A Comparative Bioavailability Study to Evaluate the Single Dose Pharmacokinetic Properties of APL-130277 With Two Different Formulations of Subcutaneous Apomorphine in a Randomized, 3-Period Crossover Design in Subjects With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 3
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
A study that compares the extent to which apomorphine becomes available in the body after taking either an investigational drug containing apomorphine or apomorphine that is injected under the skin in people with PD complicated by "OFF" episodes.
详细描述
This multi-center study will aim to evaluate the pharmacokinetics (PK) and comparative bioavailability of a single dose of APL-130277 sublingual thin film with subcutaneous (s.c.) APO-go® and s.c. APOKYN® in subjects with Parkinson's disease (PD). The dose of APOKYN® (≤ 5 mg) will be based on the subjects' current prescribed dose. The study is designed as an open-label, randomized, three-way crossover. Subjects will receive all three treatment arms with a minimum 1-day wash-out between each visit (excluding the screening visit) and will be randomly assigned to one of the six sequences
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 18 years of age.
- •Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
- •Clinically meaningful response to Levodopa (L-Dopa) with well-defined "OFF" episodes, as determined by the Investigator.
- •Receiving APOKYN® of ≤ 5 mg per dose for at least 4 weeks before the Screening Visit.
- •Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the Screening Visit. Adjunctive PD medication regimens must be maintained at a stable dose for at least 4 weeks prior to the Screening Visit with the exception that MAOB inhibitors must be maintained at a stable level for at least 8 weeks prior to the Screening Visit.
- •No planned medication change(s) or surgical intervention anticipated during the course of study.
- •Patients must experience a well-defined "OFF" episode in the morning if they do not take their morning PD medications on schedule, and must be willing to delay morning doses on the 3 study dosing days
- •Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
- •Mini-Mental State Examination (MMSE) score >
- •If female and of childbearing potential, must agree to use one of the following methods of birth control:
- •Oral contraceptive;
- •Contraceptive patch;
- •Barrier (diaphragm, sponge or condom) plus spermicidal preparations;
- •Intrauterine contraceptive system;
- •Levonorgestrel implant;
- •Medroxyprogesterone acetate contraceptive injection;
- •Complete abstinence from sexual intercourse;
- •Hormonal vaginal contraceptive ring; or
- •Surgical sterilization or partner sterile (must have documented proof).
- •Male patients must be either surgically sterile, agree to be sexually abstinent or use a barrier method of birth control (e.g., condom) or maintain a monogamous relationship with a person who is not of child-bearing potential from first study drug administration until 30days after final drug administration.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
- •Able to understand the consent form, and to provide written informed consent
排除标准
- •Atypical or secondary parkinsonism.
- •Previous treatment with any of the following: continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.
- •Contraindications to APO-go® or APOKYN® or hypersensitivity to apomorphine hydrochloride or any marcrolide antibiotic or any of the ingredients APO-go® or APOKYN® (notably sodium metabisulfite).
- •Female who is pregnant or lactating.
- •Participation in a clinical trial within 30 days prior to the Screening Visit.
- •Receipt of any investigational (ie, unapproved) medication within 30 days prior to the Screening Visit.
- •Any selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine and clozapine) or dopamine depleting agents within 30 days prior to the Screening Visit.
- •Drug or alcohol dependency in the past 12 months.
- •History of malignant melanoma.
- •Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
- •Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
- •History of clinically significant hallucinations during the past 6 months.
- •History of clinically significant impulse control disorder(s).
- •Dementia that precludes providing informed consent or would interfere with participation in the study.
- •Current suicidal ideation within one year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
- •Donation of blood plasma in the 30 days prior to first dosing.
- •Cankers or mouth sores within 30 days prior to the Screening Visit, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a patient into the study.
研究组 & 干预措施
APL-130277, sublingual thin film
APL-130277, sublingual thin film, once daily
干预措施: APL-130277 (Drug)
Subcutaneous APO-go
Subcutaneous APO-go, once daily
干预措施: APO-go (Drug)
Subcutaneous APOKYN
Subcutaneous APOKYN, once daily
干预措施: Apokyn (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: Day 1
Dose normalized maximum observed plasma concentration (Cmax)
Observed Time of the Maximum Concentration (Tmax)
时间窗: Day 1
Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.
Area Under the Concentration- Time Curve (AUC Last)
时间窗: Day 1
area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.
Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
时间窗: Day 1
Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.
Area Under the Concentration- Time Curve (AUC Inf)
时间窗: Day 1
area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
时间窗: Day 1
Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.
Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
时间窗: Day 1
Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.
Mean Residence Time (MRT)
时间窗: Day 1
Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf. AUMCinf is the area under the first moment (time.plasma concentration vs. time) curve.
Apparent Volume of Distribution After Non-intravenous Administration (V/F)
时间窗: Day 1
Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf \* λz).
Terminal-phase Half-life (t½)
时间窗: Day 1
Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.
Terminal-phase Rate Constant ( λz)
时间窗: Day 1
Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase. At least 3 data points in the terminal phase will be used in the determination of the rate constant.
次要结局
未报告次要终点