IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Blepharospasm

Blepharospasm Clinical Trial

Official title:

Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Trial With an Open-label Extension Period to Investigate the Efficacy and Safety of incobotulinumtoxinA (Xeomin) in the Treatment of Blepharospasm

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00406367
• Other study ID #: MRZ 60201-0433
• Status: Completed
• Phase: Phase 3
• First received: November 30, 2006
• Last updated: March 13, 2013
• Start date: October 2006
• Est. completion date: July 2009

Study information

• Verified date: March 2013
• 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

Patients received one injection with incobotulinumtoxinA (Xeomin) or placebo at baseline. Thereafter, all patients who entered the Open-Label Extension Period (OLEX) received up to five injection sessions of incobotulinumtoxinA (Xeomin) during the OLEX period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: July 2009
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Main Inclusion Criteria:

• Male or female pretreated outpatients between ages 18 and 80 years (inclusive)

• A clinical diagnosis of bilateral blepharospasm (BEB) characterized by spontaneous, spasmodic, intermittent or persistent involuntary contractions of the orbicular oculi muscles

• A need for injection of Botulinum toxin (defined by a Jankovic Rating Scale (JRS) severity subscore >= 2)

• On a stable dose of other medications (if any) used for focal dystonia treatment (e.g. anticholinergics and benzodiazepines) for at least 3 months prior to and expected throughout the Main Period

• Source documentation of the last two consecutive injection sessions with BOTOX® and a stable satisfactory therapeutic response directly prior to trial entry

• At least 10 weeks must have been passed between the last injection with BOTOX® for BEB and Baseline

Main Exclusion Criteria:

• Atypical variant of BEB caused by inhibition of levator palpebrae muscle

• Myotomy or denervation surgery in the affected muscles (e.g. peripheral denervation and/or spinal cord stimulation)

• The previous two injections with BOTOX® with more than 50 Units per eye

• Hypersensitivity to human serum albumin, sucrose, or Botulinum toxin A

• Neuroleptic induced blepharospasm

• Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease which might interfere with the trial

• Treatment with Botulinum toxins for any indication other than BEB within 4 months prior to Baseline and during the trial

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

• Blepharospasm

Intervention

Drug:
• incobotulinumtoxinA (Xeomin)
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection, up to 50 Units per eye; Mode of administration: intramuscular injection
• Placebo
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% Sodium chloride (NaCl), placebo volume corresponding to up to 50 Units per eye; Mode of administration: intramuscular injection

Locations

Country	Name	City	State
Canada	David King, MD - Private Practice	Halifax	Nova Scotia
United States	Baylor College of Medicine	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Merz Pharmaceuticals GmbH

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Jankovic J, Comella C, Hanschmann A, Grafe S. Efficacy and safety of incobotulinumtoxinA (NT 201, Xeomin) in the treatment of blepharospasm-a randomized trial. Mov Disord. 2011 Jul;26(8):1521-8. doi: 10.1002/mds.23658. Epub 2011 Apr 22. — View Citation

Truong DD, Gollomp SM, Jankovic J, LeWitt PA, Marx M, Hanschmann A, Fernandez HH; Xeomin US Blepharospasm Study Group. Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin(®)) injections in blepharospasm. J Neural Transm (Vienna). 2013 Se — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by a Blinded Independent Rater)	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.	Baseline, week 6	No
Secondary	Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by Subject Diary)	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.	Baseline, week 6	No
Secondary	Blepharospasm Disability Index (BSDI) Change From Baseline in the BSDI at Week 6 After Injection	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.	Baseline, week 6	No
Secondary	Patient Evaluation of Global Response (PEGR) at Final Visit	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).	Final visit (up to week 20 after injection of the Main Period)	No