Diabetes Mellitus, Monogenic Diabetes
Conditions
Keywords
GCK-MODY, glucokinase activator
Brief summary
Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial
Detailed description
Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial
Interventions
DRUGDorzagliatin
Dorzagliatin 50mg bd
DRUGmatched placebo
matched placebo
Sponsors
Chinese University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Investigators, outcome assessors
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting plasma glucose | 8 weeks | Difference in fasting plasma glucose (FPG) between treatment periods |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| • HbA1c | 8 weeks | Difference between HbA1c at end of treatment periods |
| CGM metrics time in range | 8 weeks | Time in range defined by CGM at end of treatment periods |
| CGM metric coefficient of variation | 8 weeks | Difference in % CV at end of treatment periods |
| Glucose area under the curve during OGTT | 8 weeks | Difference between AUC glucose at end of treament periods |
| Insulin area under the curve during OGTT | 8 weeks | Difference between AUC insulin at end of treament periods |
| GLP1 area under the curve during OGTT | 8 weeks | Difference between AUC GLP-1 at end of treament periods |
Countries
Hong Kong
Contacts
CONTACTElaine Chow, MD
Outcome results
None listed