Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Drug concentrations (PK; Cmax) [Срок оценки: 2 months]
• Glucose tolerance (PD) [Срок оценки: 2 months]

Вторичные конечные точки (2)

• Early-phase insulin secretion [Срок оценки: 2 months]
• Glucagon suppression [Срок оценки: 2 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Hospital of University of Pennsylvania — Philadelphia
• University of Pennsylvania Center for Human Phenomic Science (CHPS) — Philadelphia

Идентификаторы

NCT: NCT06995651 · 858421

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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