Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)

NCT ID: NCT05687500

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-20
• Study Completion Date: 2027-02-20

Brief Summary

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.

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.

Conditions

Transient; Hypoglycemia, Neonatal; Preterm; Glibenclamide Adverse Reaction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Glibenclamide oral

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

Group Type: EXPERIMENTAL

Glibenclamide

Intervention Type: DRUG

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

Pharmacokinetics study

Intervention Type: BIOLOGICAL

• 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.

C-peptide proinsulin ratio

Intervention Type: BIOLOGICAL

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

Routine biological monitoring

Intervention Type: BIOLOGICAL

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.

Interventions

Glibenclamide

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

Intervention Type: DRUG

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.

Intervention Type: 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

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Maximum Eligible Age: 34 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacques BELTRAND, Pr

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Michel POLAK

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Delphine MITANCHEZ

Role: STUDY_DIRECTOR

CHRU de Tours

Locations

Hopital Necker - Enfants malades

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Elsa KERMORVANT, Pr

Role: CONTACT

elsa.kermorvant@aphp.fr

01 71 19 61 75

Laure CHOUPEAUX, Master

Role: CONTACT

laure.choupeaux@aphp.fr

01 44 38 17 11

Facility Contacts

Elsa KERMORVANT, Pr

Role: primary

elsa.kermorvant@aphp.fr

01 71 19 61 75

Other Identifiers

P160916J

Identifier Type: -

Identifier Source: org_study_id

2021-005766-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id