Safety IssuesPhase 1NCT05258474
Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM)
A Phase 1 study testing Immediate-release nicotinamide (SAD) in people with Safety Issues and Pharmacokinetic, run by University Hospital Schleswig-Holstein at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Safety Issues, Pharmacokinetic
- What is being tested?
- Immediate-release nicotinamide (SAD)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteGermany
- Study dates
- 4 Dec 2020to 30 Mar 2022
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female patients with IBD and 18 to 75 years of age.
- Ability to understand and comply with the protocol.
- Signed written Informed Consent.
- Documented diagnosis of relapsing ileal, ileocolonic or colonic Crohn disease or relapsing ulcerative colitis.
- Concomitant therapy (background medication) for inflammatory bowel disease: none or stable 8 weeks before baseline.
- No signs of malignancy.
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- Exclusion criteria for the SAD and MAD part with healthy subjects:
- 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
Who cannot join
- Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis, infectious colitis, radiation colitis or diverticular disease (except for diverticles accompanying CD).
- Current or past diagnosis of complex fistulae or intra-abdominal or peritoneal abscesses.
- Strictures with obstructive symptoms.
- 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.
About this study
Official title: A Phase I, Double-blind, Randomised, Placebo-controlled, Single-ascending and Multiple-ascending Dose Trial 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
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.
Read the 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.
- Conditions
- Safety Issues, Pharmacokinetic
- Being tested
- controlled-ileocolonic-release nicotinamide (SAD/MAD/MD), Immediate-release nicotinamide (SAD), Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD), Placebo Immediate-release nicotinamide (SAD)
- Keywords
- Nicotinamide, Inflammatory Bowel Disease
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)Drug
Also called CICR-NAM (SAD/MAD/MD)
single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)
Immediate-release nicotinamide (SAD)Drug
Also called ImR-NAM (SAD)
single-ascending dose (SAD)
Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)Drug
Also called no active substance
single- and multiple-ascending dose (SAD/MAD)
Placebo Immediate-release nicotinamide (SAD)Drug
Also called no active substance
single-ascending dose (SAD)
| Study group | Role | What they receive |
|---|---|---|
| healthy subjects | Experimental | healthy subjects (single-ascending and multiple-ascending doses) Receives: Drug: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD); Drug: Immediate-release nicotinamide (SAD); Drug: Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD); Drug: Placebo Immediate-release nicotinamide (SAD) |
| IBD-patients | Experimental | inflammatory bowel disease patients (multiple dose) Receives: Drug: controlled-ileocolonic-release nicotinamide (SAD/MAD/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 posted28 Feb 2022
- Study start4 Dec 2020
- Primary completion30 Mar 2022
- Study completion30 Mar 2022
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
- 49 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
- NCT05258474
- Sponsor's protocol ID
- CICR-NAM
- Other IDs
- 2020-002815-23, DRKS00023384
- Status last verified
- Nov 2022
- First submitted
- 19 Aug 2021
- Last updated
- 8 Nov 2022
- 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 8 Nov 2022. 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 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
- ClinicalTrials.gov ID
- NCT05258474
- Acronym / sponsor ID
- CICR-NAM
- Conditions
- Safety Issues, Pharmacokinetic
- Keywords
- Nicotinamide, Inflammatory Bowel Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University Hospital Schleswig-HolsteinUniversity, hospital or other
- Study start
- 4 Dec 2020 (actual)
- Primary completion
- 30 Mar 2022 (actual)
- Study completion
- 30 Mar 2022 (actual)
- First posted
- 28 Feb 2022 (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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy subjects | Experimental | Drug: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD), Drug: Immediate-release nicotinamide (SAD), Drug: Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD), Drug: Placebo Immediate-release nicotinamide (SAD)healthy subjects (single-ascending and multiple-ascending doses) |
| IBD-patients | Experimental | Drug: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)inflammatory bowel disease patients (multiple dose) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Male and female patients with IBD and 18 to 75 years of age.
- Ability to understand and comply with the protocol.
- Signed written Informed Consent.
- Documented diagnosis of relapsing ileal, ileocolonic or colonic Crohn disease or relapsing ulcerative colitis.
- Concomitant therapy (background medication) for inflammatory bowel disease: none or stable 8 weeks before baseline.
Key exclusion criteria (6 listed)
- Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis, infectious colitis, radiation colitis or diverticular disease (except for diverticles accompanying CD).
- Current or past diagnosis of complex fistulae or intra-abdominal or peritoneal abscesses.
- Strictures with obstructive symptoms.
- 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.
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-ileocolonic-release nicotinamide (SAD/MAD/MD)Also: CICR-NAM (SAD/MAD/MD)single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD) | Drug | IBD-patients, healthy subjects |
| Immediate-release nicotinamide (SAD)Also: ImR-NAM (SAD)single-ascending dose (SAD) | Drug | healthy subjects |
| Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)Also: no active substancesingle- and multiple-ascending dose (SAD/MAD) | Drug | healthy subjects |
| Placebo Immediate-release nicotinamide (SAD)Also: no active substancesingle-ascending dose (SAD) | Drug | 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 8 Nov 2022.
- 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 nicotinamide (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?
The sponsor lists 15 inclusion and 6 exclusion criteria. 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 8 Nov 2022. 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 8 Nov 2022.