Spasmodic Torticollis
Conditions
Brief summary
The purpose of this study is to compare two types of botulinum toxin type A to treat the involuntary muscle contractions in the neck
Interventions
BIOLOGICALbotulinum toxin type A
200 Units at Visit 1 (Day 1)
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with cervical dystonia/spasmodic torticollis for at least 18 months * Successfully treated previously with botulinum toxin type A
Exclusion criteria
* Breast feeding, pregnant, or could become pregnant * Surgery or spinal cord stimulation for cervical dystonia * Previous injections of phenol, alcohol for cervical dystonia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Treatment Benefit | 20 Weeks | Duration of treatment benefit was measured as the time (days) from Baseline until patients had a loss of therapeutic benefit, as defined by the achievement of their Toronto Western Spasmodic Torticollis Rating Scale Duration Target Score (TDTS) \[loss of 80% of benefit\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Baseline, Week 4 | The TWSTRS is an assessment scale used to measure the impact of cervical dystonia on patients. The score is comprised of 3 subscales: Severity, Disability, and Pain, each of which is scored independently. The total of these 3 comprises the TWSTRS total score which is scored from 0 (least symptoms) to 85 (worst symptoms). Higher scores indicate a greater degree of symptom severity. |
| Global Assessment of Benefit by Patient at Week 4 | Week 4 | Patient evaluation of benefit from botulinum toxin type A treatment for cervical dystonia. Ratings were on a scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (about 100% improvement)', 0 represented 'Unchanged', and -4 represented 'Very marked worsening (about 100% worse or greater)'. |
| Global Assessment of Benefit by Physician at Week 4 | Week 4 | Physician evaluation of benefit from botulinum toxin type A treatment for cervical dystonia. Ratings were on a scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (about 100% improvement)', 0 represented 'Unchanged', and -4 represented 'Very marked worsening (about 100% worse or greater)'. |
| Physician Assessment of Cervical Dystonia Severity at Week 4 | Baseline, Week 4 | Physician assessment of cervical dystonia severity. The rating was assessed on a scale of 0 to 10, with higher scores denoting greater severity: 0 represented 'No evidence of dystonia' and 10 represented 'Worst cervical dystonia ever' |
| Toronto Western Spasmodic Torticollis Rating Scale Duration Target Score (TDTS) at Week 4 | Week 4 | The TDTS was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score representing a loss of 80% of the treatment benefit at Week 4. The TDTS is calculated from the TWSTRS score and ranges from 0 (least symptoms) to 68 (worst symptoms). The TWSTRS total score which is scored from 0 (least symptoms) to 85 (worst symptoms). |
| Patient Comparison of Benefit to Previous Injections at Week 20 | Week 20 | Patients assessed the improvement in cervical dystonia after receiving the study treatment compared to previous treatment(s). Patients were required to answer How would you rate the benefit of the current treatment of cervical dystonia with botulinum toxin type A compared to the previous treatment using the following scale?. The response options were 'much worse', 'worse', 'somewhat worse', 'same as previous', 'somewhat better', 'better', and 'much better'. |
| Patient Visual Analog Assessment of Pain at Week 4 | Baseline, Week 4 | Patients were required to assess their pain using a Visual Analog Scale in reference to their current perception of pain at that visit. This scale consisted of a line measuring 100 mm, and patients were instructed to put a mark on the line at the point that best described 'How much pain you are having right now'. Higher scores denoted higher pain intensity: 0 indicated 'No pain' and 100 indicated 'Worst possible pain'. |
| Patient Assessment of Need for Retreatment at Week 4 | Baseline, Week 4 | Patients were queried regarding their need for another injection of botulinum toxin type A for cervical dystonia. Patients were required to answer How would you rate your need for another injection of botulinum toxin type A for cervical dystonia using the following scale?. The response options included 'absolutely requires injection', 'very much requires injection', 'somewhat requires injection', and 'does not require injection'. |
| Physician Comparison of Benefit to Previous Injections at Week 20 | Week 20 | Physicians assessed the improvement in cervical dystonia after the study treatment compared to previous treatment(s) for each patient. Physicians were required to answer How would you rate the benefit of the current treatment of cervical dystonia with botulinum toxin type A compared to the previous treatment using the following scale?. The response options were 'much worse', 'worse', 'somewhat worse', 'same as previous', 'somewhat better', 'better', and 'much better'. |
Countries
Argentina, Australia, India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BOTOX® Botulinum toxin type A (BOTOX®) | 24 |
| Dysport® Botulinum toxin type A (Dysport®) | 30 |
| Total | 54 |
Baseline characteristics
| Characteristic | BOTOX® | Dysport® | Total |
|---|---|---|---|
| Age Continuous | 42.0 years STANDARD_DEVIATION 13.1 | 49.9 years STANDARD_DEVIATION 12.6 | 46.4 years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 7 Participants | 12 Participants | 19 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 24 | 12 / 30 |
| serious Total, serious adverse events | 0 / 24 | 0 / 30 |
Outcome results
Primary
Duration of Treatment Benefit
Duration of treatment benefit was measured as the time (days) from Baseline until patients had a loss of therapeutic benefit, as defined by the achievement of their Toronto Western Spasmodic Torticollis Rating Scale Duration Target Score (TDTS) \[loss of 80% of benefit\].
