Safety IssuesPhase 1NCT06378125
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 Phase 1 study testing immediate-release nicotinic acid (SAD) in people with Safety Issues and Pharmacokinetic, run by University Hospital Schleswig-Holstein at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Safety Issues, Pharmacokinetic
- What is being tested?
- immediate-release nicotinic acid (SAD)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- 19 Dec 2022to 12 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Medical Center Schleswig-Holstein, Campus Kiel
Kiel, Schleswig-Holstein, 24105
About this study
Official 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
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.
Read the 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.
- Conditions
- Safety Issues, Pharmacokinetic
- Being tested
- controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD), immediate-release nicotinic acid (SAD), Placebo controlled-ileal-release nicotinic acid (SAD/MAD), Placebo immediate-release nicotinic acid (SAD)
- Keywords
- Nicotinic Acid, Prediabetes
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)Drug
Also called CIR-NA (SAD/MAD/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.
immediate-release nicotinic acid (SAD)Drug
Also called ImR-NA (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.
Placebo controlled-ileal-release nicotinic acid (SAD/MAD)Drug
Also called no active substance (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.
Placebo immediate-release nicotinic acid (SAD)Drug
Also called no active substance (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.
| Study group | Role | What they receive |
|---|---|---|
| healthy subjects healthy subjects | Experimental | single-ascending and multipleascending doses (SAD/MAD) Receives: 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) |
| subjects with prediabetes | Experimental | multiple dose (MD) Receives: Drug: controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-Emergent Adverse Events [Safety and Tolerability]
Adverse Events (AEs) during treatment period
Measured: up to 60 days
Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Serious Adverse Events (SAEs) during treatment period
Measured: up to 60 days
Haemoglobin
Haemoglobin (Hb) in %
Measured: up to 60 days
White blood cells
White blood cell (WBC) count as x10^9/l
Measured: up to 60 days
Blood creatinine
Blood Creatinine in mmol/L
Measured: up to 60 days
Blood urea
Urea in mmol/L
Measured: up to 60 days
Blood uric acid
Uric acid in mmol/L
Measured: up to 60 days
Glomerular filtration rate
Glomerular filtration rate (GFR, automatically calculated by the laboratory based on creatinine values) GFR in ml/min/1.73m2
Measured: up to 60 days
Blood ALT
Alanine transaminase (ALT) in U/l
Measured: up to 60 days
Blood AST
Aspartate transaminase (AST) in U/l
Measured: up to 60 days
Blood GGT
Gamma glutamyl transferase (GGT) in U/l
Measured: up to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2024
- Study start19 Dec 2022
- Primary completion12 Nov 2024
- Study completion12 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Safety IssuesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Schleswig-Holstein
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susanna Nikolaus, Prof. Dr., Principal investigator, University Medical Center Schleswig-Holstein, Campus Kiel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06378125
- Sponsor's protocol ID
- CIR-NA I
- Status last verified
- Apr 2024
- First submitted
- 17 Apr 2024
- Last updated
- 27 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT06378125
- Acronym / sponsor ID
- CIR-NA I
- Conditions
- Safety Issues, Pharmacokinetic
- Keywords
- Nicotinic Acid, Prediabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University Hospital Schleswig-HolsteinUniversity, hospital or other
- Study start
- 19 Dec 2022 (actual)
- Primary completion
- 12 Nov 2024 (actual)
- Study completion
- 12 Nov 2024 (actual)
- First posted
- 22 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy subjects healthy subjects | Experimental | 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)single-ascending and multipleascending doses (SAD/MAD) |
| subjects with prediabetes | Experimental | Drug: controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)multiple dose (MD) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| controlled-ileal-release nicotinic acid (SAD/ MAD/MD) single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)Also: CIR-NA (SAD/MAD/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. | Drug | healthy subjects healthy subjects, subjects with prediabetes |
| immediate-release nicotinic acid (SAD)Also: ImR-NA (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. | Drug | healthy subjects healthy subjects |
| Placebo controlled-ileal-release nicotinic acid (SAD/MAD)Also: no active substance (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. | Drug | healthy subjects healthy subjects |
| Placebo immediate-release nicotinic acid (SAD)Also: no active substance (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. | Drug | healthy subjects healthy subjects |
Primary outcome
Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: up to 60 days
Adverse Events (AEs) during treatment period
Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Time frame: up to 60 days
Serious Adverse Events (SAEs) during treatment period
Haemoglobin
Time frame: up to 60 days
Haemoglobin (Hb) in %
White blood cells
Time frame: up to 60 days
White blood cell (WBC) count as x10^9/l
Blood creatinine
Time frame: up to 60 days
Blood Creatinine in mmol/L
Blood urea
Time frame: up to 60 days
Urea in mmol/L
Blood uric acid
Time frame: up to 60 days
Uric acid in mmol/L
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
Blood ALT
Time frame: up to 60 days
Alanine transaminase (ALT) in U/l
Blood AST
Time frame: up to 60 days
Aspartate transaminase (AST) in U/l
Blood GGT
Time frame: up to 60 days
Gamma glutamyl transferase (GGT) in U/l
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanna Nikolaus, Prof. Dr. principal investigator
University Medical Center Schleswig-Holstein, Campus Kiel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing immediate-release nicotinic acid (SAD) in people with Safety Issues and Pharmacokinetic, run by University Hospital Schleswig-Holstein at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: up to 60 days). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2024.