Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis
Purpose
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.
Conditions
- Pancreatic Insufficiency
- Cystic Fibrosis-related Diabetes
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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) C- peptide ≥1.2 ng/mL [15]. 8. 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.
Exclusion Criteria
- Established diagnosis of non-CF diabetes (e.g. type 1 diabetes). 2. Pregnancy or lactation; a negative urine pregnancy test will be required at enrollment. 3. Pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to randomization. 4. Treatment with either CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, indinavir, ritonavir, saquinavir, telithromycin, boceprevir, nelfinavir, telaprevir, conivaptan, nefazodone, etc.) or inducers (e.g. phenobarbital, other barbiturates, carbamazepine, phenytoin, rifampicin, dexamethasone, etc.). 5. Use of herbal remedies, including St. John's Wort within 14 days prior to dosing. 6. Change in CFTR modulator therapy in the previous 3 months. 7. History of clinically symptomatic pancreatitis within the last year. 8. Prior lung, liver or another solid organ transplant. 9. Abnormal kidney function: creatinine >2x upper limit of normal (ULN) or potassium >5.5mEq/L on non-hemolyzed specimen. 10. Abnormal liver function: persistent elevation of liver function tests >2.0 times ULN. 11. Uncontrolled hyperlipidemia: triglycerides >500 or cholesterol >250 mg/dl. 12. Hyperuricemia: serum uric acid >1.5 times ULN. 13. Anemia: hemoglobin <10 g/dL. 14. History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk to the subject.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Dorzagliatin |
Dorzagliatin 75 mg orally twice daily for 7 days |
|
|
Placebo Comparator Placebo |
matched-placebo orally twice daily for 7 days |
|
Recruiting Locations
Hospital of University of Pennsylvania
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
University of Pennsylvania Center for Human Phenomic Science (CHPS)
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
More Details
- NCT ID
- NCT06995651
- Status
- Recruiting
- Sponsor
- University of Pennsylvania