A Study to Compare Dysport® and Botox® in the Treatment of Cervical Dystonia

Study Overview
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Brief Summary
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to examine the non-inferiority of Dysport in the clinical efficacy and safety in comparison with Botox®, assuming a bioequivalence ratio of 2.5:1 units, in the treatment of Cervical dystonia. double blind, randomised, multi center, crossover study

Detailed Description
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Prospective, randomized, head-to-head, double-blind, cross-over study. Total patients: A group 51, B group 51 Study duration: 16 + 4 + 16 weeks. Eligible patients will be randomised at baseline to receive either Dysport® or Botox® and monitored at weeks 2, 4, 8, 12, 16 weeks. After 4 weeks of wash out period, then the patients get the other treatment (i.e, Patients who have got Dysport will be then administered with Botox) Compare the TSUI change score from baseline to 4 weeks after injection.

Official Title
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A Double Blind, Randomized, Multi-center, Cross-over Study to Demonstrate the Non-inferiority of Dysport® in Comparison With Botox®, Assuming a Bioequivalence Ratio of 2.5:1 Units, in the Cervical Dystonia

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Drug: Dysport® (abobotulinumtoxinA)
* Drug: Botox® (onabotulinumtoxinA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age of both genders, Cervical dystonia symptoms with a minimum duration of 18 months, Negative pregnancy test in sexually active women, Able to participate in the study (understand goals of botulinum toxin A treatment and sign Informed Consent Form). Exclusion Criteria: Patient with cervical contractures Known significant underlying dysphasia Patients who have received botulinum toxin treatment within the past 4 months. Contraindication to botulinum toxin treatment Any disease that might affect neuromuscular function (Myasthenia Gravis, Eaton-Lambert syndrome, ALS …) Patients who have received oral anti-spasticity medication, phenol therapy, myotomy or denervation surgery, deep brain stimulation for cervical dystonia, Patients who required more than 500 units of Dysport or 200 units of Botox. Any concomitant treatment that could interfere with the action of botulinum toxin, Subjects having participated within the last 3 months or currently participating in an investigational drug study, Pregnancy, Lactation.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dysport® to Botox®<br>Dysport® injection in first intervention period and Botox® in second intervention period (after washout period) cross over injection of Dysport® (abobotulinumtoxinA) and Botox® (onabotulinumtoxinA) | Drug: Dysport® (abobotulinumtoxinA)<br>* Cross over injection of Dysport® (<500IU), Botox® (200IU)assuming a bioequivalence ratio of 2.5:1 units<br>* Other names: Dysport® (abobotulinumtoxinA)injection;Drug: Botox® (onabotulinumtoxinA)<br>* Cross over injection of Dysport® (<500IU), Botox® (200IU)assuming a bioequivalence ratio of 2.5:1 units<br>* Other names: Botox® (onabotulinumtoxinA)injection;|
| Experimental: Botox® to Dysport®<br>Botox® injection in first intervention period and Dysport® in second intervention period (after washout period) cross over injection of Dysport® (abobotulinumtoxinA) and Botox® (onabotulinumtoxinA) | Drug: Dysport® (abobotulinumtoxinA)<br>* Cross over injection of Dysport® (<500IU), Botox® (200IU)assuming a bioequivalence ratio of 2.5:1 units<br>* Other names: Dysport® (abobotulinumtoxinA)injection;Drug: Botox® (onabotulinumtoxinA)<br>* Cross over injection of Dysport® (<500IU), Botox® (200IU)assuming a bioequivalence ratio of 2.5:1 units<br>* Other names: Botox® (onabotulinumtoxinA)injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Total Tsui Score at 4 Weeks From Baseline | Tsui scale is an impairment scale which evaluates the amplitude and duration of sustained posture and intermittent movements of the head, as well as the presence of shoulder elevation and tremor. Tsui scale (range: 0-25, higher values represent worse cervical dystonia.) Negative numbers to represent decreases of Tsui scale. | 4 weeks after injection from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Total TWSTRS Score at 4 Weeks From Baseline | TWSTRS (Toronto western spasmodic torticollis rating scale) The TWSTRS is a composite scale which covers different features of cervical dystonia(CD). The first part is based on the physical findings (severity subscale), the second part rates disability, and the third part pain. (range: 0-80, higher values represent worse cervical dystonia.) Details of the TWSTRS are displayed on the Web site http://www.wemove.org. Negative numbers to represent decreases of TWSTRS. | 4 weeks after injection from baseline | 
| CGI-I (Clinical Global Impression of Illness) | The proportion of patients with 'normal/ not at all ill' or 'borderline mildly ill' on the CGI (Clinical global impression of illness, CGI-I) 1 = normal / not at all ill'; 2 = 'borderline mildly ill'; 3 = 'mildly ill'; 4 = 'moderlately ill'; 5 = 'markedly ill'; 6 = 'severely ill'; 7 = 'the most extremely ill'. | 4, 8, 12 and 16 weeks after injection | 
| PGI-I (Patient's Global Impression of Improvement) | The proportion of patients with 'very much improved' or 'much improved' on the PGI (Patient's global impression of impairment, PGI-I) 1 = very much improved, 2= much improved, 3 = slightly improved, 4 = no change, 5 = slightly aggravated, 6 = much aggravated, and 7 = very much aggravated | 4, 8, 12 and 16 weeks after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical dystonia, botulinum toxin