Safety and efficacy of botulinum toxin type A made in China for treatment of post-stroke upper limb spasticity: a randomized double-blind controlled trial

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U, or 240 U if combined with thumb spasticity). Methods The study was a multi-center, stratified block randomized, double-blind, placebo-controlled trial. All the qualified subjects were from 15 clinical centers from September 2014 to February 2016. They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U; n=118) or placebo (n=60) in pivotal phase after informed consent signed. The study was divided into two stages. The pivotal trial phase included a one-week screening, 12-week double-blind treatment, followed by an expanded phase which included six-week open-label treatment. The tone of the wrist, finger, thumb flexors was assessed at baseline and at weeks 0, 1, 4, 6, 8, 12, 16 and 18 using Modified Ashworth Scale (MAS), disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain, muscle tone and deformity was assessed using the Global Assessment Scale. The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline. Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed -1.00(-2.00, -1.00) and 0.00(-0.50, 0.00) respectively from baseline. Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z=6.618, P<0.01). The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions, with an incidence of 8.47% (10/118), and three subjects who received placebo had three adverse reactions, with an incidence of 5.00% (3/60) during the pivotal trial phase. All adverse reactions were mild to moderate, none serious. There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups. During the expanded phase three subjects had four adverse reactions and the incidence was 1.95%. All adverse reactions were mild, none serious. Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity. Clinical Trial Registration: China Drug Trials, CTR20131191 Key words: Stroke; Upper extremity; Spasm; Botulinum toxins, type A