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 No maximum
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 |
|---|---|---|
| Dysphagia Incidence Over 10 Weeks | 10 weeks | Dysphagia Incidence (difficulty swallowing) was defined as the number of patients reporting at least 1 treatment-emergent dysphagia event at any point in the study. Occurrences of dysphagia were captured as spontaneous events or were assessed during study visits using the Structured Symptom Interview (SSI) and the Dystonia Study Group Dysphagia Interview (DSGDI) for symptoms of difficulty swallowing; coughing while eating and drinking; choking while eating or drinking; or difficulty swallowing solids or liquids. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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.' |
| 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).' |
| 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).' |
| Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Baseline, Week 4 | The TWSTRS assessments were conducted at each study visit. The TWSTRS is an assessment scale used to measure the impact of cervical dystonia on patients. It 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. |
| 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'. |
| Physician Comparison of Benefit to Previous Injections at Week 10 | Week 10 | 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'. |
| Patient Comparison of Benefit to Previous Injections at Week 10 | Week 10 | 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 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'. |
Countries
Australia, Croatia, Italy, Poland, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BOTOX® botulinum toxin type A (BOTOX®) | 75 |
| Dysport® botulinum toxin type A (Dysport®) | 70 |
| Total | 145 |
Baseline characteristics
| Characteristic | BOTOX® | Dysport® | Total |
|---|---|---|---|
| Age Continuous | 49.4 years STANDARD_DEVIATION 12.2 | 48.6 years STANDARD_DEVIATION 11.5 | 49.0 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 46 Participants | 39 Participants | 85 Participants |
| Sex: Female, Male Male | 29 Participants | 31 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 75 | 4 / 70 |
| serious Total, serious adverse events | 0 / 75 | 0 / 70 |
Outcome results
Primary
Dysphagia Incidence Over 10 Weeks
Dysphagia Incidence (difficulty swallowing) was defined as the number of patients reporting at least 1 treatment-emergent dysphagia event at any point in the study. Occurrences of dysphagia were captured as spontaneous events or were assessed during study visits using the Structured Symptom Interview (SSI) and the Dystonia Study Group Dysphagia Interview (DSGDI) for symptoms of difficulty swallowing; coughing while eating and drinking; choking while eating or drinking; or difficulty swallowing solids or liquids.
Time frame: 10 weeks
Population: Modified intent to treat: all patients who were randomized to treatment and received 1 dose at Visit 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX® | Dysphagia Incidence Over 10 Weeks | 10 Number of patients |
| Dysport® | Dysphagia Incidence Over 10 Weeks | 12 Number of patients |
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: all patients who were randomized to treatment and received 1 dose at Visit 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX® | Global Assessment of Benefit by Patient at Week 4 | 3.0 Units on a Scale |
| Dysport® | Global Assessment of Benefit by Patient at Week 4 | 3.0 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: all patients who were randomized to treatment and received 1 dose at Visit 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX® | Global Assessment of Benefit by Physician at Week 4 | 3.0 Units on a Scale |
| Dysport® | Global Assessment of Benefit by Physician at Week 4 | 3.0 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: all patients who were randomized to treatment and received 1 dose at Visit 1. 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 | 54 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Baseline | 19 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Baseline | 1 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 | 17 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Week 4 | 10 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Week 4 | 18 Number of Responses |
| BOTOX® | Patient Assessment of Need for Retreatment at Week 4 | Does not require injection at Week 4 | 2 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Does not require injection at Week 4 | 21 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Absolutely requires injection at Baseline | 54 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Absolutely requires injection at Week 4 | 15 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Baseline | 15 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Week 4 | 18 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Somewhat requires injection at Baseline | 1 Number of Responses |
| Dysport® | Patient Assessment of Need for Retreatment at Week 4 | Very much requires injection at Week 4 | 15 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 10
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 10
Population: Modified intent to treat: all patients who were randomized to treatment and received 1 dose at Visit 1. Only completed assessments at this timepoint are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Somewhat Worse | 8 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Somewhat Better | 24 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Worse | 1 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Better | 8 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Same as Previous | 30 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Much Better | 1 Number of Responses |
| BOTOX® | Patient Comparison of Benefit to Previous Injections at Week 10 | Much Worse | 0 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Much Better | 7 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Much Worse | 0 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Worse | 2 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Somewhat Worse | 10 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Same as Previous | 20 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Somewhat Better | 17 Number of Responses |
| Dysport® | Patient Comparison of Benefit to Previous Injections at Week 10 | Better | 12 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: all patients who were randomized to treatment and received 1 dose at Visit 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BOTOX® | Patient Visual Analog Assessment of Pain at Week 4 | Baseline | 30.5 Units on a Scale |
| BOTOX® | Patient Visual Analog Assessment of Pain at Week 4 | Week 4 | 8.0 Units on a Scale |
| Dysport® | Patient Visual Analog Assessment of Pain at Week 4 | Baseline | 39.5 Units on a Scale |
| Dysport® | Patient Visual Analog Assessment of Pain at Week 4 | Week 4 | 13.0 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: all patients who were randomized to treatment and received 1 dose at Visit 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BOTOX® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Baseline | 6.0 Units on a Scale |
| BOTOX® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Week 4 | 2.0 Units on a Scale |
| Dysport® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Baseline | 7.0 Units on a Scale |
| Dysport® | Physician Assessment of Cervical Dystonia Severity at Week 4 | Week 4 | 3.0 Units on a Scale |
Secondary
Physician Comparison of Benefit to Previous Injections at Week 10
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 10
Population: Modified intent to treat: all patients who were randomized to treatment and received 1 dose at Visit 1. Only completed assessments at this time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Somewhat Worse | 7 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Somewhat Better | 25 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Worse | 0 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Better | 7 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Same as Previous | 30 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Much Better | 4 Number of Responses |
| BOTOX® | Physician Comparison of Benefit to Previous Injections at Week 10 | Much Worse | 0 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Much Better | 3 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Much Worse | 0 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Worse | 1 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Somewhat Worse | 7 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Same as Previous | 31 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Somewhat Better | 15 Number of Responses |
| Dysport® | Physician Comparison of Benefit to Previous Injections at Week 10 | Better | 12 Number of Responses |
Secondary
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4
The TWSTRS assessments were conducted at each study visit. The TWSTRS is an assessment scale used to measure the impact of cervical dystonia on patients. It 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: all patients who were randomized to treatment and received 1 dose at Visit 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BOTOX® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Baseline | 40.0 Scores on a Scale |
| BOTOX® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Week 4 | 22.0 Scores on a Scale |
| Dysport® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Baseline | 39.5 Scores on a Scale |
| Dysport® | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4 | Week 4 | 25.0 Scores on a Scale |