Safety and Efficacy of NT 201 (IncobotulinumtoxinA [Xeomin]) in the Treatment of Glabellar Frown Lines

NCT00512135 | Completed Phase 3 Results

• 2 other identifiers: MRZ 60201-0609/12006-005342-36
• Study Type: interventional
• Target: 801
• Locations: 3 countries
• Sites: 25

Brief Summary

The study objective was to investigate the safety and efficacy of incobotulinumtoxinA (Xeomin) during repeat dose treatment of glabellar frown lines. 801 participants with moderate to severe glabellar frown lines at maximum frown who completed participation in one of the studies in this program, i.e. MRZ 60201-0520/1, MRZ 60201-0527/1, MRZ 60201-0724/1, or MRZ 60201-0741/1 were eligible to participate in this repeat-dose study.

Conditions

Glabellar Lines

Outcome Measures

Primary Outcomes (9)

• Incidence of Adverse Events (AEs)

  Baseline up to Month 30

• Incidence of Adverse Events of Special Interest (AESI)

  Baseline up to Month 30

• Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS)

  FWS was used to assess the severity of glabellar frown lines at maximum frown by the investigator. The 4-point scale depicted as: 0 = none, 1 = mild, 2 = moderate and 3 = severe. Responders on the FWS were defined as participants with glabellar line severity of none (0) or mild (1).

  At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

• Percentage of Responders at Rest as Assessed by the Investigator According to FWS

  FWS was used to assess the severity of glabellar frown lines at rest by the investigator. The 4-point scale depicted as: 0 = none, 1 = mild, 2 = moderate and 3 = severe. Responders on the FWS were defined as participants with glabellar line severity of none (0) or mild (1). Responders on the FWS were defined as participants with glabellar line severity of none (0) or mild (1).

  At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

• Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale

  Participant's assessment of the glabellar frown lines at maximum frown on the 4-point scale was done by asking participant the following question in local language: "How would you judge the potency of frown muscle action by comparison to sample photos at this visit?" The possible rating responses were: 0 = no muscle action at all, 1 = some even slight muscle action possible, 2 = moderately strong muscle action possible, 3 = strong muscle action possible which may cause local pallor. Responders were participants with at least 1-point improvement compared to Day 0 whereas improvement was expressed by lowering of the numerical score.

  At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

• Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale

  Participant's assessment of the glabellar frown lines at rest on the 4-point scale was done by asking participant the following question in local language: "How would you judge the degree of your glabellar lines by comparison to sample photos at this visit?" The possible rating responses were: 0 = no visible vertical line(s) at all, 1 = slightly visible vertical line(s), 2 = moderate vertical line(s) with depression, and 3 = deep vertical line(s) and depression which cannot be effaced by spreading. Responders were participants with at least 1-point improvement compared to Day 0 whereas improvement was expressed by lowering of the numerical score.

  At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

• Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown

  Number of participants are reported categorized in grades based on the assessment of the glabellar frown lines at maximum frown on the 6-point Likert scale. Participant's assessment of the glabellar frown lines at maximum frown on the 6-point Likert type scale was done by asking participant the following question in local language: "How would you judge the potency of frown muscle action at this visit?" The possible rating responses were given on a categorical scale of 6 grades between the grades 0 = none at all and 5 = very deep, with higher score reflecting higher potency.

  At evaluation visit (30 days after injection); and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

• Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest

  Number of participants are reported categorized in grades based on the assessment of the glabellar frown lines at rest on the 6-point Likert scale. Participant's assessment of the glabellar frown lines at rest on the 6-point Likert type scale was done by asking participant the following question in local language: "How would you judge the degree of your glabellar lines at this visit?" The possible rating responses were given on a categorical scale of 6 grades between the grades 0 = none at all and 5 = very deep, with higher scores reflecting higher degree of glabellar lines.

  At evaluation visit (30 days after injection); and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

• Time to Onset of Treatment Effect

  Onset of treatment effect was analyzed using number of participants with corresponding onset of treatment effect, stratified by cycles.

  From injection visit up to date of onset of treatment effect in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Study Arms (1)

IncobotulinumtoxinA (Xeomin) (20 units)

EXPERIMENTAL

IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins' (active ingredient: Clostridium Botulinum neurotoxin type A free from complexing proteins) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% sodium chloride (NaCl), 20 units, total volume 0.5 mL, mode of administration: intramuscular injection

Drug: IncobotulinumtoxinA (Xeomin) (20 units)

Interventions

IncobotulinumtoxinA (Xeomin) (20 units) DRUG

Injection of a total of 20 Units incobotulinumtoxinA (Xeomin) on day one of each of up to eight cycles, reconstituted in a total injection volume of 0.5 mL administered in five equal parts of 0.1 mL to five predefined points of the glabellar area.

