BOTOX® Treatment in Pediatric Upper Limb Spasticity

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01603602
• Collaborator: (none)
• Enrollment: 235
• Locations: 45
• Arms: 3
• Actual Duration (Months): 59.8
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with upper limb spasticity.

Condition or Disease	Intervention/Treatment	Phase
Pediatrics; Muscle Spasticity; Cerebral Palsy; Stroke	Biological: botulinum toxin Type A; Drug: Normal Saline (Placebo)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 235 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: BOTOX® Treatment in Pediatric Upper Limb Spasticity: Double-blind Study
• Actual Study Start Date: Jul 12, 2012
• Actual Primary Completion Date: Jun 29, 2017
• Actual Study Completion Date: Jul 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BOTOX® 3 U/kg Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 units (U) per kilogram (kg) of body weight (3 U/kg) into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Biological: botulinum toxin Type A; Intramuscular injections of botulinum toxin Type A into specified muscles of the upper limb on Day 1.; Other Names: BOTOX® onabotulinumtoxinA
Experimental: BOTOX® 6 U/kg Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U per kg of body weight (6 U/kg) into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Biological: botulinum toxin Type A; Intramuscular injections of botulinum toxin Type A into specified muscles of the upper limb on Day 1.; Other Names: BOTOX® onabotulinumtoxinA
Placebo Comparator: Placebo Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Drug: Normal Saline (Placebo); Intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1.

Outcome Measures

Primary Outcome Measures

1. Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6 [Baseline (Day 1) to Weeks 4 and 6]

   The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement.

2. Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 [Weeks 4 and 6]

   The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A MMRM model was used for analysis.

Secondary Outcome Measures

1. Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6 [Baseline (Day 1) to Weeks 4 and 6]

   The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the finger flexor muscle group by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. An Analysis of Covariance (ANCOVA) model was used for analysis. A negative change from Baseline indicates improvement.

2. Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale [Week 8 and 12]

   Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An ANCOVA model was used for analysis.

3. Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) [Baseline (Day 1) to Week 6]

   The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and a fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. At each visit, the investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2 - R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between slow (R2) and fast (R1) range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Minimum weight of 10 kg/22 lb

• Upper limb spasticity due to cerebral palsy or stroke

Exclusion Criteria:

• Muscular dystrophy, myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or mitochondrial disease

• Uncontrolled epilepsy

• Botulinum Toxin therapy of any serotype for any condition within the last 6 months

• Previous surgical treatment of the study limb (except tendon lengthening), or planned surgery of the study limb during the study

• Previous casting of the study limb for spasticity within 6 months or with a dynamic splint within 3 months, or planned casting or dynamic splinting for spasticity of the study limb or affected lower limb during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AMS Neurology	Pasadena	California	United States	91106
2	Harrison Clinical Management	Pomona	California	United States	91766
3	Children's Hospital Colorado Dept. of PM&R	Aurora	Colorado	United States	80045
4	Associated Neurologists of Southern CT, P.C.	Fairfield	Connecticut	United States	06824
5	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida	United States	32561
6	Axcess Medical Research, LLC	Loxahatchee Groves	Florida	United States	33470
7	Pediatric Neurology, PA	Orlando	Florida	United States	32891
8	Children's Healthcare of Atlanta Children's Rehabilitation Associates	Atlanta	Georgia	United States	30342
9	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota	United States	55101
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
11	Clinical Research Center of New Jersey	Voorhees	New Jersey	United States	08043
12	NYU Hospital for Joint Diseases	New York	New York	United States	10003
13	Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine	New York	New York	United States	10032
14	OnSite Clinical Solutions, LLC	Charlotte	North Carolina	United States	28203
15	PMG Research if Charlotte, LLC	Charlotte	North Carolina	United States	28203
16	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
17	Baylor College of Medicine Texas Children's Hospital	Houston	Texas	United States	77030
18	Road Runner Research	San Antonio	Texas	United States	78258
19	Seattle Children's Hospital	Seattle	Washington	United States	98105
20	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
21	Holland Bloorview Kids Rehab	Toronto	Ontario	Canada	M4G 1R8
22	Debrecen University Clinical Center, Orthopedic Clinic	Debrecen		Hungary	4032
23	Daegu Fatima Hospital	Daegu		Korea, Republic of	41199
24	National Health Insurance Service Ilsan Hospital	Goyang-si		Korea, Republic of	10444
25	Seoul National University Hospital	Seoul		Korea, Republic of	03080
26	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
27	Asan Medical Center	Seoul		Korea, Republic of	05505
28	Samsung Medical Center	Seoul		Korea, Republic of	06351
29	De La Salle University Medical Center	Dasmarinas	Cavite	Philippines	4114
30	Philippine Children's Medical Center	Bagong Pag-asa	Quezon City	Philippines	1104
31	Uni Centrum Kliniczne	Gdansk		Poland	80-219
32	Specjal. Gabinet Neurologiczny	Krakow		Poland	30-359
33	Centrum Medyczne "POMOC"	Lodz		Poland	93-271
34	INTERMED, Lublin	Lublin		Poland	20-058
35	CRH ŻAGIEL MED, Lublin	Lublin		Poland	20-601
36	Neuro - Dzieci I Mlodziezy Aga	Warsaw		Poland	02-315
37	NZOZ Mazowieckie Centrum	Warsaw		Poland	05-462
38	Childrens Republic Hospital	Kazan		Russian Federation	420138
39	Smolensk Regional Hospital- Regional Budget State Healthcare institution	Smolensk		Russian Federation	214018
40	Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region	Tyumen		Russian Federation	625039
41	Siriraj Hospital, Mahidol University	Bangkok		Thailand	10700
42	Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University	Chiang Mai		Thailand	50200
43	Srinagarind Hospital, Khon Kaen University	Khon Kaen		Thailand	40002
44	Ankara Diskapi Yildrim Beyazit	Ankara		Turkey	6110
45	Kocaeli Üniversitesi	Kocaeli		Turkey	41380

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Rozalina Dimitrova, Allergan

Study Documents (Full-Text)

• Study Protocol - Jul 22, 2016
• Statistical Analysis Plan - Sep 11, 2017

More Information

Additional Information:

• Additional information on study locations near you may be found at AllerganClinicalTrials.com. For any study not on AllerganClinicalTrials.com, please contact [e-mail] for assistance.

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01603602
• Other Study ID Numbers: 191622-101; 2012-000062-38
• First Posted: May 22, 2012
• Last Update Posted: Aug 14, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Muscle Spasticity; Cerebral Palsy; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Pre-assignment Detail	Pediatric participants with upper limb spasticity were randomized 1:1:1 to one of three treatment groups: BOTOX® 3 or 6 U/kg (unit per kilogram) or placebo.

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
Period Title: Overall Study
STARTED	77	78	80
COMPLETED	75	78	79
NOT COMPLETED	2	0	1

Baseline Characteristics

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo	Total
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Total of all reporting groups
Overall Participants	77	78	80	235
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.6 (3.66)	8.3 (4.48)	7.8 (4.06)	7.9 (4.07)
Sex: Female, Male (Count of Participants)
Female	27 35.1%	36 46.2%	32 40%	95 40.4%
Male	50 64.9%	42 53.8%	48 60%	140 59.6%
Race/Ethnicity, Customized (Count of Participants)
White	51 66.2%	42 53.8%	51 63.8%	144 61.3%
Black	3 3.9%	3 3.8%	3 3.8%	9 3.8%
Asian	19 24.7%	27 34.6%	18 22.5%	64 27.2%
Hispanic	2 2.6%	4 5.1%	5 6.3%	11 4.7%
Other Unspecified	2 2.6%	2 2.6%	1 1.3%	5 2.1%
Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group Change (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	3.3 (0.45)	3.3 (0.45)	3.3 (0.44)	3.3 (0.45)

Outcome Measures

1. Primary Outcome

Title	Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6
Description	The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Weeks 4 and 6

Outcome Measure Data

Analysis Population Description

Participants from the Modified Intent-to treat (mITT) population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis.

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
Measure Participants	74	76	75
Least Squares Mean (Standard Error) [score on a scale]	-1.87 (0.102)	-1.92 (0.101)	-1.21 (0.102)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	MMRM model with baseline MAS-B score as covariate; factors of age, principal muscle group, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure, stratified by age and principal muscle group categories.
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -0.938 to -0.379
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	MMRM model with baseline MAS-B score as covariate; factors of age, principal muscle group, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure, stratified by age and principal muscle group categories.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -0.992 to -0.426
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6
Description	The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A MMRM model was used for analysis.
Time Frame	Weeks 4 and 6

Outcome Measure Data

Analysis Population Description

Participants from the m ITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
Measure Participants	74	76	75
Least Squares Mean (Standard Error) [score on a scale]	1.87 (0.108)	1.88 (0.108)	1.66 (0.108)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments	MMRM model with baseline MAS-B score as covariate; factors of age, principal muscle group, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure, stratified by age and principal muscle group categories.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.082 to 0.511
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.147
	Comments	MMRM model with baseline MAS-B score as covariate; factors of age, principal muscle group, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure, stratified by age and principal muscle group categories.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -0.079 to 0.523
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6
Description	The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the finger flexor muscle group by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. An Analysis of Covariance (ANCOVA) model was used for analysis. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Weeks 4 and 6

Outcome Measure Data

Analysis Population Description

Participants from the mITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
Measure Participants	28	30	29
Least Squares Mean (Standard Error) [score on a scale]	-1.41 (0.184)	-1.46 (0.169)	-1.02 (0.170)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.111
	Comments	ANCOVA model including baseline MAS-B score of finger flexor muscle group as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.861 to 0.091
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.078
	Comments	ANCOVA model including baseline MAS-B score of finger flexor muscle group as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -0.933 to 0.051
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale
Description	Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An ANCOVA model was used for analysis.
Time Frame	Week 8 and 12

Outcome Measure Data

Analysis Population Description

Participants from the mITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
Measure Participants	77	78	80
Week 8, Active Goal	0.11 (0.148)	0.12 (0.148)	0.21 (0.148)
Week 8, Passive Goal	0.30 (0.146)	0.23 (0.146)	0.06 (0.146)
Week 12, Active Goal	0.49 (0.143)	0.26 (0.139)	0.52 (0.139)
Week 12, Passive Goal	0.71 (0.143)	0.31 (0.139)	0.11 (0.139)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Week 8, Active Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.636
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.498 to 0.305
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Week 8, Active Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.658
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.502 to 0.318
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Week 8, Passive Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.243
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.162 to 0.635
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Week 8, Passive Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.412
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.237 to 0.576
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Week 12, Active Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.904
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.408 to 0.361
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Week 12, Active Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.200
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.641 to 0.135
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Week 12, Passive Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.210 to 0.978
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Week 12, Passive Goal
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.327
	Comments	ANCOVA model including baseline MAS-B score as a covariate; factors of age, principal muscle group, treatment, study center and previous botulinum toxin exposure where age and principal muscle group were represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.194 to 0.580
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS)
Description	The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and a fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. At each visit, the investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2 - R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between slow (R2) and fast (R1) range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived.
Time Frame	Baseline (Day 1) to Week 6

Outcome Measure Data

Analysis Population Description

Participants from the mITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.

Arm/Group Title	BOTOX® 6 U/kg	BOTOX® 3 U/kg	Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
Measure Participants	77	78	80
Change from Baseline to Week 2, Elbow	33.27 (5.246)	29.58 (5.268)	21.17 (5.602)
Change from Baseline to Week 4, Elbow	31.49 (4.116)	28.63 (4.160)	16.78 (4.272)
Change from Baseline to Week 6, Elbow	37.62 (4.372)	28.00 (4.268)	16.65 (4.408)
Change from Baseline to Week 8, Elbow	31.17 (4.238)	23.14 (4.188)	15.92 (4.276)
Change from Baseline to Week 12, Elbow	14.69 (3.828)	14.06 (3.775)	10.19 (3.854)
Change from Baseline to Week 2, Wrist	-15.72 (4.096)	-24.20 (3.831)	-9.60 (3.877)
Change from Baseline to Week 4, Wrist	-22.97 (4.965)	-25.43 (4.557)	-12.33 (4.447)
Change from Baseline to Week 6, Wrist	-24.33 (5.036)	-18.47 (4.641)	-7.22 (4.570)
Change from Baseline to Week 8, Wrist	-20.87 (4.621)	-18.90 (4.307)	-3.16 (4.303)
Change from Baseline to Week 12, Wrist	-16.87 (4.927)	-15.14 (4.607)	-1.62 (4.509)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 2, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.117
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.10
	Confidence Interval	(2-Sided) 95%; -3.089 to 27.293
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 2, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.273
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.41
	Confidence Interval	(2-Sided) 95%; -6.717 to 23.527
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 4, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.71
	Confidence Interval	(2-Sided) 95%; 2.958 to 26.458
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 4, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.85
	Confidence Interval	(2-Sided) 95%; 0.203 to 23.504
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 6, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.97
	Confidence Interval	(2-Sided) 95%; 8.801 to 33.137
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 6, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.064
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.35
	Confidence Interval	(2-Sided) 95%; -0.662 to 23.362
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 8, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.25
	Confidence Interval	(2-Sided) 95%; 3.317 to 27.178
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 8, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.225
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.22
	Confidence Interval	(2-Sided) 95%; -4.488 to 18.934
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 12, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.409
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.50
	Confidence Interval	(2-Sided) 95%; -6.239 to 15.236
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 12, Elbow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.470
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.86
	Confidence Interval	(2-Sided) 95%; -6.690 to 14.419
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 2, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.263
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.13
	Confidence Interval	(2-Sided) 95%; -16.962 to 4.706
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 2, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-14.60
	Confidence Interval	(2-Sided) 95%; -25.846 to -3.360
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 4, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.64
	Confidence Interval	(2-Sided) 95%; -23.277 to 1.996
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 4, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.10
	Confidence Interval	(2-Sided) 95%; -26.260 to 0.068
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 6, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-17.11
	Confidence Interval	(2-Sided) 95%; -30.031 to -4.189
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 6, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.25
	Confidence Interval	(2-Sided) 95%; -24.622 to 2.131
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 8, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-17.71
	Confidence Interval	(2-Sided) 95%; -29.888 to -5.537
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 8, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-15.74
	Confidence Interval	(2-Sided) 95%; -28.293 to -3.194
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 6 U/kg, Placebo
	Comments	Change from Baseline to Week 12, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-15.25
	Confidence Interval	(2-Sided) 95%; -28.010 to -2.492
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	BOTOX® 3 U/kg, Placebo
	Comments	Change from Baseline to Week 12, Wrist
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments	ANCOVA model including baseline MTS as a covariate and factors of age group, treatment group, study center and botulinum toxin exposure where age group is represented by stratification categories.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.52
	Confidence Interval	(2-Sided) 95%; -26.797 to -0.243
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline (Day 1) to end of the study (Week 12)
Adverse Event Reporting Description	The Safety Population, all treated participants based on the treatment received, was used to determine the number of participants at risk for Serious Adverse Events and Adverse Events.
Arm/Group Title	BOTOX® 6 U/kg		BOTOX® 3 U/kg		Placebo
Arm/Group Description	Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).		Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT.		Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.
All Cause Mortality
	BOTOX® 6 U/kg		BOTOX® 3 U/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/77 (0%)		0/78 (0%)		0/79 (0%)
Serious Adverse Events
	BOTOX® 6 U/kg		BOTOX® 3 U/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/77 (3.9%)		1/78 (1.3%)		1/79 (1.3%)
Gastrointestinal disorders
Stomatitis	1/77 (1.3%)		0/78 (0%)		0/79 (0%)
Vomiting	1/77 (1.3%)		0/78 (0%)		0/79 (0%)
General disorders
Pyrexia	1/77 (1.3%)		0/78 (0%)		0/79 (0%)
Infections and infestations
Infectious mononucleosis	1/77 (1.3%)		0/78 (0%)		0/79 (0%)
Meningitis	0/77 (0%)		1/78 (1.3%)		0/79 (0%)
Musculoskeletal and connective tissue disorders
Osteochondrosis	0/77 (0%)		0/78 (0%)		1/79 (1.3%)
Nervous system disorders
Seizure	1/77 (1.3%)		0/78 (0%)		0/79 (0%)
Other (Not Including Serious) Adverse Events
	BOTOX® 6 U/kg		BOTOX® 3 U/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/77 (19.5%)		12/78 (15.4%)		17/79 (21.5%)
General disorders
Pyrexia	2/77 (2.6%)		3/78 (3.8%)		5/79 (6.3%)
Infections and infestations
Upper respiratory tract infection	7/77 (9.1%)		4/78 (5.1%)		2/79 (2.5%)
Viral upper respiratory tract infection	6/77 (7.8%)		4/78 (5.1%)		5/79 (6.3%)
Musculoskeletal and connective tissue disorders
Pain in extremity	2/77 (2.6%)		1/78 (1.3%)		4/79 (5.1%)
Nervous system disorders
Headache	1/77 (1.3%)		2/78 (2.6%)		4/79 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.