Open-Label Non-Inferiority Study Evaluating the Efficacy and Safety of Xeomin® in Subjects With Cervical Dystonia Flex

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).

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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.

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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.

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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).

Time frame: Baseline and 8th injection (Week 44 for Short Flex and Week 84 for Long Flex)

Population: 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.

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).

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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).

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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).

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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.

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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.

Time frame: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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).

Time frame: Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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).

Time frame: Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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).

Time frame: Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: 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.

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.

Time frame: Week 4 up to Week 112

Population: 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.