Safety Study of Botulinum Toxin Type A in Post-Upper Limb Stroke Patients With Reduced Lung Function

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00076687
• Collaborator: (none)
• Enrollment: 155
• Locations: 4
• Arms: 3
• Duration (Months): 70
• Patients Per Site: 38.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of injections of botulinum toxin Type A in patients with reduced lung function and focal upper limb poststroke spasticity

Condition or Disease	Intervention/Treatment	Phase
Stroke; Muscle Spasticity; Motor Neuron Disease	Biological: botulinum toxin Type A; Biological: botulinum toxin Type A; Drug: saline	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Biological: botulinum toxin Type A; botulinum toxin Type A 240 U injection on Day 1, Week 12, Week 18; Other Names: BOTOX®
Experimental: 2	Biological: botulinum toxin Type A; botulinum toxin Type A 360 U injection at Day 1, Week 12, Week 18; Other Names: BOTOX®
Placebo Comparator: 3	Drug: saline; Saline injection at Day 1, Week 12, Week 18

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Forced Vital Capacity (FVC) [Baseline, Week 6]

   Change from baseline in observed FVC. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6.

2. Change From Baseline in Forced Expiratory Volume (FEV1) [Baseline, Week 6]

   Change from baseline in observed FEV1 at one second. FEV1 is the maximum amount of air exhaled in one second. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6.

Secondary Outcome Measures

1. Change From Baseline in FEV1/FVC Ratio [Baseline, Week 6]

   Change from baseline in FEV1/FVC ratio. This ratio is calculated by dividing the FEV1 value by the FVC value. This represents that portion (or ratio) of FVC exhaled in one second.

2. Change From Baseline in Ashworth Scale [Baseline, Week 6]

   Change from Baseline in worst upper limb scores using the Ashworth Scale at Week 6 from Baseline. Upper limb includes finger, wrist, thumb, and elbow. Worst score was the highest value measured from the finger, wrist, thumb, or elbow at Baseline and Week 6 based on treated areas. The Ashworth Scale assesses the degree of muscle tone. It is a 5-point scale where 0 equals no increase in muscle tone and 4 equals very severe muscle rigidity. A low score indicates little or no stiffness. A high score indicates severe stiffness. A negative change from baseline score indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Abnormal pulmonary function test results;

• focal, upper limb spasticity, upper motor neuron syndrome

Exclusion Criteria:

• Previous exposure to botulinum toxin of any serotype

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Miami	Florida	United States
2		Prague		Czech Republic
3		Szeged		Hungary
4		Warsaw		Poland

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00076687
• Other Study ID Numbers: 191622-057
• First Posted: Feb 26, 2004
• Last Update Posted: Oct 3, 2011
• Last Verified: Aug 1, 2011

• Additional relevant MeSH terms: Muscle Spasticity; Stroke; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Placebo	Botulinum Toxin Type A 240 U	Botulinum Toxin Type A 360 U
Arm/Group Description	Placebo	botulinum toxin Type A 240 U	botulinum toxin Type A 360 U
Period Title: Overall Study
STARTED	48	52	55
COMPLETED	42	47	51
NOT COMPLETED	6	5	4

Baseline Characteristics

Arm/Group Title	Placebo	Botulinum Toxin Type A 240 U	Botulinum Toxin Type A 360 U	Total
Arm/Group Description	Placebo	botulinum toxin Type A 240 U	botulinum toxin Type A 360 U	Total of all reporting groups
Overall Participants	48	52	55	155
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58	55.5	55.8	56.4
Sex: Female, Male (Count of Participants)
Female	19 39.6%	13 25%	21 38.2%	53 34.2%
Male	29 60.4%	39 75%	34 61.8%	102 65.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Forced Vital Capacity (FVC)
Description	Change from baseline in observed FVC. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Placebo	Botulinum Toxin Type A 240 U	Botulinum Toxin Type A 360 U
Arm/Group Description	Placebo	botulinum toxin Type A 240 U	botulinum toxin Type A 360 U
Measure Participants	48	52	55
Baseline	2.889 (0.7804)	3.068 (0.8766)	2.923 (0.7627)
Change from Baseline at Week 6	0.057 (0.3151)	0.052 (0.2883)	-0.081 (0.2531)

2. Primary Outcome

Title	Change From Baseline in Forced Expiratory Volume (FEV1)
Description	Change from baseline in observed FEV1 at one second. FEV1 is the maximum amount of air exhaled in one second. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Placebo	Botulinum Toxin Type A 240 U	Botulinum Toxin Type A 360 U
Arm/Group Description	Placebo	botulinum toxin Type A 240 U	botulinum toxin Type A 360 U
Measure Participants	48	52	55
Baseline	2.111 (0.5944)	2.223 (0.6492)	2.168 (0.6568)
Change from Baseline at Week 6	0.049 (0.1971)	0.023 (0.2925)	-0.008 (0.2340)

3. Secondary Outcome

Title	Change From Baseline in FEV1/FVC Ratio
Description	Change from baseline in FEV1/FVC ratio. This ratio is calculated by dividing the FEV1 value by the FVC value. This represents that portion (or ratio) of FVC exhaled in one second.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Placebo	Botulinum Toxin Type A 240 U	Botulinum Toxin Type A 360 U
Arm/Group Description	Placebo	botulinum toxin Type A 240 U	botulinum toxin Type A 360 U
Measure Participants	48	52	55
Baseline	0.741 (0.1320)	0.731 (0.1260)	0.742 (0.1051)
Change from Baseline at Week 6	0.000 (0.0730)	-0.006 (0.0709)	0.019 (0.0699)

4. Secondary Outcome

Title	Change From Baseline in Ashworth Scale
Description	Change from Baseline in worst upper limb scores using the Ashworth Scale at Week 6 from Baseline. Upper limb includes finger, wrist, thumb, and elbow. Worst score was the highest value measured from the finger, wrist, thumb, or elbow at Baseline and Week 6 based on treated areas. The Ashworth Scale assesses the degree of muscle tone. It is a 5-point scale where 0 equals no increase in muscle tone and 4 equals very severe muscle rigidity. A low score indicates little or no stiffness. A high score indicates severe stiffness. A negative change from baseline score indicates improvement.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Placebo	Botulinum Toxin Type A 240 U	Botulinum Toxin Type A 360 U
Arm/Group Description	Placebo	botulinum toxin Type A 240 U	botulinum toxin Type A 360 U
Measure Participants	48	52	55
Baseline	3.19 (0.607)	2.87 (0.561)	2.96 (0.693)
Change from Baseline at Week 6	-0.60 (0.564)	-1.01 (0.801)	-1.16 (0.834)

Adverse Events

Arm/Group Title	Placebo		Botulinum Toxin Type A 240 U		Botulinum Toxin Type A 360 U
Arm/Group Description	Placebo		botulinum toxin Type A 240 U		botulinum toxin Type A 360 U
All Cause Mortality
	Placebo		Botulinum Toxin Type A 240 U		Botulinum Toxin Type A 360 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Botulinum Toxin Type A 240 U		Botulinum Toxin Type A 360 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/48 (14.6%)		9/52 (17.3%)		6/55 (10.9%)
Blood and lymphatic system disorders
Anaemia	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Cardiac disorders
Acute coronary syndrome	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Angina Pectoris	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Cardiac arrest	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Cardiac failure congestive	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Myocardial infarction	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Congenital, familial and genetic disorders
Meningocele	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
General disorders
Chest pain	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Infections and infestations
Abscess	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Acute endocarditis	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Appendicitis	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Bacteraemia	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Cellulitis	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Gastroenteritis	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Pneumonia	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Splenic abscess	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Wound infection	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Investigations
Heart rate decreased	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Hyponatraemia	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Musculoskeletal and connective tissue disorders
Mobility decreased	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/48 (2.1%)		0/52 (0%)		1/55 (1.8%)
Nervous system disorders
Convulsion	1/48 (2.1%)		0/52 (0%)		2/55 (3.6%)
Cerebral infarction	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Cognitive disorder	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Encephalitis	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Epilepsy	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Ischaemic stroke	0/48 (0%)		1/52 (1.9%)		0/55 (0%)
Syncope	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Renal and urinary disorders
Renal failure	1/48 (2.1%)		0/52 (0%)		0/55 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/48 (2.1%)		1/52 (1.9%)		0/55 (0%)
Dyspnoea	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Vascular disorders
Hypotension	1/48 (2.1%)		1/52 (1.9%)		0/55 (0%)
Hypertension	0/48 (0%)		0/52 (0%)		1/55 (1.8%)
Other (Not Including Serious) Adverse Events
	Placebo		Botulinum Toxin Type A 240 U		Botulinum Toxin Type A 360 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/48 (37.5%)		15/52 (28.8%)		17/55 (30.9%)
Gastrointestinal disorders
Diarrhoea	4/48 (8.3%)		1/52 (1.9%)		2/55 (3.6%)
Vomiting	3/48 (6.3%)		1/52 (1.9%)		1/55 (1.8%)
Infections and infestations
Upper respiratory tract infection	3/48 (6.3%)		4/52 (7.7%)		6/55 (10.9%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/48 (2.1%)		0/52 (0%)		3/55 (5.5%)
Pain in extremity	2/48 (4.2%)		3/52 (5.8%)		2/55 (3.6%)
Nervous system disorders
Headache	3/48 (6.3%)		0/52 (0%)		3/55 (5.5%)
Muscle spasticity	0/48 (0%)		3/52 (5.8%)		0/55 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/48 (4.2%)		3/52 (5.8%)		0/55 (0%)

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.