Trial Outcomes & Findings for Efficacy and Safety Dose Titration Study of Botulinum Toxin Type A to Treat Spasticity in the Leg and Arm (NCT NCT01603459)

Results Overview

Treatment-emergent Adverse Events (TEASs) are events observed from the time point of first injection until 16 weeks after last injection. Values reported here refer to the number of subjects affected.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

155 participants

Primary outcome timeframe

From baseline to week 36-48

Results posted on

2017-04-26

Participant Flow

The clinical study was conducted at 30 sites located in Canada, France, Germany, Italy, Norway, Portugal, Spain, and the United States of America.

Participant milestones

Participant milestones
Measure	IncobotulinumtoxinA (Xeomin) (up to 800 Units) IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA: Subjects to receive up to 3 injection cycle, with the dose titrated from 400 units to up to 800 units. For each injection session: solution prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400-800 units, volume 2.0 mL per 100 units; Mode of administration: Intramuscular injection.
Overall Study STARTED	155
Overall Study COMPLETED	137
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Reasons for withdrawal
Measure	IncobotulinumtoxinA (Xeomin) (up to 800 Units) IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA: Subjects to receive up to 3 injection cycle, with the dose titrated from 400 units to up to 800 units. For each injection session: solution prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400-800 units, volume 2.0 mL per 100 units; Mode of administration: Intramuscular injection.
Overall Study Adverse Event	5
Overall Study Withdrawal by Subject	5
Overall Study Lost to Follow-up	3
Overall Study Predefined discontinuation criteria	3
Overall Study Non-compliance	1
Overall Study Administrative reason	1

Baseline Characteristics

Efficacy and Safety Dose Titration Study of Botulinum Toxin Type A to Treat Spasticity in the Leg and Arm

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IncobotulinumtoxinA (Xeomin) (up to 800 Units) n=155 Participants IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA: Subjects to receive up to 3 injection cycle, with the dose titrated from 400 units to up to 800 units. For each injection session: solution prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400-800 units, volume 2.0 mL per 100 units; Mode of administration: Intramuscular injection.
Age, Continuous	53.7 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants
Sex: Female, Male Male	104 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to week 36-48

Population: Safety evaluation set (SES) - only subjects treated in the respective injection cycle were analyzed.

Treatment-emergent Adverse Events (TEASs) are events observed from the time point of first injection until 16 weeks after last injection. Values reported here refer to the number of subjects affected.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication Any TEAE	56 subjects	57 subjects	36 subjects	—	—	—
Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication Any related TEAE	7 subjects	8 subjects	4 subjects	—	—	—
Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication Any TEAE of special interest	6 subjects	8 subjects	7 subjects	—	—	—
Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication Any related TEAE of special interest	2 subjects	4 subjects	3 subjects	—	—	—
Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication Any serious TEAE	4 subjects	11 subjects	3 subjects	—	—	—
Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication Any related serious TEAE	0 subjects	0 subjects	0 subjects	—	—	—

PRIMARY outcome

Timeframe: Up to Week 48

Population: Safety evaluation set (SES) - only subjects treated in the respective injection cycle were analyzed.

A 4-point Likert scale was used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Investigator's Global Assessment of Tolerability in Subjects Very good	121 subjects	111 subjects	117 subjects	—	—	—
Investigator's Global Assessment of Tolerability in Subjects Good	29 subjects	26 subjects	20 subjects	—	—	—
Investigator's Global Assessment of Tolerability in Subjects Moderate	3 subjects	3 subjects	1 subjects	—	—	—
Investigator's Global Assessment of Tolerability in Subjects Poor	0 subjects	2 subjects	0 subjects	—	—	—
Investigator's Global Assessment of Tolerability in Subjects Missing	2 subjects	10 subjects	2 subjects	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: The full analysis set (FAS) is the subset of all subjects who were exposed to study medication at least once. Only subjects treated in the target joint in the respective cycle were analyzed.

The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=151 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=148 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=138 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Ashworth Scale (AS) Scores of the Target Joint Selected at Study Baseline Visit	3.0 units on a scale Standard Deviation 0.7	2.1 units on a scale Standard Deviation 0.9	2.7 units on a scale Standard Deviation 0.7	2.0 units on a scale Standard Deviation 0.9	2.6 units on a scale Standard Deviation 0.8	1.7 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS), observed cases, only subjects treated in the target joint in the respective cycle were analyzed.

The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=148 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Injection Cycle Baseline Visits to Respective Control Visits	-0.8 units on a scale Standard Deviation 0.9	-0.8 units on a scale Standard Deviation 0.8	-0.9 units on a scale Standard Deviation 0.9	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: Full analysis set (FAS), observed cases, only subjects treated in the target joint in the respective cycle were analyzed.

The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=148 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Study Baseline Visit to Control Visits of Injection Cycles	-0.8 units on a scale Standard Deviation 0.9	-1.0 units on a scale Standard Deviation 0.9	-1.3 units on a scale Standard Deviation 1.0	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS), observed cases, only subjects treated in the target joint in the respective cycle were analyzed.

The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=151 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=137 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit	-0.2 units on a scale Standard Deviation 0.7	-0.3 units on a scale Standard Deviation 0.8	-0.7 units on a scale Standard Deviation 0.9	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective pattern in the respective injection cycle.

