Muscle selection for onabotulinumtoxina in poststroke lower limb spasticity influences outcome: results from a double-blind, placebo-controlled phase 3 clinical trial

Toxicon ◽  
2016 ◽  
Vol 123 ◽  
pp. S26-S27
Author(s):  
Alberto Esquenazi ◽  
Carolyn Geis ◽  
Theodore H. Wein ◽  
Anthony B. Ward ◽  
Chengcheng Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lower Limb ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Selection For

scholarly journals Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity: results from the double-blind, placebo-controlled, phase 3 REFLEX study

2020 ◽  
Vol 127 (12) ◽  
pp. 1619-1629
Author(s):  
Atul T. Patel ◽  
Anthony B. Ward ◽  
Carolyn Geis ◽  
Wolfgang H. Jost ◽  
Chengcheng Liu ◽  
...  
Keyword(s):  
Lower Limb ◽  
Average Score ◽  
Tibialis Posterior ◽  
Repeated Treatment ◽  
Phase 3 ◽  
Double Blind ◽  
Post Stroke ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Flexor Digitorum

AbstractThe aim of this study in patients with post-stroke lower limb spasticity (PSLLS) was to evaluate the relationship between time of onabotulinumtoxinA treatment relative to stroke and efficacy outcomes. This was a phase 3, international, multicenter, randomized, 12-week, double-blind study, followed by a repeated treatment, open-label extension. Patients were aged 18–85 years with PSLLS (Modified Ashworth Scale [MAS] ≥ 3) of the ankle with the most recent stroke occurring ≥ 3 months before screening. Patients (double-blind phase) were randomized (n = 468) to onabotulinumtoxinA 300–400 U (300 U, mandatory ankle muscles (gastrocnemius, soleus, tibialis posterior); and ≤ 100 U, optional lower limb muscles (flexor digitorum longus, flexor hallucis longus, flexor digitorum brevis, extensor hallucis, and rectus femoris]) or placebo. Primary endpoint: MAS change from baseline (average score of weeks 4 and 6). Secondary endpoints: physician-assessed Clinical Global Impression of Change (CGI) average score of weeks 4 and 6 and physician-assessed Goal Attainment Scale (GAS; active and passive, weeks 8 and 12). When stratified by time since stroke (≤ 24 months, n = 153; > 24 months, n = 315, post hoc), patients treated ≤ 24 months post-stroke experienced greater improvements from baseline versus placebo in MAS (− 0.31 vs − 0.17), CGI (0.49 vs 0.12), and passive GAS scores (week 12, 0.37 vs 0.26). A ≥  − 1-point improvement in active (week 12; p = 0.04) and passive (week 8; p = 0.02) GAS scores versus placebo was achieved by more patients treated ≤ 24 months post-stroke; in patients treated > 24 months post-stroke, improvements were only observed in active scores (week 8; p = 0.04). OnabotulinumtoxinA 300–400 U was well tolerated, with no new safety findings.

scholarly journals Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial

2010 ◽  
Vol 257 (8) ◽  
pp. 1330-1337 ◽  
Author(s):  
Ryuji Kaji ◽  
Yuka Osako ◽  
Kazuaki Suyama ◽  
Toshio Maeda ◽  
Yasuyuki Uechi ◽  
...  
Keyword(s):  
Botulinum Toxin ◽  
Lower Limb ◽  
Controlled Trial ◽  
Botulinum Toxin Type A ◽  
Botulinum Toxin Type ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Stroke ◽  
Limb Spasticity ◽  
Lower Limb Spasticity

Abstract TMP34: OnabotulinumtoxinA Treatment in Post-stroke Lower Limb Spasticity: Long-term Results From a Phase 3 Study

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Theodore Wein ◽  
Alberto Esquenazi ◽  
Wolfgang H Jost ◽  
Anthony Ward ◽  
Tinna Kwan ◽  
...  
Keyword(s):  
Lower Limb ◽  
Goal Attainment ◽  
Long Term Results ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Post Stroke ◽  
Limb Spasticity ◽  
Lower Limb Spasticity

Introduction: Long-term efficacy of onabotulinumtoxinA (onabotA) in post-stroke lower limb spasticity (PSLLS) is not clearly established. Hypothesis: OnabotA provides sustained efficacy in PSLLS. Methods: A multicenter, phase 3, 12-week, double-blind (DB), placebo-controlled study of patients with ankle PSLLS (Modified Ashworth Scale [MAS] ≥3) was followed by an open-label (OL) extension, during which all patients received 1-3 treatment cycles (∼12-week intervals) of onabotA (≤400U). Endpoints: change from baseline in MAS and Clinical Global Impression of Change (CGI) physician rating, and percent of patients achieving passive and active goals (Goal Attainment Scale [GAS]) by physician and patient. Results: 468 patients enrolled (onabotA, n=233; placebo, n=235); 447 (95.5%) completed the DB and 249 (53.2%) completed the OL phase at DB database lock. Significant improvement in MAS achieved with onabotA in DB was sustained in OL phase (Table). Significant improvements in CGI in DB continued to improve in OL phase. During OL phase, MAS ankle change from baseline and CGI by physician raw scores and proportions of responders were largest at week 6 and generally increased over 3 OL treatment cycles. With onabotA, GAS by patient improved ( P =0.036), as did the proportion that progressed toward active ( P =0.009) and passive ( P =0.044) goal attainment by physician. The percentage of patients who met passive and active goals (GAS by physician≥0) after 1 onabotA treatment increased from 40% to 64% and 27% to 65%, respectively, after 4 treatments. Common DB treatment-related AEs (onabotA vs placebo): injection-site pain (1.7% vs 0.9%) and pain in extremity (0.4% vs 2.1%). Conclusions: OnabotA was well-tolerated and produced improvements in MAS, CGI, and GAS during the DB phase that continued into the OL phase, demonstrating long-term benefits in patients with PSLLS.

scholarly journals A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

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