Cervical Dystonia
Conditions
Brief summary
The aim of this study is to assess longer term safety and effectiveness of Dysport®.
Interventions
BIOLOGICALBotulinum toxin type A
In this long-term extension study, a dose of 500 units Dysport was administered by intramuscular injection into the clinically indicated neck muscles in a single dosing session in the first treatment cycle. This was the same dose as given in the preceding study NCT00257660 (Y-47-52120-051). Based on individual safety & efficacy, subjects could then receive up to 3 subsequent injections with doses titrated in 250 unit steps, to a minimum of 250 units and a maximum of 1000 units. Retreatment occurred approximately 12-16 weeks after the previous injection, with the exact timing based on clinical need.
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects enrolled in the Y-47-52120-051 study, who have completed all study visits up to Week 12, or up to Week 4 in the event of an early withdrawal * Returned to pre-treatment status as judged by the Investigator
Exclusion criteria
* Pure anterocollis or pure retrocollis * Known antibodies to botulinum toxin type A * Requirement for botulinum toxin injections to site(s) other than the neck and unable to avoid such treatment for the duration of the study * Known significant underlying swallowing or respiratory abnormality which might be exacerbated by botulinum toxin treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Week 4 follow-up visit | TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for each is the following: for severity from 0 (absence of severity) to 35 (max severity), for disability from 0 (no disability) to 30 (max disability) and for pain from 0 (no pain) to 20 (max pain). TWSTRS total score is the sum of the 3 component scores, with a range from 0 to a maximum of 85. For each treatment cycle, the change in TWSTRS total score is the score at week 4 minus the score at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Week 4 follow-up visit | TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for severity is from 0 (absence of severity) to 35 (max severity). For each treatment cycle, the change in TWSTRS severity subscale is the score at week 4 minus the score at baseline. |
| Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Week 4 follow-up visit | TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for disability is from 0 (no disability) to 30 (max disability). For each treatment cycle, the change in TWSTRS disability subscale is the score at week 4 minus the score at baseline. |
| Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Week 4 follow-up visit | TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for pain is from 0 (no pain) to 20 (max pain). For each treatment cycle, the change in TWSTRS pain subscale is the score at week 4 minus the score at baseline. |
Countries
Russia, United States
Participant flow
Recruitment details
Patients who completed study NCT00257660 (Y-47-52120-051)were recruited in 15 centres in US and 4 centres in Russia from February 2006 to January 2008 to participate in this study NCT00288509 (Y-47-52120-731).
Pre-assignment details
Of the 116 subjects treated in study NCT00257660, 108 subjects enrolled in this extension study NCT00288509 (Y-47-52120-731). Eight subjects completed study NCT00257660 but elected not to enroll in this extension study.
Participants by arm
| Arm | Count |
|---|---|
| Dysport 250-1000 units | 108 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Cycle 1 | Adverse Event | 1 |
| Treatment Cycle 1 | Lack of Efficacy | 1 |
| Treatment Cycle 1 | Lost to Follow-up | 2 |
| Treatment Cycle 1 | Treatment stopped according to protocol | 1 |
| Treatment Cycle 1 | Withdrawal by Subject | 1 |
| Treatment Cycle 2 | Lack of Efficacy | 1 |
| Treatment Cycle 2 | Withdrawal by Subject | 2 |
| Treatment Cycle 3 | Lack of Efficacy | 1 |
| Treatment Cycle 3 | Lost to Follow-up | 2 |
| Treatment Cycle 3 | Treatment stopped according to protocol | 1 |
| Treatment Cycle 3 | Withdrawal by Subject | 1 |
| Treatment Cycle 4 | Physician Decision | 4 |
| Treatment Cycle 4 | Treatment stopped according to protocol | 1 |
| Treatment Cycle 4 | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Dysport |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 19 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants |
| Age, Continuous | 53.5 years STANDARD_DEVIATION 13 |
| Region of Enrollment Russian Federation | 27 participants |
| Region of Enrollment United States | 81 participants |
| Sex: Female, Male Female | 67 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 84 / 108 |
| serious Total, serious adverse events | 2 / 108 |
Outcome results
Primary
Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline
TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for each is the following: for severity from 0 (absence of severity) to 35 (max severity), for disability from 0 (no disability) to 30 (max disability) and for pain from 0 (no pain) to 20 (max pain). TWSTRS total score is the sum of the 3 component scores, with a range from 0 to a maximum of 85. For each treatment cycle, the change in TWSTRS total score is the score at week 4 minus the score at baseline.
