Evaluation of Safety and Pharmacokinetics of Oral Controlled-ileal-release Nicotinic Acid (CIR-NA) Compared to Immediate-release Nicotinic Acid and Placebo in Healthy Subjects and Subjects With Prediabetes
- Conditions
- Safety IssuesPharmacokinetic
- Interventions
- Drug: controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)Drug: immediate-release nicotinic acid (SAD)Drug: Placebo controlled-ileal-release nicotinic acid (SAD/MAD)Drug: Placebo immediate-release nicotinic acid (SAD)
- Registration Number
- NCT06378125
- Lead Sponsor
- University Hospital Schleswig-Holstein
- Brief Summary
A double-blind, randomised, placebo-controlled, single-ascending and multiple-ascending dose trial to evaluate the safety and pharmacokinetics of oral controlled-ileal-release nicotinic acid (CIR-NA) compared to immediate-release nicotinic acid and placebo in healthy subjects and subjects with prediabetes.
- Detailed Description
Recently, administration of one form of vitamin B3, Nicotinamide (NAM), has been shown to improve the host-microbiome interaction in a mouse model, especially when administered in a controlled-release formulation targeting the ileocolic region. Thus, NAM and also the other form of vitamin B3, Nicotinicacid (NA), were identified as promising candidates for a gut-targeted microbiome intervention.
As the upper gastrointestinal tract efficiently absorbs amino acids and vitamins, simply increasing the NA and/or NAM content in human food would not be expected to deliver these molecules in sufficient amounts into the lower ileum and colon, where most of the microbiota are located. Moreover, adverse effects such as flushing or gastrointestinal symptoms can occur under high and immediately systemically available dosage of NA. Therefore, the novel CIR-NA formulation will be applied to deliver NA to the lower ileum and colon to tar-get the gut microbiome, while largely avoiding systemic exposure, as the terminal ileum and colon have a much lower absorptive capacity than the stomach and upper small intestine.
Both in the single- and multiple-ascending (SAD/MAD) part of the study, CIR-NA or placebo tablets will be self-administered orally, with daily doses of 100 mg (1 tablet), 200 mg (2 tablets), 500 mg (5 tablets) or 1,000 mg CIR-NA (10 tablets) or the corresponding amounts of placebo tablets. In the SAD part, an additional dose of 2,000 mg CIR-NA or placebo (20 tablets) will be self-administered.After completion of the SAD and the 200 mg MAD part in healthy subjects, an additional mul-tiple dose part (200 mg/d CIR-NA) in subjects with PreD (MD-PreD part) will start in parallel to the further dose groups of the MAD part.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description healthy subjects healthy subjects immediate-release nicotinic acid (SAD) single-ascending and multipleascending doses (SAD/MAD) healthy subjects healthy subjects Placebo controlled-ileal-release nicotinic acid (SAD/MAD) single-ascending and multipleascending doses (SAD/MAD) healthy subjects healthy subjects Placebo immediate-release nicotinic acid (SAD) single-ascending and multipleascending doses (SAD/MAD) subjects with prediabetes controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD) multiple dose (MD) healthy subjects healthy subjects controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD) single-ascending and multipleascending doses (SAD/MAD)
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University Medical Center Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Schleswig-Holstein, Germany