Clinical pattern treated at corresponding cycle of the same body side as the selected target joint. The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Extended hallux	1.7 units on a scale Standard Deviation 1.1	0.9 units on a scale Standard Deviation 0.7	1.8 units on a scale Standard Deviation 0.8	0.9 units on a scale Standard Deviation 0.7	1.9 units on a scale Standard Deviation 0.9	1.1 units on a scale Standard Deviation 0.8
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Adducted thigh	1.8 units on a scale Standard Deviation 0.5	1.5 units on a scale Standard Deviation 0.6	2.0 units on a scale Standard Deviation 1.2	1.9 units on a scale Standard Deviation 0.9	2.3 units on a scale Standard Deviation 0.8	2.0 units on a scale Standard Deviation 0.6
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Extended knee	2.6 units on a scale Standard Deviation 0.7	2.3 units on a scale Standard Deviation 0.9	2.1 units on a scale Standard Deviation 0.8	1.8 units on a scale Standard Deviation 0.9	2.2 units on a scale Standard Deviation 0.8	1.5 units on a scale Standard Deviation 0.8
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Internally rotated hip	3.0 units on a scale Standard Deviation NA NA = data not available	2.0 units on a scale Standard Deviation NA NA = data not available	2.0 units on a scale Standard Deviation 1.4	2.0 units on a scale Standard Deviation 1.4	2.7 units on a scale Standard Deviation 0.6	1.7 units on a scale Standard Deviation 0.6
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Pes equinovarus	2.8 units on a scale Standard Deviation 0.7	2.1 units on a scale Standard Deviation 0.9	2.6 units on a scale Standard Deviation 0.8	1.9 units on a scale Standard Deviation 1.0	2.5 units on a scale Standard Deviation 0.8	1.6 units on a scale Standard Deviation 0.9
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Flexed knee	2.4 units on a scale Standard Deviation 0.7	2.0 units on a scale Standard Deviation 0.7	2.4 units on a scale Standard Deviation 0.6	1.8 units on a scale Standard Deviation 0.7	2.5 units on a scale Standard Deviation 0.7	1.8 units on a scale Standard Deviation 1.0
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Internally rotated/extended/adducted shoulder	2.7 units on a scale Standard Deviation 0.6	2.2 units on a scale Standard Deviation 0.8	2.5 units on a scale Standard Deviation 0.8	2.0 units on a scale Standard Deviation 0.9	2.5 units on a scale Standard Deviation 0.8	1.9 units on a scale Standard Deviation 0.9
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Extended elbow	2.7 units on a scale Standard Deviation 0.5	1.8 units on a scale Standard Deviation 0.9	2.5 units on a scale Standard Deviation 0.6	2.1 units on a scale Standard Deviation 0.7	2.6 units on a scale Standard Deviation 0.6	1.7 units on a scale Standard Deviation 0.8
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Clenched fist	2.9 units on a scale Standard Deviation 0.7	2.0 units on a scale Standard Deviation 0.9	2.7 units on a scale Standard Deviation 0.8	1.8 units on a scale Standard Deviation 0.9	2.5 units on a scale Standard Deviation 0.7	1.5 units on a scale Standard Deviation 0.9
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Pes equinovalgus	2.8 units on a scale Standard Deviation 0.4	2.4 units on a scale Standard Deviation 1.3	2.6 units on a scale Standard Deviation 0.8	1.9 units on a scale Standard Deviation 0.7	2.3 units on a scale Standard Deviation 0.9	2.0 units on a scale Standard Deviation 1.1
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Flexed elbow	2.6 units on a scale Standard Deviation 0.7	1.9 units on a scale Standard Deviation 0.9	2.4 units on a scale Standard Deviation 0.7	1.7 units on a scale Standard Deviation 0.9	2.4 units on a scale Standard Deviation 0.8	1.4 units on a scale Standard Deviation 0.9
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Pronated forearm	2.7 units on a scale Standard Deviation 0.7	1.6 units on a scale Standard Deviation 0.9	2.4 units on a scale Standard Deviation 0.8	1.7 units on a scale Standard Deviation 1.0	2.5 units on a scale Standard Deviation 0.7	1.4 units on a scale Standard Deviation 0.8
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Flexed wrist	2.7 units on a scale Standard Deviation 0.8	1.8 units on a scale Standard Deviation 1.0	2.4 units on a scale Standard Deviation 0.9	1.5 units on a scale Standard Deviation 1.0	2.4 units on a scale Standard Deviation 0.8	1.4 units on a scale Standard Deviation 1.0
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Thumb in palm	2.4 units on a scale Standard Deviation 0.9	1.5 units on a scale Standard Deviation 1.1	2.3 units on a scale Standard Deviation 0.9	1.4 units on a scale Standard Deviation 1.0	2.2 units on a scale Standard Deviation 0.8	1.3 units on a scale Standard Deviation 1.0
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Flexed hip	—	—	—	—	1.8 units on a scale Standard Deviation 0.8	1.4 units on a scale Standard Deviation 0.9
Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity Flexed toes	1.8 units on a scale Standard Deviation 0.9	1.3 units on a scale Standard Deviation 0.8	1.6 units on a scale Standard Deviation 0.9	1.1 units on a scale Standard Deviation 0.8	1.9 units on a scale Standard Deviation 0.9	1.1 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective pattern of respective injection cycle were analyzed.

