Cervical Dystonia
Conditions
Brief summary
Study is to investigate the use of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scale in a cervical dystonia population treated with botulinum toxin type A, and placebo.
Interventions
BIOLOGICALbotulinum toxin type A
Intramuscular injections into the affected muscles. Maximum dose of 360 units. Subjects may receive up to three treatments.
BIOLOGICALbotulinum toxin type A Formulation 2
Intramuscular injections into the affected muscles. Maximum dose of 360 units. Subjects may receive up to three treatments.
DRUGNormal Saline
Intramuscular injections of placebo (normal saline) into the affected muscles for treatment cycle 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of cervical dystonia
Exclusion criteria
* Current or previous botulinum toxin treatment of any type for any condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Baseline, Week 4 | Change from baseline in observed TWSTRS score at Week 4 of Treatment Cycle 1. 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. A negative change from baseline represents improvement and a positive change from baseline indicates worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | Week 4 | Physician's global assessment of response to treatment at Week 4 of Treatment Cycle 1. Responses were measured on a 9-point scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (100% improvement)', 0 represented 'No change', and -4 represented 'Very marked worsening (about 100% worse or greater)'. |
| Patient's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | Week 4 | Patient's global assessment of response to treatment at Week 4 of Treatment Cycle 1. Responses were measured on a 9-point scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (100% improvement)', 0 represented 'No change', and -4 represented 'Very marked worsening (about 100% worse or greater)'. |
| Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Baseline, Week 4 | Change from baseline in pain as evaluated with the TWSTRS pain subscale at Week 4 of Treatment Cycle 1. The TWSTRS pain subscale scores range from 0 to 20 (0=no pain and 20=worst pain), based on severity of neck pain (0=no pain and 10=worst pain), the duration of pain (0=none and 5=most), and the degree of disability (0=none and 5=most). A negative number change from Baseline represents a decrease in pain (improvement). |
| Duration of Treatment Effect for Treatment Responders | Up to 6 Months | Duration of Treatment Effect for Treatment Responders is defined as the number of days from the date of first treatment to the first visit after Week 4 of Treatment Cycle 1, at which the Total TWSTRS score reaches at least 90% of the baseline score. A treatment responder is defined as a patient who has at least a 30% reduction in Total TWSTRS score at Week 4 after the first treatment. The TWSTRS score measures the impact of cervical dystonia on patients (0=least symptoms and 85= worst symptoms). |
Countries
Canada, Czechia, Germany, Hungary, India, Philippines, Poland, Russia, Serbia, Singapore, Slovakia, South Africa, Taiwan, Thailand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A Intramuscular injections into the affected muscles. Maximum dose of 360 units. Subjects may receive up to three treatments. | 117 |
| Botulinum Toxin Type A Formulation 2 Intramuscular injections into the affected muscles. Maximum dose of 360 units. Subjects may receive up to three treatments. | 61 |
| Placebo (Normal Saline) / Botulinum Toxin Type A Intramuscular injections of the assigned study medication into the affected muscles (placebo for treatment cycle 1 and botulinum toxin Type A for subsequent treatments). Maximum dose of 360 units. Subjects may receive up to three treatments. | 43 |
| Placebo (Normal Saline) / Botulinum Toxin Type A Formulation 2 Intramuscular injections of the assigned study medication into the affected muscles (placebo for treatment cycle 1 and botulinum toxin Type A Formulation 2 for subsequent treatments). Maximum dose of 360 units. Subjects may receive up to three treatments. | 21 |
| Total | 242 |
Baseline characteristics
| Characteristic | Botulinum Toxin Type A | Botulinum Toxin Type A Formulation 2 | Placebo (Normal Saline) / Botulinum Toxin Type A | Placebo (Normal Saline) / Botulinum Toxin Type A Formulation 2 | Total |
|---|---|---|---|---|---|
| Age, Customized <45 years | 38 Participants | 22 Participants | 13 Participants | 11 Participants | 84 Participants |
| Age, Customized >65 years | 8 Participants | 11 Participants | 6 Participants | 2 Participants | 27 Participants |
| Age, Customized Between 45 and 65 years | 71 Participants | 28 Participants | 24 Participants | 8 Participants | 131 Participants |
| Sex: Female, Male Female | 81 Participants | 43 Participants | 32 Participants | 13 Participants | 169 Participants |
| Sex: Female, Male Male | 36 Participants | 18 Participants | 11 Participants | 8 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 83 / 117 | 41 / 61 | 31 / 42 | 16 / 21 |
| serious Total, serious adverse events | 9 / 117 | 1 / 61 | 5 / 42 | 1 / 21 |
Outcome results
Primary
Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1
Change from baseline in observed TWSTRS score at Week 4 of Treatment Cycle 1. 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. A negative change from baseline represents improvement and a positive change from baseline indicates worsening.
