Cervical Dystonia
Conditions
Brief summary
The purpose of the protocol is to assess the long term safety of repeat treatment cycles of Dysport® 500 U using 2 mL dilution scheme for the treatment of Cervical Dystonia. This is an extension study to study A-TL-52120-169 (hereafter referred to as Study 169).
Interventions
BIOLOGICALBotulinum toxin type A
Dysport® (intramuscular injection), Up to 500 units (U)/vial using 2mL dilution, 3 treatment cycles
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 Study 169 that have no ongoing adverse events, which in the opinion of the Investigator are related to study treatment and that precludes them from receiving continuing therapy * Completed Study 169, or completed all study visits up to and including Week 4 and in the event of an early withdrawal after Week 4 have ≤15% reduction in TWSTRS total score at Week 4 compared to their baseline TWSTRS total score in the double-blind study, and in the Investigator's clinical judgment, would benefit from Dysport® for CD
Exclusion criteria
* Diagnosis of pure retrocollis or pure anterocollis * Requirement for Botulinum Neurotoxin (BoNT) injection to site(s) for disorders other than CD and unable to avoid such treatment(s) for the duration of the study * Known hypersensitivity to BoNT or related compounds, or any component in the study drug formulation * Allergy to cow's milk protein * Myasthenia gravis, other disease of the neuromuscular junction or clinically significant, persistent neuromuscular weakness, or disease or symptoms that could interfere with the TWSTRS scoring * Total body weight \<95 lbs (43.09 kg) * Previous phenol injections to the neck muscles * Previous myotomy or denervation surgery involving the neck or shoulder region or deep brain stimulation to treat CD * Cervical contracture that limited passive range of motion * Physiotherapy initiated \<4 weeks before study entry or expected to be initiated during the study * Treatment with aminoglycoside antibiotics within 30 days prior to study treatment * Current or expected requirement for concomitant medication that could interfere with the evaluation of study treatment * Pregnant and/or lactating females * Females of childbearing potential with a positive prestudy urine pregnancy test (a positive urine pregnancy test could be confirmed by a serum pregnancy test at the discretion of the investigator) and subjects, or their partners, who did not agree to use adequate contraception (hormonal or barrier method of birth control) prior to injection of study treatment and for the duration of study participation. Nonchildbearing potential is defined as postmenopause for at least 1 year, surgical sterilisation at least 3 months before entering the study, or hysterectomy * Individuals who had family or employee relationship to study site staff or sponsor staff involved in the conduct of the study * Any medical condition that could, as judged by the investigator, compromise compliance with the objectives and procedures of this protocol or preclude the administration of BoNT, including swallowing and other respiratory abnormality. * Subjects who were unable and/or unwilling to comply fully with the protocol and the study instructions, as judged by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each) | Mean TWSTRS total scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean differences in the TWSTRS total scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for Treatment Cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each) | The pretreatment baseline scores were defined as the TWSTRS measurement before Dysport® treatment in Study 169 for subjects who had received Dysport® in Study 169 and Day 1 of Study 170 for those subjects who had received placebo. Mean TWSTRS total scores for pretreatment baseline and for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean differences in the TWSTRS total scores from pretreatment baseline scores at Week 4 and Week 12 of each treatment cycle are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline for Studies 169 and 170 and at all post-treatment visits of each treatment cycle. |
| Treatment Response in Treatment Cycle 3 Week 4. | Week 4 Treatment Cycle 3 | Treatment response was defined as a reduction in the TWSTRS total score of at least 30% from pretreatment baseline to the Week 4 visit in Treatment Cycle 3. The pretreatment baseline scores were defined as the TWSTRS measurement before Dysport® treatment in Study 169 for subjects who had previously received Dysport® in Study 169 and Day 1 of Study 170 for those subjects who had previously received placebo. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline for Studies 169 and 170 and at all post-treatment visits of each treatment cycle. The proportion (percentage) of subjects who were treatment responders at Week 4 of Treatment Cycle 3 are presented. |
| TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Weeks 4 and 12 of treatment cycle 1, 2 and 3 (12 - 16 weeks duration each) | Mean TWSTRS severity subscale scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean differences in the TWSTRS severity subscale scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for treatment cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The severity subscale gives a score from 0 to 35, with higher values indicating a worse outcome of physical findings of CD. The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle. |
| TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Weeks 4 and 12 of treatment cycle 1, 2 and 3 (12 - 16 weeks duration each) | Mean TWSTRS disability subscale scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for Treatment Cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The disability subscale is a 6-item scale and each item is rated on a 6-point scale with higher values indicating the highest degree of disability. The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle. |
| TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each) | Mean TWSTRS pain subscale scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for Treatment Cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The pain subscale gives a score from 0 to 20, with higher values indicating greater pain experienced. The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle. |
Countries
United States
Participant flow
Recruitment details
This was an open label extension (OLE) study for study A-TL-52120-169 (Study 169). First subject enrolled: 14 March 2013; last subject completed: 13 October 2015. A-TL-52120-170 (Study 170) was conducted in 36 centres in the United States that had participated in Study 169 and enrolled adult subjects with cervical dystonia (CD).
