Phase 1 Study on the Safety, Tolerability and Pharmacokinetics/-Dynamics of Escalating Single Intravenous Doses of AK1967 (Procizumab) in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. During cardiogenic shock, upregulation of the vasoconstrictive molecule angiotensin II is a physiologic and potentially life-saving response aimed at maintaining adequate tissue perfusion. As circulating (c)DPP3 is able to effectively cleave angiotensin II, it may represent a novel factor contributing to hemodynamic instability during cardiogenic shock.
Recently, a cDPP3-antagonizing antibody called AK1967 (commonly referred to as Procizumab) has been developed. In animal models of cardiogenic- and septic shock, inhibition of cDPP3 by AK1967 resulted in improved cardiac function and survival. Furthermore, AK1967 has shown an excellent safety record in different preclinical studies. In the current study the safety, tolerability and pharmacokinetics/-dynamics of AK1967 will be investigated in healthy male subjects.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Written informed consent to participate in this trial prior to any study-mandated procedure.
- •Male subjects aged 18 to 35 years inclusive.
- •Subjects have to agree to use a reliable way of contraception with their partners from study entry until one month after study drug administration.
- •BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg and an upper limit of 100 kg.
- •Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory parameters.
排除标准
- •Unwillingness to abstain from any medication, including recreational drugs or vitamin supplements during the course of the study and within two days prior to the treatment day.
- •Unwillingness to abstain from alcohol within one day prior to the treatment day until one day after the treatment day.
- •Surgery or trauma with significant blood loss or blood donation within one month prior to the treatment day.
- •History, signs or symptoms of cardiovascular disease, in particular:
- •History of frequent vasovagal collapse or of orthostatic hypotension
- •Resting pulse rate ≤45 or ≥100 beats/min
- •Hypertension (RR systolic >160 or RR diastolic >90 mmHg)
- •Hypotension (RR systolic <100 or RR diastolic <50 mmHg)
- •Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
- •Any chronic cardiac arrhythmias (except PAC's, PVC's)
- •Renal impairment: plasma creatinine >120 μmol/L
- •Liver function tests (alkaline phosphatase, AST, ALT and/or γ-GT) above 2x the upper limit of normal.
- •History of asthma
- •Atopic constitution
- •CRP above 2x the upper limit of normal, or clinically significant acute illness, including infections, within two weeks prior to the treatment day.
- •Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to the treatment day.
- •Known or suspected of not being able to comply with the trial protocol.
- •Known hypersensitivity or allergic reactions to drug compounds, (i.e. previous adverse drug reactions).
- •Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
AK1967 3 mg/kg/body weight
干预措施: AK1967 (Procizumab) (Drug)
AK1967 6 mg/kg/body weight
干预措施: AK1967 (Procizumab) (Drug)
AK1967 12 mg/kg/body weight
干预措施: AK1967 (Procizumab) (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 28 days
Number of adverse events (AEs)
次要结局
- Pharmacokinetics of AK1967 - t1/2(28-days)
- Pharmacokinetics of AK1967 - AUC(28 days)