Placebo Usage During Treatment. 1 The use of placebo during the first IMP treatment administration ensures a rigorous, scientifically appropriate study design to assess the efficacy and safety of Dysport® in the treatment of UI due to NDO. The use of placebo is justified because: • Although UI due to NDO is a symptomatic condition, which can lead to significantly impaired quality of life, it is not life-threatening. Therefore, a single administration of placebo with the opportunity to receive active IMP treatment from as early as 12 weeks later ensures that all subjects have the opportunity to receive the active IMP without prolonged delay. All further study treatment administrations will be active IMP, for up to 2 years post randomisation, ensuring all subjects also have the opportunity to be treated with active IMP multiple times during the study, if required. • Treatment with BTX-A may be associated with an increased risk of UTIs in an NDO population that is already susceptible to UTIs. In order to accurately estimate the true incidence of UTIs associated with the active IMP, compared to the background incidence and the incidence due to the treatment administration procedure, a placebo group comparison is required. • OnabotulinumtoxinA, is not authorised or marketed for the treatment of UI due to NDO in all the planned countries where this Dysport® phase 3 program is to be conducted; therefore, its use as an active comparator in these countries would not be appropriate. An objective of this program is to confirm the efficacy of Dysport® in this indication CCI The study has been designed to ensure that subjects who receive placebo during the first study IMP administration are not exposed to the risks of being untreated for their condition. • Subjects who require oral medication (such as anticholinergics) to reduce their UI and bladder pressure can continue these during the study. This ensures that subjects remain managed on their established medications without any withholding of usual oral treatment. Thus, there is no risk of being temporarily exposed to “no treatment” if they initially receive placebo. • All subjects in the study will be required to continue to perform CIC to manage their bladder function, this ensures that the bladder is regularly and adequately emptied thus reducing the risks of upper urinary tract damage and UTIs. Thus, any safety risk of temporarily receiving inactive IMP are minimised due to the requirement for all subjects to use CIC in the study.
