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Recruiting NCT06995651

Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis

Phase I Interventional Pancreatic Insufficiency Cystic Fibrosis-related Diabetes

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Dorzagliatin, Placebo.
Who it may be relevant to
Registry conditions: Pancreatic Insufficiency, Cystic Fibrosis-related Diabetes. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Pharmacokinetic and Pharmacodynamic Effects of Dorzagliatin in Pancreatic Insufficient-Cystic Fibrosis: A Randomized Double-blind, Cross-over Trial

Overview

This study is designed to determine the pharmacokinetic and pharmacodynamic response of dorzagliatin 50 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.

Interventions

  • Drug Dorzagliatin
    Randomized, double-blind, cross-over study of Dorzagliatin 50 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.
  • Drug Placebo
    Randomized, double-blind, cross-over study of Dorzagliatin 50 mg orally twice daily for 7 days compared to matched-placebo orally twice daily for 7 days.

Primary outcome measures

  • Drug concentrations (PK; Cmax) [Time frame: 2 months]
  • Glucose tolerance (PD) [Time frame: 2 months]
Secondary outcome measures (2)
  • Early-phase insulin secretion [Time frame: 2 months]
  • Glucagon suppression [Time frame: 2 months]

Eligibility criteria

Inclusion criteria

  • Provision of signed and dated informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Male or female, aged ≥18 years on date of consent.
  • Confirmed diagnosis of CF, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria.
  • Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
  • Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD.
  • 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 \[15\].

  • 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).
  • Pregnancy or lactation; a negative urine pregnancy test will be required at enrollment.
  • Pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to randomization.
  • 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.).
  • Use of herbal remedies, including St. John's Wort within 14 days prior to dosing.
  • Change in CFTR modulator therapy in the previous 3 months.
  • History of clinically symptomatic pancreatitis within the last year.
  • Prior lung, liver or another solid organ transplant.
  • Abnormal kidney function: creatinine >2x upper limit of normal (ULN) or potassium >5.5mEq/L on non-hemolyzed specimen.
  • Abnormal liver function: persistent elevation of liver function tests >2.0 times ULN.
  • Uncontrolled hyperlipidemia: triglycerides >500 or cholesterol >250 mg/dl.
  • Hyperuricemia: serum uric acid >1.5 times ULN.
  • Anemia: hemoglobin <10 g/dL.
  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Crossover
Masking
Triple blind
Primary purpose
Treatment

Study locations

United States · 2 centers
  • Hospital of University of Pennsylvania — Philadelphia
  • University of Pennsylvania Center for Human Phenomic Science (CHPS) — Philadelphia

Identifiers

NCT: NCT06995651 · 858421

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