A Phase I, Double-Blind, Placebo-Controlled, Randomised, First in Human, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of NYR-BI03 in Healthy Participants, When Administered as an Infusion for up to 6 Hours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Participants with Treatment-Related Adverse Events
研究概览
简要总结
The goal of this clinical trial is to learn if investigational drug NYR-BI03 is safe and tolerated when given as an intravenous infusion for up to 6 hours to healthy male and female volunteers.
The study will also show what if any medical problems participants have when taking drug NYR-BI03 and it will provide information on blood levels of the drug.
Researchers will compare drug NYR-BI03 to a placebo (a similar substance that contains no drug) to see if NYR-BI03 is safe and tolerated.
Participants will be administered drug NYR-BI03 or a placebo via intravenous infusion for up to 6 hours and be assessed by physical examination and laboratory tests.
详细描述
The study is a Phase 1, double-blind, randomised, first-in-human, dose escalation study to assess the safety, tolerability, and pharmacokinetics (PK) of NYR-BI03 when administered as an intravenous (IV) infusion for up to 6 hours to healthy participants.
Six (6) ascending dose cohorts are planned. Up to 48 participants will be enrolled sequentially into the cohorts, with a total of 8 participants per cohort (6 active, 2 placebo).
Each participant will be screened within a 28-day screening period after providing voluntary, written informed consent. If eligible, participants will be admitted to the clinical unit on Day -1 for confinement and randomised to be administered a single IV dose of NYR-BI03 or placebo for up to 6 hours on Day 1.
After confinement for at least 48 hours after the start of infusion for safety assessments and collection of PK blood samples, participants will be discharged from the clinical unit on Day 3. Participants will return to the clinical unit for the End of Study visit (EOS) on Day 7 for final safety monitoring.
Safety assessments will include collection of adverse events (AEs), laboratory tests (hematology, biochemistry, coagulation, urinalysis), physical examination, basic neurological examination, pupillary response assessment, vital signs, cardiac telemetry, and 12-lead electrocardiogram (ECG). For each cohort, a sentinel group of 2 participants (1 active, 1 placebo) will be dosed at least 24 hours before the rest of the cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The study will be conducted double blinded. Authorised unblinded study staff will be clearly designated and documented and are not permitted to perform any study assessments or have contact with participants for data collection after the first dose of study product. An unblinded pharmacist will prepare the study products and strict procedures will be implemented to ensure that only designated unblinded study staff have access to the randomized treatment allocation for each participant.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and Female
- •50.0 to 105.0 kg (inclusive)
- •Body Mass Index (BMI) BMI of 18.0 to 30.0 kg/m2 (inclusive)
- •General Health Healthy, determined by a medical history
- •Contraceptive Status: Must agree to use of established highly effective contraception for the duration of the study and for at least 30 days thereafter
- •Venous Access in their left and right arm to allow collection of blood samples and drug administration.
排除标准
- •Pregnant females and lactating females are excluded from participating in the study.
- •History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations.
- •History of severe allergy or anaphylaxis.
- •A known hypersensitivity to any surgical dressing which may be used
- •History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, gynecological, ear, nose, and throat, or musculoskeletal disorders, psychiatric disorder or haematological disorders
- •Any history of uncontrolled, severe asthma during the last 5 years
- •A creatinine clearance of less than 80 mL/min
- •Any predisposing condition that might interfere with the absorption, distribution, metabolism, and/or excretion of the investigational product.
