A Randomised, Double-Blind, Placebo-Controlled Study of a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) of a FimH Antagonist, EB8018, in Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Enterome
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Number of Treatment Related Adverse Event, including Abnormal Laboratory Events to evaluate the safety and tolerability profile of single ascending and multiple ascending doses of EB8018 compared with placebo in healthy subjects
研究概览
简要总结
The purpose of this study is to determine the safety profile of single and multiple doses of EB8018 in healthy male subjects, to determine the pharmacokinetic profile of single and multiple doses of EB8018 in healthy male subjects and to assess preliminary effects of EB8018 on the healthy male gut microbiome.
详细描述
Crohn's Disease is a chronic inflammatory disease of the gastrointestinal tract. Emerging evidence suggests that the microbiome plays an important role in triggering an abnormal mucosal immune response in patients with Crohn's Disease. Independent studies have demonstrated an imbalance of the microbiome with a significant increase of E coli with invasive properties, termed adherent-invasive E coli (AIEC). These AIEC bacteria attach to the gut wall of susceptible patients via the fimbrial adhesion protein FimH, and subsequently trigger inflammation by invading and proliferating within the gut wall. EB8018 is an oral small molecule that is designed to block FimH thereby preventing the entry of AIEC into the gut wall thereby disarming the bacteria without disrupting the gut microbiome.
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 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males
- •Age ≥ 18 to ≤ 55 years of age
- •Body mass index of 19.0 to 30.0 kg/m2
- •Normal ECG, showing no clinically relevant deviations, as judged by the investigator (QTcF ≤450 ms)
排除标准
- •Subjects who have received any Investigational Medicinal Product in a clinical research study within the previous 3 months.
- •History of any drug or alcohol abuse in the past 2 years
- •Regular alcohol consumption in males >21 units per week
- •Current smokers and those who have smoked within the last 12 months
- •Positive drugs of abuse test result
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever, even inactive, is not allowed.
- •Chronic infection or acute significant infection or fever within the previous 5 weeks prior to the start of IMP administration
- •Malignancy or prior malignancy, with a disease-free interval of less than 5 years after diagnosis and intervention
研究组 & 干预措施
Single oral dose of EB8018
Single ascending doses, sequential group design
干预措施: Single Ascending Doses of EB8018 (Drug)
Single oral dose of placebo
Single doses, matching placebo
干预措施: Single Ascending Doses of placebo (Drug)
Multiple oral doses of EB8018
Multiple ascending doses, daily for 14 days
干预措施: Multiple Ascending Doses of EB8018 (Drug)
Multiple oral doses of placebo
Multiple ascending doses, daily for 14 days
干预措施: Multiple Ascending Doses of placebo (Drug)
结局指标
主要结局
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events to evaluate the safety and tolerability profile of single ascending and multiple ascending doses of EB8018 compared with placebo in healthy subjects
时间窗: Between screening and 7-10 days after the last dose
The variables for analysis will be the difference of EB8018 compared with placebo for incidence, severity and type of adverse events, including changes in vital signs, physical examinations, laboratory safety tests and ECGs
次要结局
- The amount of EB8018 in plasma(Between Day 1 predose and 48 hours after the (last) dose)
- The amount of EB8018 in urine(Between Day 1 predose and 48 hours after the (last) dose)
- The amount of EB8018 in stool(Between predose and 48 hours after the (last) dose)
- Analysis of microbiome richness(Between predose and 48 hours after the (last) dose)