Time frame: Week 4 follow-up visit
Population: The intention to treat population consisted of all 108 subjects who received Dysport.~Subjects with incomplete TWSTRS scores were not included in the TWSTRS total score analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Change in TWSTRS total score for Treatment Cycle 1 | -16.21 points on a scale | Standard Deviation 11.54 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Baseline TWSTRS total score for Treatment Cycle 1 | 42.48 points on a scale | Standard Deviation 10.23 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Week 4 TWSTRS total score for Treatment Cycle 1 | 25.81 points on a scale | Standard Deviation 12.83 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Change in TWSTRS total score for Treatment Cycle 2 | -11.40 points on a scale | Standard Deviation 10.83 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Baseline TWSTRS total score for Treatment Cycle 2 | 34.72 points on a scale | Standard Deviation 11.12 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Week 4 TWSTRS total score for Treatment Cycle 2 | 23.40 points on a scale | Standard Deviation 12.55 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Change in TWSTRS total score for Treatment Cycle 3 | -10.84 points on a scale | Standard Deviation 13 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Baseline TWSTRS total score for Treatment Cycle 3 | 32.66 points on a scale | Standard Deviation 11.68 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Week 4 TWSTRS total score for Treatment Cycle 3 | 21.84 points on a scale | Standard Deviation 12.45 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Change in TWSTRS total score for Treatment Cycle 4 | -11.27 points on a scale | Standard Deviation 11.46 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Baseline TWSTRS total score for Treatment Cycle 4 | 34.35 points on a scale | Standard Deviation 12.81 |
| Dysport | Change in Toronto Western Spasmodic Torticollis Rating Scale Total Score From Baseline | Week 4 TWSTRS total score for Treatment Cycle 4 | 23.07 points on a scale | Standard Deviation 12.62 |
Secondary
Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline
TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for disability is from 0 (no disability) to 30 (max disability). For each treatment cycle, the change in TWSTRS disability subscale is the score at week 4 minus the score at baseline.
Time frame: Week 4 follow-up visit
Population: The intention to treat population consisted of all 108 subjects who received Dysport.~All available TWSTRS disability subscale scores have been included in the disability subscale analyses. Subjects excluded from the TWSTRS total score analyses may have their available data included in the TWSTRS disability subscale score analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Change in TWSTRS disability score for cycle 1 | -4.25 points on a scale | Standard Deviation 4.39 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Baseline TWSTRS disability score for cycle 1 | 12.70 points on a scale | Standard Deviation 4.31 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Week 4 TWSTRS disability score for cycle 1 | 8.51 points on a scale | Standard Deviation 5.22 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Change in TWSTRS disability score for cycle 2 | -2.88 points on a scale | Standard Deviation 3.86 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Baseline TWSTRS disability score for cycle 2 | 10.45 points on a scale | Standard Deviation 4.56 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Week 4 TWSTRS disability score for cycle 2 | 7.63 points on a scale | Standard Deviation 4.83 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Baseline TWSTRS disability score for cycle 4 | 10.09 points on a scale | Standard Deviation 4.91 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Week 4 TWSTRS disability score for cycle 4 | 7.46 points on a scale | Standard Deviation 5.07 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Change in TWSTRS disability score for cycle 3 | -2.74 points on a scale | Standard Deviation 4.44 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Baseline TWSTRS disability score for cycle 3 | 9.73 points on a scale | Standard Deviation 4.27 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Week 4 TWSTRS disability score for cycle 3 | 6.97 points on a scale | Standard Deviation 4.67 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Disability Subscale Score as a Change From Baseline | Change in TWSTRS disability score for cycle 4 | -2.54 points on a scale | Standard Deviation 3.16 |
Secondary
Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline
TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for pain is from 0 (no pain) to 20 (max pain). For each treatment cycle, the change in TWSTRS pain subscale is the score at week 4 minus the score at baseline.
