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

NCT ID: NCT06378125

Last Updated: 2024-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-19

Study Completion Date

2024-11-12

Brief Summary

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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

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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.

Conditions

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Safety Issues Pharmacokinetic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators
Double (Participant, Investigator)

Study Groups

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healthy subjects healthy subjects

single-ascending and multipleascending doses (SAD/MAD)

Group Type EXPERIMENTAL

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

Intervention Type 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.

immediate-release nicotinic acid (SAD)

Intervention Type 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.

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

Intervention Type 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.

Placebo immediate-release nicotinic acid (SAD)

Intervention Type 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.

subjects with prediabetes

multiple dose (MD)

Group Type EXPERIMENTAL

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

Intervention Type 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.

Interventions

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

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.

Intervention Type DRUG

immediate-release nicotinic acid (SAD)

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.

Intervention Type DRUG

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

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.

Intervention Type DRUG

Placebo immediate-release nicotinic acid (SAD)

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.

Intervention Type DRUG

Other Intervention Names

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CIR-NA (SAD/MAD/MD) ImR-NA (SAD) no active substance (SAD/MAD) no active substance (SAD)

Eligibility Criteria

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Inclusion Criteria

1. Male and female subjects aged 18 to 65 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).


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

Exclusion Criteria

1. Pre-existing relevant medical conditions.
2. Clinically relevant abnormal findings in medical history or screening assessments.
3. Participation in a clinical study.
4. Use of any prescribed or over-the-counter medication, food supplements or herbal preparations.
5. Use of antibiotics (systemic or gut-acting \[non-absorbed\]).
6. 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).
7. Legal incapacity.
8. Indications that the patient may be unable to comply with the study procedures, e.g. language barriers precluding adequate understanding or cooperation
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital Schleswig-Holstein

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susanna Nikolaus, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Schleswig-Holstein, Campus Kiel

Locations

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University Medical Center Schleswig-Holstein, Campus Kiel

Kiel, Schleswig-Holstein, Germany

Site Status

Countries

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Germany

Other Identifiers

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CIR-NA I

Identifier Type: -

Identifier Source: org_study_id