Post-stroke distal lower limb spasticity impairs mobility, limiting activities of daily living, requiring additional caregiver time.
To evaluate the efficacy, safety, and sustained benefit of onabotulinumtoxinA in adults with post-stroke lower limb spasticity (PSLLS).
A multicenter, randomized, double-blind, phase 3, placebo-controlled trial.
60 study centers across North America, Europe, Russia the United Kingdom, and South Korea.
Adult patients (18 to 65 years of age) with PSLLS (Modified Ashworth Scale [MAS] ≥3) of the ankle plantar flexors and the most recent stroke ≥3 months prior to study enrollment. .
During the open-label phase, patients received ≤3 onabotulinumtoxinA treatments (≤400 U) or placebo at approximately 12-week intervals. Treatments were into the ankle plantar flexors (onabotulinumtoxinA 300 U into ankle plantar flexors; ≤100 U, optional lower limb muscles).
Main Outcome Measurements
The double-blind primary endpoint was MAS change from baseline (average score at weeks 4 and 6). Secondary measures included physician-assessed Clinical Global Impression of Change (CGI), MAS change from baseline in optional muscles, Goal Attainment Scale (GAS), and pain scale.
Of 468 patients enrolled, 450 (96%) completed the double-blind phase and 413 (88%) completed the study. Small improvements in MAS observed with onabotulinumtoxinA during the double-blind phase (onabotulinumtoxinA, –0.8; placebo, –0.6, P=0.01) were further enhanced with additional treatments through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, –1.2; placebo/onabotulinumtoxinA, –1.4). Small improvements in CGI observed during the double-blind phase (onabotulinumtoxinA, 0.9; placebo, 0.7, P=0.01) were also further enhanced through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, 1.6; placebo/onabotulinumtoxinA, 1.6). Physician- and patient-assessed GAS scores improved with each subsequent treatment. No new safety signals emerged.
OnabotulinumtoxinA significantly improved ankle MAS, CGI, and GAS scores compared with placebo; improvements were consistent and increased with repeated treatments of onabotulinumtoxinA over 1 year in patients with PSLLS.
Clinical Trial Registration URL: https://clinicaltrials.gov/ct2/show/NCT01575054?term=NCT01575054&rank=1