A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Pharmacokinetics Measurements to Determine Cmax for Carbidopa (CD) and Levodopa (LD) Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
研究概览
简要总结
This study evaluated the pharmacokinetics, motor effects, and assessed the safety of IPX066 compared with an immediate-release cabridopa-levodopa formulation in subjects with advanced Parkinson's disease.
详细描述
This was a randomized, multicenter, open-label, single and multiple oral dose, two-treatment, two-period, crossover study in LD-experienced subjects with Parkinson's disease (PD). Subjects received 7 days of one treatment (IPX066 or IR CD-LD) followed by an approximate 7-day washout period followed by another 7 days of the other treatment (IR CD-LD or IPX066). During the approximate 7-day washout period, subjects took their prestudy CD-LD regimen. Pharmacokinetic and efficacy/pharmacodynamic measurements were done on Days 1 and 8. Safety measures (electrocardiograms [ECGs], clinical laboratory tests, vital signs, adverse events [AEs], and concomitant medications) were evaluated over the course of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Male or female diagnosed with idiopathic PD, without any known cause for Parkinsonism.
- •If female and of childbearing potential, subject should be abstinent or continuing to practice and willing to continue throughout the study with appropriate contraceptives (defined as Nova ring, oral, injected, transdermal patch, implanted, or barrier). The subject must agree to take every precaution to ensure that pregnancy will not occur during the study.
- •At least 30 years old at the time of diagnosis of PD.
- •Mini Mental State Examination (MMSE) ≥ 26 at Screening Visit.
- •A responder to LD and currently being chronically treated with stable dosage of commercially available standard, orally disintegrating, or controlled-release CD LD for at least 1 month.
- •Must have predictable fluctuations between "on" and "off" states.
- •Hoehn and Yahr Stage I-IV when "on".
- •Able to provide informed consent and willing to sign Health Insurance Portability and Accountability Act (HIPAA) authorization.
- •Able and willing to comply with the protocol, including availability for all scheduled study visits and blood sample collections.
排除标准
- •Pregnant or breastfeeding.
- •Diagnosed with atypical parkinsonism.
- •History, physical findings or laboratory results suggesting a diagnosis other than PD.
- •Allergic or nonresponsive to previous CD-LD therapy.
- •Any medical (e.g., liver or kidney impairment, peptic ulcer) or condition/history that, in the Investigator's opinion, may jeopardize the subject's safety.
- •Exposure to any investigational agent within 30 days prior to Visit
- •Donated blood or plasma within 28 days.
- •Had prior functional neurosurgical treatment for PD (ablation or Deep Brain Stimulation).
研究组 & 干预措施
Sequence 1
Treatment Period 1:
IPX066 - 7 days; Washout Period - 7 days;
Treatment Period 2:
IR CD-LD- 7 days
干预措施: IPX066 (Drug)
Sequence 1
Treatment Period 1:
IPX066 - 7 days; Washout Period - 7 days;
Treatment Period 2:
IR CD-LD- 7 days
干预措施: IR CD-LD (Drug)
Sequence 2
Treatment Period 1:
IR CD-LD - 7 days; Washout period - 7 days;
Treatment Period 2:
IPX066- 7 days
干预措施: IPX066 (Drug)
Sequence 2
Treatment Period 1:
IR CD-LD - 7 days; Washout period - 7 days;
Treatment Period 2:
IPX066- 7 days
干预措施: IR CD-LD (Drug)
结局指标
主要结局
Pharmacokinetics Measurements to Determine Cmax for Carbidopa (CD) and Levodopa (LD) Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
时间窗: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm 2 (CD-LD IR first, washout, then IPX066)
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Maximum (peak) drug concentration (Cmax in nanograms/milliliter) was estimated using Single-Dose data and Multiple-Dose data.
Pharmacokinetics Measurements to Determine Area Under the Concentration-time Curve for the Dosing Interval for LD and CD Concentrations From Blood Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Treatment Arms.
时间窗: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Area under the concentration-time curve for the dosing interval (AUC Tau) in hour\*nanogram/milliliter was estimated using Single-Dose data and Multiple-Dose data.
Pharmacokinetics Measurements to Determine Tmax for Levodopa and Carbidopa Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
时间窗: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Time of maximum drug concentration (Tmax in hours) was estimated using Single-Dose data and Multiple-Dose data.
次要结局
- 8-Hour Efficacy Using Day 1 Tapping(Day 1 of each treatment period - three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period)
- "Off" Time Hours Reported by Subjects Using Parkinson's Patient Diary(Last 3 days of each treatment period, every 30 minutes over a 24-hour day beginning at 6:00 AM)
- 8-Hour Efficacy Using Day 1 Unified Parkinson's Disease Rating Scale Part III Score(Pre dosing and at hourly intervals through the 8-hour measurement period on day 1)
- Result Summary of Day 1 Dyskinesia Evaluated by Investigator Assessment for Each Treatment Period(Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period)