Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Spasticity in the Leg After a Stroke (PLUS)

Tracking Information
First Submitted Date ICMJE	November 1, 2011
First Posted Date ICMJE	November 3, 2011
Results First Submitted Date	July 26, 2016
Results First Posted Date	November 7, 2016
Last Update Posted Date	November 7, 2016
Study Start Date ICMJE	December 2011
Actual Primary Completion Date	August 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 4, 2016)	Change From Baseline in Ashworth Scale (AS) for Plantar Flexors at Week 4 [ Time Frame: Baseline and Week 4 ]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).; Co-primary Variable: Investigator's Global Assessment of Efficacy at Week 12 [ Time Frame: Baseline to Week 12 ]A 4-point Likert scale will be used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor. Investigator's Global Assessment of Efficacy at Week 12 will be a co-primary outcome measure to fulfill post marketing commitments for U.S. regulatory authorities only. Elsewhere, it will be a secondary outcome measure.
Original Primary Outcome Measures ICMJE; (submitted: November 1, 2011)	Change From Baseline in Ashworth Scale (AS) for Plantar Flexors at Week 4 [ Time Frame: Baseline to week 4 ]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).; Co-primary Variable: Investigator's Global Assessment of Efficacy at Week 12 [ Time Frame: Baseline to Week 12 ]A 4-point Likert scale will be used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor. Investigator's Global Assessment of Efficacy at Week 12 will be a co-primary outcome measure to fulfill post markting commitments for U.S. regulatory authorities only. Elswhere, it will be a secondary outcome measure.
Change History	Complete list of historical versions of study NCT01464307 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 4, 2016)	Response Rate for Plantar Flexors at All Post-Baseline Visits for Subjects With an Improvement (Reduction) of at Least 1 Point From Baseline in the Ashworth Scale (AS) [ Time Frame: Week 4, 8, and 12 ]Response is defined as an improvement (reduction) of the plantar flexor Ashworth Score by at least one score point. 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).; Ashworth Scale (AS) for Plantar Flexors at All Post-Baseline Visits [ Time Frame: Baseline, Week 4, 8, and 12 ]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). Here, 'n' specifies those subjects who were evaluated for this outcome measure at given time point.
Original Secondary Outcome Measures ICMJE; (submitted: November 1, 2011)	Response Rate for Plantar Flexors at All Post-Baseline Visits for Subjects With an Improvement (Reduction) of at Least 1 Point From Baseline in the Ashworth Scale (AS) [ Time Frame: Week 4, 8, and 12 ]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).; Change from baseline in Ashworth Scale (AS) for plantar flexors at all post-baseline visits [ Time Frame: From baseline up to week 12 ]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). Subjects with a reduction of one point were defined as responder for the aim of the primary efficacy analysis.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Spasticity in the Leg After a Stroke
Official Title ICMJE	Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Treatment of Post-stroke Spasticity of the Lower Limb
Brief Summary	The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg are effective in treating patients with increased muscle tension/uncontrollable muscle stiffness (spasticity) after a stroke.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Post-stroke Spasticity of the Lower Limb
Intervention ICMJE	Drug: IncobotulinumtoxinA (400 Units) Main period: One injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400 units, total volume 8.0 mL; Mode of administration: intramuscular injection.; Drug: Placebo Comparator Main period: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding total placebo volume 8.0 mL; Mode of administration: intramuscular injection
Study Arms	Experimental: IncobotulinumtoxinA (Xeomin) 400 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. Intervention: Drug: IncobotulinumtoxinA (400 Units); Placebo Comparator: Placebo Comparator Arm Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection. Intervention: Drug: Placebo Comparator
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 4, 2016)	290
Original Estimated Enrollment ICMJE; (submitted: November 1, 2011)	328
Actual Study Completion Date	May 2015
Actual Primary Completion Date	August 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Age from 18-80 yrs; Lower limb spasticity; Time since stroke greater than 3 months; Need for 400 U Botulinum toxin type A Exclusion Criteria: Body weight below 50kg; Fixed contractures of the lower limb; Generalized disorders of muscle activity like Myasthenia gravis that preclude use of Botulinum toxin type A; Infection at the injection site
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, Czech Republic, France, Germany, Italy, Poland, Russian Federation, Spain, United States
Removed Location Countries	Austria
Administrative Information
NCT Number ICMJE	NCT01464307
Other Study ID Numbers ICMJE	MRZ 60201/SP/3002; 2010-024579-23 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Merz Pharmaceuticals GmbH
Study Sponsor ICMJE	Merz Pharmaceuticals GmbH
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Medical Expert Merz Pharmaceuticals GmbH
PRS Account	Merz Pharmaceuticals GmbH
Verification Date	September 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP