A Multicenter, Parallel-group, Rater-blinded, Randomized Clinical Study Investigating the Efficacy, Safety, Tolerability and Pharmacokinetics of 2 Dosing Regimens of ND0612H [ ] in Subjects With Advanced Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 11
- 主要终点
- Change in Daily "OFF" Time
研究概览
简要总结
This is a multicenter, parallel-group, rater-blinded, randomized clinical study in subjects with advanced PD investigating the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing regimens of ND0612H, a solution of LD/CD delivered via a pump system as a continuous SC infusion, compared to standard oral LD/CD. After screening, subjects will undergo 1 day of standard oral LD/CD inpatient dosing followed by 2 days of inpatient treatment with 1 of 2 randomly allocated (1:1 randomization ratio) dosing regimens of ND0612H continuous SC infusion. Subjects will then continue on a maintenance dose of the assigned ND0612H dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after the last SC administration of the study drug for a total of about 2.5 months of participation for each subject enrolled into the trial.
详细描述
This phase IIa randomized, controlled, parallel-group study will be conducted in 36 subjects with advanced PD who are treated with oral LD/CD at a stable dose and have predictable morning "OFF" periods and at least 2.5 hrs of daily "OFF" periods. The study will investigate the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing regimens of ND0612H. Regimen 1 will employ continuous infusion for 24 hrs using a low infusion rate at night and a higher rate at daytime with supplemental administration of oral immediate release (IR) LD/CD in the mornings. During the inpatient period of about 3 days, the site staff will manage the administration and replacement of the infusions. On Day 4 subjects will be discharged home after they and their study partners have received training on the administration of the infusion. Subjects will then continue on a maintenance dose of the assigned ND0612 dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after the last SC administration of the study drug.
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
- Single (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
- •Male and female PD subjects of any race aged 30 to 80 years who sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
- •PD diagnosis consistent with the UK Brain Bank Criteria.
- •Modified Hoehn & Yahr scale in "ON" state of stage ≤
- •Taking at least 4 doses/day of LD (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least 2 other classes of anti-PD medications in a therapeutic dose for at least 30 consecutive days each.
- •Subjects must be stable on their anti-PD medications for at least 30 days before Day
- •Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612H treatment period.
- •Must have a minimum of 2.5 hrs of "OFF" time per day with predictable early morning "OFF" periods as estimated by the subject.
- •Must have predictable and well defined early morning "OFF" periods with a good response to LD for treatment of the early morning "OFF" in the judgement of the investigator.
- •Mini Mental State Examination (MMSE) score >
- •No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.
- •Female subjects must be surgically sterile, postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception. All female participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, a barrier method of birth control [e.g., condoms with contraceptive foams, diaphragms with contraceptive jelly], intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug.
- •Willingness and ability to comply with study requirements
排除标准
- •Atypical or secondary parkinsonism.
- •Acute psychosis or hallucinations in past 6 months.
- •Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator or the eligibility reviewer, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
- •Prior neurosurgical procedure for PD, or duodopa treatment.
- •Subjects with a history of drug abuse or alcoholism within the past 12 months.
- •Clinically significant ECG rhythm abnormalities.
- •Renal or liver dysfunction that may alter drug metabolism including: serum creatinine >1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x upper limit of normal (ULN), total serum bilirubin >2.5 mg/dL.
- •Subjects who are not willing to operate the pump system.
研究组 & 干预措施
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1
Dosing Regimen 1 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 24 hours.
干预措施: ND0612 (Levodopa/Carbidopa solution) (Drug)
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2
Dosing Regimen 2 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 14 hours. Infusion started at wake-up time supplemented with an oral IR LD/CD tablet.
干预措施: ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD (Drug)
结局指标
主要结局
Change in Daily "OFF" Time
时间窗: Baseline to Day 28
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. An "ON/OFF" Log was completed by a blinded rater starting before the first dose of LD/DDI and following the first dose at 30 min intervals for 8 hrs. The changes in "OFF" time as hours (normalized to 16 hrs of awake time) during the 8 hrs of data collection were estimated. Negative change from baseline for "OFF" time indicates improvement.
次要结局
- Change in Morning UPDRS Part III (Motor) Scores(Baseline to Day 28)
- The Percentage of Subjects With Full "ON" at Approximately 08:00 and Approximately 09:00, as Determined by the Subject(Baseline to Day 28)
- Change in Daily "Good ON" Time as Assessed by a Blinded Rater(Baseline to Day 28)
- Change in UPDRS Part II (ADL) Scores(Baseline to Day 28)
- Change in PDSS-2 Total Score(Baseline to Day 27)
- CGI-Improvement (CGI-I) Score as Assessed by Investigator(Baseline to Day 28)
- Change in PDQ-39 Summary Index and the 8-dimension Scores(Baseline to Day 27)