BOTOX(RegisteredTM) Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity
This multicenter study consists of a double-blind, placebo-controlled phase followed by an open-label phase. The total duration of study participation for each patient should not exceed 60 weeks which includes up to 15 scheduled clinic visits and up to 3 telephone visits. In this study, visits based on day 1 are referred to by [Double Quote]study week[Double Quote] and visits based on treatment are referred to by [Double Quote]treatment (cycle) week[Double Quote]. Please see Figure 1 for a study flowchart.
Double-blind Phase (Treatment 1)
This initial phase of the study is a placebo-controlled, randomized, double-blind, parallel group design. Patients will be randomized to receive 1 treatment of BOTOX 300 U plus optional dose of up to 100 U or placebo in a 1:1 ratio. Patients in the treatment group will be stratified by baseline Modified Ashworth Score and the muscles to be injected.
This 16-week period consists of the following study visits:
* screening (day -42 to day -4)
* randomization (day 1, treatment 1)
* follow-up visits at study weeks 2, 4, 6, 8, and 12
Following the completion of the double-blind single treatment phase at study week 12 (same as double-blind treatment 1 week 12), patients will enter the open-label phase. The total number of visits and the duration of the open-label phase will depend on the number and timing of treatments received by the patient. Each patient may receive up to 3 treatment cycles of BOTOX (up to 400 U per treatment) from study week 12 to study week 42, inclusive, providing they meet the retreatment criteria. Each treatment cycle begins with a treatment visit, followed by a 2-week post treatment telephone visit and clinic visits every 6 weeks (starting 6 weeks from the treatment visit) until the next treatment cycle begins or until study week 42. The exit visit will be study week 42 unless the last study treatment occurs after study week 30, then the exit visit should be 12 weeks after the last treatment visit.
Patients should receive study treatments every 12 to 14 weeks unless there is a safety concern or if the patient does not meet the retreatment criteria. Patients may be treated any time between study week 12 and study week 42, but should be re-assessed and evaluated at least every 6 weeks (counting from the last treatment visit) until he or she meets the retreatment criteria until study week 42 (the last opportunity for retreatment).
* Modified Ashworth Scale-Bohannon (MAS-B) of the ankle plantar flexors.
* Clinical Global Impression of Change (CGI) by physician
* MAS-B on optional muscles in a subset of patients who receive treatment in the optional muscles
* Goal Attainment Scaling (GAS) by physician and patient
* Pain scale
* Speed of gait (10 meter walk test)
* Modified Tardieu Scale (MTS) of ankle flexors
* Assessment of toe spasticity (for patients who receive study treatment in the toe muscle[s])
* Patient reported onset of spasticity symptom relief
* Quality of life assessments using the EQ-5D-3L and SF-36
* Male or female, >= 18 to <= 85 years of age at the screening visit
* Patients who are diagnosed with post-stroke lower limb spasticity present with equines (plantar flexion of the ankle) or equinovarus deformity, with the most recent stroke occurring at least 3 months prior to the screening visit
* A minimum body weight of 50 kg at the screening visit
* Written informed consent has been obtained
* Written documentation has been obtained in accordance with the relevant country and local privacy requirements,(e.g. Written Authorization for Use and Release of Health and Research Study Information)
* MAS-B score of >= 3 in the ankle plantar flexors at both screening and day 1 visits
* Botulinum toxin treatment-naive or if previously treated with botulinum toxin of any serotype:
>= 20 weeks prior to the day 1 visit if treated for spasticity of the study limb, or
>= 12 weeks prior to the day 1 visit if treated for an indication other than spasticity of the study limb
* Acceptable clinical laboratory results at screening at the investigator[Single Quote]s discretion
* For females of childbearing potential, a negative urine pregnancy test at screening and on the day 1 visit
* Patients who are on spasmolytic medications or muscle relaxants (eg, oral baclofen, tizanidine, dantrolene, scopolamine [oral or patch], vigabatrin, or benzodiazepine therapy) must be on a stable dose and regimen for at least 2 months prior to the day 1 visit
* Patients who are on anti-epileptic medications must be on a stable dose and regimen for at least 1 month prior to the day 1 visit