a study to examine the effect of levodopa-carbidopa intestinal gel (lcig) therapy relative to that of optimized medical treatment (omt) on non-motor symptoms (nms) associated with advanced parkinson's disease (pd)

Conditions: Advanced Parkinson's Disease

Summary: the primary objective of this study is to examine the effect of lcig relative to that of omt on nms associated with pd.

the study will consist of 3 sequential parts: part 1: screening period. the screening period will consist of 3 visits, visit 1 (v1), visit 2 (\[v2\] \[optional\]) and the randomization visit (v3) in which the participant will be assessed to determine eligibility. the duration of the screening period can be between 30 to 67 days to accommodate the required procedures, training and collection of diaries, and to allow for stabilization of anti-pd medications and medications to treat nms. all anti-pd medications and medications to treat nms are required to be stable for a minimum of 30 days prior to randomization. part 2: treatment period. those participants randomized to omt at the end of v3 will remain on their current optimized regimen. the day after randomization will be considered day 1 of their treatment period and participants will have study visits at the end of weeks 2, 6, 12, and 26. all participants randomized to the lcig group should have all anti-pd medications, with the exception of levodopa formulations, tapered off within 14 days after randomization. optional nasojujunal (nj) and/or percutaneous endoscopic gastrostomy with a jejunal tube (peg-j) placement will then occur. after that, the participant may begin initiation and titration of lcig infusion to be adjusted to obtain the optimal clinical response. the day of initial nj or peg-j placement will be considered day 1 for participants in the lcig group. study visits happen at the end of weeks 2, 6, 12, and 26. part 3: extension/transition period. eligible participants who complete the 26 week study may continue into the extension period of the study. participants in the lcig arm will have study drug dispensation every 4 weeks and will have study visits every 6 months. participants from the omt arm will undergo the nj (optional) and peg-j procedures, titration, plus have visits at 2 weeks, 6 weeks, 3 months and 6 months post nj or peg-j. participants will then continue to receive study drug every 4 weeks and will have study visits every 6 months until duodopa is commercially available. transition to a post-trial access protocol will be possible if duodopa does not become commercially available in a location.

Eligibility criteria:
inclusion criteria: 1. participant(s) must have a diagnosis of idiopathic parkinson's disease according to the united kingdom parkinson's disease society (ukpds) brain bank criteria. 2. participant(s) demonstrates persistent motor fluctuations in spite of individually optimized treatment. 3. the participant's parkinson's disease is levodopa-responsive. 4. participant(s) has had optimized treatment with available anti-pd medication and their motor symptoms are judged inadequately controlled on this optimized treatment. optimized treatment is defined as the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected regardless of any additional manipulations of levodopa and/or other antiparkinsonian medication. this will be based on the investigator's clinical judgment. 5. male or female participant(s) must be at least 30 years of age. 6. minimum parkinson's disease sleep scale 2 (pdss-2) total score of 18 at baseline assessment. exclusion criteria: 1. participant's pd diagnosis is unclear or there is a suspicion that the subject has a parkinsonian syndrome such as secondary parkinsonism (e.g. caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), parkinson-plus syndrome (e.g. multiple system atrophy, progressive supranuclear palsy, diffuse lewy body disease) or other neurodegenerative disease that might mimic the symptoms of pd. 2. participant(s) has undergone neurosurgery for the treatment of parkinson's disease. 3. known hypersensitivity to levodopa, carbidopa or radiopaque material. 4. participant(s) has contraindications to levodopa (e.g. narrow angle glaucoma, malignant melanoma). 5. participant(s) experiencing clinically significant sleep attacks or clinically significant impulsive behavior (e.g. pathological gambling, hypersexuality) at any point during the three months prior to the screening evaluation as judged by the principal investigator.

Keywords: levodopa-carbidopa intestinal gel levodopa carbidopa advanced parkinson's disease non-motor symptom scale nmss parkinson's disease sleep scale pdss-2 efficacy