A Phase 1, Open-label, Single-dose, Parallel-group Study to Evaluate the Effects of Renal Impairment on the Pharmacokinetics of ELX-02
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Pharmacokinetic Parameters- Plasma Cmax
研究概览
简要总结
Phase 1 - Pharmacokinetics in Patients with Impaired Renal Function
详细描述
The study is a two-center, Phase 1, open-label, single-dose, one-period, four-parallel-group, PK study in subjects with various severities of renal dysfunction and healthy volunteers.
Subjects will be categorized in 4 groups:
Group 1: subjects with mild renal impairment Group 2: subjects with moderate renal impairment Group 3: subjects with severe renal impairment Group 4 (control group): subjects with normal renal function
The mild (group 1) and moderate (group 2) patients with renal disease will be dosed first, in a parallel fashion. At this point, interim PK analyses will be performed and a safety committee composed of Sponsor and Contract Research Organization (CRO) members will jointly review the PK data before dosing the patients with severe renal disease (group 3). Control subjects (group 4) will be recruited after the recruitment of groups 1 to 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Male or female, non-smoker and/or light smoker
- •Have a diagnosis of renal impairment that has been stable, without any significant change in overall disease status in the last 3 months prior to screening.
- •Have an estimated glomerular filtration rate (eGFR) expressed in mL/min/1.73 m2 (Modification of Diet in Renal Disease 4-variable [MDRD4] equation) at screening within the range of:
- •Group 1 - Mild Group: 60 - 89 mL/min/1.73 m2;
- •Group 2 - Moderate Group: 30 - 59 mL/min/1.73 m2;
- •Group 3 - Severe Group: < 30 mL/min/1.73 m2 not requiring dialysis. eGFR results that are deemed inconsistent with the usual stage of renal impairment may be repeated. Subjects are categorized into severity group at screening. If the eGFR scores change on Day-1 or other visit due to a non-clinically significant change in clinical status or laboratory result, the subject keeps the original severity group.
- •Subject may have stable treated medical illnesses and underlying diseases producing the renal impairment such as diabetes, hypertension, or cardiovascular disease, providing that, in the opinion of the PI, the disease is stable.
- •Have normal or non-clinically significant findings at physical examination, vital signs and electrocardiogram (ECG) and normal limits or non-clinically significant deviations in clinical laboratory evaluations at screening.
- •Other than renal impairment, have no other conditions which may significantly impact study drug absorption or metabolism.
- •Stable medical regimen, deemed not to interact with study drug PK, for 14 days prior to dosing, except for routine daily management of electrolytes (e.g. potassium), acid-base, or other associated disorders expected in patients with renal impairment.
- •Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized since at least 6 months) must be willing to use acceptable contraceptive method throughout the study and for 30 days after study drug administration.
- •Male subjects who are not vasectomized for at least 6 months, and who are sexually active with a non-sterile female partner (sterile female partners include post-menopausal females and surgically sterile females) must be willing to use acceptable contraceptive method from dosing until at least 90 days after study drug administration.
- •Male subjects (including men who have had vasectomy) with a pregnant partner must agree to use a condom from dosing until at least 90 days after study drug administration.
- •Male subjects must be willing not to donate sperm until 90 days following study drug administration.
- •Able to understand and willing to sign the Informed Consent Form (ICF) and comply with the study restrictions.
排除标准
- •Unstable renal function or acute exacerbation of renal disease within 14 days of study drug administration, as indicated by recent history or worsening of clinical and/or laboratory signs of renal impairment.
- •Has a functioning renal transplant.
- •Major illness or surgery within 4 weeks prior to dosing.
- •Clinically significant unstable medical condition or history of any illness that may increase the risk associated with study participation or investigational drug administration or may interfere with the interpretation of study results and would make the subject inappropriate for entry into this study.
- •Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening.
- •History of allergic reactions, hypersensitivity or toxic reactions to aminoglycosides.
- •History of anaphylaxis.
- •Supine 12-lead ECG abnormalities at screening considered clinically significant.
- •Clinically significant vital sign abnormalities at screening.
- •History of significant drug or alcohol abuse within six months prior to screening.
- •Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days (or 5 half-lives, whichever is longer) prior to dosing, administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration.
- •Positive urine drug screen or alcohol test at screening.
- •Female subject with positive pregnancy test at screening.
- •Breast-feeding or pregnant subject within 6 months prior to study drug administration.
- •Use of any drugs known as strong inducer or inhibitor of hepatic drug metabolism within 30 days prior to study drug administration.
- •Use of medication other than stable medications approved by the PI and topical products without significant systemic absorption.
- •Use of prohibited medications as directed in the protocol.
- •Donation of plasma within 7 days prior to dosing. Donation or loss of blood within 30 days prior to the first dosing.
- •Any reason which, in the opinion of the PI, would prevent the subject from participating in the study.
- •Inability to be venipunctured and/or tolerate catheter venous access.
- •Presence of mitochondrial mutation(s) making the subject susceptible to aminoglycoside toxicity.
- •Presence of signs of dehydration, recent history of neuromuscular blockade or clinically significant history of vestibular impairment.
研究组 & 干预措施
ELX-02
Drug: ELX-02
干预措施: ELX-02 (Drug)
结局指标
主要结局
Pharmacokinetic Parameters- Plasma Cmax
时间窗: 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours after dosing
Peak Plasma Concentration (Cmax) of ELX-02 following a single subcutaneous (SC) dose in subjects with normal renal function, mild, moderate, or severe renal impairment
AUC0-inf
时间窗: 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours after dosing
Area under the curve (AUC0-inf) of ELX-02 plasma concentration following a single subcutaneous (SC) dose
Urine Pharmacokinetics Parameter - Ae0-t
时间窗: Pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose
Cumulative amount of unchanged drug excreted into urine (Ae0-t) of ELX-02 following a single subcutaneous (SC) dose
Pharmacokinetic Parameters- Plasma AUC0-24
时间窗: 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, and 24 hours after dosing
Area under the curve (AUC0-24) of ELX-02 plasma concentration following a single subcutaneous (SC) dose
Pharmacokinetic Parameters - Plasma Tmax
时间窗: 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, and 24 hours after dosing.
Time to maximum concentration (Tmax) of ELX-02 plasma concentration following a single subcutaneous (SC) dose
Urine Pharmacokinetic Parameter - Rmax
时间窗: Pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose
Maximum rate of urinary extraction (Rmax) of ELX-02 following a single subcutaneous (SC) dose
Number of Patients Reporting Treatment-Emergent Adverse Events (TEAEs) [Safety]
时间窗: 1-8 days
TEAEs are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the study treatment
次要结局
未报告次要终点