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

NCT ID: NCT05258474

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-04
• Study Completion Date: 2022-03-30

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.

Conditions

Safety Issues; Pharmacokinetic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

healthy subjects

healthy subjects (single-ascending and multiple-ascending doses)

Group Type: EXPERIMENTAL

controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)

Intervention Type: DRUG

single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)

Immediate-release nicotinamide (SAD)

Intervention Type: DRUG

single-ascending dose (SAD)

Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)

Intervention Type: DRUG

single- and multiple-ascending dose (SAD/MAD)

Placebo Immediate-release nicotinamide (SAD)

Intervention Type: DRUG

single-ascending dose (SAD)

IBD-patients

inflammatory bowel disease patients (multiple dose)

Group Type: EXPERIMENTAL

controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)

Intervention Type: DRUG

single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)

Interventions

controlled-ileocolonic-release nicotinamide (SAD/MAD/MD)

single- and multiple-ascending dose (SAD/MAD) or multiple dose (MD)

Intervention Type: DRUG

Immediate-release nicotinamide (SAD)

single-ascending dose (SAD)

Intervention Type: DRUG

Placebo controlled-ileocolonic-release nicotinamide (SAD/MAD)

single- and multiple-ascending dose (SAD/MAD)

Intervention Type: DRUG

Placebo Immediate-release nicotinamide (SAD)

single-ascending dose (SAD)

Intervention Type: DRUG

Other Intervention Names

CICR-NAM (SAD/MAD/MD); ImR-NAM (SAD); no active substance; no active substance

Eligibility Criteria

Inclusion Criteria

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).

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Schleswig-Holstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susanna Nikolaus, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Schleswig-Holstein, Campus Kiel

Locations

University Medical Center Schleswig-Holstein

Kiel, , Germany

Countries

Germany

Other Identifiers

2020-002815-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00023384

Identifier Type: REGISTRY

Identifier Source: secondary_id

CICR-NAM

Identifier Type: -

Identifier Source: org_study_id