Also known as: IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins (20 units)

IncobotulinumtoxinA (Xeomin) (20 units)

Eligibility Criteria

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

You may qualify if:

• Participants with 'moderate' or 'severe' glabellar frown lines at maximum frown at the beginning of each treatment cycle (as assessed by the investigator according to FWS) , stable medical condition; Completion of one former study in the Merz NT 201 glabellar program

You may not qualify if:

• Participants with preexisting neuromuscular diseases (e.g. myasthenia gravis, Lambert-Eaton syndrome) putting the participant at risk, History of Facial Nerve Palsy, Previous treatment with Botulinum Toxin in the glabellar area during the last 12 months, Previous treatment with biodegradable fillers or other procedures (e.g. chemical peeling, photo rejuvenation) in the glabellar area during the last 12 months, Previous insertion of permanent material in the glabellar area; Planned treatment with Botulinum toxin of any serotype in any body region during the study period, Any other planned facial aesthetic procedure in the glabellar area during the trial period; Any surgery in the glabellar area including surgical removal of the corrugator, procerus or depressor supercili muscles or a combination of these or scars in the glabellar area, Inability to substantially lessen glabellar frown lines even by physically spreading apart, Marked facial asymmetry or ptosis of eyelid and/or eyebrow; Any infection in the area of the injection sites.

Sponsors & Collaborators

• Merz Pharmaceuticals GmbH: lead

Study Sites (25)

Skin Care Centre

Los Angeles, California, 90069, United States

Location

About Skin Dermatology

Englewood, Colorado, 80113, United States

Location

Centre for Cosmetic Enhancement

Aventura, Florida, 33180, United States

Location

Brandt

Coral Gables, Florida, 33146, United States

Location

Advanced Dermatology Research Institute

Lincolnshire, Illinois, 60069, United States

Location

Laser &Skin Surgery Center of Indiana

Carmel, Indiana, 46032, United States

Location

Coleman

Metairie, Louisiana, 70006, United States

Location

Skin Care Physisians of Chestnut Hill

Chestnut Hill, Massachusetts, 02467, United States

Location

Schlessinger

Omaha, Nebraska, 68144, United States

Location

Image Dermatology P.C.

Montclair, New Jersey, 07042, United States

Location

Narins

White Plains, New York, 10604, United States

Location

Flynn Consulting PLLC

Raleigh, North Carolina, 27608, United States

Location

Tennessee Clinical Research Center

Nashville, Tennessee, 37215, United States

Location

Carruthers Dermatology Centre Inc.

Vancouver, British Columbia, V5Z4E1, Canada

Location

Solish

Toronto, Ontario, M5R3N8, Canada

Location

Charité Berlin - Klinik für Dermatologie

Berlin, 10117, Germany

Location

Rosenparkklinik

Darmstadt, 64297, Germany

Location

Krankenhaus Dresden Friedrichstadt

Dresden, 01067, Germany

Location

Johann-Wolfgang-Goethe- Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universität Hamburg

Hamburg, 20146, Germany

Location

SCIderm GmbH

Hamburg, 20354, Germany

Location

Uniklinik Saarland

Homburg / Saar, 66421, Germany

Location

Dr. Michael Sebastian

Mahlow, 15831, Germany

Location

Dr. Hans-Ulrich Voigt

München, 80333, Germany

Location

Dr. Thomas Dirschka

Wuppertal, 42275, Germany

Location

Related Publications (1)

• Rzany B, Flynn TC, Schlobe A, Heinz M, Harrington L. Long-term results for incobotulinumtoxinA in the treatment of glabellar frown lines. Dermatol Surg. 2013 Jan;39(1 Pt 1):95-103. doi: 10.1111/dsu.12008. Epub 2012 Nov 27.

  PMID: 23190342 RESULT

MeSH Terms

Interventions

incobotulinumtoxinA; 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

Results Point of Contact

• Title: Public Disclosure Manager
• Organization: Merz Pharmaceuticals GmbH

clinicaltrials@merz.com

+49 69 1503 1

Study Officials

• Berthold Rzany, Prof. Dr. med Sc.M.

  Division of Evidence Based Medicine dEBM, Department of Dermatology, Venerology and Allergology , Charité - University Medicine, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Timothy Corcoran Flynn, MD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 7, 2007
• Study Start: June 18, 2007
• Primary Completion: December 28, 2009
• Study Completion: December 28, 2009
• Last Updated: April 2, 2021
• Results First Posted: April 2, 2021

Record last verified: 2021-03

Locations

DE (10); US (13); CA (2)