Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis

Inclusion Criteria:

1. Provision of signed and dated informed consent form.

2. Stated willingness to comply with all study procedures and availability for theduration 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 analysisaccording to CFF diagnostic criteria.

5. Pancreatic insufficiency defined by clinical requirement for pancreatic enzymereplacement.

6. Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, ordiagnosed CFRD.

7. There will be no restriction on enrollment of individuals with CFRD but withoutfasting hyperglycemia (fasting hyperglycemia is defined as fasting glucose ≥126mg/dL) a. Individuals with CFRD and fasting hyperglycemia (defined as above or by the useof 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 methodfor the during of study participation; oral contraceptives, intra-uterine devices,Norplant®, Depo- Provera®, and barrier devices with spermicide are acceptablecontraceptive methods; condoms used alone are not acceptable.

Exclusion Criteria:

1. Established diagnosis of non-CF diabetes (e.g. type 1 diabetes).

2. Pregnancy or lactation; a negative urine pregnancy test will be required atenrollment.

3. Pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4weeks 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.) orinducers (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 timesULN.

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 mightconfound the results of the study or pose an additional risk to the subject.