A Phase IIa Multicenter, Randomized, Double-blind, Placebo-controlled Study Followed by an Open-label Period, to Evaluate the Safety, Tolerability, and Levodopa Pharmacokinetics in Levodopa-treated Parkinson's Disease Patients With Motor Fluctuations, Administered With Repeated Subcutaneous ND0612
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 3
- 主要终点
- Safety
研究概览
简要总结
This is a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics (PK) of ND0612 in Parkinson's disease (PD) patients on an optimized oral levodopa (LD) regimen and experiencing ≥2 h/day of OFF time. Safety and tolerability, PK profile, pump usability, and the potential clinical effect of ND0612 will be explored in subjects with PD and motor fluctuations.
详细描述
During Period 1, patients continued on their current standard of care (SoC) levodopa/carbidopa (LD/CD) and were randomized at 2:1 ratio to 14 days of adjunct treatment with ND0612 (daily LD/CD dose of 270/63 mg) or placebo infusion. During Period 2, patients were randomized to receive 7 days open-label treatment with ND0612 or ND0612 plus oral entacapone. Patients then entered a 4-week safety follow-up period.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women with idiopathic PD whose diagnosis was confirmed by presence of at least two of the cardinal signs (resting tremor, bradykinesia, rigidity) and lacking any other known or suspected cause of parkinsonism.
- •Patients who experienced motor fluctuations averaging at least two hours daily in the "OFF" state during the waking hours (including morning akinesia), corresponding to the end-of-dose deterioration phenomenon ("wearing off") confirmed by the baseline home diaries.
- •Modified Hoehn and Yahr stage < 5 in the "OFF" state.
- •Patients who were taking optimized LD/decarboxylase inhibitor therapy (based on the investigator's judgment) that was stable for at least 14 days prior to baseline. Patients were to receive at least three daily doses of LD (which could include a bedtime dose) with at least three hours between doses.
- •Patients treated with dopaminergic agonists and other anti-PD drugs were to be on stable doses for at least 30 days prior to baseline and those doses were to remain constant throughout the study period.
- •Women who were postmenopausal, surgically sterilized, or using adequate birth control. Women of childbearing potential were to have a negative pregnancy test (beta human chorionic gonadotropin [hCG] serum) at screening.
- •Patients between the ages of 30 and
- •Patients willing and able to give informed consent.
- •Patients and/or caregivers able to understand and follow instructions for use of SC delivery pump.
- •Patients who demonstrated the ability to keep accurate diaries of PD symptoms (ON-OFF diaries).
排除标准
- •Patients treated with controlled release formulation of LD/CD. (Note: Patients treated with Entacapone, Tolcapone, or Stalevo were allowed to participate in Period 1 but were excluded from Period 2 participation)
- •Patients with a clinically significant or unstable medical or surgical condition which would preclude safe and complete study participation. Such conditions may include gastrointestinal, cardiovascular, pulmonary, hepatic, renal, or metabolic diseases or malignancies as determined by medical history, physical exam, laboratory tests, or ECG.
- •History of melanoma or significant skin disorders.
- •Patients with significant cognitive impairment as defined by a MMSE score of <
- •Patients treated with dopaminergic agonists, anticholinergics, monoamine oxidase (MAO)-B inhibitors, or antipsychotics that need dose adjustment in the 30 days prior to Study Baseline.
- •Patients with clinically significant psychiatric illness, including major depression (according to Diagnostic and Statistical Manual of Mental Disorders [DSM] IV criteria for major depressive episode) or other problems that might compromise their ability to provide consent or participate fully in the study.
- •Patients with a history of alcohol or substance abuse within the past two years.
- •Patients who have taken experimental medications within 60 days prior to baseline.
- •Patients who have undergone a neurosurgical intervention for PD (e.g. pallidotomy, thalamotomy, transplantation, or deep brain stimulation procedures).
- •Patients with severe disabling dyskinesias.
- •Patients with hearing, visual or motor impairments that prevent them from using the pump or reacting effectively to errors.
研究组 & 干预措施
Period 2. ND0612 + Entacapone
A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment + Entacapone 200 mg 3 times/day (every 6 hours during waking hours) for 7 days
干预措施: Entacapone (Drug)
Period 1. Placebo
A 24h SC infusion of saline in addition to the current standard of care treatment for 14 days
干预措施: Placebo (Drug)
Period 1. ND0612
A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment for 14 days
干预措施: ND0612 (Drug)
Period 2. ND0612
A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment for 7 days
干预措施: ND0612 (Drug)
Period 2. ND0612 + Entacapone
A 24h SC infusion of levodopa/carbidopa 270/63 mg daily in addition to the current standard of care treatment + Entacapone 200 mg 3 times/day (every 6 hours during waking hours) for 7 days
干预措施: ND0612 (Drug)
结局指标
主要结局
Safety
时间窗: 14 days
1. Incidence and frequency of adverse events, of dopaminergic adverse events 2. Adverse events reporting related to the ND0612 subcutaneous administration, Draize score 3. Vital signs, physical exam, Laboratory measurements
Levodopa pharmacokinetics (LD PK)
时间窗: 1hr and 2hr predose, 0h, 0.5 hr, 1hr, 1.5hr, 2hr, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr, 9hr and 10hr hours post oral LD dose
LD PK parameters: Cmax, Area under the Curve (AUC), T\>1000ng/ml, through levels at baseline and during treatment at 14 days.
Tolerability
时间窗: 14 days
Withdrawal rates and discontinuations due to adverse events
次要结局
- LD dose adjustment(14 days)
- Pump Usability(14 days)