NCT04653766已完成1 期
A Phase I, Double Blind, Placebo Controlled, Single Ascending Dose Study of Intravenously Administered Ir-CPI to Evaluate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability in Healthy Male Volunteers
Bioxodes S.A.1 个研究点 分布在 1 个国家目标入组 32 人开始时间: 2019年9月12日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT)
研究概览
简要总结
The purpose of this First-in-Human study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Ir-CPI, a novel dual inhibitor of FXIIa and FXIa, following IV administration of single ascending doses in healthy male volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Participants must satisfy all of the following inclusion criteria before being allowed to enter the study:
- •Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
- •Male participants between 18 and 55 years of age, inclusive at screening.
- •Otherwise healthy with no clinically significant abnormalities as determined by medical history, physical examination, blood chemistry assessments, haematological assessments, coagulation and urinalysis, measurement of vital signs, and ECG. Isolated out-of-range values judged by the PI (or designated physician) to be of no clinical significance can be allowed. This determination must be recorded in the participant's source documents.
- •Have a body weight in the range of 50 to 90 kg inclusive at screening. Have a body mass index (BMI) of 19 to 28 kg/m2 inclusive at screening.
- •Agree to abstain from alcohol intake 24 hours before administration of study drug, during the in-patient period of the study and 24 hours prior to all other ambulatory visits, up until and including the discharge visit.
- •Agree not to use prescription medications within 14 days prior to study drug administration and through the duration of the study, unless approved by the PI and Sponsor medical monitor.
- •Non-smokers or abstinence from tobacco or nicotine-containing products for at least 3 months prior to screening.
- •Agree not to use over-the-counter (OTC) medications [including decongestants, antihistamines, and herbal medication (including herbal tea and St. John's Wort)], within 14 days prior to study drug administration through the discharge visit, unless approved by the PI and Sponsor medical monitor. Occasional use of paracetamol at recommended doses is allowed. Special rules apply for aspirin, corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDS (see exclusion criteria 6-7-8-9)
- •Venous access (both arms) sufficient to allow blood sampling and study drug administration as per protocol.
- •Participants and their partners of childbearing potential [meaning who are not surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (absence of menstrual periods for at least 12 consecutive months)] must be willing to use 2 methods of contraception: - a highly effective method of birth control starting at screening. Highly effective methods of birth control are defined as those that result in a low failure rate (i.e. Pearl Index less than 1% per year) when used consistently and correctly, such as implants, rings, patches, injectable or combined oral contraceptives, intrauterine devices (IUDs), or sexual abstinence (periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation methods, declaration of abstinence for the duration of the trial, and withdrawal are not acceptable methods of contraception) . - and a local barrier form of contraception. Acceptable barrier methods are either the participant's use of a condom or the partner's use of an occlusive cap or diaphragm, or spermicides. Participants will not donate sperm from the selection visit and up to 90 days after the infusion. In case of sterile or vasectomised participants, no contraception will be required for their partners of childbearing potential.
- •Willing/able to adhere to the study visit schedule and other requirements, prohibitions and restrictions specified in this protocol.
排除标准
- •If any of the following exclusion criteria apply, the participant must not enter the study:
- •Currently have or have a history of any clinically significant medical illness or medical disorders the PI considers should exclude the participant, including (but not limited to) cardiovascular disease, neuromuscular, haematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
- •History of personal or familial bleeding disorders; including prolonged or unusual bleeding.
- •History of deficiency in factor XII (FXII) or haemophilia type A (FVII) or type B (FIX) or type C (FXI).
- •History of cerebral bleeding (e.g. after a car accident), stroke and cerebrovascular accident (CVA).
- •Anamnestic history of Lyme disease or tick-borne encephalitis.
- •Use of Acetylsalicylic-Acid (ASA)-containing OTC medications within 1 month prior to screening.
- •Chronic administration of NSAIDs, chronic use of corticosteroids within 1 month prior to screening.