Time frame: 20 Weeks
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided at least 1 post-dose assessment measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX® | Duration of Treatment Benefit | 112.5 Days |
| Dysport® | Duration of Treatment Benefit | 107.0 Days |
Secondary
Global Assessment of Benefit by Patient at Week 4
Patient evaluation of benefit from botulinum toxin type A treatment for cervical dystonia. Ratings were on a scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (about 100% improvement)', 0 represented 'Unchanged', and -4 represented 'Very marked worsening (about 100% worse or greater)'.
Time frame: Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided at least 1 post-dose assessment measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX® | Global Assessment of Benefit by Patient at Week 4 | 2.0 Units on a Scale |
| Dysport® | Global Assessment of Benefit by Patient at Week 4 | 2.0 Units on a Scale |
Secondary
Global Assessment of Benefit by Physician at Week 4
Physician evaluation of benefit from botulinum toxin type A treatment for cervical dystonia. Ratings were on a scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (about 100% improvement)', 0 represented 'Unchanged', and -4 represented 'Very marked worsening (about 100% worse or greater)'.
Time frame: Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided at least 1 post-dose assessment measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX® | Global Assessment of Benefit by Physician at Week 4 | 2.0 Units on a Scale |
| Dysport® | Global Assessment of Benefit by Physician at Week 4 | 2.0 Units on a Scale |
Secondary
Patient Assessment of Need for Retreatment at Week 4
Patients were queried regarding their need for another injection of botulinum toxin type A for cervical dystonia. Patients were required to answer How would you rate your need for another injection of botulinum toxin type A for cervical dystonia using the following scale?. The response options included 'absolutely requires injection', 'very much requires injection', 'somewhat requires injection', and 'does not require injection'.
Time frame: Baseline, Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided as least 1 post-dose assessment measure. Only completed assessments at the time points are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Absolutely requires injection at Baseline | 19 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Baseline | 5 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Baseline | 0 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Does not require injection at Baseline | 0 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Absolutely requires injection at Week 4 | 1 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Week 4 | 7 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Week 4 | 4 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Does not require injection at Week 4 | 11 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Does not require injection at Week 4 | 17 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Absolutely requires injection at Baseline | 24 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Absolutely requires injection at Week 4 | 4 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Baseline | 5 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Week 4 | 3 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Baseline | 0 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Week 4 | 5 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Does not require injection at Baseline | 0 Number of Responses |
Secondary
Patient Comparison of Benefit to Previous Injections at Week 20
Patients assessed the improvement in cervical dystonia after receiving the study treatment compared to previous treatment(s). Patients were required to answer How would you rate the benefit of the current treatment of cervical dystonia with botulinum toxin type A compared to the previous treatment using the following scale?. The response options were 'much worse', 'worse', 'somewhat worse', 'same as previous', 'somewhat better', 'better', and 'much better'.
