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IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Blepharospasm

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ClinicalTrials.gov Identifier: NCT00406367
Recruitment Status : Completed
First Posted : December 4, 2006
Results First Posted : November 16, 2010
Last Update Posted : March 15, 2013
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 Blepharospasm
Interventions Drug: incobotulinumtoxinA (Xeomin)
Drug: Placebo
Enrollment 109
Recruitment Details  
Pre-assignment Details  
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo
Hide Arm/Group Description incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Period Title: Main Period - 6 to 20 Weeks
Started 75 34
Completed 70 32
Not Completed 5 2
Reason Not Completed
Withdrawal Criteria Occurred             4             0
Consent Withdrawn             1             0
Lost to Follow-up             0             1
Dosing Error At Visit 2 (Baseline)             0             1
Period Title: Open-Label Ext. Period - up to 68 Weeks
Started 102 0 [1]
Completed 82 0
Not Completed 20 0
Reason Not Completed
Lost to Follow-up             2             0
Consent Withdrawn             6             0
Withdrawal Criteria Occurred             4             0
Lack of Efficacy             4             0
Subjects Needed Further Injection             1             0
Subject Received Botox Injection             1             0
Injection in Wrong Muscle             1             0
OLEX Drug Given at Baseline             1             0
[1]
In the Open-Label Extension Period no placebo treatment arm was given.
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo Total
Hide Arm/Group Description incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection Total of all reporting groups
Overall Number of Baseline Participants 75 34 109
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 75 participants 34 participants 109 participants
61.5  (11.0) 62.6  (8.7) 61.9  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 34 participants 109 participants
Female
49
  65.3%
22
  64.7%
71
  65.1%
Male
26
  34.7%
12
  35.3%
38
  34.9%
1.Primary Outcome
Title Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by a Blinded Independent Rater)
Hide Description

The Jankovic Rating Scale (JRS) is used for classification of the patient's individual symptoms of blepharospasm and for determination of the therapeutic efficacy of study medication. The JRS sumscore is the sum of the two components of the scale:

  • JRS-Severity score which ranges from 0 (=absence of severity) to 4 (=maximum severity)
  • JRS-Frequency score which ranges from 0 (=no frequency) to 4 (=maximum frequency) The change from baseline was calculated as the score at the corresponding visit minus the baseline score.
Time Frame Baseline, week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population: all participants randomized were included in the primary efficacy analysis; Last Observation Carried Forward (LOCF) imputation technique used for missing values
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo
Hide Arm/Group Description:
incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection
Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Overall Number of Participants Analyzed 75 34
Least Squares Mean (Standard Error)
Unit of Measure: Points on a scale
-0.8  (0.13) 0.2  (0.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection incobotulinumtoxinA (Xeomin), Placebo
Comments The null hypothesis in the analysis of covariance (ANCOVA) model was the absence of difference in the change from baseline in the JRS severity subscore between incobotulinumtoxinA (Xeomin) and placebo. The ANCOVA model was performed 2-sided (type-I error=5 percent) and change from baseline in the JRS Severity subscore assessed by a blinded Independent Rater as dependent variable. The independent variables were treatment, baseline JRS Severity subscore, gender, age, dose group, and pooled center.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No type I-error adjustment was necessary in this study.
Method ANCOVA
Comments Indepent variables in the model were treatment, baseline JRS-Severity score, gender, age, dose, and pooled center.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.4 to -0.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by Subject Diary)
Hide Description

The Jankovic Rating Scale (JRS) is used for classification of the patient's individual symptoms of blepharospasm and for determination of the therapeutic efficacy of study medication. The JRS sumscore is the sum of the two components of the scale:

