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

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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:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Moderate to Severe Glabellar Frown Lines
Interventions Drug: IncobotulinumtoxinA (Xeomin) (20 Units)
Drug: Placebo
Enrollment 271
Recruitment Details  
Pre-assignment Details  
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description 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, 20 units; mode of administration: intramuscular injection Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
Period Title: Overall Study
Started 182 89
Completed 181 87
Not Completed 1 2
Reason Not Completed
Lost to Follow-up             1             0
Withdrawal by Subject             0             2
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo Total
Hide Arm/Group Description 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, 20 units; mode of administration: intramuscular injection Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin) Total of all reporting groups
Overall Number of Baseline Participants 182 89 271
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 182 participants 89 participants 271 participants
46.9  (9.32) 45.7  (11.41) 46.5  (10.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 182 participants 89 participants 271 participants
Female
170
  93.4%
84
  94.4%
254
  93.7%
Male
12
   6.6%
5
   5.6%
17
   6.3%
1.Primary Outcome
Title 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
Hide Description

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.
Time Frame Baseline to Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): All randomized subjects treated with study medication. Missing values were imputed by the evaluations made at Day 7 according to the LOCF (last observation carried forward). If no ratings for Day 7 were available values were set to 'no 2-point responder'.
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description:
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, 20 units; mode of administration: intramuscular injection
Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
Overall Number of Participants Analyzed 182 89
Measure Type: Number
Unit of Measure: Particpants
87 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IncobotulinumtoxinA (Xeomin) (20 Units), Placebo
Comments The efficacy of the treatment was confirmed, if H0 was rejected at a given alpha of 5%, that means if the two sided p-value is ≤ 0.05. Power of 90%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference response rate
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.40 to 0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.037
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Responders at Rest at Day 30 by Investigator's Assessment on Facial Wrinkle Scale (FWS)
Hide Description 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.
Time Frame Baseline to Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases. Responder defined as having a rating of none or mild
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description:
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, 20 units; mode of administration: intramuscular injection
Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
Overall Number of Participants Analyzed 182 89
Measure Type: Number
Unit of Measure: Participants
157 50
3.Secondary Outcome
Title 1-point Responders at Rest at Day 30 by Patient's Assessment on 4-point Scale
Hide Description

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.
Time Frame Baseline to Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases.
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description:
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, 20 units; mode of administration: intramuscular injection
Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
Overall Number of Participants Analyzed 182 89
Measure Type: Number
Unit of Measure: Participants
137 13
4.Secondary Outcome
Title Responders at Maximum Frown at Day 30 by Investigator's Rating on FWS
Hide Description 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.
Time Frame Baseline to Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases. Responder as having a rating of none or mild
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description:
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, 20 units; mode of administration: intramuscular injection
Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
Overall Number of Participants Analyzed 182 89
Measure Type: Number
Unit of Measure: Participants
139 0
5.Secondary Outcome
Title 1-point Responders at Maximum Frown at Day 30 by Patient's Assessment on 4-point Scale
Hide Description

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.
Time Frame Baseline to Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases.
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description:
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, 20 units; mode of administration: intramuscular injection
Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
Overall Number of Participants Analyzed 182 89
Measure Type: Number
Unit of Measure: Participants
152 10
Time Frame All SAEs/AEs after injection were reported. All subjects experiencing SAEs/AEs were to be monitored until AE was resolved or stabilized or until a plausible explanation for the cause of the event had been found.
Adverse Event Reporting Description Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of Adverse Events includes all non-serious AEs.
 
Arm/Group Title IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Hide Arm/Group Description 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, 20 units; mode of administration: intramuscular injection Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin)
All-Cause Mortality
IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/182 (0.00%)      1/89 (1.12%)    
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Renal cell carcinoma † 1 [1]  0/182 (0.00%)  0 1/89 (1.12%)  1
Surgical and medical procedures     
Nephrectomy † 1 [2]  0/182 (0.00%)  0 1/89 (1.12%)  1
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
[1]
Start date: 06JAN2009 Stop date: 10JAN2009 Moderate intensity Not related to study treatment Recovered/resolved
[2]
Start date: 06JAN2009 Stop date: 06JAN2009 Moderate intensity Not related to study treatment Recovered/resolved
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
IncobotulinumtoxinA (Xeomin) (20 Units) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/182 (19.23%)      18/89 (20.22%)    
Infections and infestations     
Nasopharyngitis † 1  9/182 (4.95%)  10 5/89 (5.62%)  6
Sinusitis † 1  6/182 (3.30%)  6 4/89 (4.49%)  4
Upper respiratory tract infection † 1  4/182 (2.20%)  4 0/89 (0.00%)  0
Pharyngitis streptococcal † 1  3/182 (1.65%)  3 2/89 (2.25%)  2
Musculoskeletal and connective tissue disorders     
Musculoskeletal stiffness † 1  0/182 (0.00%)  0 2/89 (2.25%)  2
Nervous system disorders     
Headache † 1  17/182 (9.34%)  20 5/89 (5.62%)  6
Sinus headache † 1  7/182 (3.85%)  7 1/89 (1.12%)  1
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain † 1  4/182 (2.20%)  4 1/89 (1.12%)  1
Skin and subcutaneous tissue disorders     
Actinic keratosis † 1  0/182 (0.00%)  0 2/89 (2.25%)  2
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
No results to be published without written agreement by sponsor; manuscripts to be sent to sponsor at least 6 wks before submission. Sponsor to give written opinion within 30 d. Sponsor is entitled to exert influence on the contents of publications, to postpone publications up to 36 months after end of the study, and to name co-authors. In case of justified doubts of sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Matthias Zerm
Organization: Merz Pharmaceuticals GmbH
Phone: 0049-69-1503 ext 865
EMail: matthias.zerm@merz.de
Layout table for additonal information
Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT00770211    
Other Study ID Numbers: MRZ 60201 - 0741 / 1
First Submitted: October 8, 2008
First Posted: October 9, 2008
Results First Submitted: August 9, 2011
Results First Posted: September 13, 2011
Last Update Posted: October 7, 2011