Pre-assignment details
Subjects who completed Study 169 and had no on-going Adverse Events (AEs) or whose Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score between Weeks 4 and 8 was reduced by ≤15% from baseline were invited to participate in this OLE study. 112 of the 134 subjects in Study 169 were enrolled into Study 170 (signed informed consent).
Participants by arm
| Arm | Count |
|---|---|
| Total Dysport® Subjects received up to 3 doses of Dysport® 500 U/vial, 2 mL dilution on Day 1 of up to 3 treatment cycles. Subjects who were BoNT treatment naïve at the start of Study 169 received a starting dose of 500U/2 mL Dysport®, and subjects who were non-naïve to BoNT treatment received the same dose they had received on Day 1 of Study 169. Subjects received Dysport® by intramuscular injection into the same neck muscles that had been used for injection in Study 169. Retreatment occurred every 12 to 16 weeks, dependent on the investigator's clinical judgment. Follow-up visits occurred at Weeks 4 and 12 of each treatment cycle. Subjects were determined to have completed the study at Week 12 of Treatment Cycle 3. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). | 112 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Patient decision | 12 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Sponsor's decision | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Total Dysport® |
|---|---|
| Age, Customized 18-24 years | 0 Participants |
| Age, Customized 25-34 years | 1 Participants |
| Age, Customized 35-44 years | 13 Participants |
| Age, Customized 45-54 years | 34 Participants |
| Age, Customized 55-64 years | 33 Participants |
| Age, Customized 65-74 years | 26 Participants |
| Age, Customized +75 years | 5 Participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 70 / 112 |
| serious Total, serious adverse events | 7 / 112 |
Outcome results
Primary
TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3.
Mean TWSTRS total scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean differences in the TWSTRS total scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for Treatment Cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle.
Time frame: Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each)
Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 1-Day 1 | 37.7 units on a scale | Standard Deviation 13.58 |
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 1-Week 4 | 30.1 units on a scale | Standard Deviation 13.16 |
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 1-Week 12/Cycle 2-Day 1 | 32.6 units on a scale | Standard Deviation 11.96 |
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 2-Week 4 | 27.0 units on a scale | Standard Deviation 12.07 |
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 2-Week 12/Cycle 3-Day 1 | 31.1 units on a scale | Standard Deviation 12.51 |
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 3-Week 4 | 27.4 units on a scale | Standard Deviation 13.1 |
| Total Dysport® | TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 3-Week 12 | 30.1 units on a scale | Standard Deviation 12.76 |
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 4. The mean difference in the TWSTRS total scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 1 is presented.95% CI: [-9.79, -6.28]
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 12. The mean difference in the TWSTRS total scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 1 is presented.95% CI: [-7.36, -2.68]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 4. The mean difference in the TWSTRS total scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 2 is presented.95% CI: [-7.42, -4.47]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 12. The mean difference in the TWSTRS total scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 2 is presented.95% CI: [-3.37, -0.27]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 4. The mean difference in the TWSTRS total scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 3 was determined.95% CI: [-5.99, -2.2]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 12. The mean difference in the TWSTRS total scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 3 was determined.95% CI: [-3.11, 0.81]
Secondary
Treatment Response in Treatment Cycle 3 Week 4.
Treatment response was defined as a reduction in the TWSTRS total score of at least 30% from pretreatment baseline to the Week 4 visit in Treatment Cycle 3. The pretreatment baseline scores were defined as the TWSTRS measurement before Dysport® treatment in Study 169 for subjects who had previously received Dysport® in Study 169 and Day 1 of Study 170 for those subjects who had previously received placebo. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline for Studies 169 and 170 and at all post-treatment visits of each treatment cycle. The proportion (percentage) of subjects who were treatment responders at Week 4 of Treatment Cycle 3 are presented.
Time frame: Week 4 Treatment Cycle 3
Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit. For Treatment Cycle 3 there were 91 evaluable subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Dysport® | Treatment Response in Treatment Cycle 3 Week 4. | 51.6 percentage of participants |
Secondary
TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3.
