Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM)
Primary Purpose
Safety Issues, Pharmacokinetic
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)
Immediate-release nicotinamide (SAD)
Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)
Placebo Immediate-release nicotinamide (SAD)
Sponsored by
About this trial
This is an interventional other trial for Safety Issues focused on measuring Nicotinamide, Inflammatory Bowel Disease
Eligibility Criteria
Main inclusion and exclusion criteria
Inclusion criteria for the SAD and MAD parts with healthy subjects:
- Male and female subjects aged 18 to 75 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-IBD part:
- 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.
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
Exclusion criteria for the MD-IBD part:
- 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
Sites / Locations
- University Medical Center Schleswig-Holstein
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
healthy subjects
IBD-patients
Arm Description
healthy subjects (single-ascending and multiple-ascending doses)
inflammatory bowel disease patients (multiple dose)
Outcomes
Primary Outcome Measures
Treatment-Emergent Adverse Events [Safety and Tolerability]
Adverse Events (AEs) during treatment period
Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Serious Adverse Events (SAEs) during treatment period
Haemoglobin
Haemoglobin (Hb) in %
White blood cells
White blood cell (WBC) count as x10^9/l
Blood creatinine
Blood Creatinine in mmol/L
Blood urea
Urea in mmol/L
Blood uric acid
Uric acid in mmol/L
Glomerular filtration rate
Glomerular filtration rate (GFR, automatically calculated by the laboratory based on creatinine values) GFR in ml/min/1.73m2
Blood ALT
Alanine transaminase (ALT) in U/l
Blood AST
Aspartate transaminase (AST) in U/l
Blood GGT
Gamma glutamyl transferase (GGT) in U/l
Secondary Outcome Measures
Full Information
NCT ID
NCT05258474
First Posted
August 19, 2021
Last Updated
November 5, 2022
Sponsor
University Hospital Schleswig-Holstein
1. Study Identification
Unique Protocol Identification Number
NCT05258474
Brief Title
Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM)
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
December 4, 2020 (Actual)
Primary Completion Date
March 30, 2022 (Actual)
Study Completion Date
March 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Schleswig-Holstein
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Safety Issues, Pharmacokinetic
Keywords
Nicotinamide, Inflammatory Bowel Disease
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
healthy subjects
Arm Type
Experimental
Arm Description
healthy subjects (single-ascending and multiple-ascending doses)
Arm Title
IBD-patients
Arm Type
Experimental
Arm Description
inflammatory bowel disease patients (multiple dose)
Intervention Type
Drug
Intervention Name(s)
controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)
Other Intervention Name(s)
CICR-NAM (SAD/MAD/MD)
Intervention Description
single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)
Intervention Type
Drug
Intervention Name(s)
Immediate-release nicotinamide (SAD)
Other Intervention Name(s)
ImR-NAM (SAD)
Intervention Description
single-ascending dose (SAD)
Intervention Type
Drug
Intervention Name(s)
Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)
Other Intervention Name(s)
no active substance
Intervention Description
single- and multiple-ascending dose (SAD/MAD)
Intervention Type
Drug
Intervention Name(s)
Placebo Immediate-release nicotinamide (SAD)
Other Intervention Name(s)
no active substance
Intervention Description
single-ascending dose (SAD)
Primary Outcome Measure Information:
Title
Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Adverse Events (AEs) during treatment period
Time Frame
up to 60 days
Title
Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Description
Serious Adverse Events (SAEs) during treatment period
Time Frame
up to 60 days
Title
Haemoglobin
Description
Haemoglobin (Hb) in %
Time Frame
up to 60 days
Title
White blood cells
Description
White blood cell (WBC) count as x10^9/l
Time Frame
up to 60 days
Title
Blood creatinine
Description
Blood Creatinine in mmol/L
Time Frame
up to 60 days
Title
Blood urea
Description
Urea in mmol/L
Time Frame
up to 60 days
Title
Blood uric acid
Description
Uric acid in mmol/L
Time Frame
up to 60 days
Title
Glomerular filtration rate
Description
Glomerular filtration rate (GFR, automatically calculated by the laboratory based on creatinine values) GFR in ml/min/1.73m2
Time Frame
up to 60 days
Title
Blood ALT
Description
Alanine transaminase (ALT) in U/l
Time Frame
up to 60 days
Title
Blood AST
Description
Aspartate transaminase (AST) in U/l
Time Frame
up to 60 days
Title
Blood GGT
Description
Gamma glutamyl transferase (GGT) in U/l
Time Frame
up to 60 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Main inclusion and exclusion criteria
Inclusion criteria for the SAD and MAD parts with healthy subjects:
Male and female subjects aged 18 to 75 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-IBD part:
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.
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
Exclusion criteria for the MD-IBD part:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanna Nikolaus, Prof. Dr.
Organizational Affiliation
University Medical Center Schleswig-Holstein, Campus Kiel
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Schleswig-Holstein
City
Kiel
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Pharmacokinetics of Oral Controlled-ileocolonic-release Nicotinamide (CICR-NAM)
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