A Phase 1, Open-Label, Partially Randomized, 3-Part, Parallel Group Trial to Evaluate the Pharmacokinetic Profile of Glepaglutide (ZP1848) After a Single Intravenous Injection and After Multiple Subcutaneous Injections in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Pharmacokinetic parameter - total body clearance
研究概览
简要总结
The primary objective of the trial is to characterize the pharmacokinetic (PK) profiles of glepaglutide and its primary active metabolites following once-daily and once-weekly subcutaneous (SC) injections and after a single intravenous (IV) infusion in healthy subjects.
Glepaglutide is a proposed International Nonproprietary Name for ZP1848
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations
- •Body Mass index between 18 and 30.0 kg/m2
- •Able to comply with all the trial procedures
- •females will not be pregnant or lactating
- •If female of childbearing potential or male agree to use contraception as defined in the protocol
- •Male subjects must also be willing to refrain from donating sperm from trial Check-in until 90 days after the last dose
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
- •History of bowel obstruction, stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and/or cholecystectomy or hernia repair will be allowed).
- •Clinically significant abnormality on 12-lead ECG
- •Clinically significant abnormality in hematology, clinical chemistry, or urinalysis
- •History of alcoholism or drug/chemical abuse within 2 years
- •Alcohol consumption of > 21 units per week for males and > 14 units for females
- •Positive urine drug screen
- •Positive hepatitis panel and/or positive human immunodeficiency test
- •Receipt of any investigational product within 30 days or 5 half-lives
- •Previous exposure to GLP-1, GLP-2, human growth hormone, or analogs thereof 30 days prior to Check-in
- •Use or intend to use any medications/products known to be strong inhibitors or strong inducers of cytochrome P450 3A enzyme, including St. John's wort
- •Use of tobacco, smoking cessation products, or products containing nicotine (including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine lozenges, or nicotine gum ) within 3 months prior to Screening
- •Receipt of blood products within 2 months prior to Check-in and throughout the trial.
- •Donation of blood or significant blood loss from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening and throughout the trial.
- •Poor peripheral venous access.
研究组 & 干预措施
Group A
1 mg glepaglutide once daily, given as single SC injections on Days 1 to 7
干预措施: Glepaglutide (Drug)
Group B
5 mg glepaglutide once daily, given as single SC injections on Days 1 to 7
干预措施: Glepaglutide (Drug)
Group C
5 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36
干预措施: Glepaglutide (Drug)
Group D
10 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36
干预措施: Glepaglutide (Drug)
Group E
1 mg glepaglutide, given as an IV infusion at a rate of 4 mg/h for 15 minutes on Day 1
干预措施: Glepaglutide (Drug)
结局指标
主要结局
Pharmacokinetic parameter - total body clearance
时间窗: Day 0 to Day 22
Total body clearance after IV administration
Pharmacokinetic parameter - Volume of distribution
时间窗: Day 0- Day 22
Volume of distribution after IV dosing
Pharmacokinetic parameter - apparent volume of distribution
时间窗: Day 0 to Day 73
Vss/F and Vz/F for subcutaneous doses
Pharmacokinetic parameter - half life
时间窗: Day 0 up to Day 73
Half life of glepaglutide and active metabolites
Pharmacokinetic parameter - Apparent clearance
时间窗: Day 0 to Day 73
CL/F for subcutaneous doses
次要结局
- Pharmacodynamic parameter - plasma citrulline levels(Day 0 to Day 73)
- Safety and tolerability - ECGs(Day 0 to Day 73)
- Pharmacokinetic parameter - Cmax(Day 0 to Day 73)
- Pharmacokinetic parameter - tmax(Day 0 to Day 73)
- ADA incidence(Day 0 to Day 73)
- Safety and tolerability - AEs(Day 0 to Day 73)
- Pharmacokinetic parameter - AUC(Day 0 to Day 73)