An Open-Label, Single-Arm, Baseline-Controlled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of ABT-SLV187 Monotherapy in Subjects With Advanced Parkinson's Disease and Persistent Motor-Complications Despite Optimized Treatment With Available Anti-Parkinsonian Medication
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 主要终点
- Average Daily Normalized "Off" Time: Change From Baseline To The Final PEG-J Visit
研究概览
简要总结
The primary objective of this study is to measure the efficacy of ABT-SLV187 in subjects with advanced Parkinson's disease.
详细描述
The study was composed of a screening period followed by 2 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 (N-J) tube placement.
- N-J Test Period (2 to 14 days): first hospitalization period, Baseline assessments, placement of N-J tube, and optimization of levodopa-carbidopa intestinal gel (LCIG) treatment via N-J tube and infusion pump (participant was hospitalized for N-J tube placement but hospitalization was not required for entire duration of LCIG treatment optimization).
- PEG-J Period (12 weeks): second hospitalization period; placement of PEG-J tube; further optimization of LCIG treatment.
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
- •Diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria.
- •Subjects have 4 or 5 in modified Hohn and Yahr (H & Y) classification of disease severity at "Off" state determined by the UPDRS Part V at Screening Visit
- •The subject's advanced Parkinson's disease must be levodopa-responsive as judged by the Investigator.
- •Subjects have had optimal treatment with available Parkinson's disease medication as defined by local standards of care and, based upon the judgment of the Investigator, and their symptoms are judged inadequately controlled on this optimized treatment. Optimized treatment is defined as the maximum therapeutic effect obtained with available anti-parkinsonian pharmacological therapy when no further improvement is expected regardless of any additional manipulations of levodopa and/or other anti parkinsonian medication; this will be based on the Investigator's best clinical judgment.
- •Presence of a recognizable "Off" and "On" state (motor fluctuations) as confirmed by UPDRS Part III (in both "On" and "Off" states), and by the Parkinson's Disease Diary© which must be observed and confirmed at Screening Visit
- •Subjects must be experiencing a minimum of 3 hours per day of "Off" time, as estimated by the Investigator and supported by the UPDRS at Screening Visit 1 and the Parkinson's Disease Diaries at baseline. The "Off" time must occur during a continuous 16-hour interval, including the portion of the day during which the subject is awake the majority of the time (e.g., 5 AM to 9 PM, 7 AM to 11 PM).
排除标准
- •Parkinson's disease diagnosis is unclear or a suspicion of other parkinsonian syndromes exists, such as secondary Parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson's-plus syndromes (e.g., multiple system atrophy, progressive supranuclear palsy) or the other neurodegenerative diseases that might mimic the symptoms of Parkinson's disease .
- •Subjects who have undergone neurosurgery for the treatment of Parkinson's disease .
- •Current primary psychiatric diagnosis of acute psychotic disorder or other uncontrolled primary psychiatric diagnoses, (e.g., bipolar disorder or major depressive disorder per Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) criteria.
- •Alzheimer's disease; or other significant cognitive impairment or dementia (defined as Mini-Mental State Examination (MMSE) total score < 24).
- •Subject has significant current suicidal ideation within the previous year as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening or any history of suicide attempts.
- •A low B12 level or low-normal B12 level (less than 300 pg/mL) with elevated methylmalonic acid (MMA). Note: Abnormal Vitamin B12 of questionable clinical significance (i.e., indeterminate or low normal results) prior to or at Screening Visit 2 require appropriate interpretation in conjunction with MMA and homocysteine laboratory values prior to proceeding further into the study.
研究组 & 干预措施
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants received LCIG via the N-J tube during the nasojejunal (N-J) 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 PEG-J 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).
干预措施: Levodopa-carbidopa intestinal gel (Drug)
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants received LCIG via the N-J tube during the nasojejunal (N-J) 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 PEG-J 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).
干预措施: CADD-Legacy® 1400 ambulatory infusion pump (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants received LCIG via the N-J tube during the nasojejunal (N-J) 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 PEG-J 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).
干预措施: PEG tube (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
All participants received LCIG via the N-J tube during the nasojejunal (N-J) 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 PEG-J 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).
干预措施: J-tube (Device)
结局指标
主要结局
Average Daily Normalized "Off" Time: Change From Baseline To The Final PEG-J Visit
时间窗: Baseline (end of screening period) and Final PEG-J Visit (up to 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
- Number of Participants With Potentially Clinically Significant Values for 12-lead Electrocardiogram (ECG)(From Baseline (end of screening period) to Final PEG-J Visit (up to week 12))
- Parkinson's Disease Questionnaire (PDQ-39) Mobility, Emotional Well-Being, Stigma, Social Support, Cognition, Communication, and Bodily Discomfort Domain Scores: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Average Daily Normalized "On" Time Without Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Parkinson's Disease Questionnaire (PDQ-39) Summary Index: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Patient Global Impression of Change (PGI-C) Score at the Final PEG-J Visit(Final PEG-J Visit (up to week 12))
- Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl Score: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Clinical Global Impression - Change (CGI-I) Score at the Final PEG-J Visit(Final PEG-J Visit (up to week 12))
- Average Daily Normalized "On" Time With Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Unified Parkinson's Disease Rating Scale (UPDRS) Total Score: Change From Baseline To The Final PEG-J Visit(Baseline and Final PEG-J Visit (up to Week 12))
- Average Daily Normalized "Off" Time Excluding Subjects Who Did Not Receive LCIG During the Entire PEG-J Period: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Average Daily Normalized "Off" Time Including All PD Diaries Regardless if They Were Completed After the Subject Had Used a Concomitant Anti-Parkinsonian Medication: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters(From Baseline (end of screening period) to Final PEG-J Visit (up to week 12))
- Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Final PEG-J Visit (up to week 12))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From N-J placement to the end of study or early termination of treatment, including the removal of PEG-J (up to 17 weeks), plus 30 days.)
- Number of Participants With Potentially Clinically Significant Values for Hematology Parameters(From Baseline (end of screening period) to Final PEG-J Visit (up to week 12))
- Average Daily Normalized "Off" Time at Baseline and Each Visit: Change From Baseline To The Final PEG-J Visit(Baseline (end of screening period) and Weeks 2, 4, 6, 8, 10, and 12)
- Number of Participants With Potentially Clinically Significant Vital Sign Parameters(From Baseline (end of screening period) to Final PEG-J Visit (up to week 12))