Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis

NCT ID: NCT06995651

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2027-07-31

Brief Summary

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dorzagliatin

Dorzagliatin 75 mg orally twice daily for 7 days

Group Type: EXPERIMENTAL

Dorzagliatin

Intervention Type: DRUG

Randomized, double-blind, cross-over study of Dorzagliatin 75 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Placebo

Intervention Type: DRUG

Randomized, double-blind, cross-over study of Dorzagliatin 75 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Placebo

matched-placebo orally twice daily for 7 days

Group Type: PLACEBO_COMPARATOR

Dorzagliatin

Intervention Type: DRUG

Randomized, double-blind, cross-over study of Dorzagliatin 75 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Placebo

Intervention Type: DRUG

Randomized, double-blind, cross-over study of Dorzagliatin 75 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Interventions

Dorzagliatin

Randomized, double-blind, cross-over study of Dorzagliatin 75 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Intervention Type: DRUG

Placebo

Randomized, double-blind, cross-over study of Dorzagliatin 75 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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) 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

1. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael R Rickels, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Hospital of University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

University of Pennsylvania Center for Human Phenomic Science (CHPS)

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Paola Alvarado, MSCR

Role: CONTACT

Phone: 215-746-2081

Email: Paola.Alvarado@Pennmedicine.upenn.edu

Other Identifiers

858421

Identifier Type: -

Identifier Source: org_study_id