A Phase 1, Placebo-Controlled Trial to Evaluate the Impact of Intravenous (IV) Bendavia™ (MTP-131) on Endothelial Reactivity Dysfunction Induced by Cigarette Smoking
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Analysis of variance (ANOVA) between group mean endothelial function (EndoPAT Index) following smoking a single cigarette with and without Bendavia
研究概览
简要总结
This will be a phase 1 randomized, double-blind, 2-period, 2-sequence crossover trial enrolling 6 healthy volunteers to assess the impact of IV-administered Bendavia on the endothelial dysfunction induced by a single cigarette.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy adult male smokers between 18 and 65 years of age with signed informed consent
排除标准
- •Serum sodium level below the lower limit of sites' clinical laboratory normal range at screening, D-1 and 6
- •Cholesterol level ≥ 240 mg/dL
- •Hypertension (blood pressure SBP > 140, DBP > 90 mmHg)
- •Body mass index < 18 or > 32 kg/m2,
- •Creatinine clearance calculated by the Cockcroft and Gault method calculated to be < 90 mL/min,
- •Additional laboratory abnormalities determined as clinically significant by the Principal Investigator at laboratory screening
- •Clinically significant abnormalities on physical examination,
- •History or evidence of renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) system dysfunction,
- •History of seizures or history of epilepsy,
- •History of serious (Principal Investigator judgment) mental illness,
- •Receipt of investigational medicinal product within 30 days prior to the planned date of study drug administration,
- •Positive serology for human immunodeficiency virus type 1 or 2, or hepatitis B surface antigen,
- •Fever > 37.5°C at the time of planned dosing,
- •Suspicion, or recent history, of alcohol or substance abuse,
- •Donated blood or blood products within the past 30 days,
- •Employee or family member of the investigational site,
- •Subjects who are either unwilling to agree to refrain from use or found to be using Nicotine (or nicotine products) including cigarettes from 12 hours prior to start of each study drug infusion through to the completion of endothelial function testing, Alcohol, Caffeine, Xanthine-containing food or beverages and over-the-counter medications with the exception of Tylenol from 24 hours prior to dosing and throughout the confinement periods, Supplementary antioxidant vitamins from 7 days prior to dosing and throughout the confinement periods, Prescription medications from 14 days prior to and 7 days post treatment
- •Subjects having previous exposure to Bendavia.
研究组 & 干预措施
Placebo
Intravenous infusion of saline (0.9%) for 4 hours with smoking of one unfiltered cigarette at 30 minutes post-study-drug administration start
干预措施: Sterile saline (0.9%) (Drug)
Placebo
Intravenous infusion of saline (0.9%) for 4 hours with smoking of one unfiltered cigarette at 30 minutes post-study-drug administration start
干预措施: Cigarette smoking (Other)
Bendavia
Intravenous infusion of Bendavia (0.25mg/kg/hr) for 4 hours with smoking of one unfiltered cigarette at 30 minutes post-study-drug administration start
干预措施: Bendavia (Drug)
Bendavia
Intravenous infusion of Bendavia (0.25mg/kg/hr) for 4 hours with smoking of one unfiltered cigarette at 30 minutes post-study-drug administration start
干预措施: Cigarette smoking (Other)
结局指标
主要结局
Analysis of variance (ANOVA) between group mean endothelial function (EndoPAT Index) following smoking a single cigarette with and without Bendavia
时间窗: Baseline, +30, +60, +90 minutes post-study-drug administration start
Endothelial function will be determined using EndoPAT 2000 (Itamar Medical Ltd) prior to and after smoking of one unfiltered cigarette and prior to and after initiation of study drug. Group comparison of endothelial function (EndoPAT Index) between placebo and active study drug within a subject will be performed. EndoPAT quantifies the endothelium-mediated changes in vascular tone. A post-occlusion to pre-occlusion ratio is calculated providing the EndoPAT index.
次要结局
- Anova between group mean inflammatory laboratory marker (hs-CRP; mg/L) after smoking one cigarette with and without Bendavia(Baseline to 24 hours post-study-drug administration)
- ANOVA between group means of urinary 8-isoprostane (ng/mg of creatinine) after smoking one cigarette with and without Bendavia(Baseline to 48 hours post-study-drug administration)
- Number adverse events with and without Bendavia(Baseline to Study Day 10)
- Assessment of Bendavia exposure measured by area Under the Curve (AUC; ng*hr/mL)(Baseline to 48 hours post-study-drug administration)
- ANOVA between group means of urinary 8-hydroxy-2'-deoxyguanosine (pg/mL) after smoking one cigarette with and without Bendavia(Baseline to 48 hours post-study-drug administration)