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| Name | Class |
|---|---|
| Merz North America, Inc. | INDUSTRY |
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This study will compare Xeomin®, a botulinum toxin medication, in shorter treatment intervals (Short Flex dosing) to the standard interval dosing (Long Flex dosing) to determine if the response to treatment is comparable in both how it works and any side effects. Xeomin® is approved by the United States Food and Drug Administration (FDA) for the treatment of cervical dystonia (CD). The use of Xeomin® is investigational in regards to shorter treatment intervals. An investigational use is one that is not approved by the FDA.
Dystonia is a movement disorder which is characterized by sustained, involuntary muscle contractions which frequently causes twisting and repetitive movements or abnormal postures of the trunk, neck, face, or arms and legs. In focal dystonia, the abnormal movements involve a single area of the body. A commonly described form of focal dystonia is cervical dystonia (CD). Botulinum toxin treatment can be offered as a treatment option for the treatment of CD.
The current practice for botulinum toxin injection treatment is to inject patients every 3 months. However, not all patients receive continuing benefit from botulinum toxin injections for an entire 3 months. In a recent survey, approximately 45% of patients report that they would prefer a treatment cycle of less than 10 weeks.This study will compare Xeomin®, a botulinum toxin treatment, in shorter treatment intervals (Short Flex dosing) to the standard interval dosing (Long Flex dosing) to determine if the response to treatment is comparable in both how it works and any side effects. Xeomin® is approved by the United States Food and Drug Administration (FDA) for the treatment of CD. The use of Xeomin® is investigational in regards to shorter treatment intervals. An investigational use is one that is not approved by the FDA.
The purpose of this research study is to evaluate the efficacy of the Short Flex dosing of Xeomin® compared to the Long Flex dosing regimen of Xeomin®, using a standard scale completed by the doctors and subjects as well as questionnaires that ask subjects to rate symptoms of CD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Xeomin® Short Flex | Active Comparator | short flex dosing of Xeomin. It is a botulinum toxin type A produced from fermentation of Hall strain Clostridium botulinum serotype A. |
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| Xeomin® Long Flex | Active Comparator | long flex dosing of Xeomin. It is a botulinum toxin type A produced from fermentation of Hall strain Clostridium botulinum serotype A. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xeomin® | Biological | Xeomin is botulinum toxin type A produced from fermentation of Hall strain Clostridium botulinum serotype A |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Based on Blinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of cervical dystonia (CD) on participants. A blinded rater performed all TWSTRS-Severity subscale assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity). | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in TWSTRS Total Score Based on Blinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participants. The scale comprised of 3 subscales: Severity, Disability, and Pain, each of which was scored independently. A blinded rater performed all TWSTRS assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity); TWSTRS-Disability subscale score ranges from 0 (no disability) to 30 (maximum disability); and TWSTRS-Pain subscale score ranges from 0 (no pain) to 20 (maximum pain). The total of these 3 comprises the TWSTRS total score which is scored from 0 (no symptoms) to 85 (worst symptoms). Higher scores indicate a greater impact of CD on participant. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Kulagowski, MD | Merz North America, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Merz Investigative Site #001234 | Birmingham | Alabama | 35294-0017 | United States | ||
| Merz Investigative Site 001017 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35330880 | Result | Comella C, Hauser RA, Isaacson SH, Truong D, Oguh O, Hui J, Molho ES, Brodsky M, Furr-Stimming E, Comes G, Hast MA, Charles D. Efficacy and safety of two incobotulinumtoxinA injection intervals in cervical dystonia patients with inadequate benefit from standard injection intervals of botulinum toxin: Phase 4, open-label, randomized, noninferiority study. Clin Park Relat Disord. 2022 Mar 14;6:100142. doi: 10.1016/j.prdoa.2022.100142. eCollection 2022. |
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A total of 283 participants were screened and randomized in the study. Of these, 282 participants were treated and 207 participants completed the study.
