An Open-label, Randomized 26-Week Study Comparing Levodopa-Carbidopa INteStInal Gel (LCIG) THerapy to Optimized Medical Treatment (OMT) on Non-Motor Symptoms (NMS) in Subjects With Advanced Parkinson's Disease - INSIGHTS Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 89
- 试验地点
- 38
- 主要终点
- Change From Baseline to Week 26 in the NMSS Total Score
研究概览
简要总结
The primary objective of this study is to examine the effect of LCIG relative to that of OMT on NMS associated with PD.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant(s) must have a diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria.
- •Participant(s) demonstrates persistent motor fluctuations in spite of individually optimized treatment.
- •The participant's Parkinson's disease is levodopa-responsive.
- •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.
- •Male or female participant(s) must be at least 30 years of age.
- •Minimum Parkinson's Disease Sleep Scale 2 (PDSS-2) total score of 18 at Baseline assessment.
排除标准
- •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.
- •Participant(s) has undergone neurosurgery for the treatment of Parkinson's disease.
- •Known hypersensitivity to levodopa, carbidopa or radiopaque material.
- •Participant(s) has contraindications to levodopa (e.g. narrow angle glaucoma, malignant melanoma).
- •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.
研究组 & 干预措施
Optimized Medical Treatment (OMT)
Participants randomized to continue OMT remain on their current optimized regimen. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose (after NJ and/or PEG-J placement), in order to transition to commercially available LCIG.
干预措施: Optimized Medical Treatment (Drug)
Optimized Medical Treatment (OMT)
Participants randomized to continue OMT remain on their current optimized regimen. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose (after NJ and/or PEG-J placement), in order to transition to commercially available LCIG.
干预措施: Levodopa-Carbidopa Intestinal Gel (Drug)
Optimized Medical Treatment (OMT)
Participants randomized to continue OMT remain on their current optimized regimen. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose (after NJ and/or PEG-J placement), in order to transition to commercially available LCIG.
干预措施: Nasojejunal (NJ) tube (Device)
Optimized Medical Treatment (OMT)
Participants randomized to continue OMT remain on their current optimized regimen. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose (after NJ and/or PEG-J placement), in order to transition to commercially available LCIG.
干预措施: Percutaneous endoscopic gastrostomy with a jejunal (PEG-J) tube (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
Participants randomized to LCIG at an individually optimized dose (after NJ and/or PEG-J placement), in accordance with the LCIG approved product label for countries participating in the study. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
The total daily dose of LCIG was composed of 3 components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. The continuous infusion is expected to run over a period of 16 consecutive hours each day.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose, in order to transition to commercially available LCIG.
干预措施: Levodopa-Carbidopa Intestinal Gel (Drug)
Levodopa-Carbidopa Intestinal Gel (LCIG)
Participants randomized to LCIG at an individually optimized dose (after NJ and/or PEG-J placement), in accordance with the LCIG approved product label for countries participating in the study. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
The total daily dose of LCIG was composed of 3 components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. The continuous infusion is expected to run over a period of 16 consecutive hours each day.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose, in order to transition to commercially available LCIG.
干预措施: Nasojejunal (NJ) tube (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
Participants randomized to LCIG at an individually optimized dose (after NJ and/or PEG-J placement), in accordance with the LCIG approved product label for countries participating in the study. During the 26-week treatment phase, changes to anti-PD and NMS medications are to remain stable and can only be made if medically indicated.
The total daily dose of LCIG was composed of 3 components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. The continuous infusion is expected to run over a period of 16 consecutive hours each day.
Eligible participants may elect to enter an extension/transition follow-up period to receive an individually optimized LCIG dose, in order to transition to commercially available LCIG.
干预措施: Percutaneous endoscopic gastrostomy with a jejunal (PEG-J) tube (Device)
结局指标
主要结局
Change From Baseline to Week 26 in the NMSS Total Score
时间窗: Baseline, Week 26
The NMSS consists of 30 questions in 9 domains (cardiovascular/falls, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, GI tract, urinary, sexual function, miscellaneous). Score of each question is calculated by multiplying severity\*frequency. Severity and frequency are rated using a scale ranging from 0 (none) to 3 (severe) for severity and from 1 (rarely) to 4 (very frequent) for frequency. Total score is the sum of 9 domains, and ranges from 0 to 360, with a lower value indicating a more desirable outcome. Repeated-measure analysis.
Change From Baseline to Week 26 in the Modified PDSS-2 Total Score
时间窗: Baseline, Week 26
The PDSS-2 addresses PD-specific sleep disturbances such as restless leg syndrome (RLS), morning akinesia, pain, and sleep apnea. The frequency is assessed for the 15 sleep problems based on a 5-point Likert-type scale (ranging from 0 \[never\] to 4 \[very often\]). Scores are calculated for each of the 3 domains (motor symptoms at night, PD symptoms at night, and disturbed sleep) as well as a total score. The PDSS-2 domain scores range from 0 to 20 and the total score is a sum of the 3 domains and ranges from 0 to 60. Repeated measure analysis.
次要结局
- Change From Baseline at Week 26 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score(Baseline, Week 26)
- Change From Baseline to Week 26 in the Modified PDSS-2 Domain Scores(Baseline, Week 26)
- Clinical Global Impression of Change (CGI-C) Final Score(End of Treatment Period (up to Week 26))
- Change From Baseline to Week 26 in the NMSS Domain Scores(Baseline, Week 26)
- Change From Baseline at Week 26 in Geriatric Depression Scale (GDS-15) Score(Baseline, Week 26)
- Change From Baseline at Week 26 in King's PD Pain Scale (KPPS) Score(Baseline, Week 26)
- Patient Global Impression of Change (PGIC) Final Score(End of Treatment Period (up to Week 26))
- Change From Baseline to Week 26 in Parkinson's Disease Questionnaire (PDQ-8) Summary Index Score(Baseline, Week 26)
- Change From Baseline at Week 26 in UPDRS Parts I, III, and IV Score(Baseline, Week 26)
- Change From Baseline at Week 26 in Parkinson's Anxiety Scale (PAS) Total Score(Baseline, Week 26)