A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics of Ampreloxetine Following a Single-dose in Subjects With Mild, Moderate, and Severe Hepatic Impairment and in Matching Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Plasma AUC0-inf
研究概览
简要总结
An open-label study to characterize the effects of mild, moderate, and severe Hepatic Impairment (HI) on the pharmacokinetics (PK) of ampreloxetine following a single oral dose in comparison with healthy volunteers with normal hepatic function.
详细描述
This is a multicenter, non-randomized, open label, parallel group, single dose, 2-part study being conducted in adult subjects with mild, moderate, or severe HI (Child-Pugh Class A, B, and C), and in matching healthy subjects. The healthy matching group will be comparable to the corresponding hepatic impairment groups by matching subjects by weight (±20% of group mean), age (±10 years of group mean), and sex (equal ratios across groups).
The study will be conducted in two sequential parts:
In Part A, following a 28-day screening period, 6 subjects each with mild or moderate HI and 6 matching healthy subjects who meet eligibility criteria will be enrolled and administered a single Dose A (Day 1).
In Part B, following a 28-day screening period, 6 subjects with severe hepatic impairment will receive a single Dose A (Day 1). Furthermore, the Sponsor may choose to enroll up to 6 additional healthy subjects in Part B to ensure matching of subjects across all groups for weight, age, and sex is maintained.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Subjects:
- •has a body mass index (BMI) of 19 to 40 kg/m2, inclusive, and weight of at least 55 kg.
- •clinical labs within normal ranges
- •creatinine clearance of >70 mL/min
- •women must be non-pregnant and non-lactating, male and females must agree to highly effective methods of contraception
- •additional criteria apply
- •Subjects with Impaired Hepatic Function additional criteria:
- •Subject has mild (Child-Pugh Class A [5 to 6 points]), moderate (Child-Pugh Class B [7 to 9 points]), or severe (Child-Pugh Class C [10-15 points]) liver disease
- •has stable hepatic impairment defined as no clinically significant change in disease status within the last 30 days
- •must be on a stable dose of medication and/or treatment regimen at least 30 days before dosing
- •Additional inclusion criteria apply
排除标准
- •Subjects with normal hepatic function:
- •history of reactions or hypersensitivity to ampreloxetine or known intolerance to other norepinephrine reuptake inhibitors (NRI) or serotonin norepinephrine reuptake inhibitors (SNRI).
- •personal or family history of congenital long QT syndrome
- •history of untreated closed angle glaucoma
- •history of orthostatic hypotension or orthostatic tachycardia or a history of dizziness, lightheadedness or fainting, or a feeling of blacking out upon standing
- •has used nephrotoxic or hepatotoxic medications 30 days before Day-2
- •routinely uses more than 2 grams of acetaminophen daily
- •has used tobacco-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, e cigarettes, vaporizers) within 3 months before Screening or has a positive cotinine result at Screening or Day -2
- •used any CYP1A2 inhibitor or inducer within 7 days or 5 half lives, whichever is longer, prior to ampreloxetine dosing or requires concomitant use
- •has used monoamine oxidase inhibitors (MAO-I) within 7 days or 5 half lives, whichever is longer, prior to ampreloxetine dosing or requires concomitant use
- •additional exclusion criteria apply
- •Subjects with impaired hepatic function additional criteria:
- •has severe ascites that could potentially interfere with respiratory function
- •current severe hepatic encephalopathy
- •history of liver transplantation, hepatocellular carcinoma, or acute liver disease
- •has biliary liver cirrhosis
- •has uncontrolled hypertension (SBP >180 mm Hg and DBP (Diastolic blood pressure) >110 mm Hg)
- •has an abnormal ECG at Screening or Day -2, including QTcF (Fridericia's corrected QT Interval) >470 msec
- •additional exclusion criteria apply
研究组 & 干预措施
Normal Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with normal hepatic function
干预措施: Ampreloxetine (Drug)
Mild Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with mild hepatic impairment
干预措施: Ampreloxetine (Drug)
Moderate Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with moderate hepatic impairment
干预措施: Ampreloxetine (Drug)
Severe Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with severe hepatic impairment
干预措施: Ampreloxetine (Drug)
结局指标
主要结局
Plasma AUC0-inf
时间窗: Plasma AUC0-inf will be measured from Day 1 to Day 15
Estimation of AUC from time zero extrapolated to infinity
Plasma AUC0-t
时间窗: Plasma AUC0-t will be measured Day 1 to Day 15
Estimation of Area under the concentration-time curve, from time zero to the last measured time point
Plasma Cmax
时间窗: up to Day 21
Estimation of maximum observed plasma concentration
次要结局
- Number of subjects with clinically significant vital sign abnormalities(up to Day 21)
- Number of subjects with change in C-SSRS scores(up to Day 21)