This is a phase I clinical trial which includes only healthy subjects and subjects with prediabetes.
Conditions
Interventions
Group 1: SAD (= single ascending dose) Dose level 1: Gelatin capsules containing 100 mg immediate-release nicotinic acid (ImR-NA) and tablets containing 100 mg nicotinic acid (NA) for ileal release (C
Sponsors
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Healthy subjects (SAD and MAD parts): 2. Healthy subjects without relevant medical conditions; the following criteria have to be fulfilled at screening and baseline assessment: (a) heart rate: heart rate of 45 to 99 bpm (heart rate 10 pack-years) Subjects with prediabetes (MD-PreD part): 2. Previously diagnosed prediabetes with confirmation via the HbA1c level (5.7 to 10 pack-years).
Exclusion criteria
Exclusion criteria: Healthy subjects and subjects with PreD 1. Clinically relevant abnormal findings in medical history or screening assessments which, in the opinion of the Investigator, may put the subject at risk when participating in the study or provide difficulties in interpreting the study data 2. Current or history of malignancy except for completely resected basal cell carcinoma and squamous cell carcinoma of the skin 3. History of severe allergy or anaphylactic reactions 4. Known hypersensitivity to any component of the NA or placebo formulations 5. Participation in a clinical study within 4 weeks prior to enrolment in this study or intake of an IMP within the last 8 weeks or 5 half-lives (whichever is longer) prior to the first dose of IMP (or longer if necessary, as judged by the Investigator) 6. Use of any prescribed or over-the-counter medication, food supplements or herbal preparations within 2 weeks prior to the first dose of IMP. Paracetamol, topical allergy medicines and oral contraceptives according to label are allowed 7. Use of antibiotics (systemic or gut-acting [non-absorbed]) within 8 weeks prior to the first dose of IMP 8. Alcohol or drug abuse within the last 2 years 9. Blood donation or major blood loss (= 500 mL) within the last 3 months prior to the first dose of IMP 10. Pregnant or breastfeeding women 11. Women of childbearing potential (WoCBP) not using highly effective contraception till at least 1 month after last dosing of IMP 12. Male participants with female partners of childbearing potential not willing to use a condom during intercourse and to have their female partners use a highly effective contraception till at least 1 month after last dosing of IMP 13. Legal incapacity 14. Indications that the subject may be unable to comply with the study procedures, e.g. language barriers precluding adequate understanding or cooperation 15. Any circumstances which could contradict a study participation and lead the Investigator to assess the subject as unsuitable for study participation for any other reason 16. Findings in the screening ileocolonoscopy which could interfere with the assessment of local tolerability or require therapeutic or preventive intervention like polypectomy (only in the highest MAD dose group)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation based on AEs, SAEs, laboratory assessments (haematology, clinical chemistry), physical examination, vital signs, ECG, and local tolerability assessed by ile-ocolonoscopy with serial biopsies (only in the highest MAD dose group) | — |
Secondary
| Measure | Time frame |
|---|---|
| • Pharmacokinetics of NA and its main metabolites Nicotinamide (NAM), N-methylnicotinamide (NMN), N-methyl-2-pyridone-5-carboxamide (2-Py) and Nicotinuric Acid NUA in plasma • Relative bioavailability of CIR-NA compared to ImR-NA • Dose-depending bioavailability of CIR-NA after single doses and multiple doses • Comparison of PK and bioavailability of CIR-NA in healthy subjects and in subjects with prediabetes. • Changes in urine concentrations of NA and its main metabolites NAM, NMN, 2-Py and NUA | — |
Countries
Germany
Contacts
Public ContactMatthias Laudes
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Outcome results
None listed