Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM)

November 5, 2022 updated by: University Hospital Schleswig-Holstein

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Kiel, Germany
        • University Medical Center Schleswig-Holstein

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Main inclusion and exclusion criteria

Inclusion criteria for the SAD and MAD parts with healthy subjects:

  1. Male and female subjects aged 18 to 75 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).

Inclusion criteria for the MD-IBD part:

  1. Male and female patients with IBD and 18 to 75 years of age.
  2. Ability to understand and comply with the protocol.
  3. Signed written Informed Consent.
  4. Documented diagnosis of relapsing ileal, ileocolonic or colonic Crohn disease or relapsing ulcerative colitis.
  5. Concomitant therapy (background medication) for inflammatory bowel disease: none or stable 8 weeks before baseline.
  6. No signs of malignancy.

Exclusion criteria for the SAD and MAD part with healthy subjects:

  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

Exclusion criteria for the MD-IBD part:

  1. Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis, infectious colitis, radiation colitis or diverticular disease (except for diverticles accompanying CD).
  2. Current or past diagnosis of complex fistulae or intra-abdominal or peritoneal abscesses.
  3. Strictures with obstructive symptoms.
  4. 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).
  5. Legal incapacity.
  6. Indications that the patient may be unable to comply with the study procedures, e.g. language barriers precluding adequate understanding or cooperation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: healthy subjects
healthy subjects (single-ascending and multiple-ascending doses)
Drug: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)
single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)
Other Names:
  • CICR-NAM (SAD/MAD/MD)
Drug: Immediate-release nicotinamide (SAD)
single-ascending dose (SAD)
Other Names:
  • ImR-NAM (SAD)
Drug: Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)
single- and multiple-ascending dose (SAD/MAD)
Other Names:
  • no active substance
Drug: Placebo Immediate-release nicotinamide (SAD)
single-ascending dose (SAD)
Other Names:
  • no active substance
Experimental: IBD-patients
inflammatory bowel disease patients (multiple dose)
Drug: controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)
single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)
Other Names:
  • CICR-NAM (SAD/MAD/MD)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: up to 60 days
Adverse Events (AEs) during treatment period
up to 60 days
Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Time Frame: up to 60 days
Serious Adverse Events (SAEs) during treatment period
up to 60 days
Haemoglobin
Time Frame: up to 60 days
Haemoglobin (Hb) in %
up to 60 days
White blood cells
Time Frame: up to 60 days
White blood cell (WBC) count as x10^9/l
up to 60 days
Blood creatinine
Time Frame: up to 60 days
Blood Creatinine in mmol/L
up to 60 days
Blood urea
Time Frame: up to 60 days
Urea in mmol/L
up to 60 days
Blood uric acid
Time Frame: up to 60 days
Uric acid in mmol/L
up to 60 days
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
up to 60 days
Blood ALT
Time Frame: up to 60 days
Alanine transaminase (ALT) in U/l
up to 60 days
Blood AST
Time Frame: up to 60 days
Aspartate transaminase (AST) in U/l
up to 60 days
Blood GGT
Time Frame: up to 60 days
Gamma glutamyl transferase (GGT) in U/l
up to 60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Schleswig-Holstein

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Susanna Nikolaus, Prof. Dr., University Medical Center Schleswig-Holstein, Campus Kiel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 4, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 19, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 16, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CICR-NAM
  • 2020-002815-23 (EudraCT Number)
  • DRKS00023384 (Registry Identifier: DRKS - German Clinical Trials Register)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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