Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM)
- Conditions
- PharmacokineticSafety Issues
- Interventions
- Registration Number
- NCT05258474
- Lead Sponsor
- University Hospital Schleswig-Holstein
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description healthy subjects controlled-ileocolonic-release nicotinamide (SAD/MAD/MD) healthy subjects (single-ascending and multiple-ascending doses) healthy subjects Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD) healthy subjects (single-ascending and multiple-ascending doses) IBD-patients controlled-ileocolonic-release nicotinamide (SAD/MAD/MD) inflammatory bowel disease patients (multiple dose) healthy subjects Placebo Immediate-release nicotinamide (SAD) healthy subjects (single-ascending and multiple-ascending doses) healthy subjects Immediate-release nicotinamide (SAD) healthy subjects (single-ascending and multiple-ascending doses)
- Primary Outcome Measures
Name Time Method Blood urea up to 60 days Urea in mmol/L
Blood ALT up to 60 days Alanine transaminase (ALT) in U/l
Haemoglobin up to 60 days Haemoglobin (Hb) in %
Blood creatinine up to 60 days Blood Creatinine in mmol/L
Treatment-Emergent Adverse Events [Safety and Tolerability] up to 60 days Adverse Events (AEs) during treatment period
Glomerular filtration rate 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 up to 60 days Uric acid in mmol/L
Treatment-Emergent Serious Adverse Events [Safety and Tolerability] up to 60 days Serious Adverse Events (SAEs) during treatment period
White blood cells up to 60 days White blood cell (WBC) count as x10\^9/l
Blood AST up to 60 days Aspartate transaminase (AST) in U/l
Blood GGT up to 60 days Gamma glutamyl transferase (GGT) in U/l
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University Medical Center Schleswig-Holstein
🇩🇪Kiel, Germany