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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT01464307
First received: November 1, 2011
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Post-stroke Spasticity of the Lower Limb.
Drug: IncobotulinumtoxinA (400 Units)
Drug: Placebo Comparator
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merz Pharmaceuticals GmbH:

Primary Outcome Measures:
  • Change from baseline in Ashworth Scale (AS) for plantar flexors at Week 4 [ Time Frame: Baseline to week 4 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 328
Study Start Date: December 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Placebo Comparator: Placebo Comparator Arm
Placebo to incobotulinumtoxinA (Xeomin) powder for solution for 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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01464307

  Show 53 Study Locations
Sponsors and Collaborators
Merz Pharmaceuticals GmbH
Investigators
Study Director: Medical Expert Merz Pharmaceuticals GmbH
  More Information

No publications provided

Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT01464307     History of Changes
Other Study ID Numbers: MRZ 60201/SP/3002, 2010-024579-23
Study First Received: November 1, 2011
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Canada: Health Canada
Austria: Agency for Health and Food Safety
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Additional relevant MeSH terms:
Muscle Spasticity
Stroke
Cerebral Infarction
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Botulinum Toxins, Type A
Botulinum Toxins
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014