Time frame: Week 20
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided as least 1 post-dose assessment measure. Only completed assessments at this time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Somewhat Worse | 0 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Somewhat Better | 8 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Worse | 0 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Better | 0 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Same as Previous | 8 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Much Better | 3 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 20 | Much Worse | 0 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Much Better | 4 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Much Worse | 0 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Worse | 1 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Somewhat Worse | 1 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Same as Previous | 11 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Somewhat Better | 4 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 20 | Better | 0 Number of Responses |
Secondary
Patient Visual Analog Assessment of Pain at Week 4
Patients were required to assess their pain using a Visual Analog Scale in reference to their current perception of pain at that visit. This scale consisted of a line measuring 100 mm, and patients were instructed to put a mark on the line at the point that best described 'How much pain you are having right now'. Higher scores denoted higher pain intensity: 0 indicated 'No pain' and 100 indicated 'Worst possible pain'.
Time frame: Baseline, Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided as least 1 post-dose assessment measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BOTOX® | Patient Visual Analog Assessment of Pain at Week 4 | Baseline | 49.5 Units on a Scale |
| BOTOX® | Patient Visual Analog Assessment of Pain at Week 4 | Week 4 | 20.5 Units on a Scale |
| Dysport® | Patient Visual Analog Assessment of Pain at Week 4 | Baseline | 52.0 Units on a Scale |
| Dysport® | Patient Visual Analog Assessment of Pain at Week 4 | Week 4 | 28.0 Units on a Scale |
Secondary
Physician Assessment of Cervical Dystonia Severity at Week 4
Physician assessment of cervical dystonia severity. The rating was assessed on a scale of 0 to 10, with higher scores denoting greater severity: 0 represented 'No evidence of dystonia' and 10 represented 'Worst cervical dystonia ever'
Time frame: Baseline, Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided as least 1 post-dose assessment measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BOTOX® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Baseline | 7.0 Units on a Scale |
| BOTOX® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Week 4 | 4.0 Units on a Scale |
| Dysport® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Baseline | 8.0 Units on a Scale |
| Dysport® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Week 4 | 4.0 Units on a Scale |
Secondary
Physician Comparison of Benefit to Previous Injections at Week 20
Physicians assessed the improvement in cervical dystonia after the study treatment compared to previous treatment(s) for each patient. Physicians were required to answer How would you rate the benefit of the current treatment of cervical dystonia with botulinum toxin type A compared to the previous treatment using the following scale?. The response options were 'much worse', 'worse', 'somewhat worse', 'same as previous', 'somewhat better', 'better', and 'much better'.
Time frame: Week 20
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided as least 1 post-dose assessment measure. Only completed assessments at this time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Somewhat Worse | 0 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Somewhat Better | 4 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Worse | 0 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Better | 0 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Same as Previous | 13 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Much Better | 1 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 20 | Much Worse | 0 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Much Better | 1 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Much Worse | 0 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Worse | 1 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Somewhat Worse | 3 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Same as Previous | 13 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Somewhat Better | 5 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 20 | Better | 1 Number of Responses |
Secondary
Toronto Western Spasmodic Torticollis Rating Scale Duration Target Score (TDTS) at Week 4
The TDTS was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score representing a loss of 80% of the treatment benefit at Week 4. The TDTS is calculated from the TWSTRS score and ranges from 0 (least symptoms) to 68 (worst symptoms). The TWSTRS total score which is scored from 0 (least symptoms) to 85 (worst symptoms).
Time frame: Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided at least 1 post-dose assessment measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX® | Toronto Western Spasmodic Torticollis Rating Scale Duration Target Score (TDTS) at Week 4 | 37.0 Scores on a Scale |
| Dysport® | Toronto Western Spasmodic Torticollis Rating Scale Duration Target Score (TDTS) at Week 4 | 41.0 Scores on a Scale |
Secondary
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4
The TWSTRS is an assessment scale used to measure the impact of cervical dystonia on patients. The score is comprised of 3 subscales: Severity, Disability, and Pain, each of which is scored independently. The total of these 3 comprises the TWSTRS total score which is scored from 0 (least symptoms) to 85 (worst symptoms). Higher scores indicate a greater degree of symptom severity.
Time frame: Baseline, Week 4
Population: Modified Intent to Treat: included all patients who were randomized to treatment, received treatment at Visit 1, and provided at least 1 post-dose assessment measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BOTOX® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Baseline | 42.0 Scores on a Scale |
| BOTOX® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Week 4 | 26.0 Scores on a Scale |
| Dysport® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Baseline | 43.5 Scores on a Scale |
| Dysport® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Week 4 | 27.0 Scores on a Scale |