A Phase 1 Open Label Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PHIN-214 in Adults With Child Pugh A and B Cirrhosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 74
- 试验地点
- 9
- 主要终点
- maximum tolerated dose or optimal beneficial dose of PHIN-214 in multiple ascending dose; safety and tolerability.
研究概览
简要总结
This 2-part study will evaluate PHIN-214 given as a single one-time dose (Part 1) and in multiple doses (given as daily doses for 28-days) (in Part 2). Specifically, this study evaluates PHIN-214, to determine the safety, tolerability, and pharmacokinetic effects of PHIN-214, and to establish the maximum tolerated dose or optimal beneficial dose in patients with Child Pugh A and B Cirrhosis.
详细描述
PHIN-214 action has similar actions as another medication called "terlipressin or TERLIVAZ®." Terlipressin has been shown to reduce portal hypertension, improve renal function, and induce natriuresis in cirrhotic patients with ascites without hepatorenal syndrome (HRS). It is approved in several countries including the US for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered using multiple IV doses given by bolus injections in the hospital.
This study is an open label, first in human study of PHIN-214. PHIN-214 is a terlipressin derivative administered subcutaneously. It is a partial V1a agonist which is designed to reduce splanchnic blood pooling and portal hypertension. A resultant increase in systemic pressure and renal arterial pressure may increase kidney perfusion and creatinine clearance.
This study will evaluate a single dose of PHIN-214 (in Part 1) and in Part 2, daily doses of PHIN-214 for up to 28-days (called multiple ascending doses) of PHIN-214 to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of PHIN-214 in subjects with advanced cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 否
入选标准
- •History of cirrhosis based on histology or a combination of clinical, radiological, or biochemical assessment and classified as Child-Pugh A or B
- •Participants may be male or female aged 18 to 75 years.
- •Body mass index (BMI) within the range 18 to 40 kg/m2 (inclusive) at screening.
- •Female participants must be non-pregnant, non-lactating, or of non-childbearing potential or using highly efficient contraception for the full duration of the study
排除标准
- •Significant abnormalities in medical history or on physical examination, including: respiratory disease requiring therapy or history of respiratory failure, cardiovascular disease or hypertension, electrocardiogram abnormalities or history of significant EKG abnormalities.
- •History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, or any other disorder associated with fluid or sodium imbalance.
- •Significant kidney disease
- •Hepatic encephalopathy (HE) or altered mental status requiring hospitalization; variceal bleeding or upper gastrointestinal bleeding; or type 1 hepatorenal syndrome with acute kidney injury (HRS-AKI) during the previous 3 months prior to Screening.
- •Acute-on-chronic liver failure.
- •Recipient of a patent transjugular intrahepatic portosystemic shunt (TIPS).
- •Known positive HIV serology confirmed by HIV viral load.
- •Subjects with acute infections, including acute viral hepatitis (subjects with chronic hepatitis B are eligible if treatment regimen is stable ≥ 3 months prior to study inclusion).
研究组 & 干预措施
single dose of PHIN-214
Participants in Part 1 will receive one dose of PHIN-214 administered subcutaneously. Dose level will be assigned in ascending doses to observe initial safety and tolerability. A Safety Committee will review information from each patient and determine the dose level for the subsequent participants.
干预措施: PHIN-214 Subcutaneous injection (Drug)
multiple daily dosing of PHIN-214
Participants in Part 2 will be trained to give themselves a daily dose of PHIN-214 at home by subcutaneous injection for 28-days. The dose level assigned to each participant will be determined by a Safety Committee after reviewing information from the last participants' experience and compilation of experiences on all previous participants. Dose level advancement will be guided throughout the study by the experiences and information collected from each participant.
干预措施: PHIN-214 Subcutaneous injection (Drug)
结局指标
主要结局
maximum tolerated dose or optimal beneficial dose of PHIN-214 in multiple ascending dose; safety and tolerability.
时间窗: may be up to six weeks
Incidence of adverse effects (type and severity), incidence of dose limiting toxicities, changes in key laboratory measures
Pharmacokinetics of PHIN-214 metabolite
时间窗: up to six weeks
plasma concentration of PHIN-214 metabolite
Pharmacokinetics of PHIN-214
时间窗: up to six weeks
plasma concentration of PHIN-214
次要结局
- Immunogenicity of PHIN-214(up to six weeks)