Pharmacokinetic, Safety Issues
Conditions
Keywords
Nicotinamide, Inflammatory Bowel Disease
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.
Interventions
DRUGcontrolled-ileocolonic-release nicotinamide (SAD/MAD/MD)
single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)
DRUGImmediate-release nicotinamide (SAD)
single-ascending dose (SAD)
DRUGPlacebo controlled-ileocolonic-release nicotinamide (SAD/MAD)
single- and multiple-ascending dose (SAD/MAD)
DRUGPlacebo Immediate-release nicotinamide (SAD)
single-ascending dose (SAD)
Sponsors
University Hospital Schleswig-Holstein
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Main inclusion and
Exclusion criteria
Inclusion criteria for the SAD and MAD parts with healthy subjects: 1. Male and female subjects aged 18 to 75 years. 2. Healthy subjects without relevant medical conditions. 3. Ability to understand and comply with the protocol. 4. Signed written Informed Consent. 5. A BMI of 18.5 to 29.99 kg/m². 6. Non-smoker or light smoker (average of \<7 cigarettes per week) and no history of longterm, heavy smoking (\>10 pack-years). Inclusion criteria for the MD-IBD part: 1. Male and female patients with IBD and 18 to 75 years of age. 2. Ability to understand and comply with the protocol. 3. Signed written Informed Consent. 4. Documented diagnosis of relapsing ileal, ileocolonic or colonic Crohn disease or relapsing ulcerative colitis. 5. Concomitant therapy (background medication) for inflammatory bowel disease: none or stable 8 weeks before baseline. 6. No signs of malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events [Safety and Tolerability] | up to 60 days | Adverse Events (AEs) during treatment period |
| Treatment-Emergent Serious Adverse Events [Safety and Tolerability] | up to 60 days | Serious Adverse Events (SAEs) during treatment period |
| Haemoglobin | up to 60 days | Haemoglobin (Hb) in % |
| White blood cells | up to 60 days | White blood cell (WBC) count as x10\^9/l |
| Blood creatinine | up to 60 days | Blood Creatinine in mmol/L |
| Blood urea | up to 60 days | Urea in mmol/L |
| Blood uric acid | up to 60 days | Uric acid in mmol/L |
| 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 ALT | up to 60 days | Alanine transaminase (ALT) in U/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 |
Countries
Germany
Outcome results
None listed