Clinical pattern treated at corresponding cycle of the same body side as the selected target joint. The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Internally rotated/extended/adducted shoulder	-0.5 units on a scale Standard Deviation 0.8	-0.6 units on a scale Standard Deviation 0.8	-0.5 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Flexed elbow	-0.7 units on a scale Standard Deviation 0.8	-0.7 units on a scale Standard Deviation 0.8	-0.9 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Extended elbow	-0.9 units on a scale Standard Deviation 0.8	-0.5 units on a scale Standard Deviation 0.9	-0.8 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Pronated forearm	-1.1 units on a scale Standard Deviation 0.6	-0.7 units on a scale Standard Deviation 0.7	-1.0 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Flexed wrist	-0.9 units on a scale Standard Deviation 0.8	-0.9 units on a scale Standard Deviation 0.8	-1.0 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Clenched fist	-0.9 units on a scale Standard Deviation 0.8	-0.9 units on a scale Standard Deviation 0.8	-1.1 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Thumb in palm	-0.9 units on a scale Standard Deviation 1.0	-0.9 units on a scale Standard Deviation 1.1	-0.9 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Flexed hip	—	—	-0.4 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Aducted thigh	-0.3 units on a scale Standard Deviation 0.5	-0.1 units on a scale Standard Deviation 0.7	-0.1 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Internally rotated hip	-1.0 units on a scale Standard Deviation NA NA = data not available	0.0 units on a scale Standard Deviation 0.0	-1.0 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Flexed knee	-0.4 units on a scale Standard Deviation 0.5	-0.6 units on a scale Standard Deviation 0.6	-0.8 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Extended knee	-0.4 units on a scale Standard Deviation 0.5	-0.4 units on a scale Standard Deviation 0.7	-0.7 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Pes equinovarus	-0.7 units on a scale Standard Deviation 0.8	-0.7 units on a scale Standard Deviation 0.8	-0.8 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Pes equinovalgus	-0.4 units on a scale Standard Deviation 1.1	-0.7 units on a scale Standard Deviation 0.7	-0.3 units on a scale Standard Deviation 0.7	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Extended hallux	-0.8 units on a scale Standard Deviation 0.9	-0.9 units on a scale Standard Deviation 1.0	-0.8 units on a scale Standard Deviation 1.3	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits Flexed toes	-0.5 units on a scale Standard Deviation 0.8	-0.5 units on a scale Standard Deviation 0.8	-0.8 units on a scale Standard Deviation 0.7	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: Full analysis set (FAS) - only subjects treated in the respective pattern of respective injection cycle were analyzed.

Clinical pattern treated at corresponding cycle of the same body side as the selected target joint. The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Internally rotated/extended/adducted shoulder	-0.5 units on a scale Standard Deviation 0.8	-0.6 units on a scale Standard Deviation 0.9	-0.5 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Flexed elbow	-0.7 units on a scale Standard Deviation 0.8	-0.9 units on a scale Standard Deviation 0.8	-1.2 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Extended elbow	-0.9 units on a scale Standard Deviation 0.8	-0.7 units on a scale Standard Deviation 0.8	-0.9 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Pronated forearm	-1.1 units on a scale Standard Deviation 0.6	-1.0 units on a scale Standard Deviation 0.9	-1.1 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Flexed wrist	-0.9 units on a scale Standard Deviation 0.8	-1.1 units on a scale Standard Deviation 0.9	-1.2 units on a scale Standard Deviation 1.1	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Clenched fist	-0.9 units on a scale Standard Deviation 0.8	-1.1 units on a scale Standard Deviation 0.9	-1.4 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Thumb in palm	-0.9 units on a scale Standard Deviation 1.0	-1.0 units on a scale Standard Deviation 1.2	-1.1 units on a scale Standard Deviation 1.3	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Flexed hip	—	—	-0.6 units on a scale Standard Deviation 1.5	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Adducted thigh	-0.3 units on a scale Standard Deviation 0.5	-0.1 units on a scale Standard Deviation 0.7	-0.6 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Internally rotated hip	-1.0 units on a scale Standard Deviation NA NA = data not available	-0.5 units on a scale Standard Deviation 0.7	-0.7 units on a scale Standard Deviation 1.5	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Flexed knee	-0.4 units on a scale Standard Deviation 0.5	-0.4 units on a scale Standard Deviation 0.8	-0.4 units on a scale Standard Deviation 1.2	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Extended knee	-0.4 units on a scale Standard Deviation 0.5	-0.4 units on a scale Standard Deviation 0.6	-0.6 units on a scale Standard Deviation 0.6	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Pes equinovarus	-0.7 units on a scale Standard Deviation 0.8	-0.8 units on a scale Standard Deviation 0.9	-1.1 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Pes equinovalgus	-0.4 units on a scale Standard Deviation 1.1	-0.9 units on a scale Standard Deviation 0.6	-0.4 units on a scale Standard Deviation 0.7	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Extended hallux	-0.8 units on a scale Standard Deviation 0.9	-0.9 units on a scale Standard Deviation 1.1	-0.2 units on a scale Standard Deviation 1.3	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles Flexed toes	-0.5 units on a scale Standard Deviation 0.8	-0.5 units on a scale Standard Deviation 0.7	-0.6 units on a scale Standard Deviation 0.8	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective pattern of respective injection cycle were analyzed.

