Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP) (GALOP)

The purpose of this study is to confirm hypothesis that Glibenclamide can be administered orally and is an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

Study Overview

• Status: Active, not recruiting
• Conditions: Preterm; Transient; Hypoglycemia, Neonatal; Glibenclamide Adverse Reaction
• Intervention / Treatment: Drug: Glibenclamide; Biological: Pharmacokinetics study; Biological: C-peptide proinsulin ratio; Biological: Routine biological monitoring

Detailed Description

Transient hyperglycemia of premature newborns results from an overall decrease in insulin sensitivity, which is responsible at the beta cell level for abnormalities of intragranular cleavage of proinsulin into insulin, leading to reduced active insulin secretion. Intravenous administration of exogenous insulin can be used to combat insulin resistance and lower blood glucose, but it is difficult to manage in premature newborns and is associated with a substantial risk of hypoglycemia. Glibenclamide, which stimulates endogenous insulin secretion and can be administered orally, might be an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Necker - Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newborn less than 34 week of amenorrhea corrected age
• Birth weight < 1500 g
• Birth term < 32 week of amenorrhea
• Hyperglycemia ≥ 10 mmol/l in 2 measurements, 3 hours apart after potential reduction of glucose intakes following each department's protocol
• Secure venous access point (umbilical venous catheter or epicutaneo-cava catheter)
• Enteral feeding considered before inclusion or already established
• Consent obtained from persons holding parental authority
• Beneficiary of social security

Exclusion Criteria

• Contraindication to enteral feeding (at the discretion of the clinician responsible for the child)
• Contraindication to glibenclamide according to current SPC
• Foetal growth restriction (FGR) birth weight < 3rd percentile (AUDIPOG definition)
• Severe birth defect, including cardiac malformation associated with a risk of myocardial ischemia
• Severe sepsis requiring mechanical ventilation or haemodynamic support
• Severe renal dysfunction (serum creatinine > 120 µmol/l)
• Severe hepatocellular failure (V factor less than the standard laboratory range for the age) and/or severe cholestasis (> 50 µmol/L)
• Hyperglycemia associated with an error in administering glucose infusion
• Profound hypophosphoremia (< 1 mmol/l)
• Hypersensitivity to glibenclamide or other sulphonylureas or sulphonamides, or one of the excipients
• Patient with continuous insulin IV administration
• Patient treated with miconazole

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Glibenclamide oral; Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk

Drug: Glibenclamide; Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk; Biological: Pharmacokinetics study; For the first 10 patients during the test phase, four 0.2 ml samples will be taken at H3, H6, H10, and H24 (+/- 1 hour) after the first dose; an additional sample will be taken for patients whose blood sugar levels stabilize beyond 24 hours, after 6 hours of stable blood sugar levels (4-10 mmol/l);; For subsequent patients included during phase II:; 1 sample of 0.2 ml within the first 24 hours of treatment, during a care assessment.; 1 sample of 0.2 ml within the first 24 hours of treatment, during a care assessment; 1 sample of 0.2 ml per day at each daily check-up as part of care during the treatment period.; In centers that are unable to perform the samples and the appropriate techniques for centralizing these PK points, these samples will not be taken. PK parameters of glibenclamide will be determined using nonlinear analysis: area under the plasma concentration time curve (AUC), absorption constant, apparent clearance and volume of distribution.; Biological: C-peptide proinsulin ratio; blood sampling at before first administration and after 24 hours for measurement of C-peptide proinsulin ratio if it is impossible to collect both volumes, the C-peptide collection will be prioritized; Biological: Routine biological monitoring; If there are not performed as part of standard care, biological monitoring of ALT, AST, complete blood count, hemostasis, urea, creatinine, blood ionogram, total bilirubin and conjugated bilirubin will be done before first administration at the following time frame : 48 hours after the first administration than each days during treatment period, and 48 hours after the end of treatment. Transaminases and hemostasis will be done only in case of clinical indication before the first administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose control	The primary evaluation criteria is 72 hours blood glucose control on glibenclamide treatment (success of the treatment). This is defined as the non-use of insulin and absence of severe hypoglycemia (< 1.5 mmol/l) or persistent moderate hypoglycemia (< 2.6 mmol/l in 2 successive measurements (dextro) at an interval of more than 3 hours)	At 72 hours after the first administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall success of the treatment	Overall success of the treatment defined by continuation to the end of treatment without recourse to insulin.	At 36 week of amenorrhea corrected age
Blood glucose profile on glibenclamide	Time between the start of glibenclamide treatment and the 1st blood glucose < 10 mmol/l	At the end of treatment assessed up to 15 days
Blood glucose profile on glibenclamide	Time between the start of glibenclamide treatment and the 1st blood glucose < 8 mmol/l	At the end of treatment assessed up to 15 days
Blood glucose profile on glibenclamide	Proportion of time spent within the target blood glucose range (≥ 4 and < 10 mmol/l) during the period of glibenclamide treatment	At the end of treatment assessed up to 15 days
Blood glucose profile on glibenclamide	Proportion of time spent above the target level (≥ 10 mmol/l) during the period of glibenclamide treatment	At the end of treatment assessed up to 15 days
Blood glucose profile on glibenclamide	Proportion of time spent in hypoglycemia (< 2.6 mmol/l) during the period of glibenclamide treatment	At the end of treatment assessed up to 15 days
Duration of glibenclamide treatment	Duration of glibenclamide treatment.	At the end of treatment assessed up to 15 days
Nutritional intakes and growth	Carbohydrate	At the end of treatment assessed up to 15 days
Nutritional intakes and growth:	lipid	At the end of treatment assessed up to 15 days
Nutritional intakes and growth:	protein	At the end of treatment assessed up to 15 days
Nutritional intakes and growth:	mean caloric intake (kcal/kg/day) during treatment	At the end of treatment assessed up to 15 days
Nutritional intakes and growth:	mean weight gain (g/kg/day)	At the end of treatment assessed up to 15 days
Nutritional intakes and growth	Carbohydrate	At 36 week of amenorrhea corrected age
Nutritional intakes and growth:	lipid	At 36 week of amenorrhea corrected age
Nutritional intakes and growth:	protein	At 36 week of amenorrhea corrected age
Nutritional intakes and growth:	mean caloric intake (kcal/kg/day) during treatment	At 36 week of amenorrhea corrected age
Nutritional intakes and growth:	mean weight gain ((g/kg/day)	At 36 week of amenorrhea corrected age
Number of children with episode of hypoglycemia	Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia	At 72 hours after first administration
Number of children with episode of hypoglycemia	Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia	At the end of treatment assessed up to 15 days
Type of adverse reactions on glibenclamide	evaluation of the type of adverse reactions identified during the study	At 36 week of amenorrhea corrected age
Number of adverse reactions on glibenclamide	evaluation of number of adverse reactions identified during the study	At 36 week of amenorrhea corrected age
Number of participants with co-morbidity	Neonatal morbidity assessed at 36 WA corrected age: intraventricular haemorrhage, periventricular leukomalacia, retinopathy of premature newborns, haemodynamic disorders, ulcerative necrotising enterocolitis	At 36 week of amenorrhea corrected age
Mortality	Mortality will be assessed	At 36 week of amenorrhea corrected age
Dose adjustment	Number of dose adjustments, to evaluate the easy of use	At the end of treatment assessed up to 15 days
ease of use by caregivers	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score	At day one of treatment
ease of use by caregivers	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score	At day two of treatment
ease of use by caregivers	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score	At day three of treatment
Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 3 hours after the first administration
Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 6 hours after the first administration
Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 10 hours after the first administration
Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 24 hours after the first administration
Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 24 hours of blood glucose stabilization

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Director: Jacques BELTRAND, Pr, Assistance Publique - Hopitaux de Paris; Study Director: Michel POLAK, Assistance Publique - Hopitaux de Paris; Study Director: Delphine MITANCHEZ, CHRU de Tours

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2023
• Primary Completion (Actual): October 30, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: preterm; glibenclamide; transient hypoglycemia
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Premature Birth; Hypoglycemia; Sulfur Compounds; Organic Chemicals; Amides; Sulfones; Urea; Sulfonylurea Compounds; Glyburide
• Other Study ID Numbers: P160916J; 2021-005766-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No