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IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Cervical Dystonia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT00407030
First received: November 30, 2006
Last updated: August 19, 2011
Last verified: August 2011
History of Changes
  Purpose

At baseline patients received incobotulinumtoxinA (Xeomin) or placebo. Thereafter, all patients who entered the extension period were treated with up to five injection sessions of incobotulinumtoxinA (Xeomin) during the extension period.


Condition Intervention Phase
Cervical Dystonia
 Drug: incobotulinumtoxinA (Xeomin) (240 Units)
Drug: incobotulinumtoxinA (Xeomin) (120 Units)
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Trial With a Double-blind Parallel-group Extension Period to Investigate the Efficacy and Safety of Different Doses of IncobotulinumtoxinA (Xeomin) in the Treatment of Cervical Dystonia

Resource links provided by NLM:

MedlinePlus related topics: Botox Dystonia
U.S. FDA Resources

Further study details as provided by Merz Pharmaceuticals GmbH:

Primary Outcome Measures:
  • Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Injection of the Main Period - Xeomin (240 Units) Versus Placebo [ Time Frame: Baseline, week 4 ] [ Designated as safety issue: No ]

    The TWSTRS-Total score is the sum of scores of the three components of the scale:

    • TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity)
    • TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain)
    • TWSTRS-Disability score which ranges from 0 (=no disability) to 30 (=maximum disability).

    The TWSTRS total score ranges from 0 (=best value) to 85 (=worst value). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.


  • Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Injection of the Main Period - Xeomin (120 Units) Versus Placebo [ Time Frame: Baseline, week 4 ] [ Designated as safety issue: No ]

    The TWSTRS-Total score is the sum of scores of the three components of the scale:

    • TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity)
    • TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain)
    • TWSTRS-Disability score which ranges from 0 (=no disability) to 30 (=maximum disability).

    The TWSTRS total score ranges from 0 (=best value) to 85 (=worst value). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.


  • Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Injection of the Main Period - Xeomin (240 Units) Versus Xeomin (120 Units) [ Time Frame: Baseline, week 4 ] [ Designated as safety issue: No ]

    The TWSTRS-Total score is the sum of scores of the three components of the scale:

    • TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity)
    • TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain)
    • TWSTRS-Disability score which ranges from 0 (=no disability) to 30 (=maximum disability).

    The TWSTRS total score ranges from 0 (=best value) to 85 (=worst value). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.



Secondary Outcome Measures:
  • Change From Baseline in the TWSTRS-Total Score [ Time Frame: Baseline, week 8, final visit (up to 20 weeks after injection of the Main Period) ] [ Designated as safety issue: No ]

    The TWSTRS-Total score is the sum of scores of the three components of the scale:

    • TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity)
    • TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain)
    • TWSTRS-Disability score which ranges from 0 (=no disability) to 30 (=maximum disability).

    The TWSTRS total score ranges from 0 (=best value) to 85 (=worst value). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.


  • Change From Baseline in the TWSTRS Disability Subscore [ Time Frame: Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period) ] [ Designated as safety issue: No ]
    TWSTRS-Disability score which ranges from 0 (=no disability)to 30 (=maximum disability). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.

  • Change From Baseline in the TWSTRS Severity Subscore [ Time Frame: Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period) ] [ Designated as safety issue: No ]
    TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.

  • Change From Baseline in the TWSTRS Pain Subscore [ Time Frame: Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period) ] [ Designated as safety issue: No ]
    TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.

  • Patient Evaluation of Global Response (PEGR) at Final Visit [ Time Frame: Final visit (up to 20 weeks after injection of the Main Period) ] [ Designated as safety issue: No ]
    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).


Enrollment: 233
Study Start Date: July 2006
Study Completion Date: June 2009
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: incobotulinumtoxinA (Xeomin) (240 Units)
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 dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 240 units, total volume 4.8mL; Mode of administration: intramuscular injection
 Drug: incobotulinumtoxinA (Xeomin) (240 Units)
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (240 Units)
Experimental: incobotulinumtoxinA (Xeomin) (120 Units)
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 dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 120 units, total volume 4.8 mL; Mode of administration: intramuscular injection
 Drug: incobotulinumtoxinA (Xeomin) (120 Units)
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (120 Units)
Placebo Comparator: 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% NaCl, corresponding total placebo volume 4.8 mL; Mode of administration: intramuscular injection
 Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Male or female outpatients between ages 18 and 75 years inclusive)
  • A clinical diagnosis of cervical dystonia (i.e. spasmodic torticollis) with predominantly rotational form and a need for injection (determined by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total score)
  • TWSTRS-Total score >= 20
  • TWSTRS-Severity score >= 10
  • TWSTRS-Disability score >= 3
  • TWSTRS-Pain score >= 1
  • On a stable dose of 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
  • For pre-treated patients only: Source documentation of the last two consecutive injection sessions with Botulinum Toxin and stable therapeutic response directly prior to trial entry
  • For pre-treated patients only: At least 10 weeks must have been passed between the last injection with Botulinum Toxin for cervical dystonia and baseline
  • For pre-treated patients only: The most recent injection with Botulinum Toxin must have been maximal 300 Units of type A or 12,000 Units of type B

Main Exclusion Criteria:

  • Traumatic torticollis or tardive torticollis
  • TWSTRS-Severity score for anterocollis >= 2 points (pure anterocollis)
  • TWSTRS-Severity score for retrocollis >= 2 points (pure retrocollis)
  • Myotomy or denervation surgery in the affected muscles (e.g. peripheral denervation and/or spinal cord stimulation)
  • Hypersensitivity to human serum albumin, sucrose, or Botulinum Toxin Type A
  • Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease which might interfere with the trial
  • Current swallowing disorder of any origin (dysphagia scale >= 3, i.e. severe, with swallowing difficulties and requiring a change in diet)
  • Marked limitation on passive range of motion that suggests contractures or other structural abnormality, e.g. cervical contractures or cervical spine syndrome
  • Treatment with Botulinum Toxins for any indication other than cervical dystonia within 4 months prior to baseline and during the trial
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00407030

Locations
United States, Texas
Dallas, Texas, United States
Sponsors and Collaborators
Merz Pharmaceuticals GmbH
Investigators
Study Chair: Cynthia Comella, M.D. Rush University Medical Center, 1725 West Harrison Street, Suite 755, Chicago, 60612 Illinois, USA
  More Information

Publications:

Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT00407030     History of Changes
Other Study ID Numbers: MRZ 60201-0408
Study First Received: November 30, 2006
Results First Received: August 31, 2010
Last Updated: August 19, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dystonia
Dystonic Disorders
Torticollis
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
 Botulinum Toxins, Type A
Botulinum Toxins
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013