The study was conducted at 43 sites in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Xeomin Short Flex | Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days. |
| FG001 | Xeomin Long Flex |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Baseline in TWSTRS Total Score Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participant. The scale comprised of 3 subscales: Severity, Disability, and Pain, each of which was scored independently. An unblinded rater performed all TWSTRS assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity); TWSTRS-Disability subscale score ranges from 0 (no disability) to 30 (maximum disability); and TWSTRS-Pain subscale score ranges from 0 (no pain) to 20 (maximum pain). 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 impact of CD on participant. | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Baseline in TWSTRS Severity Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of cervical dystonia (CD) on participants. An unblinded rater performed all TWSTRS-Severity subscale assessments for a given participant. TWSTRS-Severity score ranges from 0 (absence of severity) to 35 (maximum severity). | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Baseline in TWSTRS Disability Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participant. An unblinded rater performed all TWSTRS-Disability subscale assessments for a given participant. TWSTRS-Disability score ranges from 0 (no disability) to 30 (maximum disability). | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Baseline in TWSTRS Pain Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participants. An unblinded rater performed all TWSTRS-Pain subscale assessments for a given participant. TWSTRS-Pain score ranges from 0 (no pain) to 20 (maximum pain). | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Control Visit Week 4 After First Injection in Investigator-Rated Global Response at Week 4 After the 8th Injection | The Investigator-Rated Global Response assessment for each Xeomin treatment was scored using a 9-point scale with a score ranging from -4 to +4 as follows: -4 (very marked worsening); -3 (marked worsening); -2 (moderately worsening); 1 (minimally worsening); 0 (no change); +1 (minimally improved); +2 (moderately improved); +3 (significantly improved); +4 (complete abolishment of signs and symptoms). | Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Control Visit Week 4 After First Injection in Subject-Rated Global Response at Week 4 After the 8th Injection | The Subject-Rated Global Response assessment for each Xeomin treatment was scored using a 9-point scale with a score ranging from -4 to +4 as follows: -4 (very marked worsening); -3 (marked worsening); -2 (moderately worsening); 1 (minimally worsening); 0 (no change); +1 (minimally improved); +2 (moderately improved); +3 (significantly improved); +4 (complete abolishment of signs and symptoms). | Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Control Visit Week 4 After First Injection in Subject Satisfaction Score at Week 4 After the 8th Injection | The Subject Satisfaction assessment for each Xeomin treatment was scored using a 10-point scale to answer the question, "How satisfied are you at the moment with your current therapy? Score ranges from: 1 (completely satisfied) to 10 (completely unsatisfied). | Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Baseline in Clinical Global Impression-Severity | Assessment of Clinical Global Impression Severity was scored using a 7-point scale for severity of illness, in response to the question, "Considering your total clinical experience with this particular population, how ill is the participant at this time?" With scores as: 0 (not assessed); 1 (normal, not ill at all); 2 (borderline ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill); 6 (severely ill); and 7 (among the most extremely ill participants). | Baseline and 8th injection (Week 44 for Short Flex and Week 84 for Long Flex) |
| Change From Baseline in Cervical Dystonia Impact Profile-58 (CDIP-58) Total Score at Week 4 After the 8th Injection | The CDIP-58 assesses the health impact of CD. The CDIP-58 is composed of eight domains: head and neck (6 items; 6 to 30 points), pain and discomfort (5 items; 5 to 25 points), upper limb activities (9 items; 9 to 45 points), walking (9 items; 9 to 45 points), sleep (4 items; 4 to 20 points), annoyance (8 items; 8 to 40 points), mood (7 items; 7 to 35 points), and psychosocial functioning (10 items; 10 to 50 points). Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Transformation to a 0 to 100 scale for the sum scores of the sub- and total scales were done using the following formula (all single items have scores from 1 to 5): S0 to 100 =25 * ([ SO / NI] - 1), S0 to 100 = transformed sum score. SO = sum score of the original sub- / total scale. NI = number of items in the sub- / total scale. Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas positive changes indicate worsening. | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection | The CDIP-58 assesses the health impact of CD. The CDIP-58 is composed of eight domains: head and neck (6 items; 6 to 30 points), pain and discomfort (5 items; 5 to 25 points), upper limb activities (9 items; 9 to 45 points), walking (9 items; 9 to 45 points), sleep (4 items; 4 to 20 points), annoyance (8 items; 8 to 40 points), mood (7 items; 7 to 35 points), and psychosocial functioning (10 items; 10 to 50 points). Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Negative changes from the baseline scores indicate improvement in the impact of CD on health whereas positive changes indicate worsening. | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