  • JRS-Severity score which ranges from 0 (=absence of severity) to 4 (=maximum severity)
  • JRS-Frequency score which ranges from 0 (=no frequency) to 4 (=maximum frequency) The change from baseline was calculated as the score at the corresponding visit minus the baseline score.
Time Frame Baseline, week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population by using the Last Observation Carried Forward (LOCF) imputation technique for missing values
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo
Hide Arm/Group Description:
incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection
Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Overall Number of Participants Analyzed 67 32
Mean (Standard Deviation)
Unit of Measure: Points on a scale
-0.75  (1.24) 0.16  (1.07)
3.Secondary Outcome
Title Blepharospasm Disability Index (BSDI) Change From Baseline in the BSDI at Week 6 After Injection
Hide Description The Blepharospasm Disability Index is a scale for the assessment of impairment of specific activities of daily living caused by blepharospasm. The BSDI consists of six items (driving a vehicle; reading; watching TV; shopping; getting about on foot (walking); doing everyday activities), each ranges from 0 (=no impairment) to 4 (=no longer possible due to illness). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.
Time Frame Baseline, week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population by using the Last Observation Carried Forward (LOCF) imputation technique for missing values
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo
Hide Arm/Group Description:
incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection
Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Overall Number of Participants Analyzed 75 34
Mean (Standard Deviation)
Unit of Measure: Points on a scale
-0.4  (0.69) 0.11  (0.67)
4.Secondary Outcome
Title Patient Evaluation of Global Response (PEGR) at Final Visit
Hide Description The PEGR is a descriptive subjective 9-point response scale ranging from "complete abolishment of signs and symptoms" (value=+4) down to "very marked worsening" (value=-4).
Time Frame Final visit (up to week 20 after injection of the Main Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population with missing values imputed by "no effect".
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo
Hide Arm/Group Description:
incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection
Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Overall Number of Participants Analyzed 75 34
Mean (Standard Deviation)
Unit of Measure: Points on a scale
1.3  (2.09) -0.6  (2.16)
Time Frame All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection.
Adverse Event Reporting Description The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
 
Arm/Group Title incobotulinumtoxinA (Xeomin) Placebo
Hide Arm/Group Description incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
All-Cause Mortality
incobotulinumtoxinA (Xeomin) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
incobotulinumtoxinA (Xeomin) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/74 (0.00%)      1/34 (2.94%)    
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/74 (0.00%)  0 1/34 (2.94%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
incobotulinumtoxinA (Xeomin) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/74 (60.81%)      13/34 (38.24%)    
Eye disorders     
Dry eye  1  14/74 (18.92%)  16 4/34 (11.76%)  4
Eyelid ptosis  1  14/74 (18.92%)  14 2/34 (5.88%)  2
Vision blurred  1  4/74 (5.41%)  4 2/34 (5.88%)  2
Visual disturbance  1  6/74 (8.11%)  6 0/34 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea  1  6/74 (8.11%)  6 0/34 (0.00%)  0
Dry mouth  1  11/74 (14.86%)  11 1/34 (2.94%)  1
Dysphagia  1  3/74 (4.05%)  3 2/34 (5.88%)  2
Infections and infestations     
Nasopharyngitis  1  4/74 (5.41%)  4 2/34 (5.88%)  2
Respiratory tract infection  1  5/74 (6.76%)  5 1/34 (2.94%)  1
Upper respiratory tract infection  1  1/74 (1.35%)  1 3/34 (8.82%)  3
Nervous system disorders     
Headache  1  7/74 (9.46%)  7 1/34 (2.94%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/74 (5.41%)  4 0/34 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
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 weeks before submission. Sponsor to give written opinion within 30 days. 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: Angelika Hanschmann
Organization: Merz Pharmaceuticals GmbH
Phone: ++49-69-1503 ext 538
EMail: angelika.hanschmann@merz.de
Layout table for additonal information
Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT00406367    
Other Study ID Numbers: MRZ 60201-0433
First Submitted: November 30, 2006
First Posted: December 4, 2006
Results First Submitted: August 31, 2010
Results First Posted: November 16, 2010
Last Update Posted: March 15, 2013