A Phase I, Double-blind, Randomised, Placebo-controlled, Single-ascending and Multiple-ascending Dose Trial to Evaluate Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM) Compared to Immediate-release Nicotinamide and Placebo in Healthy Subjects and in Patients With Inflammatory Bowel Diseases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Haemoglobin
研究概览
简要总结
Double-blind, randomised, placebo-controlled phase I trial with single-ascending and multiple-ascending dose to evaluate safety and pharmacokinetics of oral controlled-ileocolonic-release nicotinamide (CICR-NAM) compared to immediate-release nicotinamide and placebo in healthy subjects and in patients with inflammatory bowel diseases.
详细描述
Nicotinamide (NAM) has been implicated in the restoration and maintenance of a healthy gut microbiome. Conventional NAM formulations are designed for systemic NAM supplementation and therefore release NAM in the stomach and upper small intestine for maximum absorption. In contrast, the novel CICR-NAM tablets (controlled-ileocolonic-release nicotinamide) start releasing in the lower small intestine for topical delivery of NAM to the microbiota and the mucosa in the ileum and colon, also leading to a reduced systemic exposure. This clinical Phase I trial investigates the safety and tolerability of CICR-NAM in single- and multiple-ascending doses (1, 2 and 4 g). At the beginning of the trial, single-dose pharmacokinetics (PK) of 1 g of conventional immediate-release NAM and CICR-NAM are compared. At the end of the trial, patients with inflammatory bowel diseases (IBD) receive a medium multiple dose (2 g for 4 weeks) to compare their exposure, PK and safety data with those of healthy subjects at the same dose level.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
healthy subjects
healthy subjects (single-ascending and multiple-ascending doses)
干预措施: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD) (Drug)
healthy subjects
healthy subjects (single-ascending and multiple-ascending doses)
干预措施: Immediate-release nicotinamide (SAD) (Drug)
healthy subjects
healthy subjects (single-ascending and multiple-ascending doses)
干预措施: Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD) (Drug)
healthy subjects
healthy subjects (single-ascending and multiple-ascending doses)
干预措施: Placebo Immediate-release nicotinamide (SAD) (Drug)
IBD-patients
inflammatory bowel disease patients (multiple dose)
干预措施: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD) (Drug)
结局指标
主要结局
Haemoglobin
时间窗: up to 60 days
Haemoglobin (Hb) in %
Blood creatinine
时间窗: up to 60 days
Blood Creatinine in mmol/L
Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: up to 60 days
Adverse Events (AEs) during treatment period
Blood urea
时间窗: up to 60 days
Urea in mmol/L
Glomerular filtration rate
时间窗: up to 60 days
Glomerular filtration rate (GFR, automatically calculated by the laboratory based on creatinine values) GFR in ml/min/1.73m2
Blood uric acid
时间窗: up to 60 days
Uric acid in mmol/L
Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
时间窗: up to 60 days
Serious Adverse Events (SAEs) during treatment period
White blood cells
时间窗: up to 60 days
White blood cell (WBC) count as x10\^9/l
Blood ALT
时间窗: up to 60 days
Alanine transaminase (ALT) in U/l
Blood AST
时间窗: up to 60 days
Aspartate transaminase (AST) in U/l
Blood GGT
时间窗: up to 60 days
Gamma glutamyl transferase (GGT) in U/l
次要结局
未报告次要终点