Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis

Phase 1

Not yet recruiting

• Conditions: Pancreatic Insufficiency; Cystic Fibrosis-related Diabetes
• Interventions: Drug: Dorzagliatin; Drug: Placebo

• Registration Number: NCT06995651
• Lead Sponsor: University of Pennsylvania

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-08
• Study First Submitted QC: 2025-05-20
• Study First Posted: 2025-05-29
• Last Update Submitted: 2025-05-30
• Last Update Posted: 2025-06-04
• Study Start: 2025-07
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Dorzagliatin	Dorzagliatin	Dorzagliatin 75 mg orally twice daily for 7 days
Dorzagliatin	Placebo	Dorzagliatin 75 mg orally twice daily for 7 days
Placebo	Dorzagliatin	matched-placebo orally twice daily for 7 days
Placebo	Placebo	matched-placebo orally twice daily for 7 days

Primary Outcome Measures

Name	Time	Method
Drug concentrations (PK; Cmax)	2 months	Assessed by the peak glucose during a standardized mixed-meal tolerance test following 7-day administration of study drug
Glucose tolerance (PD)	2 months

Secondary Outcome Measures

Name	Time	Method
Early-phase insulin secretion	2 months	Assessed by insulin secretory rate and
Glucagon suppression	2 months	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.

Trial Locations

Locations (2)

Hospital of University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania Center for Human Phenomic Science (CHPS); 🇺🇸 Philadelphia, Pennsylvania, United States