Moderate to Severe Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)Phase 3ULTRA INCT04594213
Safety and Efficacy Study of the Simultaneous Treatment of Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines and Lateral Canthal Lines) in Subjects With Moderate to Severe Upper Facial Lines
A Phase 3 study testing NT 201 in people with Moderate to Severe Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines), run by Merz North America, Inc. at 12 sites in United States.
Trial summary
The purpose of this study is to investigate the safety and efficacy of NT 201 (active ingredient: Botulinum (neuro)toxin type A, free from complexing proteins) in the combined treatment of wrinkles in the upper face (Upper Facial Lines [UFL]): Horizontal Forehead Lines [HFL], Glabellar Frown Lines [GFL], and Lateral… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Moderate to Severe Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)
- What is being tested?
- NT 201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 362 participants
- Where
- 12 sitesUnited States
- Study dates
- 23 Sep 2020to 9 May 2022
- Phase
- Phase 3
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Outpatients (male or female) 18 years of age or older.
- Horizontal forehead lines (HFL), glabellar frown lines (GFL), and symmetrical lateral canthal lines (LCL) of moderate to severe intensity at maximum contraction as assessed by the investigator and subject according to Merz Aesthetics Scales (MAS).
Who cannot join
- Previous treatment with botulinum neurotoxin (BoNT) of any serotype in the face within the last 12 months before injection.
- Any facial cosmetic procedure within the last 12 months before baseline injection.
- Previous treatment with any biodegradable filler in the face within the last 12 months before injection.
- Any previous insertion of permanent material in the face (regardless of the time between previous treatment and this study).
- Any medical condition that may put the subject at increased risk with exposure to NT201.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Merz Investigational Site
Aventura, Florida, 33180
Merz Investigational Site
Boca Raton, Florida, 33431
Merz Investigational Site
Encino, California, 91436
Merz Investigational Site
Greenwood Village, Colorado, 80111
Merz Investigational Site
Metairie, Louisiana, 70006
Merz Investigational Site
Nashville, Tennessee, 37215
Merz Investigational Site
New York, New York, 10028
Merz Investigational Site
New York, New York, 10065
Merz Investigational Site
New York, New York, 10075
Merz Investigational Site
Newport Beach, California, 92663
Merz Investigational Site
San Diego, California, 92121
Merz Investigational Site
Washington D.C., District of Columbia, 20037
About this study
Official title: A Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Simultaneous Treatment of Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)
The purpose of this study is to investigate the safety and efficacy of NT 201 (active ingredient: Botulinum (neuro)toxin type A, free from complexing proteins) in the combined treatment of wrinkles in the upper face (Upper Facial Lines [UFL]): Horizontal Forehead Lines [HFL], Glabellar Frown Lines [GFL], and Lateral Canthal Lines [LCL]). It is a prospective, randomized, double-blind, placebo-controlled, multicenter study with a placebo-control main period (MP) followed by an open-label extension (OLEX) period.
- Being tested
- NT 201, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NT 201Drug
Also called IncobotulinumtoxinA, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing protein
Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% NaCl.
PlaceboDrug
Solution for injection prepared by reconstitution of powder with percent (%) Sodium Chloride (NaCl).
| Study group | Role | What they receive |
|---|---|---|
| Main Period: Placebo (Group P) | Placebo comparator | Subjects will receive placebo injection in all three UFL (GFL, HFL and LCL) on Day 1 of main period. Receives: Drug: Placebo |
| Main Period: NT 201 (Group U) | Experimental | Subjects will receive a total of 64 Units (U) of NT 201: 20 U of NT 201 injection both in the GFL area and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 of main period. Receives: Drug: NT 201 |
| Main Period: NT 201 and Placebo (Group G and H) | Experimental | Subjects will receive a total of 40 U of NT 201: 20 U of NT 201 injection both in the GFL and HFL area, and placebo injection in the LCL area on Day 1 of main period. Receives: Drug: NT 201; Drug: Placebo |
| OLEX: NT 201 (Main Period: Group P) | Experimental | Subjects will receive a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period. Receives: Drug: NT 201 |
| OLEX: NT 201 (Main Period: Group U) | Experimental | Subjects will receive a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period. Receives: Drug: NT 201 |
| OLEX: NT 201 (Main Period: Group G and H) | Experimental | Subjects will receive a total of 64 U of NT 201: 20 U of NT 201 injection both in the GFL and in the HFL area, and 24 U of NT 201 injection in the LCL area (12 U per side) on Day 1 (Visit 8) and Visit 13 of OLEX period. Receives: Drug: NT 201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main Period: Percentage of Glabellar Frown Line (GFL) Responders at Day 30
The Merz aesthetics scales (MAS) are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. GFL-response was defined as a score of 0 (no) or 1 (mild) and at least two-grade improvement from baseline to Day 30 of main period on MAS for GFL at maximum contraction as assessed by both the investigator and the subject. The MAS for GFL ranged as 0 to 4 where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".