Time frame: Week 4 follow-up visit
Population: The intention to treat population consisted of all 108 subjects who received Dysport.~All available TWSTRS pain subscale scores have been included in the pain subscale analyses. Subjects excluded from the TWSTRS total score analyses may have their available data included in the TWSTRS pain subscale score analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Change in TWSTRS pain score for cycle 1 | -4.53 points on a scale | Standard Deviation 4.57 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Baseline TWSTRS pain score for cycle 1 | 10.08 points on a scale | Standard Deviation 4.64 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Week 4 TWSTRS pain score for cycle 1 | 5.37 points on a scale | Standard Deviation 4.97 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Change in TWSTRS pain score for cycle 2 | -2.99 points on a scale | Standard Deviation 4.27 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Baseline TWSTRS pain score for cycle 2 | 8.12 points on a scale | Standard Deviation 5.35 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Week 4 TWSTRS pain score for cycle 2 | 5.22 points on a scale | Standard Deviation 5.34 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Change in TWSTRS pain score for cycle 3 | -2.41 points on a scale | Standard Deviation 5.04 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Baseline TWSTRS pain score for cycle 3 | 7.16 points on a scale | Standard Deviation 5.19 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Week 4 TWSTRS pain score for cycle 3 | 4.65 points on a scale | Standard Deviation 5.01 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Change in TWSTRS pain score for cycle 4 | -2.81 points on a scale | Standard Deviation 4.85 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Baseline TWSTRS pain score for cycle 4 | 7.72 points on a scale | Standard Deviation 5.57 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Pain Subscale Score as a Change From Baseline | Week 4 TWSTRS pain score for cycle 4 | 4.97 points on a scale | Standard Deviation 5.14 |
Secondary
Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline
TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for severity is from 0 (absence of severity) to 35 (max severity). For each treatment cycle, the change in TWSTRS severity subscale is the score at week 4 minus the score at baseline.
Time frame: Week 4 follow-up visit
Population: The intention to treat population consisted of all 108 subjects who received Dysport.~All available TWSTRS severity subscale scores have been included in the severity subscale analyses. Subjects excluded from the TWSTRS total score analyses may have their available data included in the TWSTRS severity subscale score analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Change in TWSTRS severity score for cycle 1 | -7.68 points on a scale | Standard Deviation 5.72 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Baseline TWSTRS severity score for cycle 1 | 19.79 points on a scale | Standard Deviation 4.29 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Week 4 TWSTRS severity score for cycle 1 | 11.90 points on a scale | Standard Deviation 5.54 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Change in TWSTRS severity score for cycle 2 | -5.52 points on a scale | Standard Deviation 5.54 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Baseline TWSTRS severity score for cycle 2 | 16.05 points on a scale | Standard Deviation 5.1 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Week 4 TWSTRS severity score for cycle 2 | 10.54 points on a scale | Standard Deviation 5.43 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Change in TWSTRS severity score for cycle 3 | -5.68 points on a scale | Standard Deviation 6.21 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Baseline TWSTRS severity score for cycle 3 | 15.79 points on a scale | Standard Deviation 5.32 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Week 4 TWSTRS severity score for cycle 3 | 10.23 points on a scale | Standard Deviation 5.95 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Change in TWSTRS severity score for cycle 4 | -5.78 points on a scale | Standard Deviation 5.57 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Baseline TWSTRS severity score for cycle 4 | 16.53 points on a scale | Standard Deviation 5.64 |
| Dysport | Toronto Western Spasmodic Torticollis Rating Scale Severity Subscale as a Change From Baseline | Week 4 TWSTRS severity score for cycle 4 | 10.96 points on a scale | Standard Deviation 5.95 |