Clinical pattern treated at corresponding cycle of the same body side as the selected target joint. The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Internally rotated/extended/adducted shoulder	-0.0 units on a scale Standard Deviation 0.7	0.0 units on a scale Standard Deviation 0.9	-0.3 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Flexed elbow	-0.2 units on a scale Standard Deviation 0.7	-0.3 units on a scale Standard Deviation 0.8	-0.8 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Extended elbow	-0.2 units on a scale Standard Deviation 0.7	-0.1 units on a scale Standard Deviation 0.9	-0.2 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pronated forearm	-0.3 units on a scale Standard Deviation 0.9	-0.1 units on a scale Standard Deviation 0.7	-0.7 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Flexed wrist	-0.2 units on a scale Standard Deviation 0.7	-0.2 units on a scale Standard Deviation 1.0	-0.7 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Clenched fist	-0.2 units on a scale Standard Deviation 0.7	-0.3 units on a scale Standard Deviation 0.7	-0.8 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Thumb in palm	-0.2 units on a scale Standard Deviation 0.9	-0.3 units on a scale Standard Deviation 0.9	-0.8 units on a scale Standard Deviation 1.1	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Flexed hip	—	-0.2 units on a scale Standard Deviation 1.0	-0.3 units on a scale Standard Deviation 1.4	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Adducted thigh	0 units on a scale Standard Deviation 0	-0.3 units on a scale Standard Deviation 0.5	-0.4 units on a scale Standard Deviation 0.8	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Internally rotated hip	-0.5 units on a scale Standard Deviation 0.7	0.3 units on a scale Standard Deviation 0.6	0.0 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Flexed knee	0.1 units on a scale Standard Deviation 0.9	0.4 units on a scale Standard Deviation 1.2	-0.4 units on a scale Standard Deviation 1.1	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Extended knee	-0.1 units on a scale Standard Deviation 0.4	0.1 units on a scale Standard Deviation 0.5	-0.4 units on a scale Standard Deviation 0.7	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pes equinovarus	-0.1 units on a scale Standard Deviation 0.6	-0.2 units on a scale Standard Deviation 0.7	-0.7 units on a scale Standard Deviation 0.9	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pes equinovalgus	-0.2 units on a scale Standard Deviation 0.4	-0.1 units on a scale Standard Deviation 0.6	-0.4 units on a scale Standard Deviation 0.5	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Extended hallux	0.0 units on a scale Standard Deviation 1.2	0.6 units on a scale Standard Deviation 1.3	-0.2 units on a scale Standard Deviation 1.0	—	—	—
Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Flexed toes	-0.0 units on a scale Standard Deviation 0.7	0.2 units on a scale Standard Deviation 0.7	-0.4 units on a scale Standard Deviation 0.7	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The REPAS is a summary 26-item test used to assess resistance to passive movement in all four limbs of the body. It provides a global evaluation of spasticity status, as well as per hemibody and per limb. 16 items describe the condition of both upper limbs, 10 that of both lower limbs. Each item is rated by using the Ashworth Scale. The sum of the values represent the REPAS score which may range from zero (no resistance for any item) to 104 (limbs rigid for all items). Here, the hemi-REPAS was evaluated, i.e. the maximum value for the treated body side was 52.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=138 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Resistance to Passive Movement Scale (REPAS) Scores of Treated Side	24.8 units on a scale Standard Deviation 6.7	20.2 units on a scale Standard Deviation 7.1	24.0 units on a scale Standard Deviation 7.0	18.1 units on a scale Standard Deviation 7.6	22.9 units on a scale Standard Deviation 7.2	15.7 units on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The REPAS is a summary 26-item test used to assess resistance to passive movement in all four limbs of the body. It provides a global evaluation of spasticity status, as well as per hemibody and per limb. 16 items describe the condition of both upper limbs, 10 that of both lower limbs. Each item is rated by using the Ashworth Scale. The sum of the values represent the REPAS score which may range from zero (no resistance for any item) to 104 (limbs rigid for all items). Here, the hemi-REPAS was evaluated, i.e. the maximum value for the treated body side was 52.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Resistance to Passive Movement Scale (REPAS) Score of Treated Side From Injection Cycle Baseline Visits to Respective Control Visits	-4.6 units on a scale Standard Deviation 3.9	-5.9 units on a scale Standard Deviation 4.2	-7.1 units on a scale Standard Deviation 4.8	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: The full analysis set is the subset of all subjects who were exposed to study medication at least once.

The REPAS is a summary 26-item test used to assess resistance to passive movement in all four limbs of the body. It provides a global evaluation of spasticity status, as well as per hemibody and per limb. 16 items describe the condition of both upper limbs, 10 that of both lower limbs. Each item is rated by using the Ashworth Scale. The sum of the values represent the REPAS score which may range from zero (no resistance for any item) to 104 (limbs rigid for all items). Here, the hemi-REPAS was evaluated, i.e. the maximum value for the treated body side was 52.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Resistance to Passive Movement Scale (REPAS) Score of Treated Side From Study Baseline Visit to Control Visits of Injection Cycles	-4.6 units on a scale Standard Deviation 3.9	-6.7 units on a scale Standard Deviation 4.6	-9.0 units on a scale Standard Deviation 5.5	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: The full analysis set is the subset of all subjects who were exposed to study medication at least once.

