Study to Assess Impact of Dysport Injections Early After Stroke on Upper Limb Spasticity Progression

The appearance of increased muscle tone was assessed using the MAS (scale ranges from 0 [no increase in muscle tone] to 4 [affected part rigid in flexion or extension]). For confirmation of reinjection criteria appearance, a subject had to have a MAS score in the primary targeted muscle group of ≥2 and at least 1 of the following 4 criteria confirming signs of symptomatic spasticity in the UL:

• A Numeric Pain Rating Scale (NPRS) pain score ≥ 4 (NPRS ranges from 0 [no pain] to 10 [severe pain])
• An impact on passive function measured by a score of ≥ 1 on the 4-point Likert scale (scale ranges from 0 [no impact] to 3 [severe impact])
• An impact on active function measured by a score of ≥ 1 on the 4-point Likert scale
• An involuntary movements score ≥1 on the 4-point Likert scale in relevant upper limb.

Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.

Increased muscle tone in the primary muscle group (selected by the investigator at the first visit, based on his/her clinical judgement and in agreement with the subject, in one of the following muscle groups: elbow flexors or pronators, wrist flexors, or finger flexors) was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). Least Squares (LS) mean change from baseline to each subsequent visit (including the subject's last study visit) of the MAS score is reported.

The Fugl-Meyer assessment is a validated tool for measuring motor functioning, balance, sensation, and joint functioning in the upper or lower limbs of subjects with post-stroke hemiplegia. The assessment scale is comprised of 155 items across 5 domains: motor functioning, sensory functioning, balance, joint range of motion and joint pain. For this study, only the UL motor part was assessed using the following criteria:

A. Upper Extremity (from 0 to 36) B. Wrist (from 0 to 10) C. Hand (from 0 to 14) D. Coordination / Speed (from 0 to 6)

Total motor function scores (A-D [from 0 to 66]) were calculated and LS mean changes from baseline up to (but not including) the visit when the reinjection criteria were met were reported.

Higher values for change from baseline indicated a better outcome.

Global assessment of changes was assessed by the investigator from Week 4 up to (but not including) the visit when the reinjection criteria were met. This endpoint was assessed by the investigator using a 5-point Likert scale to answer the following question: How does your patient feel compared to his/her condition at the first visit?

• Much better
• Better
• No change
• Worse
• Much worse

Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.

The number of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). All concomitant therapies in the indication of "Post Stroke UL Spasticity" were counted by subject from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.

The duration of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). Overall duration of concomitant therapies in the indication of "Post Stroke UL Spasticity" was computed for the period from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.