GZR18 injection effects on stomach emptying and interactions with digoxin, rosuvastatin, and warfarin

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

We will test whether repeated under-the-skin injections of GZR18 change how quickly the stomach empties and alter blood levels of digoxin, rosuvastatin, and warfarin in adults who are overweight or have obesity.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: Gan & Lee Pharmaceuticals. (industry)
• Locations: 1 site (Beijing)
• Trial ID: NCT07128888 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label, fixed-sequence Phase 1 study enrolling about 60 adults with BMI 26–35 kg/m2 to receive subcutaneous GZR18 injections. The protocol includes up to 4 weeks of screening, a 16-week single-drug administration and dose-escalation period, followed by a 6-week combined-drug administration phase, for an individual participation time of roughly 26 weeks. The study will measure gastric emptying and the pharmacokinetics of oral digoxin, rosuvastatin, and warfarin before and after repeated GZR18 dosing. Enrollment will include at least one-quarter of subjects from each gender and requires normal or non-clinically significant baseline safety testing.

Who should consider this trial

Good fit: Adults aged 18–50 with BMI between 26 and 35 kg/m2, without clinically significant medical abnormalities, who can receive subcutaneous injections and attend all study visits are ideal candidates.

Not a fit: People outside the age or BMI range, those with significant medical conditions or abnormal baseline tests, or those unable to travel to the Beijing site likely would not benefit from participating.

Why it matters

Potential benefit: If successful, the study could clarify safe dosing and timing when GZR18 is used with commonly prescribed heart and cholesterol medications, reducing interaction risks.

How similar studies have performed: Other early-phase programs of weight-loss injections (for example GLP-1 receptor agonists) have shown slowed gastric emptying and changes in absorption of some oral drugs, but GZR18's specific interaction profile in humans is novel and untested.

Eligibility criteria

Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Where this trial is running

Beijing

• Study site 01 — Beijing, China (RECRUITING)

Study contacts

• Study coordinator: yue Liu

Conditions: Obesity or Overweight