Evaluation of Empagliflozin on Glycemic Control in Patients with HNF1A-MODY: A Randomized, Double-Blind, Crossover Clinical Trial

The primary objective of this study is to investigate the **glucose-lowering effect** of empagliflozin 25 mg once daily in patients with **Maturity-onset diabetes of the young type 3 (HNF1A-MODY)**. This is clinically relevant as HNF1A-MODY is a genetic form of diabetes characterized by impaired insulin secretion, and effective glucose management is crucial for reducing the risk of diabetes-related complications. The study evaluates the efficacy of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, in lowering plasma glucose levels in this specific patient population. No secondary objectives are provided in the source data.

The clinical trial focuses on individuals diagnosed with **Maturity-onset diabetes of the young type 3 (HNF1A-MODY)**. The study population includes both male and female participants aged 18 years and older. Participants are required to have diabetes caused by a heterozygous mutation in the HNF1A-gene and must be on stable glucose-lowering treatment for at least 60 days prior to the screening visit. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to be on at least one glucose-lowering medication in a fixed dose. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include informed consent and a Hemoglobin A1c level of at least 48 mmol/mol. The selection process ensures that participants meet these criteria to assess the glucose-lowering effect of empagliflozin 25 mg once daily.

The clinical trial is designed to evaluate the **glucose-lowering** effect of **empagliflozin** 25 mg once daily in patients with **Maturity-onset diabetes of the young type 3 (HNF1A-MODY)**. This study is a randomized, double-blind, crossover trial, which ensures that neither the participants nor the investigators know which treatment the participants are receiving at any given time, thereby minimizing bias. The trial is expected to run until January 1, 2025, with recruitment having commenced on June 1, 2023. Participants will be involved in the study for a maximum treatment period of six months.

The trial will include several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as informed consent, age of at least 18 years, and stable glucose-lowering treatment for 60 days prior to the screening. Participants must have diabetes caused by a heterozygous mutation in the HNF1A-gene and a Hemoglobin A1c level of at least 48 mmol/mol. Following the screening, participants will be randomized to receive either the active treatment, **Jardiance 25 mg film-coated tablets**, or a placebo tablet, both administered orally. The primary endpoint is the mean difference in mean sensor glucose measured by continuous glucose monitoring (CGM) during the last 10 or 14 days of each treatment period.

Secondary endpoints include various CGM metrics, serum fructosamine, glycated albumin, 24-hour urinary glucose excretion, and fasting ketone levels, among others. Follow-up visits will be scheduled to monitor these parameters and ensure participant safety. The end-of-study visit will conclude the trial, assessing the overall outcomes and any adverse events. Participants may be withdrawn from the study early if they experience significant adverse effects or if they fail to comply with the study protocol. The trial is categorized as a Phase 4 study, focusing on the safety and efficacy of the treatment in a specific patient population.

The clinical trial involves the administration of **Jardiance 25 mg film-coated tablets**, which contain the active substance **empagliflozin**. This medication is provided in the form of film-coated tablets and is administered orally. The dosage for the trial is set at 25 mg once daily. The maximum treatment period for participants is six months. Empagliflozin is a chemical substance, and its primary role in the trial is to investigate its glucose-lowering effect in patients with HNF1A-MODY. The medication is encapsulated to ensure proper delivery and absorption. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.

In addition to the experimental medication, a **placebo tablet** is used as a comparator treatment in this randomized, double-blind, crossover trial. The placebo is designed to mimic the appearance of the Jardiance tablets but does not contain any active pharmaceutical ingredients. The use of a placebo allows for the assessment of the true efficacy of empagliflozin by providing a control against which the experimental treatment can be compared. The placebo is administered in the same manner as the active treatment, ensuring that the study remains blinded and that any observed effects can be attributed to the active substance.

The efficacy of empagliflozin in patients with HNF1A-MODY will be assessed through a randomized, double-blind, crossover clinical trial. The primary endpoint for evaluating efficacy is the mean difference in mean sensor glucose levels between empagliflozin and placebo, as measured by continuous glucose monitoring (CGM) during the last 10 or 14 days of each treatment period, depending on the CGM device used. This assessment will be conducted in the principal stratum of participants.

Secondary endpoints include various parameters measured by CGM, such as the coefficient of variation (CV%), standard deviation, and the percentage of time glucose levels are within, above, or below specified ranges. Additional secondary endpoints involve serum or plasma fructosamine and glycated albumin levels, 24-hour urinary glucose excretion (UGE), and the 24-hour renal threshold of glucose excretion estimated using CGM and 24h UGE. Other measures include fasting urinary glucose-to-creatinine ratio, fasting ketone levels, fasting capillary blood glucose, body weight, and the number of hypoglycemic events stratified by severity. The trial will also monitor the number of participants with specific fasting ketone levels.