An Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Subjects With Advanced Parkinson's Disease and Severe Motor Fluctuations Despite Optimized Treatment With Available Parkinson's Disease Medications
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 354
- 试验地点
- 83
- 主要终点
- Number of Participants With Sleep Attacks During the Post-PEG Long-Term Treatment Period
研究概览
简要总结
The primary objective of this study will be to provide further evidence of the long-term safety and tolerability of levodopa-carbidopa intestinal gel (Duodopa®) over 12-months in participants with advanced Parkinson's disease (PD) and severe motor fluctuations.
详细描述
The study was composed of a screening period followed by 3 sequential on-treatment periods, as follows:
- Screening Period (up to 28 days): determination of eligibility and discontinuation of antiparkinsonian disease medications other than levodopa-carbidopa immediate release (LC-oral) prior to nasojejunal (NJ) tube placement.
- NJ Test Period (2 to 14 days): first hospitalization period, Baseline assessments, placement of NJ tube, and optimization of levodopa-carbidopa intestinal gel (LCIG) treatment via NJ tube and infusion pump (participant was hospitalized for NJ tube placement but hospitalization was not required for entire duration of LCIG treatment optimization).
- PEG-J Period (2 to 14 days): second hospitalization period; placement of PEG-J tube; further optimization of LCIG treatment.
- Post PEG-J Long-Term Treatment Period (Day 28 to Day 378): LCIG administration via a permanent PEG-J tube and infusion pump, with dosage adjusted according to clinical condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Idiopathic Parkinson's disease (PD) according to United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
- •Levodopa-responsive with severe motor fluctuations
- •Recognizable off and on state (motor fluctuations) confirmed by diary
排除标准
- •Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists such as secondary parkinsonism
- •Undergone surgery for the treatment of PD
- •Contraindications to levodopa (such as narrow angle glaucoma)
研究组 & 干预措施
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants were to receive LCIG, via the NJ tube during the nasojejunal (NJ) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment.
The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the Post-PEG-J Long-Term Treatment Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour), in most instances.
干预措施: Levodopa-carbidopa intestinal gel (Drug)
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants were to receive LCIG, via the NJ tube during the nasojejunal (NJ) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment.
The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the Post-PEG-J Long-Term Treatment Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour), in most instances.
干预措施: CADD-Legacy® 1400 ambulatory infusion pump (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants were to receive LCIG, via the NJ tube during the nasojejunal (NJ) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment.
The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the Post-PEG-J Long-Term Treatment Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour), in most instances.
干预措施: PEG tube (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants were to receive LCIG, via the NJ tube during the nasojejunal (NJ) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment.
The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the Post-PEG-J Long-Term Treatment Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour), in most instances.
干预措施: J-tube (Device)
结局指标
主要结局
Number of Participants With Sleep Attacks During the Post-PEG Long-Term Treatment Period
时间窗: During the Post-PEG Long-Term Treatment Period (Day 28 through Day 378)
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters
时间窗: Screening through Day 378
Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively.
Number of Participants With Confirmed Cases of Melanoma
时间窗: Screening up to Day 378
A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination or end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis.
Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and During the Post-PEG Long-term Treatment (PPLT) Period
时间窗: Baseline, during the Post-PEG Long-term Treatment Period (Day 28 through Day 378)
The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs
时间窗: Screening through Day 378 + 30 days
AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE.
Number of Participants With Device Complications During the Percutaneous Endoscopic Gastrostomy - With Jejunal Extension Tube (PEG-J) Surgery and Post-PEG Long Term Treatment Periods
时间窗: PEG-J Surgery Period (from 2 to 14 days) through the Long Term Treatment Period (Day 28 to Day 378)
Complications of the infusion device were collected during the PEG-J Surgery and Post-PEG Long-Term Treatment periods. Pump, PEG-J, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and post-procedural hemorrhage.
Number of Participants With Potentially Clinically Significant Values for Hematology Parameters
时间窗: Screening through Day 378
Potentially clinically significant values for red blood cells (RBCs), hemoglobin, and hematocrit are specified for females (f) and males (m) separately in the category rows.
Number of Participants With Sleep Attacks at Baseline
时间窗: Baseline
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Endpoint
时间窗: Baseline, Endpoint (last Post-PEG Long-Term Period visit up to Day 378)
The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions regarding issues with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst "On" time (dyskinesia \[involuntary muscle movement\]).
Number of Participants With Device Complications During the Nasojejunal (NJ) Test Period
时间窗: NJ Test Period (from 2 to 14 days)
Complications of the infusion device were collected during the NJ Test period. Pump, intestinal tube, NJ tube, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and post-procedural hemorrhage.
Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters
时间窗: Screening through Day 378
Terms abbreviated in the table include aspartate aminotransferase (AST), upper limit of normal (ULN), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), female (f), and male (m).
Number of Participants With Potentially Clinically Significant Vital Sign Parameters
时间窗: up to 56 weeks
Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively.
Number of Participants Taking at Least 1 Concomitant Medication During the Study
时间窗: Screening up to Day 378
Concomitant medications include those started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study.
次要结局
- Change From Baseline in Average Daily "Off" Time at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Month 12(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Summary Index at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Endpoint(Baseline, Endpoint (last post-baseline visit up to Day 378))