The REPAS is a summary 26-item test used to assess resistance to passive movement in all four limbs of the body. It provides a global evaluation of spasticity status, as well as per hemibody and per limb. 16 items describe the condition of both upper limbs, 10 that of both lower limbs. Each item is rated by using the Ashworth Scale. The sum of the values represent the REPAS score which may range from zero (no resistance for any item) to 104 (limbs rigid for all items). Here, the hemi-REPAS was evaluated, i.e. the maximum value for the treated body side was 52.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=137 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Resistance to Passive Movement Scale (REPAS) Score of Treated Side From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit	-0.8 units on a scale Standard Deviation 4.2	-1.9 units on a scale Standard Deviation 4.7	-5.5 units on a scale Standard Deviation 5.3	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The FAC examines the independence and ambulation of subjects whereby supervision/physical assistance from 1 person is allowed. Subjects are classified to following categories: Level 0: no functional ambulation; Level 1: Ambulator-dependent for physical assistance (Level II); Level 2: Ambulator-dependent for physical assistance (Level I); Level 3: Ambulator-dependent for supervision; Level 4: Ambulator-independent, level surface only; Level 5: Ambulator-independent.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=138 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Functional Ambulation Classification (FAC) Scale Scores	3.5 units on a scale Standard Deviation 1.4	3.7 units on a scale Standard Deviation 1.3	3.7 units on a scale Standard Deviation 1.3	3.8 units on a scale Standard Deviation 1.3	3.8 units on a scale Standard Deviation 1.3	3.9 units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The FAC examines the independence and ambulation of subjects whereby supervision/physical assistance from 1 person is allowed. Subjects are classified to following categories: Level 0: no functional ambulation; Level 1: Ambulator-dependent for physical assistance (Level II); Level 2: Ambulator-dependent for physical assistance (Level I); Level 3: Ambulator-dependent for supervision; Level 4: Ambulator-independent, level surface only; Level 5: Ambulator-independent.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Functional Ambulation Classification (FAC) Score From Injection Cycle Baseline Visits to Respective Control Visits	0.1 units on a scale Standard Deviation 0.5	0.1 units on a scale Standard Deviation 0.4	0.1 units on a scale Standard Deviation 0.4	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The FAC examines the independence and ambulation of subjects whereby supervision/physical assistance from 1 person is allowed. Subjects are classified to following categories: Level 0: no functional ambulation; Level 1: Ambulator-dependent for physical assistance (Level II); Level 2: Ambulator-dependent for physical assistance (Level I); Level 3: Ambulator-dependent for supervision; Level 4: Ambulator-independent, level surface only; Level 5: Ambulator-independent.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Functional Ambulation Classification (FAC) Score From Study Baseline Visit to Control Visits of Injection Cycles	0.1 units on a scale Standard Deviation 0.5	0.3 units on a scale Standard Deviation 0.6	0.4 units on a scale Standard Deviation 0.7	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The FAC examines the independence and ambulation of subjects whereby supervision/physical assistance from 1 person is allowed. Subjects are classified to following categories: Level 0: no functional ambulation; Level 1: Ambulator-dependent for physical assistance (Level II); Level 2: Ambulator-dependent for physical assistance (Level I); Level 3: Ambulator-dependent for supervision; Level 4: Ambulator-independent, level surface only; Level 5: Ambulator-independent.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=137 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Functional Ambulation Classification (FAC) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit	0.2 units on a scale Standard Deviation 0.5	0.3 units on a scale Standard Deviation 0.6	0.4 units on a scale Standard Deviation 0.8	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline Visit to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

