Study on Gastric Emptying Effect and Drug-Drug Interactions of GZR18 Injection

Официальное название

A Study to Evaluate the Effect of GZR18 Injection on Gastric Emptying and Its Drug-Drug Interactions With Digoxin, Rosuvastatin Calcium and Warfarin Sodium in Obese or Overweight Subjects

Обзор

This is a single-center, open-label, fixed-sequence phase I clinical study to evaluate the effect of GZR18 Injection on gastric emptying and the effect of repeated SC injections of GZR18 Injection on the pharmacokinetics of oral digoxin tablets, rosuvastatin calcium tablets and warfarin sodium tablets. A total of 60 obese or overweight subjects are planned to be enrolled, with no less than one-quarter of the subjects from either gender. The study duration for each subject in this study is approximately 26 weeks: including a screening period of up to 4 weeks (W-28 to D-1), single-drug administration and dose escalation stages of 16 weeks (W1D1 to W16D7) and the combined drug administration stage of 6 weeks (W17D1 to W23D1)

Вмешательства

• Препарат GZR18 injection,digoxin tablets, rosuvastatin calcium tablets and warfarin sodium tablets
  GZR18 injection: 3 mg-36 mg，16 weeks; Warfarin Sodium Tablets:2.5mg，twice; Rosuvastatin Calcium Tablets：10mg，twice; Digoxin Tablets:0.25mg，twice

Первичные конечные точки

• Cmax:Maximum plasma concentration [Срок оценки: through study completion,up to 16 weeks]
• AUC0-last:Area under the plasma concentration-time curve at 0 h to last observation time-point after a single dose. [Срок оценки: through study completion,up to 16 weeks]
• AUC0-inf:Area under the plasma concentration-time curve at 0 h to infinity after a single dose. [Срок оценки: through study completion,up to 16 weeks]

Вторичные конечные точки (5)

• Tmax:Time of Maximum Drug Concentration [Срок оценки: through study completion,up to 16 weeks]
• t1/2: Elimination half-life [Срок оценки: through study completion,up to 16 weeks]
• CL/F: Apparent clearance rate [Срок оценки: through study completion,up to 16 weeks]
• Vz/F:Apparent Volume of Distribution associated with the Terminal Phase following Oral Administration [Срок оценки: through study completion,up to 16 weeks]
• PD:Area under the international normalized ratio-time curve (INRAUC) and maximum international normalized ratio postdose (INRMAX) for warfarin [Срок оценки: through study completion,up to 16 weeks]

Критерии участия

Критерии включения

• 1.Obese Chinese subjects, who voluntarily sign the Informed Consent Form (ICF), can receive SC injection, fully understand the content, process and possible adverse reactions of the trial, and are able to follow the regulations on contraindications and restrictions specified in this protocol.

2\. Male or female, 18 to 50 years of age at signing the ICF (both inclusive).

3\. Body mass index (BMI) within 26-35 kg/m2 (both ends inclusive) at screening.

4\. No abnormality or not clinically significant abnormality as judged by the investigator in physical examination, vital signs, routine laboratory tests (hematology, blood chemistry, urinalysis, thyroid function and coagulation), 12-lead ECG, ultrasonography of liver, gallbladder, pancreas, and spleen + both kidneys, chest imaging examination and other results. (abnormal indicators related to obesity or overweight, and the investigator assesses that they have no impact on this study, they can be enrolled)

5\. Subjects of childbearing potential with no birth plan from the signing of the ICF to 8 weeks after the last dose, willingness to take effective contraceptive measures, and no plan for sperm or ovum donation. Females of childbearing potential must not be lactating and must have negative results for blood pregnancy test at screening (including D-1).

Критерии исключения

• 1.Subjects with a previous or existing history of heart, liver, kidney, gastrointestinal tract, respiratory system, nervous system, psychiatric disorders, endocrine diseases (except obesity), malignant tumors and other diseases that are judged by the investigator to have an impact on the evaluation of the results of this study.

2\. History or existing diseases that increase the risk of subjects, such as hypoglycemia, acute or chronic pancreatitis, pancreatic injury, history of symptomatic gallbladder disease; cholelithiasis with high risk of acute biliary pancreatitis at screening (e.g., silt-like lithiasis, gallbladder or bile duct stone ≤ 5 mm in diameter)，newly diagnosed cholecystitis at screening.

3\. Subjects with previous or existing clinically significant digestive system diseases who are judged unsuitable for the study by the investigator, such as history of active peptic ulcer or hemorrhage, inflammatory bowel disease, abnormal gastric emptying (such as gastric paresis or pyloric stenosis, gastric outlet obstruction), continuous use of drugs affecting gastrointestinal motility for ≥ 1 week (including but not limited to domperidone, mosapride, macrolides), and acute hemorrhoidal attacks within the past three months.

4\. History or family history of previous or existing medullary thyroid carcinoma, multiple endocrine neoplasia type 2.

5\. Subjects who have used any drugs that alter the activity of drug metabolizing enzymes or transporters within 4 weeks prior to screening, or subjects with acute diseases or concomitant medication from the screening period to before administration of the investigational medicinal product (IMP).

6\. Subjects with severe infection or unexplained infection within 4 weeks before screening.

7\. Major surgery within 6 months prior to screening, or scheduled surgery or hospitalization during the study.

8\. Subjects with allergic constitution prior to screening, or a history of bronchial asthma, eczema and other allergic diseases (except mild seasonal allergy), or a history of severe food allergy (such as laryngeal edema, shock), or known allergy to any ingredient in investigational medicinal products (IMPs) \[GLP-1 receptor (GLP-1R) agonist, paracetamol, digoxin, rosuvastatin, warfarin and their excipients\].

9\. Use of any prescription drugs, over-the-counter drugs or Chinese herbal medicines within 2 weeks prior to screening; or use of any GLP-1R agonists or drugs with the same mechanism of action to GLP-1R agonists \[such as GLP-1R/glucagon receptor (GCGR) agonists or gastric inhibitory polypeptide receptor (GIPR)/GLP-1R agonists or GIPR/GLP-1R/GCGR agonists\] within 6 months prior to screening; or use of any weight loss drugs within 6 months prior to screening.

10\. Subjects who have been vaccinated within 1 month before screening or are scheduled for vaccination during the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Study site 01 — Пекин

Идентификаторы

NCT: NCT07128888 · GZR18-BWM-104

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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