Pharmacokinetic and Pharmacodynamic Effects of Dorzagliatin in Pancreatic Insufficient-Cystic Fibrosis: A Randomized Double-blind, Cross-over Trial
This study is designed to determine the pharmacokinetic and pharmacodynamic response of dorzagliatin 75 mg twice daily following 7-day administration in individuals with pancreatic insufficient cystic fibrosis and abnormal glucose tolerance when compared to randomized, double-blind 7-day administration of placebo in a cross-over fashion. We hypothesize that dorzagliatin administration will result in significant drug concentrations and improved glucose tolerance, early-phase insulin secretion, glucagon suppression, and hepatic glycogen storage assessed during a standardized mixed-meal tolerance test.
• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged ≥18 years on date of consent.
• Confirmed diagnosis of CF, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria.
• Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
• Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD.
• There will be no restriction on enrollment of individuals with CFRD but without fasting hyperglycemia (fasting hyperglycemia is defined as fasting glucose ≥126 mg/dL)
• a. Individuals with CFRD and fasting hyperglycemia (defined as above or by the use of basal insulin therapy) must also have a HbA1c ≤8% and a random (non-fasting) C- peptide ≥1.2 ng/mL \[15\].
• For females of reproductive potential: use of highly effective contraception method for the during of study participation; oral contraceptives, intra-uterine devices, Norplant®, Depo- Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.