A Randomized, Double-Blind, Double-Dummy, Efficacy, Safety and Tolerability Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects Receiving Optimized Treatments With Parkinson Medicinal Products Who Continue to Experience Persistent Motor Fluctuations
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 15
- 主要终点
- Change From Baseline to Week 12 in Average Daily Normalized "Off" Time
研究概览
简要总结
The primary objective of this study was to demonstrate the superiority of levodopa - carbidopa intestinal gel over treatment with optimized oral levodopa/carbidopa during 12 weeks.
详细描述
Study S187.3.001 (NCT00357994) and Study S187.3.002 (NCT00660387) were 2 identically designed, Phase 3, 12-week, randomized, double-blind, double-dummy, parallel-group, multicenter studies recruiting subjects from distinct sites. These studies evaluated the efficacy, safety, and tolerability of levodopa-carbidopa intestinal gel (LCIG) in the treatment of levodopa-responsive subjects with advanced PD who had persistent severe motor fluctuations, despite optimized treatment with oral levodopa-carbidopa, concomitant with other available antiparkinsonian medications. Participants were randomized to either LCIG active gel + placebo capsules or levodopa-carbidopa immediate release (IR) active capsules + placebo gel. Both treatment arms received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration, active LCIG or placebo gel. Data from these 2 studies were combined for analysis. The decision to combine the study data for analysis was made before enrollment was completed for both studies.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 participants who demonstrate some identifiable 'on response,' established by Investigator observation
- •Demonstrate severe motor fluctuations in spite of individually optimized treatment and where therapy options are indicated
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
- •Subjects with any neurological deficit that may interfere with the study assessments
研究组 & 干预措施
Levodopa-Carbidopa Intestinal Gel (LCIG) + Placebo Capsules
Participants were randomized to LCIG (levodopa, 20 mg/mL and carbidopa monohydrate, 5 mg/mL) and placebo capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of LCIG.
干预措施: Levodopa carbidopa intestinal gel (LCIG) (Drug)
Levodopa-Carbidopa Intestinal Gel (LCIG) + Placebo Capsules
Participants were randomized to LCIG (levodopa, 20 mg/mL and carbidopa monohydrate, 5 mg/mL) and placebo capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of LCIG.
干预措施: Placebo (PBO) oral capsules (Drug)
Levodopa-Carbidopa Intestinal Gel (LCIG) + Placebo Capsules
Participants were randomized to LCIG (levodopa, 20 mg/mL and carbidopa monohydrate, 5 mg/mL) and placebo capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of LCIG.
干预措施: CADD-Legacy® 1400 ambulatory infusion pump (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG) + Placebo Capsules
Participants were randomized to LCIG (levodopa, 20 mg/mL and carbidopa monohydrate, 5 mg/mL) and placebo capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of LCIG.
干预措施: PEG tube (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG) + Placebo Capsules
Participants were randomized to LCIG (levodopa, 20 mg/mL and carbidopa monohydrate, 5 mg/mL) and placebo capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of LCIG.
干预措施: J-tube (Device)
Placebo Gel + Levodopa-Carbidopa Capsules
Participants were randomized to placebo intestinal gel and oral levodopa-carbidopa (levodopa, 100 mg and carbidopa, 25 mg) Immediate Release (IR) capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of placebo.
干预措施: Placebo gel (Drug)
Placebo Gel + Levodopa-Carbidopa Capsules
Participants were randomized to placebo intestinal gel and oral levodopa-carbidopa (levodopa, 100 mg and carbidopa, 25 mg) Immediate Release (IR) capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of placebo.
干预措施: Levodopa carbidopa (LC) oral encapsulated immediate release (IR) tablets (Drug)
Placebo Gel + Levodopa-Carbidopa Capsules
Participants were randomized to placebo intestinal gel and oral levodopa-carbidopa (levodopa, 100 mg and carbidopa, 25 mg) Immediate Release (IR) capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of placebo.
干预措施: CADD-Legacy® 1400 ambulatory infusion pump (Device)
Placebo Gel + Levodopa-Carbidopa Capsules
Participants were randomized to placebo intestinal gel and oral levodopa-carbidopa (levodopa, 100 mg and carbidopa, 25 mg) Immediate Release (IR) capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of placebo.
干预措施: PEG tube (Device)
Placebo Gel + Levodopa-Carbidopa Capsules
Participants were randomized to placebo intestinal gel and oral levodopa-carbidopa (levodopa, 100 mg and carbidopa, 25 mg) Immediate Release (IR) capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of placebo.
干预措施: J-tube (Device)
结局指标
主要结局
Change From Baseline to Week 12 in Average Daily Normalized "Off" Time
时间窗: Baseline, Week 12
Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for "off" time indicates improvement.
次要结局
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Week 12(Baseline, Week 12)
- Change From Baseline in EuroQual Quality of Life - 5 Dimensions (EQ-5D) Summary Index at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Questions 32, 33, and 34 at Week 12(Baseline, Week 12)
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Week 12(Baseline, Week 12)
- Change From Baseline in Average Daily Normalized "On" Time Without Troublesome Dyskinesia at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Week 12(Baseline, Week 12)
- Change From Baseline in UPDRS Part III Score at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Week 12(Baseline, Week 12)
- Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Week 12(Baseline, Week 12)
- Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Week 12(Baseline, Week 12)
- Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Week 12(Baseline, Week 12)
- Employment Impairment (EMP) I Status at Baseline(Baseline)
- Employment Impairment (EMP) II Status at Week 12(Week 12 (or early termination))
- Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Week 12(Baseline, Week 12)
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Week 12(Baseline, Week 12)