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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Drug: incobotulinumtoxinA (Xeomin) (240 Units)
* Drug: incobotulinumtoxinA (Xeomin) (120 Units)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: incobotulinumtoxinA (Xeomin) (240 Units)<br>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)<br>* incobotulinumtoxinA (Xeomin, also known as NT 201 or Botulinum toxin type A (150 kiloDalton), free from complexing proteins) (240 Units)<br>|
| Experimental: incobotulinumtoxinA (Xeomin) (120 Units)<br>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)<br>* incobotulinumtoxinA (Xeomin, also known as NT 201 or Botulinum toxin type A (150 kiloDalton), free from complexing proteins) (120 Units)<br>|
| Placebo Comparator: Placebo<br>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<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Baseline, week 4 | 
| 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 | 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. | Baseline, week 4 | 
| 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) | 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. | Baseline, week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the TWSTRS-Total Score | 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. | Baseline, week 8, final visit (up to 20 weeks after injection of the Main Period) | 
| Change From Baseline in the TWSTRS Disability Subscore | 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. | Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period) | 
| Change From Baseline in the TWSTRS Severity Subscore | 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. | Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period) | 
| Change From Baseline in the TWSTRS Pain Subscore | 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. | Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period) | 
| 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 20 weeks after injection of the Main Period) |