Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis
Brief description of study
The primary objectives are to determine the pharmacokinetic (PK) and pharmacodynamic (PD) response of dorzagliatin 75 mg twice daily following 7-day administration in individuals with PI-CF and abnormal glucose tolerance (EGI, IGT or CFRD) when compared to 7-day administration of placebo according to a randomized, double-blind cross-over study design. The primary outcome variables are drug concentrations (PK; Cmax) and glucose tolerance (PD) as assessed by the peak glucose during a standardized mixed meal tolerance test following 7-day administration of study drug. Documentation of appropriate drug exposure and post-prandial glucose lowering effects in individuals with PI-CF would support a role for glucokinase activation enhancing post-prandial glucose tolerance in this population. The secondary endpoints are early-phase insulin secretion and glucagon suppression assessed by insulin secretory rate and glucagon incremental area under- the-curve (iAUC) analyses during the mixed-meal tolerance test following 7-day administration of study drug. iAUC analyses for GLP-1 and GIP will be assessed as potential effect modifiers. These outcomes would support a role for glucokinase activation affecting the impaired islet function that characterizes PI-CF, possibly mediated in part through effects on incretin secretion.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Medical Research
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Age: 18 years - 99 years
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Gender: All
1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female, aged ≥18 years on date of consent.
4. Confirmed diagnosis of CF, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria.
5. Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
6. Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD.
7. 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) Cpeptide ≥1.2 ng/mL [15].
8. For females of reproductive potential who are sexually active with a partner of the opposite sex: use of highly effective contraception method for the during of study participation; hormonal contraceptives, intra-uterine devices, contraceptive implants, used together with a barrier method are acceptable contraceptive methods; barrier devices with or without spermicide used alone are not acceptable.
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