkle improvement was assessed 2 weeks after injection using digital photography and 3D imaging systems. Antera 3D was used to quantify the indentation index and maximal wrinkle relaxation length. Morpheus imaging was employed for three-dimensional visualization of muscle contraction and to evaluate maximal wrinkle depth. Measurements were taken on both lateral and medial sections of the forehead.
Measured: Baseline and 2 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2025
- Study start14 Jun 2022
- Primary completion26 Aug 2022
- Study completion7 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Forehead RhytidesStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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)
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Collaborators
- Korea International Cooperation Agency
- Responsible party
- Principal investigator, Ngoc Ha Nguyen, Yonsei University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07072806
- Sponsor's protocol ID
- 4-2021-1097
- Status last verified
- Jul 2025
- First submitted
- 9 Jul 2025
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared due to privacy concerns and institutional policies that restrict data sharing beyond the research team. Data were collected under a protocol that did not include participant consent for public or external data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diffusion Characteristics and Efficacy of Letibotulinum Toxin A in Forehead Wrinkle Treatment
- ClinicalTrials.gov ID
- NCT07072806
- Acronym / sponsor ID
- 4-2021-1097
- Conditions
- Forehead Rhytides
- Keywords
- Diffusion, botulinum toxin, forehead wrinkle, split-face, controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Collaborators
- Korea International Cooperation Agency
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 26 Aug 2022 (actual)
- Study completion
- 7 Sep 2022 (actual)
- First posted
- 18 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Does letibotulinum toxin A reduce forehead wrinkles as effectively as other botulinum toxin A products?
- Does letibotulinum toxin A show more localized (smaller) diffusion after injection?
Researchers will compare letibotulinum toxin A with prabotulinum toxin A and onabotulinum toxin A (Botox®) to evaluate their diffusion profiles and wrinkle-reduction effects.
Participants will:
- Receive botulinum toxin A injections on each side of the forehead (split-face design)
- Undergo wrinkle assessments and sweat gland function testing using 3D imaging and iodine-starch tests
- Return to the clinic 2 weeks after treatment for follow-up evaluation
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Treatment arm A | Active comparator | Drug: Letibotulinum toxin A, Drug: Prabotulinum toxin AThe 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. |
| Treatment arm B | Active comparator | Drug: Letibotulinum toxin A, Drug: Onabotulinum toxin AThe 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Exclusion criteria included a history of BoNT-A injection or cosmetic procedures near the fore-head/orbital area within the past year; signs of infection or inflammation at the injection site; compen-satory frontal hyperactivity; neuromuscular disorders including myasthenia gravis or amyotrophic lateral sclerosis; use of anticoagulants, aminoglycosides, curare-like agents, or neuromuscular inhibitors (stable doses of muscle relaxants or benzodiazepines are permitted); and hypersensitivity to the inves-tigational product or iodine.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Letibotulinum toxin AAlso: BotulaxLetibotulinum 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. | Drug | Treatment arm A, Treatment arm B |
| Prabotulinum toxin AAlso: NabotaPrabotulinum 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. | Drug | Treatment arm A |
| Onabotulinum toxin AAlso: BotoxOnabotulinum 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. | Drug | Treatment arm B |
Primary outcome
Area of Anhidrosis
Time frame: 2 weeks post-injection
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.
1 secondary outcome
Wrinkle Improvement
Time frame: Baseline and 2 weeks post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared due to privacy concerns and institutional policies that restrict data sharing beyond the research team. Data were collected under a protocol that did not include participant consent for public or external data sharing.
Related trials for Forehead Rhytides
Active, not recruitingEarly Phase 1
A Pilot Study Testing Onabotulinum Toxin A Versus Incobotulinum Toxin A Injections for Facial Wrinkles
Wrinkles
Not yet recruitingPhase 3
A Prospective, Multicenter, Blind, Randomized Controlled, Optimal Clinical Trial to Evaluate the Safety and Efficacy of Medical Collagen Fillers for Facial Dermal Tissue Filling to Correct Frontal Wrinkles (crow's Feet)
Intentional Correction of Forehead Wrinkles (crow's Feet)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Letibotulinum toxin A, Prabotulinum toxin A and Onabotulinum toxin A in people with Forehead Rhytides, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area of Anhidrosis (time frame: 2 weeks post-injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.