Evaluation of Controlled-Ileal-Release Nicotinic Acid for Remission Induction in Prediabetes: A Phase II Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this Phase II, randomised, double-blind, placebo-controlled trial is to assess the **efficacy** of oral controlled-ileal-release nicotinic acid (CIR-NA) in inducing remission of **prediabetes** at week 26. This is clinically relevant as achieving remission in prediabetes can potentially prevent the progression to type 2 diabetes mellitus (T2DM), thereby reducing associated complications and healthcare burdens.

The secondary objectives are to evaluate the progression of prediabetes to T2DM and to measure individual levels of fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), and the 2-hour oral glucose tolerance test (oGTT) at week 26. These assessments are crucial for understanding the metabolic changes and the potential impact of CIR-NA on glucose regulation in individuals with prediabetes.

The clinical trial involves **participants** diagnosed with **prediabetes**, aiming to evaluate the efficacy of CIR-NA on the remission of this condition at week 26. The study population includes both male and female subjects aged 18 to less than 80 years, with a body mass index of at least 20 kg/m². Participants were selected based on their diagnosis of prediabetes according to the current EASD/DDG guidelines. The trial does not include a vulnerable population, and the sponsor has not provided the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of oral controlled-ileal-release **nicotinic acid** (CIR-NA) in inducing remission in subjects with **prediabetes**. The trial is set to commence recruitment on September 1, 2025, and is expected to conclude by May 1, 2028. The primary objective is to assess the remission of prediabetes at week 26, with secondary endpoints including the progression to type 2 diabetes mellitus, fasting plasma glucose levels, glycated hemoglobin (HbA1c) levels, and 2-hour oral glucose tolerance test levels, all evaluated at week 26.

Participants will be involved in the study for a maximum treatment period of 185 days. The study will include an initial screening visit to confirm eligibility based on criteria such as age (18 to <80 years), body mass index (≥20 kg/m²), and a diagnosis of prediabetes according to current EASD/DDG guidelines. Following the screening, eligible participants will be randomized to receive either CIR-NA or a placebo, administered orally in the form of film-coated tablets. The maximum daily dose of CIR-NA is 200 mg, with a total dose not exceeding 37 grams over the treatment period.

Study visits will be scheduled at regular intervals to monitor the participants' health status and treatment response. These visits will include assessments of the primary and secondary endpoints, as well as safety evaluations. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted to determine the overall efficacy and safety of the intervention. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with study procedures, or if the investigator deems it necessary for their safety.

The clinical trial involves the administration of **CIR-NA (controlled-ileal-release nicotinic acid)**, which is the experimental medication under investigation. This medication is formulated as a **film-coated tablet** and is intended for oral administration. The active substance in CIR-NA is **nicotinic acid**, also known as **vitamin B3**, **niacin**, or **vitamin PP**. The maximum daily dose of CIR-NA is 200 mg, with a total maximum dose of 37 grams over the course of the treatment period, which spans up to 185 days. The primary objective of the trial is to evaluate the efficacy of CIR-NA in inducing remission in subjects with prediabetes by week 26. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled trial. The placebo is referred to as **Placebo CIR-NA** and is designed to match the experimental medication in appearance but does not contain the active substance, nicotinic acid. The placebo serves to ensure that any observed effects can be attributed to the active treatment rather than psychological or other non-specific effects. The trial is structured to maintain blinding, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias in the assessment of the treatment's efficacy and safety.

The efficacy of the investigational product, CIR-NA (controlled-ileal-release **nicotinic acid**), will be assessed in a Phase II, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the remission of prediabetes at week 26. Secondary endpoints include the progression of prediabetes to type 2 diabetes mellitus, fasting plasma glucose levels, glycated hemoglobin (HbA1c) levels, and 2-hour oral Glucose Tolerance Test levels, all measured at week 26.

Data collection will occur at specified timepoints, with the primary and secondary endpoints being assessed at the conclusion of the 26-week treatment period. The trial will utilize validated laboratory tests to measure fasting plasma glucose and HbA1c levels, as well as the oral Glucose Tolerance Test to evaluate glucose metabolism. The analysis of these parameters will provide insights into the efficacy of CIR-NA in inducing remission of prediabetes and preventing its progression to type 2 diabetes mellitus.