Change in goal attainment T-scores from respective injection cycle baseline visit. GAS measures the extent to which subject's individual goals are achieved in course of intervention. Subject and treating team have to identify 2 personal goals for each treated limb at each injection cycle. Investigator rates the GAS score for each injection cycle. Degree of goal attainment is rated on 5-point scale (-2, -1, 0, +1, +2; study baseline set to -1) and in order to account for interindividual differences in the number of goals, ratings are computed with the Kiresuk formula (Kiresuk \& Sherman, Community Mental Health Journal. 1968;4(6):443-53) resulting in T-scores measuring the degree of goal attainment at each visit. A score of 50 indicates that the individual has reached the expected level of achievement for all goals. The size of change from measurement to measurement indicates incremental change towards or away from goal attainment. Positive values indicate a higher goal attainment.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=135 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Goal Attainment Scale (GAS) Scores for Upper and Lower Limb, Respectively Upper limb	7.178 units on a scale Standard Deviation 9.254	10.601 units on a scale Standard Deviation 9.211	13.028 units on a scale Standard Deviation 8.765	—	—	—
Goal Attainment Scale (GAS) Scores for Upper and Lower Limb, Respectively Lower limb	8.222 units on a scale Standard Deviation 9.649	10.914 units on a scale Standard Deviation 9.251	13.579 units on a scale Standard Deviation 10.196	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which are assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). One of the domains will be selected per subject per injection cycle. Arithmetic means are built on each patient's target domain value.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=151 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=128 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Disability Assessment Scale (DAS) Scores in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb	2.6 units on a scale Standard Deviation 0.5	2.0 units on a scale Standard Deviation 0.7	2.4 units on a scale Standard Deviation 0.6	1.7 units on a scale Standard Deviation 0.7	2.2 units on a scale Standard Deviation 0.6	1.5 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which are assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). One of the domains will be selected per subject per injection cycle. Arithmetic means are built on each patient's target domain value change.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=128 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Disability Assessment Scale (DAS) Score in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb From Injection Cycle Baseline Visits to Respective Control Visits	-0.6 units on a scale Standard Deviation 0.7	-0.7 units on a scale Standard Deviation 0.7	-0.7 units on a scale Standard Deviation 0.8	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which are assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). One of the domains will be selected per subject per injection cycle. Arithmetic means are built on each patient's target domain value change.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=143 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=128 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Disability Assessment Scale (DAS) Score in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb From Study Baseline Visit to Control Visits of Injection Cycles	-0.6 units on a scale Standard Deviation 0.7	-0.9 units on a scale Standard Deviation 0.8	-1.0 units on a scale Standard Deviation 0.9	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which are assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). One of the domains will be selected per subject per injection cycle. Arithmetic means are built on each patient's target domain value change.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=151 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=127 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of Disability Assessment Scale (DAS) Score in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit.	-0.2 units on a scale Standard Deviation 0.6	-0.3 units on a scale Standard Deviation 0.7	-0.9 units on a scale Standard Deviation 0.9	—	—	—

SECONDARY outcome

Timeframe: Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

Investigator assessment. The global assessment of efficacy will be assessed by the investigator, the subject, and the caregiver using a 4-point Likert scale with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Global Assessment of Efficacy Scores Frequency 1 (very good)	7 subjects	21 subjects	38 subjects	—	—	—
Global Assessment of Efficacy Scores Frequency 2 (good)	79 subjects	89 subjects	87 subjects	—	—	—
Global Assessment of Efficacy Scores Frequency 3 (moderate)	63 subjects	28 subjects	11 subjects	—	—	—
Global Assessment of Efficacy Scores Frequency 4 (poor)	3 subjects	3 subjects	1 subjects	—	—	—
Global Assessment of Efficacy Scores Missing	3 subjects	11 subjects	3 subjects	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. It evaluates the general impact of a subject's health in 5 dimensions, i.e., on the ability to perform daily physical activities as well as on pain perception and mood. Each dimension is scored on 1 out of 3 categories specific to each dimension, generally meaning: 1= no problem; 2 = moderate problems; 3 = severe problems.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=138 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Pain/discomfort: Frequency 2	85 subjects	75 subjects	88 subjects	70 subjects	79 subjects	58 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Usual activities: Frequency 1	11 subjects	19 subjects	16 subjects	21 subjects	15 subjects	17 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Usual activities: Frequency 2	113 subjects	108 subjects	119 subjects	110 subjects	113 subjects	111 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Usual activities: Frequency 3	31 subjects	28 subjects	17 subjects	17 subjects	12 subjects	10 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Pain/discomfort: Frequency 1	53 subjects	73 subjects	56 subjects	74 subjects	57 subjects	77 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Pain/discomfort: Frequency 3	17 subjects	7 subjects	8 subjects	5 subjects	4 subjects	3 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Anxiety/depression: Frequency 1	72 subjects	82 subjects	83 subjects	93 subjects	78 subjects	85 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Anxiety/depression: Frequency 2	69 subjects	67 subjects	63 subjects	49 subjects	57 subjects	49 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Anxiety/depression: Frequency 3	14 subjects	6 subjects	6 subjects	7 subjects	5 subjects	4 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Mobility: Frequency 1	12 subjects	27 subjects	14 subjects	24 subjects	19 subjects	20 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Mobility: Frequency 2	139 subjects	125 subjects	136 subjects	122 subjects	119 subjects	116 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Mobility: Frequency 3	4 subjects	3 subjects	2 subjects	3 subjects	2 subjects	2 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Self-care: Frequency 1	30 subjects	31 subjects	30 subjects	24 subjects	24 subjects	22 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Self-care: Frequency 2	96 subjects	100 subjects	101 subjects	104 subjects	101 subjects	107 subjects
EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores Self-care: Frequency 3	29 subjects	24 subjects	21 subjects	20 subjects	15 subjects	9 subjects

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values represent better outcome).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit n=140 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 n=138 Participants Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Visual Analogue Scale (VAS) of EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores	59.9 units on a scale Standard Deviation 18.9	66.7 units on a scale Standard Deviation 17.6	67.2 units on a scale Standard Deviation 17.0	69.9 units on a scale Standard Deviation 16.6	67.1 units on a scale Standard Deviation 17.9	68.9 units on a scale Standard Deviation 17.7

