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

• 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 marketing commitments for U.S. regulatory authorities only. Elsewhere, it will be a secondary outcome measure.

• 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.

• 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.

• 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

• 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

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