| Time to Offset of Xeomin Effects by Injection Cycle | The Offset Questionnaire was a single question: "On most days last week, have you noticed that your CD symptoms are better, worse or the same as the week prior? Time to offset of effect was calculated from date of first onset of effect to date of offset of effects. | Week 4 up to Week 112 |
| Fountain Valley |
| California |
| 92708 |
| United States |
| Merz Investigative Site #001225 | Loma Linda | California | 92354-3450 | United States |
| Merz Investigative Site #001219 | Los Angeles | California | 90033 | United States |
| Merz Investigative Site # 001276 | Manchester | Connecticut | 06040 | United States |
| Merz Investigative Site #001231 | Washington D.C. | District of Columbia | 20007 | United States |
| Merz Investigative Site #001076 | Boca Raton | Florida | 33486 | United States |
| Merz Investigative Site #001019 | Gainesville | Florida | 32610 | United States |
| Merz Investigative Site #001046 | Jacksonville | Florida | 32209 | United States |
| Merz Investigative Site #001075 | Melbourne | Florida | 32901 | United States |
| Merz Investigative Site #001217 | Port Charlotte | Florida | 33980 | United States |
| Merz Investigative Site #1253 | Tampa | Florida | 33613 | United States |
| Merz Investigative Site #001055 | Atlanta | Georgia | 30329 | United States |
| Merz Investigative Site# 01255 | Chicago | Illinois | 60611 | United States |
| Merz Investigative Site #001215 | Chicago | Illinois | 60612 | United States |
| Merz Investigative Site # 01069 | Des Moines | Iowa | 50309 | United States |
| Merz Investigative Site #001110 | Overland Park | Kansas | 66211 | United States |
| Merz Investigative Site # 001071 | Elkridge | Maryland | 21075 | United States |
| Merz Investigative Site # 001018 | Detroit | Michigan | 48201-2153 | United States |
| Merz Investigative Site #001030 | Farmington Hills | Michigan | 48334 | United States |
| Merz Investigative Site # 0001275 | Eagan | Minnesota | 55121 | United States |
| Merz Investigative Site #1250 | St Louis | Missouri | 63104 | United States |
| Merz Investigative Site #001210 | St Louis | Missouri | 63110 | United States |
| Merz Investigative Site #001221 | Albany | New York | 12208 | United States |
| Merz Investigative Site #001233 | New York | New York | 10003 | United States |
| Merz Investigative Site #1256 | New York | New York | 10029-6574 | United States |
| Merz Investigative Site# 01252 | Charlotte | North Carolina | 28207 | United States |
| Merz Investigative Site #001005 | Durham | North Carolina | 27705 | United States |
| Merz Investigative Site# 01260 | Raleigh | North Carolina | 27607 | United States |
| Merz Investigative Site #001009 | Winston-Salem | North Carolina | 27157 | United States |
| Merz Investigative Site #1265 | Cincinnati | Ohio | 45219 | United States |
| Merz Investigative Site #001220 | Tulsa | Oklahoma | 74136 | United States |
| Merz Investigative Site #1033 | Portland | Oregon | 97239 | United States |
| Merz Investigative Site #1251 | Portland | Oregon | 97239 | United States |
| Merz Investigative Site # 0001271 | Hershey | Pennsylvania | 17033 | United States |
| Merz Investigative Site #1249 | Philadelphia | Pennsylvania | 19107 | United States |
| Merz Investigative Site #001206 | Nashville | Tennessee | 37232-2551 | United States |
| Merz Investigative Site #1074 | Dallas | Texas | 75214 | United States |
| Merz Investigative Site #001223 | Dallas | Texas | 75231 | United States |
| Merz Investigative Site # 001216 | Houston | Texas | 77030 | United States |
| Merz Investigative Site# 001266 | Houston | Texas | 77030 | United States |
| Merz Investigative Site #001224 | Kirkland | Washington | 98034 | United States |
| Merz Investigative Site #1270 | Seattle | Washington | 98122 | United States |
Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
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| COMPLETED |
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| NOT COMPLETED |
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The safety evaluation set (SES) included all participants who were randomly assigned and received at least one study treatment, Xeomin Short-Flex or Long-Flex injection.
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| ID | Title | Description |
|---|---|---|
| BG000 | Xeomin Short Flex | Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days. |
| BG001 | Xeomin Long Flex | Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Based on Blinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of cervical dystonia (CD) on participants. A blinded rater performed all TWSTRS-Severity subscale assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity). | The per protocol set (PPS) included all participants in the full analysis set (FAS) who was responsive to unilateral brow injection (UBI) at the 4-week control visit after initial injection or had no major protocol deviations. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in TWSTRS Total Score Based on Blinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participants. The scale comprised of 3 subscales: Severity, Disability, and Pain, each of which was scored independently. A blinded rater performed all TWSTRS assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity); TWSTRS-Disability subscale score ranges from 0 (no disability) to 30 (maximum disability); and TWSTRS-Pain subscale score ranges from 0 (no pain) to 20 (maximum pain). The total of these 3 comprises the TWSTRS total score which is scored from 0 (no symptoms) to 85 (worst symptoms). Higher scores indicate a greater impact of CD on participant. | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in TWSTRS Total Score Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participant. The scale comprised of 3 subscales: Severity, Disability, and Pain, each of which was scored independently. An unblinded rater performed all TWSTRS assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity); TWSTRS-Disability subscale score ranges from 0 (no disability) to 30 (maximum disability); and TWSTRS-Pain subscale score ranges from 0 (no pain) to 20 (maximum pain). 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 impact of CD on participant. | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in TWSTRS Severity Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of cervical dystonia (CD) on participants. An unblinded rater performed all TWSTRS-Severity subscale assessments for a given participant. TWSTRS-Severity score ranges from 0 (absence of severity) to 35 (maximum severity). | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in TWSTRS Disability Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participant. An unblinded rater performed all TWSTRS-Disability subscale assessments for a given participant. TWSTRS-Disability score ranges from 0 (no disability) to 30 (maximum disability). | The FAS was the subset of the SES participants who were randomly assigned and received at least one injection and for whom a TWSTR-Severity value by a blinded rater (primary variable) was available at the baseline injection visit and the control visit 4 weeks after the 8th injection. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in TWSTRS Pain Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection | The validated assessment scale TWSTRS was used to measure the impact of CD on participants. An unblinded rater performed all TWSTRS-Pain subscale assessments for a given participant. TWSTRS-Pain score ranges from 0 (no pain) to 20 (maximum pain). | The FAS was the subset of the SES participants who were randomly assigned and received at least one injection and for whom a TWSTR-Severity value by a blinded rater (primary variable) was available at the baseline injection visit and the control visit 4 weeks after the 8th injection. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Control Visit Week 4 After First Injection in Investigator-Rated Global Response at Week 4 After the 8th Injection | The Investigator-Rated Global Response assessment for each Xeomin treatment was scored using a 9-point scale with a score ranging from -4 to +4 as follows: -4 (very marked worsening); -3 (marked worsening); -2 (moderately worsening); 1 (minimally worsening); 0 (no change); +1 (minimally improved); +2 (moderately improved); +3 (significantly improved); +4 (complete abolishment of signs and symptoms). | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | score on a scale | Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Control Visit Week 4 After First Injection in Subject-Rated Global Response at Week 4 After the 8th Injection | The Subject-Rated Global Response assessment for each Xeomin treatment was scored using a 9-point scale with a score ranging from -4 to +4 as follows: -4 (very marked worsening); -3 (marked worsening); -2 (moderately worsening); 1 (minimally worsening); 0 (no change); +1 (minimally improved); +2 (moderately improved); +3 (significantly improved); +4 (complete abolishment of signs and symptoms). | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Least Squares Mean | Standard Error | score on a scale | Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Control Visit Week 4 After First Injection in Subject Satisfaction Score at Week 4 After the 8th Injection | The Subject Satisfaction assessment for each Xeomin treatment was scored using a 10-point scale to answer the question, "How satisfied are you at the moment with your current therapy? Score ranges from: 1 (completely satisfied) to 10 (completely unsatisfied). | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | score on a scale | Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in Clinical Global Impression-Severity | Assessment of Clinical Global Impression Severity was scored using a 7-point scale for severity of illness, in response to the question, "Considering your total clinical experience with this particular population, how ill is the participant at this time?" With scores as: 0 (not assessed); 1 (normal, not ill at all); 2 (borderline ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill); 6 (severely ill); and 7 (among the most extremely ill participants). | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 8th injection (Week 44 for Short Flex and Week 84 for Long Flex) |