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. It evaluates the general impact of a subject's health in 5 dimensions, i.e., on the ability to perform daily physical activities as well as on pain perception and mood. Each dimension is scored on 1 out of 3 categories specific to each dimension, generally meaning: 1= no problem; 2 = moderate problems; 3 = severe problems). In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values indicate better outcome). This table: Frequency -2/-1= improvement by two/one categories; 0 = no change; +1/+2 worsening by one/two categories.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Mobility: Frequency -1	18 Subjects	11 Subjects	6 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Mobility: Frequency 0	135 Subjects	136 Subjects	128 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Mobility: Frequency 1	2 Subjects	2 Subjects	4 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Self-care: Frequency -1	19 Subjects	7 Subjects	11 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Self-care: Frequency 0	123 Subjects	127 Subjects	121 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Self-care: Frequency 1	13 Subjects	14 Subjects	6 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Usual activities: Frequency -2	0 Subjects	0 Subjects	1 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Usual activities: Frequency -1	20 Subjects	18 Subjects	7 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Usual activities: Frequency 0	126 Subjects	116 Subjects	126 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Usual activities: Frequency 1	9 Subjects	14 Subjects	4 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Pain/discomfort: Frequency -2	1 Subjects	2 Subjects	0 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Pain/discomfort: Frequency -1	39 Subjects	30 Subjects	29 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Pain/discomfort: Frequency 0	105 Subjects	105 Subjects	102 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Pain/discomfort: Frequency 1	9 Subjects	12 Subjects	7 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Pain/discomfort: Frequency 2	1 Subjects	0 Subjects	0 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Anxiety/depression:Frequency -2	0 Subjects	0 Subjects	1 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Anxiety/depression:Frequency -1	27 Subjects	18 Subjects	17 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Anxiety/depression: Frequency 0	119 Subjects	121 Subjects	111 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Anxiety/depression: Frequency 1	9 Subjects	9 Subjects	9 Subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits Anxiety/depression: Frequency 2	0 Subjects	1 Subjects	0 Subjects	—	—	—

SECONDARY outcome

Timeframe: From Cycle Baseline to Week 4 of Each Cycle

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values represent better outcome).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change in Visual Analogue Scale of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits	6.7 units on a scale Standard Deviation 14.1	2.4 units on a scale Standard Deviation 12.4	1.7 units on a scale Standard Deviation 12.4	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. It evaluates the general impact of a subject's health in 5 dimensions, i.e., on the ability to perform daily physical activities as well as on pain perception and mood. Each dimension is scored on 1 out of 3 categories specific to each dimension, generally meaning: 1= no problem; 2 = moderate problems; 3 = severe problems). In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values indicate better outcome). This table: Frequency -2/-1= improvement by two/one categories; 0 = no change; +1/+2 worsening by one/two categories.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=155 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=149 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=138 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Mobility: Frequency -1	18 subjects	16 subjects	14 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Mobility: Frequency 0	135 subjects	127 subjects	118 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Mobility: Frequency 1	2 subjects	5 subjects	5 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Self-care: Frequency -1	19 subjects	20 subjects	25 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Self-care: Frequency 0	123 subjects	110 subjects	100 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Self-care: Frequency 1	13 subjects	18 subjects	13 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Usual activities: Frequency -2	0 subjects	1 subjects	1 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Usual activities: Frequency -1	20 subjects	31 subjects	31 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Usual activities: Frequency 0	126 subjects	103 subjects	98 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Usual activities: Frequency 1	9 subjects	13 subjects	8 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Pain/discomfort: Frequency -2	1 subjects	3 subjects	3 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Pain/discomfort: Frequency -1	39 subjects	40 subjects	42 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Pain/discomfort: Frequency 0	105 subjects	93 subjects	85 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Pain/discomfort: Frequency 1	9 subjects	13 subjects	8 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Pain/discomfort: Frequency 2	1 subjects	0 subjects	0 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Anxiety/depression:Frequency -2	0 subjects	7 subjects	6 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Anxiety/depression:Frequency -1	27 subjects	28 subjects	32 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Anxiety/depression:Frequency 0	119 subjects	100 subjects	85 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Anxiety/depression:Frequency 1	9 subjects	14 subjects	15 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles Anxiety/depression:Frequency 2	0 subjects	0 subjects	0 subjects	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 4, 16-20 and 28-36

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. It evaluates the general impact of a subject's health in 5 dimensions, i.e., on the ability to perform daily physical activities as well as on pain perception and mood. Each dimension is scored on 1 out of 3 categories specific to each dimension, generally meaning: 1= no problem; 2 = moderate problems; 3 = severe problems). In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values indicate better outcome). This table: Positive values indicate improvement