- •Chronic administration of clopidogrel, ticlopidin, dipyridamole, Coumadin-like anticoagulants, new oral anticoagulant dabigatran, rivaroxaban, apixaban or edoxaban within 3 months prior to screening.
- •Administration of unfractionated heparin, low molecular weight heparin, fibrinolytic agents and anti-FXa within 3 months prior to screening.
- •Have an active acute or chronic infection or diagnosed latent infection.
- •Systolic blood pressure (SBP) greater than 150 or less than 90 mmHg, diastolic blood pressure (DBP) greater than 90 or less than 50 mmHg, and heart rate (HR) greater than 100 or less than 40 bpm.
- •Acute clinically relevant illness within 7 days prior to study drug administration or have had a major illness or hospitalisation within 1 month prior to study drug administration.
- •Major or traumatic surgery within 12 weeks of screening.
- •Any participant who plans to undergo elective surgery within 4 weeks prior to study drug administration and through the discharge visit.
- •Positive serology test for HIV antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies at screening.
- •Recent history (within previous 6 months) of alcohol or drug abuse.
- •Have positive urine toxicology screen at screening or D -1 for substances of abuse including amphetamines, benzodiazepine, cocaine, opiates, barbiturate and cannabinoids.
- •Have a positive alcohol breath test at screening or D-
- •Consumes, on average, more than approximately 500 mg/day of caffeine (as contained in 5 cups of tea or coffee or 8 cans of caffeine-containing soda or other caffeinated products per day).
- •Donated blood (i.e. 500 mL) within 3 months before D
- •Have a history of active drug and/or food allergy or other active allergic disease requiring the constant use of medications, or a history of severe allergic reaction, angioedema or anaphylaxis.
- •Received any other experimental therapy or new investigational drug within 30 days or 5 half-lives (whichever is longer) of study drug administration.
研究组 & 干预措施
Ir-CPI - Dose 1
Experimental
Participants received a single intravenous dose of 1.5 mg/kg of Ir-CPI during 6 hours
干预措施: Ir-CPI - Dose 1 (Drug)
Ir-CPI - Dose 2
Experimental
Participants received a single intravenous dose of 3.0 mg/kg of Ir-CPI during 6 hours
干预措施: Ir-CPI - Dose 2 (Drug)
Ir-CPI - Dose 3
Experimental
Participants received a single intravenous dose of 6.0 mg/kg of Ir-CPI during 6 hours
干预措施: Ir-CPI - Dose 3 (Drug)
Ir-CPI - Dose 4
Experimental
Participants received a single intravenous dose of 9.0 mg/kg of Ir-CPI during 6 hours
干预措施: Ir-CPI - Dose 4 (Drug)
Placebo
Placebo Comparator
Participants received a single intravenous dose of placebo during 6 hours
干预措施: Placebo (Drug)
结局指标
主要结局
Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT)
时间窗: At pre-dose (baseline), 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose and at the discharge visit (Day 10 ± 2 days)
These safety aPTT results were readily available to the PI for safety follow-up during and after the study drug administration. Safety aPTT was followed up "at the bedside" at regular time-points (as opposed to the PD biomarker aPTT, which was assessed by the central laboratory alongside the PK time-points). An aPTT ratio was calculated by dividing the aPTT value (in sec) of the specific time-point (aPTTt) by the baseline aPTT value (in sec) (aPTTbaseline) of the same participant (aPTT ratio = aPTTt/aPTTbaseline). The baseline time-point was considered as having an aPTT ratio of 1. Concerning the row titles, for example, Day 1 H02:00 corresponds to aPTT ratio results obtained on Day 1, 2 hours after the start of the infusion.
次要结局
- Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI(Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only))
- Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI(Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only))
- Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf)(Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only))
- Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT)(Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days))
- Measurement of the Effect of Ir-CPI on Factor XI Activity(Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days))
- Measurement of the Effect of Ir-CPI on Factor XII Activity(Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days))
研究者
研究点 (1)
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