Evaluation of Oral Glibenclamide Efficacy in Managing Transient Hyperglycemia in Premature Infants Weighing Less Than 1500g

The primary objective of this study is to evaluate the **72-hour efficacy** of an enteral suspension of glibenclamide in controlling transient hyperglycaemia in premature infants weighing less than 1500 grams. This is clinically relevant as transient hyperglycaemia is a common condition in premature infants, and effective management is crucial for preventing potential complications associated with elevated blood glucose levels.

Secondary objectives include:

• Assessing the overall efficacy of a suspension of glibenclamide in controlling hyperglycaemia.
• Evaluating the glycaemic profile under glibenclamide, including time to glycaemic control and time spent in the glycaemic target range.
• Assessing caloric intake and early neonatal growth in premature infants treated with glibenclamide.
• Evaluating the safety and tolerability of glibenclamide.
• Assessing the ease of use of glibenclamide.
• Evaluating the pharmacokinetics of enteral glibenclamide.

The clinical trial focuses on evaluating the efficacy of an enteral suspension of glibenclamide in managing **transient hyperglycaemia** in premature infants. The study population includes newborns of both genders, less than 34 weeks post-menstrual age, with a birth weight under 1500 grams, and a gestational age of less than 32 weeks. Participants must exhibit hyperglycaemia, defined as blood glucose levels of 10 mmol/l or higher, confirmed by two measurements taken at least three hours apart. The trial does not specifically target a vulnerable population. Participants are required to have secure venous access and must have started or be considered for enteral feeding prior to enrollment. Consent from legal guardians and social security beneficiary status are also prerequisites. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **glibenclamide** in managing transient hyperglycemia in premature infants. This is a phase 4, randomized, double-blind, controlled trial. The trial aims to assess the 72-hour efficacy of an enteral suspension of glibenclamide in controlling hyperglycemia in premature infants weighing less than 1500 grams. The trial is expected to run from May 2023 to February 2027, with participant involvement lasting up to 15 days. The study includes several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility criteria are confirmed, including gestational age, birth weight, and hyperglycemia levels. Follow-up visits are scheduled to monitor glycemic control, assess the need for insulin, and evaluate any adverse reactions. The primary endpoint is the success of glycemic control within 72 hours, defined by the non-use of insulin and the absence of severe or persistent moderate hypoglycemia. Secondary endpoints include overall treatment success, glycemic profile, nutritional intake, growth, and neonatal morbidity. Participants may be withdrawn from the study if they experience severe adverse reactions or if consent is withdrawn by legal guardians. The trial's design ensures rigorous monitoring and data collection to evaluate the safety and efficacy of glibenclamide in this vulnerable population.

The clinical trial involves the administration of **AMGLIDIA 6 mg/mL oral suspension**, which contains the active substance **glibenclamide**. This pharmaceutical form is an oral suspension, designed for administration via oral, nasogastric tube, or percutaneous endoscopic gastrostomy tube. The medication is intended for the treatment of transient hyperglycemia in premature infants weighing less than 1500 g. The maximum daily dose is 0.4 mg/kg, with a total maximum dose of 0.4 mg/kg over a treatment period not exceeding 15 days. The formulation is not specifically pediatric, and the active substance is of chemical origin. The product is classified under the ATC code A10BB01, indicating its role as a sulfonylurea used in diabetes management.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies as deemed necessary by the clinical investigators. These may include other **sulfonylureas** as comparator treatments, although specific details regarding their use are not provided in the trial documentation. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed treatment regimen. The trial aims to evaluate the efficacy of the enteral suspension of glibenclamide over a 72-hour period in controlling hyperglycemia in the specified patient population.

The efficacy of the clinical trial titled "GALOP: Oral Glibenclamide in premature hyperglycemia" will be assessed primarily through the evaluation of **glycaemic control** over a 72-hour period following treatment with glibenclamide. The primary endpoint is defined as the successful management of glycaemia without the use of insulin and the absence of severe hypoglycaemia, characterized by blood glucose levels below 1.5 mmol/L, or persistent moderate hypoglycaemia, defined as blood glucose levels below 2.6 mmol/L in two successive capillary measurements taken more than three hours apart.

Secondary endpoints include the overall success of the treatment, which is determined by the continuation to the end of treatment without insulin use, and the glycaemic profile under glibenclamide. Additional secondary measures involve the duration of glibenclamide treatment, nutritional intakes and growth, the number of children experiencing moderate or severe hypoglycaemia within the first 72 hours and throughout the treatment, and the number and type of adverse reactions to glibenclamide. Neonatal morbidity, assessed at 36 weeks post-menstrual age, and mortality at the same age will also be evaluated. Other secondary endpoints include the number of dose adjustments, ease of use assessment score by caregivers, and plasma concentrations of glibenclamide.