Measured: Day 30
Main Period: Percentage of Horizontal Forehead Lines (HFL) Responders at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. HFL-response was defined as a score of 0 (no) or 1 (mild) and at least two-grade improvement from baseline to Day 30 of main period on MAS for HFL at maximum contraction as assessed by both the investigator and the subject. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Percentage of Lateral Canthal Lines (LCL) Responders at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. LCL-response was defined as a score of 0 (no) or 1 (mild) and at least two-grade improvement from baseline to Day 30 of main period on MAS for both left and right LCL at maximum contraction as assessed by both the investigator and the subject. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Secondary outcomes (13)
Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for GFL at Maximum Contraction as Assessed by the Investigator at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for GFL ranged as 0 to 4 where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".
Measured: Day 30
Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for HFL at Maximum Contraction as Assessed by the Investigator at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for Both Left and Right LCL at Maximum Contraction as Assessed by the Investigator at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for GFL at Maximum Contraction as Assessed by the Subject at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for GFL ranged as 0 to 4 where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".
Measured: Day 30
Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for HFL at Maximum Contraction as Assessed by the Subject at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Percentage of Subjects With a Score of 0 (no) or 1 (Mild) on MAS for Both Left and Right LCL at Maximum Contraction as Assessed by the Subject at Day 30
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Subjects
The GAIS is a 7-point Likert scale capturing the global aesthetic improvement ranging from +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the subject. GAIS as assessed by the subject at Day 30 was analyzed using an analysis of covariance (ANCOVA) model.
Measured: Day 30
Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 on MAS for GFL at Maximum Contraction as Assessed by the Investigator
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for GFL ranged as 0 to 4 where 0 is "No glabellar lines", 1 is "Mild glabellar lines", 2 is "Moderate glabellar lines", 3 is "Severe glabellar lines" and 4 is "Very severe glabellar lines".
Measured: Day 30
Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 on MAS for HFL at Maximum Contraction as Assessed by the Investigator
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for HFL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Percentage of Subjects With at Least One-grade Improvement From Baseline to Day 30 on MAS for Both Left and Right LCL at Maximum Contraction as Assessed by the Investigator
The MAS are 5-point scales used to identify responders in a clinical context. They are validated photograph-based outcome instruments designed specifically for assessment of each upper facial area. The MAS for LCL ranged as 0 to 4 where 0 is "No lines", 1 is "Mild lines", 2 is "Moderate lines", 3 is "Severe lines" and 4 is "Very severe lines".
Measured: Day 30
Main Period: Global Aesthetic Improvement Scale (GAIS) at Day 30 as Assessed by the Investigator
The GAIS is a 7-point Likert scale capturing the global aesthetic improvement ranging from +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the investigator. GAIS as assessed by the investigator at Day 30 was analyzed using an ANCOVA model.
Measured: Day 30
Main Period: Number of Subjects With Related Treatment-Emergent Adverse Events (TEAEs)
TEAEs during the Main Period are defined as adverse events (AEs) with onset or worsening on or after date and time of first dose of study treatment and before date and time of first administration of study treatment in the OLEX period or the final study visit, if subject was not treated in the OLEX period. An AE is considered to be related if a causal relationship between study treatment and the AE is at least reasonably possible.
Measured: Up to 22 Weeks
OLEX Period: Number of Subjects With Related TEAEs
TEAEs of the OLEX period are defined as AEs with onset or worsening on or after date and time of first dose of study treatment in the OLEX period up to and including the final study visit. An AE is considered to be related if a causal relationship between study treatment and the AE is at least reasonably possible.
Measured: Up to 39 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2020
- Study start23 Sep 2020
- Primary completion15 Apr 2021
- Study completion9 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Moderate to Severe Upper Facial Lines (Horizontal Forehead Lines, Glabellar Frown Lines, and Lateral Canthal Lines)Studies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 362 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merz North America, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merz Pharmaceuticals GmbH
- Responsible party
- Sponsor
- Investigators
- Merz Medical Expert, Study director, Merz North America, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04594213
- Sponsor's protocol ID
- M602011071
- Acronym
- ULTRA I
- Status last verified
- Apr 2024
- First submitted
- 13 Oct 2020
- Last updated
- 8 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pavicic T, Burgess C, Fabi S, Nestor MS, Bee EK, Imhof M, Dersch H, Sudimac V. Aesthetic Improvements Over Time: Long-Term Efficacy and Additional Outcomes of IncobotulinumtoxinA in the Simultaneous Treatment of Upper Facial Lines. J Cosmet Dermatol. 2025 Sep;24(9):e70460. doi: 10.1111/jocd.70460.
PubMed 40968493Joseph J, Sudimac V, Mersmann S, Kerscher M. IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results From Two Randomized, Double-Blind, Placebo-Controlled, Phase III Studies. Aesthet Surg J. 2025 Feb 18;45(3):293-304. doi: 10.1093/asj/sjae222.
PubMed 39475143