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| Secondary | Change From Baseline in Cervical Dystonia Impact Profile-58 (CDIP-58) Total Score at Week 4 After the 8th Injection | The CDIP-58 assesses the health impact of CD. The CDIP-58 is composed of eight domains: head and neck (6 items; 6 to 30 points), pain and discomfort (5 items; 5 to 25 points), upper limb activities (9 items; 9 to 45 points), walking (9 items; 9 to 45 points), sleep (4 items; 4 to 20 points), annoyance (8 items; 8 to 40 points), mood (7 items; 7 to 35 points), and psychosocial functioning (10 items; 10 to 50 points). Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Transformation to a 0 to 100 scale for the sum scores of the sub- and total scales were done using the following formula (all single items have scores from 1 to 5): S0 to 100 =25 * ([ SO / NI] - 1), S0 to 100 = transformed sum score. SO = sum score of the original sub- / total scale. NI = number of items in the sub- / total scale. Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas positive changes indicate worsening. | The FAS was the subset of the SES participants who were randomly assigned and received at least one injection and for whom a TWSTR-Severity value by a blinded rater (primary variable) was available at the baseline injection visit and the control visit 4 weeks after the 8th injection. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection | The CDIP-58 assesses the health impact of CD. The CDIP-58 is composed of eight domains: head and neck (6 items; 6 to 30 points), pain and discomfort (5 items; 5 to 25 points), upper limb activities (9 items; 9 to 45 points), walking (9 items; 9 to 45 points), sleep (4 items; 4 to 20 points), annoyance (8 items; 8 to 40 points), mood (7 items; 7 to 35 points), and psychosocial functioning (10 items; 10 to 50 points). Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Negative changes from the baseline scores indicate improvement in the impact of CD on health whereas positive changes indicate worsening. | The FAS was the subset of the SES who were randomly assigned and received at least one injection and for whom a TWSTR-Severity value by a blinded rater (primary variable) was available at the baseline injection visit and the control visit 4 weeks after the 8th injection. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex) |
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| Secondary | Time to Offset of Xeomin Effects by Injection Cycle | The Offset Questionnaire was a single question: "On most days last week, have you noticed that your CD symptoms are better, worse or the same as the week prior? Time to offset of effect was calculated from date of first onset of effect to date of offset of effects. | FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment. | Posted | Mean | Standard Deviation | weeks | Week 4 up to Week 112 |
|
|
Baseline up to Day 875
The investigator asked the participant for adverse events (AEs) systematically at each visit.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Xeomin Short Flex | Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days. | 1 | 142 | 15 | 142 | 77 | 142 |
| EG001 | Xeomin Long Flex | Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days. | 1 | 140 | 11 | 140 | 77 | 140 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Burning sensation | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Cerebral artery stenosis | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Faeces discoloured | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Microcytic anaemia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Early satiety | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Vascular graft thrombosis | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Bronchioloalveolar carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Colon cancer stage III | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Sinus arrest | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Sinus node dysfunction | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Aortic thrombosis | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Intermittent claudication | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Peripheral artery stenosis | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Peripheral ischaemia | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Colon operation | Surgical and medical procedures | MedDRA 19.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysphagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
|
Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Public Disclosure Manager | Merz Pharmaceuticals GmbH | +49 69 1503 1 | clinicaltrials@merz.com |
| ID | Term |
|---|---|
| D014103 | Torticollis |
| ID | Term |
|---|---|
| D004421 | Dystonia |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C545476 | incobotulinumtoxinA |
| D001905 | Botulinum Toxins |
| D019274 | Botulinum Toxins, Type A |
| ID | Term |
|---|---|
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Black or African American |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Native Hawaiian or other Pacific Islander |
|
| Other |
|
| Xeomin Long Flex |
Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days. |
|
|
| Xeomin Long Flex |
Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days. |
|
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| Units | Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| OG001 | Xeomin Long Flex | Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days. |
|
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| Participants |
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