Clinical trial NCT00512135: Safety and Efficacy of NT 201 (IncobotulinumtoxinA [Xeomin]) in the Treatment of Glabellar Frown Lines
Official title: A Prospective, Open-label, Multicenter, Repeat-dose Trial to Investigate the Safety and Efficacy of NT 201, Free of Complexing Proteins, in the Treatment of Glabellar Frown Lines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glabellar Lines
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2007-08-07
Enrollment: 801
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This was a prospective, multicenter, open-label, non-control group design Phase 3 clinical study. Approximately 880 participants who were to complete former studies in this program (370 participants from studies MRZ 60201-0520/1 (8) and MRZ 60201-0527/1 (8) as well as approximately 510 participants from studies MRZ 60201-0724/1 (10) and MRZ 60201-0741/1) (11) were expected to enroll in this study in 26 centers in the United States, Canada and Germany. Participants with moderate to severe glabellar frown lines at maximum frown who completed participation in one of these four "feeder" studies in the frown line program were eligible to participate in this repeated dose study. Each participant received a dose of 20 units incobotulinumtoxinA (Xeomin) intramuscular injection on Visit 1 (Day 0 of Cycle 1). Re-injections with 20 U NT 201 could be performed on Day 0 of a subsequent cycle for up to 8 cycles (one cycle \>= 85 days). Intervals between treatments were at least three months or 12 weeks, i.e., \>= 85 days. For a new treatment cycle to start, the participant had to request a re-injection. The investigator then had to assess if the glabellar frown lines had relapsed to 'moderate' or 'severe'. In this case, a new injection could be administered. The treatment duration per participant was 24 months and up to eight cycles for participants enrolled from studies MRZ 60201-0520/1 and MRZ 60201-0527/1 and 6 months and up to two cycles for participants enrolled from studies MRZ 60201-0724/1 and MRZ 60201-0741/1, respectively. Participants enrolled from studies MRZ 60201-0520/1 and MRZ 60201-0527/1 participated at least one year in the study whereas participants enrolled from studies MRZ 60201-0724/1 and MRZ 60201-0741/1 participated for six months and up to two cycles.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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.

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Baseline up to Month 30
measure: Incidence of Adverse Events of Special Interest (AESI)
timeFrame: Baseline up to Month 30
measure: Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS)
timeFrame: 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)
measure: Percentage of Responders at Rest as Assessed by the Investigator According to FWS
timeFrame: 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)
measure: Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale
timeFrame: 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)
measure: Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale
timeFrame: 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)
measure: Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown
timeFrame: 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)
measure: Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest
timeFrame: 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)
measure: Time to Onset of Treatment Effect
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Skin Care Centre
state: California
city: Englewood
country: United States
facility: About Skin Dermatology
state: Colorado
city: Aventura
country: United States
facility: Centre for Cosmetic Enhancement
state: Florida
city: Coral Gables
country: United States
facility: Brandt
state: Florida
city: Lincolnshire
country: United States
facility: Advanced Dermatology Research Institute
state: Illinois
city: Carmel
country: United States
facility: Laser &Skin Surgery Center of Indiana
state: Indiana
city: Metairie
country: United States
facility: Coleman
state: Louisiana
city: Chestnut Hill
country: United States
facility: Skin Care Physisians of Chestnut Hill
state: Massachusetts
city: Omaha
country: United States
facility: Schlessinger
state: Nebraska
city: Montclair
country: United States
facility: Image Dermatology P.C.
state: New Jersey
city: White Plains
country: United States
facility: Narins
state: New York
city: Raleigh
country: United States
facility: Flynn Consulting PLLC
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: Vancouver
country: Canada
facility: Carruthers Dermatology Centre Inc.
state: British Columbia
city: Toronto
country: Canada
facility: Solish
state: Ontario
city: Berlin
country: Germany
facility: Charité Berlin - Klinik für Dermatologie
city: Darmstadt
country: Germany
facility: Rosenparkklinik
city: Dresden
country: Germany
facility: Krankenhaus Dresden Friedrichstadt
city: Frankfurt / Main
country: Germany
facility: Johann-Wolfgang-Goethe- Universitätsklinikum Frankfurt
city: Hamburg
country: Germany
facility: Universität Hamburg
city: Hamburg
country: Germany
facility: SCIderm GmbH
city: Homburg / Saar
country: Germany
facility: Uniklinik Saarland
city: Mahlow
country: Germany
facility: Dr. Michael Sebastian
city: München
country: Germany
facility: Dr. Hans-Ulrich Voigt
city: Wuppertal
country: Germany
facility: Dr. Thomas Dirschka
Study officials:
affiliation: Division of Evidence Based Medicine dEBM, Department of Dermatology, Venerology and Allergology , Charité - University Medicine, Berlin, Germany
name: Berthold Rzany, Prof. Dr. med Sc.M.
role: PRINCIPAL_INVESTIGATOR
name: Timothy Corcoran Flynn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.