Mean TWSTRS disability subscale scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for Treatment Cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The disability subscale is a 6-item scale and each item is rated on a 6-point scale with higher values indicating the highest degree of disability. The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle.
Time frame: Weeks 4 and 12 of treatment cycle 1, 2 and 3 (12 - 16 weeks duration each)
Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score at Cycle 1-Day 1 | 11.5 units on a scale | Standard Deviation 6.63 |
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score at Cycle1-Week 4 | 8.8 units on a scale | Standard Deviation 6.41 |
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score Cycle1-Week 12/Cycle 2-Day 1 | 9.4 units on a scale | Standard Deviation 5.64 |
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score at Cycle 2-Week 4 | 7.9 units on a scale | Standard Deviation 5.76 |
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score Cycle2-Week 12/Cycle 3-Day 1 | 8.7 units on a scale | Standard Deviation 5.82 |
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score at Cycle 3-Week 4 | 8.1 units on a scale | Standard Deviation 6.07 |
| Total Dysport® | TWSTRS Disability Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean disability score at Cycle 3-Week 12 | 8.6 units on a scale | Standard Deviation 6.41 |
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 4. The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 3 was determined.95% CI: [-1.45, 0.12]
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 4. The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 1 was determined.95% CI: [-3.64, -2.12]
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 12.The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 1 was determined.95% CI: [-2.79, -0.86]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 4. The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 2 was determined.95% CI: [-2.44, -1.04]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 12. The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 2 was determined.95% CI: [-1.55, -0.12]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 12.The mean difference in the TWSTRS disability subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 3 was determined.95% CI: [-0.85, 0.7]
Secondary
TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3.
Mean TWSTRS pain subscale scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for Treatment Cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The pain subscale gives a score from 0 to 20, with higher values indicating greater pain experienced. The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle.
Time frame: Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each)
Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 1-Day 1 | 9.0 units on a scale | Standard Deviation 5.32 |
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 1-Week 4 | 7.4 units on a scale | Standard Deviation 5.1 |
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 1-Week 12/Cycle 2-Day 1 | 7.5 units on a scale | Standard Deviation 5.03 |
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 2- Week 4 | 6.3 units on a scale | Standard Deviation 5.11 |
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 2-Week 12/Cycle 3-Day 1 | 7.2 units on a scale | Standard Deviation 4.98 |
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 3-Week 4 | 6.5 units on a scale | Standard Deviation 5.01 |
| Total Dysport® | TWSTRS Pain Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean pain score at Cycle 3-Week 12 | 7.1 units on a scale | Standard Deviation 4.85 |
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 4. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 1 was determined.95% CI: [-2.39, -0.92]
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 12. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 1 was determined.95% CI: [-2.22, -0.66]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 4.The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 2 was determined.95% CI: [-1.84, -0.58]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 12. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 2 was determined.95% CI: [-1.08, 0.18]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 4. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 3 was determined.95% CI: [-1.57, 0.19]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 12. The mean difference in the TWSTRS pain subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 3 was determined.95% CI: [-0.85, 0.73]
Secondary
TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3.
Mean TWSTRS severity subscale scores for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean differences in the TWSTRS severity subscale scores from treatment cycle baseline (defined as Day 1 in each cycle) at the Week 4 and Week 12 visits for treatment cycles 1, 2 and 3 are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The severity subscale gives a score from 0 to 35, with higher values indicating a worse outcome of physical findings of CD. The score was assessed by the investigator at baseline and at all post-treatment visits of each treatment cycle.
Time frame: Weeks 4 and 12 of treatment cycle 1, 2 and 3 (12 - 16 weeks duration each)
Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score at Cycle 1-Day 1 | 17.3 units on a scale | Standard Deviation 4.69 |
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score at Cycle 1-Week 4 | 13.9 units on a scale | Standard Deviation 5.21 |
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score Cycle 1-Week 12/Cycle 2-Day 1 | 15.7 units on a scale | Standard Deviation 4.97 |
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score at Cycle 2-Week 4 | 12.8 units on a scale | Standard Deviation 4.97 |
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score Cycle 2-Week12/Cycle 3-Day 1 | 15.3 units on a scale | Standard Deviation 4.87 |
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score at Cycle 3-Week 4 | 12.7 units on a scale | Standard Deviation 5.78 |
| Total Dysport® | TWSTRS Severity Subscale Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean severity score at Cycle 3-Week 12 | 14.3 units on a scale | Standard Deviation 5.29 |
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 4. The mean difference in the TWSTRS severity subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 1 was determined.95% CI: [-4.46, -2.52]
Comparison: Cycle 1-Day 1 vs Cycle 1-Week 12. The mean difference in the TWSTRS severity subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 1 was determined.95% CI: [-2.81, -0.7]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 4. The mean difference in the TWSTRS severity subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 2 was determined.95% CI: [-3.75, -2.23]
Comparison: Cycle 2-Day 1 vs Cycle 2-Week 12. The mean difference in the TWSTRS severity subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 2 was determined.95% CI: [-1.33, 0.27]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 4. The mean difference in the TWSTRS severity subscale scores from treatment cycle baseline (Day 1) at the Week 4 visit for Treatment Cycle 3 was determined.95% CI: [-3.64, -1.83]
Comparison: Cycle 3-Day 1 vs Cycle 3-Week 12. The mean difference in the TWSTRS severity subscale scores from treatment cycle baseline (Day 1) at the Week 12 visit for Treatment Cycle 3 was determined.95% CI: [-2, -0.02]
Secondary
TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3.
