IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Glabellar Frown Lines

Moderate to Severe Glabellar Frown Lines Clinical Trial

Official title:

A Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Investigate the Efficacy and Safety of IncobotulinumtoxinA (Xeomin), Free of Complexing Proteins, in the Treatment of Glabellar Frown Lines.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00770211
• Other study ID #: MRZ 60201 - 0741 / 1
• Status: Completed
• Phase: Phase 3
• First received: October 8, 2008
• Last updated: October 5, 2011
• Start date: October 2008
• Est. completion date: June 2009

Study information

• Verified date: October 2011
• Source: Merz Pharmaceuticals GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study objective is to show the superior efficacy of IncobotulinumtoxinA (Xeomin) over placebo by evaluation of treatment success analyzing the investigator's rating on the Facial Wrinkle Scale and the patient's assessment on a 4-point scale. 255 female and male patients with moderate to severe glabellar frown lines will be randomized in a 2:1 ratio to receive one injection of IncobotulinumtoxinA (Xeomin) or placebo and will be followed up until day 120.

Description:

The study was a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter phase 3 clinical trial. Approximately 285 females and males with moderate to severe glabellar frown lines at maximum frown were to be screened during a screening period of four months in order to randomize approximately 255 subjects into one treatment and one placebo group at a ratio of 2 : 1. After the single injection treatment with a total dose of 20 Units IncobotulinumtoxinA (Xeomin) or corresponding placebo, the subjects were observed over 120 days. During the study participation the subjects performed seven visits.

Eight (8) sites in the United States participated in this trial. The study was led by one Lead PI and a Co-Lead PI who was assisting the Lead PI. The role of the Lead PI and the Co-Lead PI was executed by one of the PIs of this study, respectively. The PI at each site was a medical doctor who was experienced in aesthetic dermatology, i.e. who had several years (>= 2 years) of experience in treatment of glabellar frown lines with BTX-A preparations. The PI was the person who led the team at one trial site and who was responsible for the conduct of the clinical trial at the site. The sub-investigator was a member of the team designated by the PI to perform important trial-related decisions. A maximum number of two sub-investigators could be authorized for injection and rating if necessary. At each site, ideally one investigator was to inject and rate all subjects. Injecting and rating sub-investigators had to be medical doctors with several years of experience in treatment of glabellar frown lines with BTX-A preparations. A subject had to be rated by the same investigator at all visits. Another phase 3 trial MRZ 60201-0724/1 (NCT00770029) with design and endpoints identical to those in this trial was performed in order to compare efficacy and safety results with a second study population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 271
• Est. completion date: June 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 or over

• Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on Facial Wrinkle Scale as assessed by investigator's rating: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe')

• Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on Facial Wrinkle Scale as assessed by patient's assessment: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe')

• Stable medical condition

Exclusion Criteria:

• Previous treatment with Botulinum toxin of any serotype in the glabellar area within the last 8 month

• Previous treatment with any facial aesthetic procedure (e.g. injection with biodegradable fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 month

• Previous insertion of permanent material in the glabellar area (regardless of the time between previous treatment and this study)

• Planned treatment with Botulinum toxin of any serotype in any other body region during the study period

• Any surgery in the glabellar area including surgical removal of the corrugator, procerus, or depressor supercilii muscles or a combination of these, or scars in the glabellar area and the surrounding areas (including eye brow)

• Any other planned facial aesthetic procedure during the trial period

• Inability to substantially lessen glabellar frown lines even by physically spreading them apart

• Marked facial asymmetry or ptosis of eyelid and/or eyebrow

• History of facial nerve palsy

• Any infection in the area of the injection sites

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Moderate to Severe Glabellar Frown Lines

Intervention

Drug:
• IncobotulinumtoxinA (Xeomin) (20 Units)
The treatment will be administered only once at day 0 at five injection sites in the glabellar area. The total dose of 20 Units IncobotulinumtoxinA (Xeomin) is reconstituted in a total injection volume of 0.5 mL that is to be injected to the five sites in equal aliquots of 0.1 mL.
• Placebo
The treatment will be administered only once at day 0 at five injection sites in the glabellar area. Volume of Placebo equivalent to IncobotulinumtoxinA (Xeomin).

Locations

Country	Name	City	State
United States	Center for Cosmetic Enhancement	Aventura	Florida
United States	Laser & Skin Surgery Center of Indiana	Carmel	Indiana
United States	Frederic Brandt	Coral Gables	Florida
United States	About Skin Dermatoloy	Englewood	Colorado
United States	Advanced Dermatology Research Institute	Lincolnshire	Illinois
United States	Image Dermatology P.C.	Montclair	New Jersey
United States	Joel Schlessinger	Omaha	Nebraska
United States	Rhoda Narins	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merz Pharmaceuticals GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Endpoint Treatment Success (CETS) Constituted by 2 Variables: 2-point Responders at Maximum Frown (Frown as Much as Possible) at Day 30 by Investigator's Rating on the Facial Wrinkle Scale and the Patient's Assessment on 4-point Scale	Composite endpoint CETS constituted by two efficacy variables: The investigator's assessment on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3.; Patient's assessment on the 4-point scale in comparison to sample photos: 0 = No muscle action at all; 1 = Some even slight muscle action possible i.e. visible furrows; 2 = Moderately strong muscle action possible i.e. visible muscle bulges; 3 = Strong muscle action possible which may cause local pallor.; A subject was a responder only if a 2-point improvement compared to baseline occurred simultaneously for both variables.	Baseline to Day 30	No
Secondary	Responders at Rest at Day 30 by Investigator's Assessment on Facial Wrinkle Scale (FWS)	The investigator's assessment at rest (no muscle action in the face, no frown at all) on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3. A responder was defined as a subject with a rating of none = 0 or mild = 1.	Baseline to Day 30	No
Secondary	1-point Responders at Rest at Day 30 by Patient's Assessment on 4-point Scale	Patient's assessment at rest (no muscle action in the face, no frown at all) on the 4-point scale in comparison to sample photos: 0 = No visible vertical line(s) at all (i.e. no visible upright line); 1 = Slightly visible vertical line(s) (i.e. slightly visible upright line); 2 = Moderate vertical line(s) with depression (i.e. upright line with deepening); 3 = Deep vertical line(s) and depression which cannot be effaced by spreading (i.e. cannot be smoothed out).; A subject was a responder if a 1-point improvement occurred compared to baseline.	Baseline to Day 30	No
Secondary	Responders at Maximum Frown at Day 30 by Investigator's Rating on FWS	The investigator's assessment at maximum frown (frown as much as possible) on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3. A responder was defined as a subject with a rating of none = 0 or mild = 1.	Baseline to Day 30	No
Secondary	1-point Responders at Maximum Frown at Day 30 by Patient's Assessment on 4-point Scale	Patient's assessment at maximum frown (frown as much as possible) on the 4-point scale in comparison to sample photos: 0 = No muscle action at all; 1 = Some even slight muscle action possible i.e. visible furrows; 2 = Moderately strong muscle action possible i.e. visible muscle bulges; 3 = Strong muscle action possible which may cause local pallor.; A subject was a responder if a 1-point improvement occurred compared to baseline.	Baseline to Day 30	No