Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial

Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial

Inclusion Criteria:

1. Age ≥18 and <75 years
2. body mass index (BMI) >18 and <30 kg/m2
3. fasting plasma glucose >5.6 mmol/L at screening
4. Participants with GCK-MODY had and are heterozygous carriers of a pathogenic or likely pathogenic GCK mutation at screening based on guidelines published by the American College of Medical Genetics and Genomics (ACMG), Association for Clinical Genomic Science (ACGS) and the ClinGen Monogenic Diabetes Expert Panel (MDEP) .

Exclusion Criteria:

1. Body weight <45kg at screening
2. Current or planning pregnancy or lactating
3. troke or cardiovascular disease within 6 months of recruitment
4. severe renal dysfunction (estimated glomerular filtration rate <30mL/min/1.73m2 or renal replacement therapy)
5. severe hepatic dysfunction (aspartate transaminase and/or alanine transaminase > 3 times upper limit of normal)
6. history of drug abuse or excessive alcohol intake
7. severe hypoglycemia within 6 months prior to screening
8. anaemia with Hb <10 g/dL at screening
9. excessive blood loss >300mL within 1 month of screening
10. use of strong or moderate CYP3A4 inhibitors or inducers
11. use of sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolidinediones, acarbose in the 6 weeks prior to randomisation
12. use of long-term high-dose corticosteroids at randomisation
13. serious concurrent infections at time of screening

Investigators, outcome assessors