A Phase 1, Open-Label Evaluation of the Pharmacokinetics and Safety of a Single Dose of Apraglutide in Subjects With Normal and Impaired Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- VectivBio AG
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Area Under the Curve to Infinity (AUCinf) of Apraglutide
研究概览
简要总结
The primary objective is to assess the pharmacokinetics (PK) of apraglutide in subjects with hepatic impairment compared with matched control subjects with normal hepatic function following single subcutaneous (SC) dose administration.
详细描述
A two stage design, open label, multi-center, non-randomized trial to evaluate the the safety and tolerability of a single subcutaneous dose of apraglutide in subjects with varying degrees of hepatic function. The hepatic function will estimated with the Child-Pugh classification.
Part 1: 8 subjects with moderate hepatic impairment (Cohort 1) and 8 subjects with normal hepatic function (Cohort 2).
Part 2: 8 subjects with mild hepatic impairment (Cohort 3) and 8 subjects with normal hepatic function (from Cohort 2 where possible and additional subject). Part 2 will be conducted only if the geometric mean ratio (GMR) of area under the curve extrapolated to infinity (AUCinf) or area under the curve from zero to the last measurable point (AUClast) for the moderate hepatic impairment group compared to the control group is ≥2.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Participants:
- •Age between 18 and 75 years inclusive
- •Subjects who are willing and able to comply with the study procedures
- •Subjects able to understand and willing to sign the informed consent
- •Body mass index (BMI) of ≥18 to ≤35 kg/m2; and a total body weight of >50 kg (110 lb).
- •Women of childbearing potential (WOCBP) on highly effective method of contraception during the trial and for 1 month after the end of trial (EOT) visit. Sterilized or infertile or postmenopausal females.
- •Male subjects with a female partner of childbearing potential: highly effective methods of contraception and no sperm donation during the trial and for 1 month after (EOT) visit.
- •Participants with impaired hepatic function:
- •Confirmed and documented diagnosis of cirrhosis
- •Moderate liver disease (Child-Pugh B): clinically stable for at least 1 month prior to screening
- •Mild liver disease (Child-Pugh A): clinically stable for at least 1 month prior to screening
排除标准
- •History of clinically significant GI, bronchopulmonary, neurological, cardiovascular, endocrine, or allergic disease
- •Known hypersensitivity to the investigational medicinal product (IMP), any of their excipients or drugs of the same class
- •If capable of reproduction, unwilling to use an effective form of contraception
- •If a female of child-bearing potential, a positive urine/blood pregnancy test
- •Breast-feeding women
- •Positive urine/blood test for alcohol and drugs of abuse at Screening and on Day-1
- •Use of prohibited medications or herbal remedies
- •Known presence or history of intestinal polyps
- •Known presence or history of any type of cancer
- •Pancreatic events such as acute pancreatitis, pancreatic duct stenosis, pancreas infection, and increased blood amylase and lipase (>2.0-5.0×upper limit of normal range)
- •Participation in an investigational drug or device study within 30 days prior to Screening
- •Donation of blood over 500 mL within 2 months prior to Screening
- •Heavy use of tobacco products (i.e., smokes more than 10 cigarettes per day)
- •Concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial
- •Any intercurrent clinically significant illness in the previous 28 days before Day 1 of this study
- •Positive blood screen for human immunodeficiency virus (HIV) antigen/antibody combo, hepatitis A (HAV), hepatitis B surface antigen (HBsAgB), or hepatitis C virus (HCV)
- •Unwillingness or inability to comply with the study protocol for any other reason
研究组 & 干预措施
Part 1: Moderate hepatic impairment
Child-Pugh B
干预措施: Apraglutide (Drug)
Part 1: Normal hepatic function
干预措施: Apraglutide (Drug)
Part 2: Mild hepatic impairment
Child-Pugh A
干预措施: Apraglutide (Drug)
结局指标
主要结局
Area Under the Curve to Infinity (AUCinf) of Apraglutide
时间窗: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a lower limit of quantification (LLOQ) of 1 ng/mL and an upper limit of 200 ng/mL. Plasma pharmacokinetic (PK) parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. AUCinf was calculated as: AUCinf = AUC from time zero to the last quantifiable concentration (AUClast) + (Clast/kel) where Clast was the observed concentration at the last time point with concentrations above the lower limit of quantification and kel was the terminal elimination rate constant.
Area Under the Curve (AUC) From Time Zero to 168 Hours Post-dose (AUC0-168h) of Apraglutide
时间窗: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, and 168 hours post-dose
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used.
Maximum Observed Plasma Concentration (Cmax) of Apraglutide
时间窗: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Cmax was the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
次要结局
- Time of Maximum Plasma Concentration (Tmax) of Apraglutide(Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose)
- Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide(Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose)
- Terminal Elimination Rate Constant (Kel) of Apraglutide(Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose)
- Terminal Half-life (t1/2) of Apraglutide(Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose)
- Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide(Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Day 1 to Day 14)