- •History of abnormal bleeding tendencies, clotting disorders or thrombophlebitis unrelated to venipuncture or intravenous cannulation
- •A positive test for hepatitis B surface antigen, a history of hepatitis C without a negative polymerase chain reaction (PCR) test, a history of HIV infection or demonstration of HIV antibodies
- •Any evidence of organ dysfunction, or any clinically significant clinical laboratory value which, in the opinion of the Investigator would jeopardize the safety of the participant or impact on the validity of the study results,
- •Liver function test (including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) >1.5 x upper limit of normal
- •Alcohol Use Those who may have difficulty abstaining from alcohol during the 48 hr prior to dose administration and until completion of the inpatient stay
- •History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or positive urine drug screen for drugs of abuse
- •Taking any prescription medications within 14 days prior to dose administration and/or likely to require prescription medication during the study
- •Taking over-the-counter (OTC) medications or herbal supplements for 10 days prior to dose administration and/or likely to require or be unwilling to refrain from using OTC medications or herbal supplements during the study (with the exception of paracetamol, contraceptives, vitamin and other nutrient supplement use, at the discretion of the Investigator)
- •Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines, (e.g. coffee, tea, cola and chocolate) during the 24 hr prior to dose administration and whilst confined at the clinical study facility.
- •Psychiatric Disorder History of any psychiatric illness which may impair the ability to provide written informed consent
- •Protocol Compliance: Poor compliers or those unlikely to attend.
- •Recent Study Participation Receipt of any drug as part of a research study within 30 days or 5 half-lives, whichever is longer, of initial dose administration in this study
- •Standard blood donation within the 12-week period before dose administration
- •Unusual dietary habits and excessive or unusual vitamin intakes
- •Vaccination or immunizations within 30 days of initial dose administration
- •Participants with a risk of QT/ corrected QT interval (QTc) prolongation, namely: a. A marked baseline prolongation of corrected QTcF interval >450 ms in males and >470 ms in females in two ECGs, or b. A history of risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
研究组 & 干预措施
NYR-BI03 intravenous infusion
NYR-BI03 administered in escalating doses as a continuous intravenous infusion for up to 6 hours
干预措施: NYR-BI03 (Drug)
Placebo intravenous infusion
Placebo comparator administered as a continuous intravenous infusion for up to 6 hours
干预措施: Matching placebo (all cohorts) (Drug)
结局指标
主要结局
Number of Participants with Treatment-Related Adverse Events
时间窗: From enrollment up to and including follow-up assessments on Day 7
The safety and tolerability of NYR-BI03 in healthy volunteers, when administered as a 3 hour or 6 hour intravenous (IV) infusion.
次要结局
- Area under the plasma concentration versus time curve (AUC) of NYR-BI03(For 3-hour infusion: Pre-infusion, +10minutes, +30 minutes, 1, 2, 3, 3.5, 4, 6 , 9 hours. For 6-hour infusion: Pre-infusion, +10minutes, +30 minutes and 1, 3, 4, 6, 6.5, 7, 9, 12, 24 hours.)
- Maximum observed blood concentration (Cmax) of NYR-BI03(For 3-hour infusion: Pre-infusion, +10minutes, +30 minutes, 1, 2, 3, 3.5, 4, 6 , 9 hours. For 6-hour infusion: Pre-infusion, +10minutes, +30 minutes and 1, 3, 4, 6, 6.5, 7, 9, 12, 24 hours.)
- Tmax (time of occurrence of Cmax) of NYR-BI03(For 3-hour infusion: Pre-infusion, +10minutes, +30 minutes, 1, 2, 3, 3.5, 4, 6 , 9 hours. For 6-hour infusion: Pre-infusion, +10minutes, +30 minutes and 1, 3, 4, 6, 6.5, 7, 9, 12, 24 hours.)
- Apparent terminal half-life (T1/2) of NYR-BI03(For 3-hour infusion: Pre-infusion, +10minutes, +30 minutes, 1, 2, 3, 3.5, 4, 6 , 9 hours. For 6-hour infusion: Pre-infusion, +10minutes, +30 minutes and 1, 3, 4, 6, 6.5, 7, 9, 12, 24 hours.)
- Total body clearance from blood (CL) of NYR-BI03 calculated as Dose/AUC(For 3-hour infusion: Pre-infusion, +10minutes, +30 minutes, 1, 2, 3, 3.5, 4, 6 , 9 hours. For 6-hour infusion: Pre-infusion, +10minutes, +30 minutes and 1, 3, 4, 6, 6.5, 7, 9, 12, 24 hours.)