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=154 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=148 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=137 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change in Visual Analogue Scale of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles	6.7 units on a scale Standard Deviation 14.1	9.6 units on a scale Standard Deviation 16.3	8.6 units on a scale Standard Deviation 17.0	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. It evaluates the general impact of a subject's health in 5 dimensions, i.e., on the ability to perform daily physical activities as well as on pain perception and mood. Each dimension is scored on 1 out of 3 categories specific to each dimension, generally meaning: 1= no problem; 2 = moderate problems; 3 = severe problems). In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values indicate better outcome). This table: Frequency -2/-1= improvement by two/one categories; 0 = no change; +1/+2 worsening by one/two categories.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=152 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=140 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=137 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pain/discomfort: Frequency 0	100 subjects	89 subjects	81 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Mobility: Frequency -1	10 subjects	13 subjects	16 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Mobility: Frequency 0	137 subjects	121 subjects	116 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Mobility: Frequency 1	5 subjects	5 subjects	4 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Self-care: Frequency -1	20 subjects	24 subjects	30 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Self-care: Frequency 0	120 subjects	99 subjects	97 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Self-care: Frequency 1	12 subjects	17 subjects	10 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Usual activities: Frequency -2	1 subjects	1 subjects	1 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Usual activities: Frequency -1	21 subjects	26 subjects	33 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Usual activities: Frequency 0	125 subjects	106 subjects	96 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Usual activities: Frequency 1	5 subjects	7 subjects	7 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pain/discomfort: Frequency -2	0 subjects	0 subjects	3 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pain/discomfort: Frequency -1	32 subjects	35 subjects	40 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pain/discomfort: Frequency 1	20 subjects	15 subjects	13 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Pain/discomfort: Frequency 2	0 subjects	1 subjects	0 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Anxiety/depression: Frequency -2	2 subjects	4 subjects	5 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Anxiety/depression: Frequency -1	29 subjects	28 subjects	30 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Anxiety/depression: Frequency 0	108 subjects	91 subjects	89 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Anxiety/depression: Frequency 1	12 subjects	17 subjects	13 subjects	—	—	—
Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit Anxiety/depression: Frequency 2	1 subjects	0 subjects	0 subjects	—	—	—

SECONDARY outcome

Timeframe: From Study Baseline to Week 12-16, 24-32 and 36-48

Population: Full analysis set (FAS) - only subjects treated in the respective injection cycle were analyzed.

The EQ-5D is a common quality of life questionnaire to be filled out by the subject. It evaluates the general impact of a subject's health in 5 dimensions, i.e., on the ability to perform daily physical activities as well as on pain perception and mood. Each dimension is scored on 1 out of 3 categories specific to each dimension, generally meaning: 1= no problem; 2 = moderate problems; 3 = severe problems). In addition, the subject was to indicate on a visual analogue scale, ranging from 0 to 100, how good or bad their own health was on the examination day (higher values indicate better outcome). This table: Positive values indicate improvement.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA (Xeomin): Injection Cycle 1 Baseline Visit n=151 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 1 Control Visit 1 n=139 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 400 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 2 Baseline Visit n=136 Participants Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 2 Control Visit 1 Subjects to receive IncobotulinumtoxinA fixed total body dose of 600 units Intramuscular injection.	IncobotulinumtoxinA (Xeomin): Injection Cycle 3 Baseline Visit Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.	IncobotulinumtoxinA(Xeomin): Injection Cycle 3 Control Visit 1 Subjects to receive IncobotulinumtoxinA total body dose of 800 units Intramuscular injection.
Change in Visual Analogue Scale of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit	7.1 units on a scale Standard Deviation 16.3	6.9 units on a scale Standard Deviation 15.8	10.5 units on a scale Standard Deviation 17.5	—	—	—

Adverse Events

IncobotulinumtoxinA (Xeomin) (up to 800 Units)

Serious events: 17 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IncobotulinumtoxinA (Xeomin) (up to 800 Units) n=155 participants at risk IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA: Subjects to receive up to 3 injection cycle, with the dose titrated from 400 units to up to 800 units. For each injection session: solution prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400-800 units, volume 2.0 mL per 100 units; Mode of administration: Intramuscular injection.
Nervous system disorders Convulsion	2.6% 4/155 • From the time point of first injection until 16 weeks after last injection
Nervous system disorders Epilepsy	1.9% 3/155 • From the time point of first injection until 16 weeks after last injection
Nervous system disorders Cerebral infarction	1.3% 2/155 • From the time point of first injection until 16 weeks after last injection
Nervous system disorders Ischemic stroke	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Infections and infestations Pneumonia	1.3% 2/155 • From the time point of first injection until 16 weeks after last injection
Infections and infestations Bronchopneumonia	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Infections and infestations Meningitis bacterial	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Infections and infestations Sepsis	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Infections and infestations Sinusitis	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Cardiac disorders Cardiac failure	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Gastrointestinal disorders Abdominal pain	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Hepatobiliary disorders Cholecystitis	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Musculoskeletal and connective tissue disorders Muscular weakness	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.65% 1/155 • From the time point of first injection until 16 weeks after last injection

Other adverse events

Other adverse events
Measure	IncobotulinumtoxinA (Xeomin) (up to 800 Units) n=155 participants at risk IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA: Subjects to receive up to 3 injection cycle, with the dose titrated from 400 units to up to 800 units. For each injection session: solution prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400-800 units, volume 2.0 mL per 100 units; Mode of administration: Intramuscular injection.
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 10/155 • Number of events 12 • From the time point of first injection until 16 weeks after last injection
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.2% 8/155 • Number of events 8 • From the time point of first injection until 16 weeks after last injection
Injury, poisoning and procedural complications Fall	7.7% 12/155 • Number of events 17 • From the time point of first injection until 16 weeks after last injection
Gastrointestinal disorders Diarrhoea	6.5% 10/155 • Number of events 13 • From the time point of first injection until 16 weeks after last injection
Infections and infestations Nasopharyngitis	6.5% 10/155 • Number of events 13 • From the time point of first injection until 16 weeks after last injection

Additional Information

Public Disclosure Manager

Merz Pharmaceuticals GmbH

Phone: +49 69 1503 1

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER