BOTOX® Treatment in Adult Patients With Post-Stroke Lower Limb Spasticity

• ClinicalTrials.gov Identifier: NCT01575054
• Recruitment Status: Completed
• First Posted: April 11, 2012
• Results First Posted: February 1, 2016
• Last Update Posted: September 28, 2016
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Study Description

Brief Summary:

This study will evaluate the safety and efficacy of BOTOX® in the treatment of adult post-stroke lower limb spasticity.

Condition or disease	Intervention/treatment	Phase
Muscle Spasticity	Biological: botulinum toxin Type A; Drug: Normal Saline	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 468 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: May 2012
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: botulinum toxin Type A; Double-Blind Study Phase (12 weeks): On Day 1, botulinum toxin Type A 300 U will be given by intramuscular injections into specified muscles of the lower limb, and an optional dose of 100 U may be injected into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period.	Biological: botulinum toxin Type A; Double-Blind Study Phase (12 weeks): On Day 1, botulinum toxin Type A 300 U will be given by intramuscular injections into specified muscles of the lower limb, and an optional dose of 100 U may be injected into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period.; Other Names: BOTOX®; onabotulinumtoxin A
Normal Saline (Placebo) Followed by botulinum toxin Type A; Double-Blind Study Phase (12 weeks): On Day 1, normal saline (placebo) will be given by intramuscular injections into specified muscles of the lower limb, and optional injections may be administered into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period.	Biological: botulinum toxin Type A; Double-Blind Study Phase (12 weeks): On Day 1, botulinum toxin Type A 300 U will be given by intramuscular injections into specified muscles of the lower limb, and an optional dose of 100 U may be injected into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period.; Other Names: BOTOX®; onabotulinumtoxin A; Drug: Normal Saline; Double-Blind Study Phase (12 weeks): On Day 1, normal saline (placebo) will be given by intramuscular injections into specified muscles of the lower limb, and optional injections may be administered into additional lower limb muscles.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of Ankle Plantar Flexors Using a 6-Point Scale [ Time Frame: Baseline, 6 Weeks ]
   The MAS-B is a 6-point scale used to evaluate spasticity based on grading the resistance encountered in the ankle flexors by passively moving the ankle plantar flexor muscles through their range of motion. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Scores are converted to a 0 to 5 grade. The average of the weeks 4 and 6 MAS-B ankle change from baseline is the primary end point. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.

Secondary Outcome Measures :

1. Clinical Global Impression (CGI) of Overall Change by Physician Using a 9-Point Scale [ Time Frame: Baseline, 6 weeks ]
   The CGI is a 9-point scale evaluating change from baseline status by the Physician. Scores range from +4 (very marked improvement) to -4 (very marked worsening). The average of the weeks 4 and 6 CGI by Physician score is used as a secondary end point. Higher scores indicate a greater improvement from baseline.
2. Goal Attainment Scores on the 6-Point Physician-Assessed Goal Attainment Scale (GAS) [ Time Frame: Week 8 ]
   The physician-assessed GAS is an individualized, goal-oriented 6-point scale used to track functional improvement toward active and passive goals. GAS scoring ranged from -3 to 2 (-3 = worse than start; 0 = expected goal/attained the defined therapeutic goal; 2 = much more than expected/improvements clearly exceeded the defined therapeutic goal). Active and Passive Goal scores are presented.
3. Change From Baseline in Average Pain Score While Walking on the 11-Point Pain Scale [ Time Frame: Baseline, Week 6 ]
   The patient is asked to select a number that best describes his/her pain while walking on an 11-point scale from 0 = "no pain" to 10 = "pain as bad as can be imagined". Patients are instructed to recall their average pain in the study limb during the 48-hour period prior to the visit. Patients with a baseline pain score >0 are included in the analyses.
4. Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of Optional Muscles Using a 6-Point Scale [ Time Frame: Baseline, Week 6 ]
   The MAS-B is a 6-point scale used to evaluate spasticity based on grading the resistance encountered in the optional muscles by passively moving the muscles through their range of motion. Optional muscles treated include: Rectus Femoris, Flexor Digitorum Longus, Flexor Hallucis Longus, and Extensor Hallucis. The scores range from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Scores are converted to a 0 to 5 grade. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of post-stroke lower limb spasticity for at least 3 months
• Minimum body weight of 50 kg

• Never treated with botulinum toxin of any serotype for any reason, or if previously treated with botulinum toxin of any serotype, if previously treated for spasticity in the affected lower limb, must have been administered

  • 20 weeks before Day 1, or if previously treated for any other indication must have been administered ≥12 weeks prior to Day 1

Exclusion Criteria:

• Spasticity in the opposite leg that requires treatment
• Casting of the study limb within 6 months or planned casting during the first 12 weeks of the study
• Treatment modalities in the study limb including ultrasound, electrical nerve stimulation, electrical stimulation, acupuncture within 1 month of Day 1 or treatments planned during the study
• Not able to perform 10 meter walking test independently with or without assistive device
• Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis

Contacts and Locations

Locations

United States, California

Downey, California, United States

United States, Florida

Daytona Beach, Florida, United States

Canada, Quebec

Montreal, Quebec, Canada

Czech Republic

Prague, Czech Republic

Germany

Wiesbaden, Germany

Würzburg, Germany

Hungary

Budapest, Hungary

Korea, Republic of

Gyeonggi-Do, Korea, Republic of

Poland

Krakow, Poland

Russian Federation

Krasnoyarsk, Russian Federation

United Kingdom

Stoke-on-Trent, England, United Kingdom

Fazakerley, Liverpool, United Kingdom

Sponsors and Collaborators

Allergan

Investigators

• Study Director: Medical Director; Allergan

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wein T, Esquenazi A, Jost WH, Ward AB, Pan G, Dimitrova R. OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial. PM R. 2018 Jul;10(7):693-703. doi: 10.1016/j.pmrj.2017.12.006. Epub 2018 Jan 9.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01575054
• Other Study ID Numbers: 191622-116; 2011-004980-63 ( EudraCT Number )
• First Posted: April 11, 2012
• Results First Posted: February 1, 2016
• Last Update Posted: September 28, 2016
• Last Verified: August 2016

Additional relevant MeSH terms:

Muscle Spasticity; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents