A systematic review and network meta-analysis of IPX066 and other common therapies for management of symptoms in patients with advanced Parkinson’s disease (patients experiencing wearing-off on levodopa therapy)

Trial description: The aim of this research is to undertake a comparison of IPX066 and other pharmacological therapies commonly used for the management of symptoms of advanced Parkinson’s disease (patients experiencing wearing-off on levodopa therapy).The objectives are: - To perform a systematic review to identify all relevant literature - To perform a Bayesian network meta-analysis to estimate the treatment effect of each treatment strategy relative to immediate-release levodopa therapy, and provide estimates of comparative effectiveness for all pair-wise comparisons within the network.Study selection will be performed after each iterative search on the following criteria:Population: - patients with Parkinson’s disease receiving levodopa therapy who have developed motor fluctuations or complications (known as advanced Parkinson’s disease). Primary Comparators: - levodopa-carbidopa extended release of immediate release - dopamine agonists (alone or in combination with levodopa) - MAO-B inhibitors (alone or in combination with levodopa) - COMT inhibitor (alone or in combination with levodopa)Primary Outcome: - Off time (data will be extracted as number of hours and/or percentage of waking hours, and will be analysed as change from baseline in number of hours, with conversion from the latter where required). Studies that do not report any of the primary or secondary outcomes will be excluded.Secondary Outcomes:Quality of life and health status: Unified Parkinson’s Disease Rating Scale; PDQ-39 (Parkinson’s disease questionnaire); SF-36; EQ-5DMortalityPatient withdrawals (overall and due to adverse events)Key adverse events: Dyskinesia (when reported as an adverse event); Nausea; Somnolence; Hypotension (including postural hypotension); Hallucinations; InsomniaStudy Designs Included: Randomised controlled trials (RCTs), including crossover trials, of more than 1 week duration, (only data from first phase of crossover trials included), reported in English. A narrative synthesis of the systematic review results will be presented.Evidence about treatment effects will be synthesised using a network meta-analysis. The main results of each analysis will be presented as the mean, median and 95% credible interval of the posterior distribution of the effect of each treatment/class of treatment relative to the reference treatment. Heterogeneity between studies will be summarised as the mean, median and 95% credible interval for the between-study standard deviation.