Time frame: Baseline, Week 4
Population: Intent-To-Treat: All enrolled patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Baseline | 40.4 Scores on a Scale | Standard Deviation 9.14 |
| Botulinum Toxin Type A | Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Change from Baseline at Week 4 | -10.3 Scores on a Scale | Standard Deviation 9.77 |
| Botulinum Toxin Type A Formulation 2 | Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Baseline | 41.5 Scores on a Scale | Standard Deviation 9.4 |
| Botulinum Toxin Type A Formulation 2 | Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Change from Baseline at Week 4 | -13.6 Scores on a Scale | Standard Deviation 10.2 |
| Placebo (Normal Saline) | Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Baseline | 39.6 Scores on a Scale | Standard Deviation 9.52 |
| Placebo (Normal Saline) | Change From Baseline in Observed Total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Score at Week 4 of Treatment Cycle 1 | Change from Baseline at Week 4 | -5.6 Scores on a Scale | Standard Deviation 8.58 |
Secondary
Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1
Change from baseline in pain as evaluated with the TWSTRS pain subscale at Week 4 of Treatment Cycle 1. The TWSTRS pain subscale scores range from 0 to 20 (0=no pain and 20=worst pain), based on severity of neck pain (0=no pain and 10=worst pain), the duration of pain (0=none and 5=most), and the degree of disability (0=none and 5=most). A negative number change from Baseline represents a decrease in pain (improvement).
Time frame: Baseline, Week 4
Population: Intent-to-Treat: All enrolled patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Baseline | 9.7 Scores on a Scale | Standard Deviation 4.04 |
| Botulinum Toxin Type A | Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Change from Baseline at Week 4 | -2.8 Scores on a Scale | Standard Deviation 3.72 |
| Botulinum Toxin Type A Formulation 2 | Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Change from Baseline at Week 4 | -4.1 Scores on a Scale | Standard Deviation 4.15 |
| Botulinum Toxin Type A Formulation 2 | Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Baseline | 10.0 Scores on a Scale | Standard Deviation 3.41 |
| Placebo (Normal Saline) | Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Baseline | 9.7 Scores on a Scale | Standard Deviation 4.13 |
| Placebo (Normal Saline) | Change From Baseline in Pain as Evaluated With the TWSTRS Pain Subscale at Week 4 of Treatment Cycle 1 | Change from Baseline at Week 4 | -1.3 Scores on a Scale | Standard Deviation 3.59 |
Secondary
Duration of Treatment Effect for Treatment Responders
Duration of Treatment Effect for Treatment Responders is defined as the number of days from the date of first treatment to the first visit after Week 4 of Treatment Cycle 1, at which the Total TWSTRS score reaches at least 90% of the baseline score. A treatment responder is defined as a patient who has at least a 30% reduction in Total TWSTRS score at Week 4 after the first treatment. The TWSTRS score measures the impact of cervical dystonia on patients (0=least symptoms and 85= worst symptoms).
Time frame: Up to 6 Months
Population: Intent-to-Treat: All enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Botulinum Toxin Type A | Duration of Treatment Effect for Treatment Responders | 111.0 Days |
| Botulinum Toxin Type A Formulation 2 | Duration of Treatment Effect for Treatment Responders | 99.0 Days |
| Placebo (Normal Saline) | Duration of Treatment Effect for Treatment Responders | 99.0 Days |
Secondary
Patient's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1
Patient's global assessment of response to treatment at Week 4 of Treatment Cycle 1. Responses were measured on a 9-point scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (100% improvement)', 0 represented 'No change', and -4 represented 'Very marked worsening (about 100% worse or greater)'.
Time frame: Week 4
Population: Intent-to-Treat: All enrolled patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin Type A | Patient's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | 1.3 Scores on a Scale | Standard Deviation 1.31 |
| Botulinum Toxin Type A Formulation 2 | Patient's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | 1.5 Scores on a Scale | Standard Deviation 1.07 |
| Placebo (Normal Saline) | Patient's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | 0.6 Scores on a Scale | Standard Deviation 1.06 |
Secondary
Physician's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1
Physician's global assessment of response to treatment at Week 4 of Treatment Cycle 1. Responses were measured on a 9-point scale of +4 to -4, with higher scores denoting improvement in cervical dystonia: +4 was 'Complete abolishment of signs and symptoms (100% improvement)', 0 represented 'No change', and -4 represented 'Very marked worsening (about 100% worse or greater)'.
Time frame: Week 4
Population: Intent-to-Treat: All enrolled patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin Type A | Physician's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | 1.3 Scores on a Scale | Standard Deviation 1.13 |
| Botulinum Toxin Type A Formulation 2 | Physician's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | 1.6 Scores on a Scale | Standard Deviation 1.04 |
| Placebo (Normal Saline) | Physician's Global Assessment of Response to Treatment at Week 4 of Treatment Cycle 1 | 0.8 Scores on a Scale | Standard Deviation 1 |