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

• ClinicalTrials.gov Identifier: NCT00770211
• Recruitment Status: Completed
• First Posted: October 9, 2008
• Results First Posted: September 13, 2011
• Last Update Posted: October 7, 2011
• Sponsor: Merz Pharmaceuticals GmbH
• Information provided by (Responsible Party): Merz Pharmaceuticals GmbH

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Moderate to Severe Glabellar Frown Lines	Drug: IncobotulinumtoxinA (Xeomin) (20 Units); Drug: Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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.
• Study Start Date: October 2008
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: IncobotulinumtoxinA (Xeomin) (20 Units); 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); 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.; Other Name: IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins' (20 Units)
Placebo Comparator: Placebo; Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding to total placebo volume 0.5 mL; mode of administration: intramuscular injection	Drug: 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).

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Baseline to Day 30 ]

   Composite endpoint CETS constituted by two efficacy variables:

   1. The investigator's assessment on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3.
   2. 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.

Secondary Outcome Measures :

1. Responders at Rest at Day 30 by Investigator's Assessment on Facial Wrinkle Scale (FWS) [ Time Frame: Baseline to Day 30 ]
   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.
2. 1-point Responders at Rest at Day 30 by Patient's Assessment on 4-point Scale [ Time Frame: Baseline to Day 30 ]

   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.

3. Responders at Maximum Frown at Day 30 by Investigator's Rating on FWS [ Time Frame: Baseline to Day 30 ]
   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.
4. 1-point Responders at Maximum Frown at Day 30 by Patient's Assessment on 4-point Scale [ Time Frame: Baseline to Day 30 ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Colorado

About Skin Dermatoloy

Englewood, Colorado, United States, 80113

United States, Florida

Center for Cosmetic Enhancement

Aventura, Florida, United States, 33180

Frederic Brandt

Coral Gables, Florida, United States, 33146

United States, Illinois

Advanced Dermatology Research Institute

Lincolnshire, Illinois, United States, 60069

United States, Indiana

Laser & Skin Surgery Center of Indiana

Carmel, Indiana, United States, 46032

United States, Nebraska

Joel Schlessinger

Omaha, Nebraska, United States, 68144

United States, New Jersey

Image Dermatology P.C.

Montclair, New Jersey, United States, 07042

United States, New York

Rhoda Narins

White Plains, New York, United States, 10604-2926

Sponsors and Collaborators

Merz Pharmaceuticals GmbH

Investigators

• Principal Investigator: William Hanke, MD
• Principal Investigator: Rhoda Narins, MD

More Information

• Responsible Party: Merz Pharmaceuticals GmbH
• ClinicalTrials.gov Identifier: NCT00770211
• Other Study ID Numbers: MRZ 60201 - 0741 / 1
• First Posted: October 9, 2008
• Results First Posted: September 13, 2011
• Last Update Posted: October 7, 2011
• Last Verified: October 2011

Additional relevant MeSH terms:

Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents