Cervical Dystonia
Conditions
Keywords
cervical dystonia, botulinum toxin
Brief summary
1. 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. 2. double blind, randomised, multi center, crossover study
Detailed description
1. Prospective, randomized, head-to-head, double-blind, cross-over study. 2. Total patients: A group 51, B group 51 3. 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) 4. Compare the TSUI change score from baseline to 4 weeks after injection.
Interventions
DRUGDysport® (abobotulinumtoxinA)
Cross over injection of Dysport® (\<500IU), Botox® (200IU)assuming a bioequivalence ratio of 2.5:1 units
DRUGBotox® (onabotulinumtoxinA)
Cross over injection of Dysport® (\<500IU), Botox® (200IU)assuming a bioequivalence ratio of 2.5:1 units
Sponsors
Ipsen
Medical Research Collaborating Center, Seoul, Korea
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of Total Tsui Score at 4 Weeks From Baseline | 4 weeks after injection 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of Total TWSTRS Score at 4 Weeks From Baseline | 4 weeks after injection 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. |
| CGI-I (Clinical Global Impression of Illness) | 4, 8, 12 and 16 weeks after injection | 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'. |
| PGI-I (Patient's Global Impression of Improvement) | 4, 8, 12 and 16 weeks after injection | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Reduction of Total TWSTRS at Each Visit From Baseline | 8, 12 and 16 weeks after injection | TWSTRS scale (Toronto western spasmodic torticollis rating scale, range: 0-80, higher values represent worse cervical dystonia.) Negative numbers to represent decreases of TWSTRS scale. |
| Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 4, 8, 12 and 16 weeks after injection | Pain subscale of TWSTRS scale.(Range: 0-20) Negative numbers to represent decreases of TWSTRS pain subscale. |
| Reduction of Tsui Score at Each Visit From Baseline | 8, 12 and 16 weeks after injection | Tsui scale (range: 0-25, higher values represent worse cervical dystonia.) Negative numbers to represent decreases of Tsui scale. |
Countries
South Korea
Participant flow
Recruitment details
Participants recruited from movement disorder clinics at 7 hospitals in Korea, between August 2009 and March 2010.
Pre-assignment details
103 participants recruited; 103 screened, 1 excluded (1 refused participation).
Participants by arm
| Arm | Count |
|---|---|
| Dysport® First, Then Botox® Dysport® injection in first intervention period and Botox® in second intervention period (after washout period) | 46 |
| Botox® First, Then Dysport® Botox® injection in first intervention period and Dysport® in second intervention period (after washout period) | 48 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Lost to Follow-up | 1 | 3 |
| First Intervention | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Botox® First, Then Dysport® | Dysport® First, Then Botox® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 38 Participants | 80 Participants |
| Age, Continuous | 53.35 years STANDARD_DEVIATION 10.18 | 53.24 years STANDARD_DEVIATION 11.44 | 53.29 years STANDARD_DEVIATION 10.76 |
| Region of Enrollment Korea, Republic of | 48 participants | 46 participants | 94 participants |
| Sex: Female, Male Female | 31 Participants | 26 Participants | 57 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 94 |
| other Total, other adverse events | 14 / 94 | 19 / 94 |
| serious Total, serious adverse events | 0 / 94 | 0 / 94 |
Outcome results
Primary
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.
Time frame: 4 weeks after injection from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | Reduction of Total Tsui Score at 4 Weeks From Baseline | -3.98 units on a scale | Standard Deviation 3.89 |
| Botox® (onabotulinumtoxinA) | Reduction of Total Tsui Score at 4 Weeks From Baseline | -4.77 units on a scale | Standard Deviation 4.1 |
p-value: 0.05Paired-t test
Secondary
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'.
Time frame: 4, 8, 12 and 16 weeks after injection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 4 weeks after injection | 16.0 percentage of participants scoring 1or2 |
| Dysport® (abobotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 8 weeks after injection | 16.0 percentage of participants scoring 1or2 |
| Dysport® (abobotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 12 weeks after injection | 11.7 percentage of participants scoring 1or2 |
| Dysport® (abobotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 16 weeks after injection | 8.5 percentage of participants scoring 1or2 |
| Botox® (onabotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 16 weeks after injection | 11.7 percentage of participants scoring 1or2 |
| Botox® (onabotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 4 weeks after injection | 13.8 percentage of participants scoring 1or2 |
| Botox® (onabotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 12 weeks after injection | 14.9 percentage of participants scoring 1or2 |
| Botox® (onabotulinumtoxinA) | CGI-I (Clinical Global Impression of Illness) | 8 weeks after injection | 14.9 percentage of participants scoring 1or2 |
Secondary
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
Time frame: 4, 8, 12 and 16 weeks after injection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 4 weeks after injection | 35.1 percentage of patients scoring 1 or 2 |
| Dysport® (abobotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 8 weeks after injection | 33.0 percentage of patients scoring 1 or 2 |
| Dysport® (abobotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 12 weeks after injection | 20.2 percentage of patients scoring 1 or 2 |
| Dysport® (abobotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 16 weeks after injection | 7.4 percentage of patients scoring 1 or 2 |
| Botox® (onabotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 16 weeks after injection | 9.6 percentage of patients scoring 1 or 2 |
| Botox® (onabotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 4 weeks after injection | 36.2 percentage of patients scoring 1 or 2 |
| Botox® (onabotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 12 weeks after injection | 27.7 percentage of patients scoring 1 or 2 |
| Botox® (onabotulinumtoxinA) | PGI-I (Patient's Global Impression of Improvement) | 8 weeks after injection | 36.2 percentage of patients scoring 1 or 2 |
Secondary
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.
Time frame: 4 weeks after injection from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | Reduction of Total TWSTRS Score at 4 Weeks From Baseline | -9.76 units on a scale | Standard Deviation 10.25 |
| Botox® (onabotulinumtoxinA) | Reduction of Total TWSTRS Score at 4 Weeks From Baseline | -8.78 units on a scale | Standard Deviation 10.11 |
Other Pre-specified
Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline
Pain subscale of TWSTRS scale.(Range: 0-20) Negative numbers to represent decreases of TWSTRS pain subscale.
Time frame: 4, 8, 12 and 16 weeks after injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 4 weeks after injections | -1.45 units on a scale | Standard Deviation 4.05 |
| Dysport® (abobotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 8 weeks after injections | -1.96 units on a scale | Standard Deviation 3.97 |
| Dysport® (abobotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 12 weeks after injections | -1.40 units on a scale | Standard Deviation 4.08 |
| Dysport® (abobotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 16 weeks after injections | -0.97 units on a scale | Standard Deviation 3.85 |
| Botox® (onabotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 16 weeks after injections | -1.76 units on a scale | Standard Deviation 3.75 |
| Botox® (onabotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 4 weeks after injections | -1.19 units on a scale | Standard Deviation 4.16 |
| Botox® (onabotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 12 weeks after injections | -2.07 units on a scale | Standard Deviation 3.97 |
| Botox® (onabotulinumtoxinA) | Reduction of Pain Associated With Cervical Dystonia at Each Visit From Baseline | 8 weeks after injections | -2.28 units on a scale | Standard Deviation 3.5 |
Other Pre-specified
Reduction of Total TWSTRS at Each Visit From Baseline
TWSTRS scale (Toronto western spasmodic torticollis rating scale, range: 0-80, higher values represent worse cervical dystonia.) Negative numbers to represent decreases of TWSTRS scale.
Time frame: 8, 12 and 16 weeks after injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | Reduction of Total TWSTRS at Each Visit From Baseline | Reduction of TWSTRS from Baseline at 8 Weeks | -11.16 units on a scale | Standard Deviation 10.85 |
| Dysport® (abobotulinumtoxinA) | Reduction of Total TWSTRS at Each Visit From Baseline | Reduction of TWSTRS from Baseline at 12 Weeks | -8.95 units on a scale | Standard Deviation 11.64 |
| Dysport® (abobotulinumtoxinA) | Reduction of Total TWSTRS at Each Visit From Baseline | Reduction of TWSTRS from Baseline at 16 Weeks | -5.15 units on a scale | Standard Deviation 8.73 |
| Botox® (onabotulinumtoxinA) | Reduction of Total TWSTRS at Each Visit From Baseline | Reduction of TWSTRS from Baseline at 8 Weeks | -9.98 units on a scale | Standard Deviation 9.9 |
| Botox® (onabotulinumtoxinA) | Reduction of Total TWSTRS at Each Visit From Baseline | Reduction of TWSTRS from Baseline at 12 Weeks | -8.66 units on a scale | Standard Deviation 10.45 |
| Botox® (onabotulinumtoxinA) | Reduction of Total TWSTRS at Each Visit From Baseline | Reduction of TWSTRS from Baseline at 16 Weeks | -5.34 units on a scale | Standard Deviation 9.76 |
Other Pre-specified
Reduction of Tsui Score at Each Visit From Baseline
Tsui scale (range: 0-25, higher values represent worse cervical dystonia.) Negative numbers to represent decreases of Tsui scale.
Time frame: 8, 12 and 16 weeks after injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport® (abobotulinumtoxinA) | Reduction of Tsui Score at Each Visit From Baseline | Reduction in Tsui Score at 12 Weeks from Baseline | -3.20 units on a scale | Standard Deviation 4.48 |
| Dysport® (abobotulinumtoxinA) | Reduction of Tsui Score at Each Visit From Baseline | Reduction in Tsui Score at 8 Weeks from Baseline | -4.33 units on a scale | Standard Deviation 3.69 |
| Dysport® (abobotulinumtoxinA) | Reduction of Tsui Score at Each Visit From Baseline | Reduction in Tsui Score at 16 Weeks from Baseline | -1.69 units on a scale | Standard Deviation 3.99 |
| Botox® (onabotulinumtoxinA) | Reduction of Tsui Score at Each Visit From Baseline | Reduction in Tsui Score at 8 Weeks from Baseline | -4.23 units on a scale | Standard Deviation 4.08 |
| Botox® (onabotulinumtoxinA) | Reduction of Tsui Score at Each Visit From Baseline | Reduction in Tsui Score at 12 Weeks from Baseline | -3.31 units on a scale | Standard Deviation 4.18 |
| Botox® (onabotulinumtoxinA) | Reduction of Tsui Score at Each Visit From Baseline | Reduction in Tsui Score at 16 Weeks from Baseline | -1.85 units on a scale | Standard Deviation 4.16 |