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Completed

NCT Number: NCT06378125

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

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.

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Key information

Conditions

Safety Issues Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases Pharmacokinetic Prediabetic State

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University Medical Center Schleswig-Holstein, Campus Kiel

Kiel, Schleswig-Holstein, 24105, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Main inclusion and exclusion criteria

Inclusion criteria

for the SAD and MAD parts with healthy subjects:

  • Male and female subjects aged 18 to 65 years.
  • Healthy subjects without relevant medical conditions.
  • Ability to understand and comply with the protocol.
  • Signed written Informed Consent.
  • A BMI of 18.5 to 29.99 kg/m².
  • 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-Part (subjects with prediabetes):

  • Male and female subjects aged 18 to 65 years.
  • Previously diagnosed prediabetes with confirmation via the HbA1c level (5.7 to < 6.5%) at the screening visit.
  • Subjects without relevant medical conditions and without clinically significant impairment of renal or hepatic function.
  • Ability to understand and comply with the protocol.
  • Signed written Informed Consent.
  • A body mass index of 25 to 40 kg/m², both inclusive .
  • Non-smoker or light smoker (average of <7 cigarettes per week) and no history of longterm, heavy smoking (>10 pack-years).

Exclusion criteria

for the SAD, MAD and MD part with healthy subjects and subjects with prediabetes:

  • Pre-existing relevant medical conditions.
  • Clinically relevant abnormal findings in medical history or screening assessments.
  • Participation in a clinical study.
  • Use of any prescribed or over-the-counter medication, food supplements or herbal preparations.
  • Use of antibiotics (systemic or gut-acting [non-absorbed]).
  • Pregnant or breastfeeding women or women of childbearing potential and male participants with female partners of childbearing age not using highly effective contraception till at least 1 month after last dosing of investigational medicinal product (IMP).
  • Legal incapacity.
  • Indications that the patient may be unable to comply with the study procedures, e.g. language barriers precluding adequate understanding or cooperation

Treatment and study plan

controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)

Drug

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.

Other names: CIR-NA (SAD/MAD/MD)

immediate-release nicotinic acid (SAD)

Drug

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.

Other names: ImR-NA (SAD)

Placebo controlled-ileal-release nicotinic acid (SAD/MAD)

Drug

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.

Other names: no active substance (SAD/MAD)

Placebo immediate-release nicotinic acid (SAD)

Drug

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.

Other names: no active substance (SAD)

Primary outcomes

  1. Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time frame: up to 60 days

    Adverse Events (AEs) during treatment period

  2. Treatment-Emergent Serious Adverse Events [Safety and Tolerability]

    Time frame: up to 60 days

    Serious Adverse Events (SAEs) during treatment period

  3. Haemoglobin

    Time frame: up to 60 days

    Haemoglobin (Hb) in %

  4. White blood cells

    Time frame: up to 60 days

    White blood cell (WBC) count as x10^9/l

  5. Blood creatinine

    Time frame: up to 60 days

    Blood Creatinine in mmol/L

  6. Blood urea

    Time frame: up to 60 days

    Urea in mmol/L

  7. Blood uric acid

    Time frame: up to 60 days

    Uric acid in mmol/L

  8. Glomerular filtration rate

    Time frame: up to 60 days

    Glomerular filtration rate (GFR, automatically calculated by the laboratory based on creatinine values) GFR in ml/min/1.73m2

  9. Blood ALT

    Time frame: up to 60 days

    Alanine transaminase (ALT) in U/l

  10. Blood AST

    Time frame: up to 60 days

    Aspartate transaminase (AST) in U/l

  11. Blood GGT

    Time frame: up to 60 days

    Gamma glutamyl transferase (GGT) in U/l

Sponsors and collaborators

Lead sponsor

University Hospital Schleswig-Holstein

Other

Registry information

Official study title

A Phase I, 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

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Apr 22, 2024
Registry last updated
Nov 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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