The pretreatment baseline scores were defined as the TWSTRS measurement before Dysport® treatment in Study 169 for subjects who had received Dysport® in Study 169 and Day 1 of Study 170 for those subjects who had received placebo. Mean TWSTRS total scores for pretreatment baseline and for Week 4 and Week 12 of treatment cycles 1, 2 and 3 are presented. The mean differences in the TWSTRS total scores from pretreatment baseline scores at Week 4 and Week 12 of each treatment cycle are also presented. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline for Studies 169 and 170 and at all post-treatment visits of each treatment cycle.
Time frame: Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each)
Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at baseline for Study 169 | 42.2 units on a scale | Standard Deviation 10.3 |
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 1-Week 4 | 30.1 units on a scale | Standard Deviation 13.16 |
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 1-Week 12 | 32.6 units on a scale | Standard Deviation 11.96 |
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 2-Week 4 | 27.0 units on a scale | Standard Deviation 12.07 |
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 2-Week 12 | 31.1 units on a scale | Standard Deviation 12.51 |
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 3-Week 4 | 27.4 units on a scale | Standard Deviation 13.1 |
| Total Dysport® | TWSTRS Total Scores at Pretreatment Baseline, Week 4 and Week 12 for Treatment Cycles 1, 2 and 3. | Mean TWSTRS score at Cycle 3-Week 12 | 30.1 units on a scale | Standard Deviation 12.76 |
Comparison: Pretreatment baseline vs Cycle 1-Week 4. The mean difference in the TWSTRS total scores from baseline (pretreatment measurement before receiving Dysport® in Study 169 or for subjects who received placebo in Study 169, baseline was Day 1 of Cycle 1 of Study 170) at the Week 4 visit for Treatment Cycle 1 is presented.95% CI: [-13.38, -9.56]
Comparison: Pretreatment baseline vs Cycle 1-Week 12. The mean difference in the TWSTRS total scores from baseline (pretreatment measurement before receiving Dysport® in Study 169 or for subjects who received placebo in Study 169, baseline was Day 1 of Cycle 1 of Study 170) at the Week 12 visit for treatment Cycle 1 is presented.95% CI: [-11.08, -6.71]
Comparison: Pretreatment baseline vs Cycle 2-Week 4. The mean difference in the TWSTRS total scores from baseline (pretreatment measurement before receiving Dysport® in Study 169 or for subjects who received placebo in Study 169, baseline was Day 1 of Cycle 1 of Study 170) at the Week 4 visit for Treatment Cycle 2 is presented.95% CI: [-16.74, -12.11]
Comparison: Pretreatment baseline vs Cycle 2-Week 12. The mean difference in the TWSTRS total scores from baseline (pretreatment measurement before receiving Dysport® in Study 169 or for subjects who received placebo in Study 169, baseline was Day 1 of Cycle 1 of Study 170) at the Week 12 visit for Treatment Cycle 2 is presented.95% CI: [-12.92, -8.22]
Comparison: Pretreatment baseline vs Cycle 3-Week 4. The mean difference in the TWSTRS total scores from baseline (pretreatment measurement before receiving Dysport® in Study 169 or for subjects who received placebo in Study 169, baseline was Day 1 of Cycle 1 of Study 170) at the Week 4 visit for Treatment Cycle 3 is presented.95% CI: [-17.18, -12.1]
Comparison: Pretreatment baseline vs Cycle 3-Week 12. The mean difference in the TWSTRS total scores from baseline (pretreatment measurement before receiving Dysport® in Study 169 or for subjects who received placebo in Study 169, baseline was Day 1 of Cycle 1 of Study 170) at the Week 12 visit for Treatment Cycle 3 is presented.95% CI: [-14.02, -9.39]