Bioequivalence Study of Sitagliptin/Metformin Extended-Release Tablets in Healthy Subjects

Bioequivalence Study of Two Formulations of a Sitagliptin/Metformin Hydrochloride Extended-Release Tablet in Healthy Chinese Subjects Under Fasting and Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Trial

The main purpose of this study is to compare the pharmacokinetics (how the body absorbs and clears the drug) and evaluate the bioequivalence of two formulations of sitagliptin/metformin hydrochloride extended-release tablets (50 mg/500 mg) in healthy adult subjects. The test product is manufactured by Qilu Pharmaceutical (Hainan) Co., Ltd., and the reference product is Janumet® XR.

The study is designed as a single-center, open-label, randomized, single-dose, two-period, two-sequence crossover trial. It consists of two separate parts: a fasting study and a fed study.

Participants will be randomly assigned to receive either the test formulation or the reference formulation in the first period. After a washout period of at least 5 days, participants will receive the alternate formulation in the second period. Blood samples will be collected at designated time points before and after dosing to measure the blood concentration of sitagliptin and metformin. Safety will also be continuously monitored throughout the study by assessing adverse events, vital signs, electrocardiograms (ECGs), and clinical laboratory tests.

Inclusion Criteria:

• Sign the informed consent form before the trial, and fully understand the trial content, process, and possible adverse reactions.
• Able to complete the study according to the requirements of the study protocol.
• Subjects voluntarily agree to use effective non-pharmacological contraception methods from the signing of informed consent (14 days prior to signing for female subjects) until 3 months after the last dose, with no plans for pregnancy, sperm donation, or egg donation.
• Male and female subjects aged 18 years and above.
• Male subjects weighing ≥ 50.0 kg and female subjects weighing ≥ 45.0 kg; Body Mass Index (BMI) within the range of 19.0 to 27.0 kg/m^2 (inclusive).

Exclusion Criteria:

• History of specific allergies (e.g., urticaria, exfoliative dermatitis, angioedema, or bronchial hyperresponsiveness), or allergic constitution (e.g., allergic to two or more drugs, foods such as milk and pollen), or known allergy to the components or analogs of this drug.
• Serious history of cardiovascular, hepatic, renal, gastrointestinal, neurological, endocrine, respiratory, or psychiatric abnormalities, which the investigator considers inappropriate for participation.
• Clinically significant abnormal findings as judged by the investigator, including physical examination, vital signs, electrocardiogram, or clinical laboratory tests.
• History of or current pancreatitis.
• History of hypoglycemia.
• Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m^2.
• History of dysphagia or any gastrointestinal disease affecting drug absorption (e.g., gastric or small bowel resection, atrophic gastritis, gastrointestinal bleeding, obstruction, etc.).
• Difficulty in blood collection, intolerance to venipuncture, or history of needle/blood phobia.
• Female subjects who are pregnant, lactating, or have a positive pregnancy test result.
• Positive for any one or more of the following: Hepatitis B surface antigen, Hepatitis C antibody, HIV antibody, or Syphilis antibody.
• History of drug abuse within 5 years, use of illicit drugs within 3 months prior to screening, or positive urine drug screen.
• Consumption of more than 14 units of alcohol per week on average within 3 months prior to screening, or refusal to abstain from alcohol from 48 hours prior to dosing in each period until the end of blood collection for that period, or positive alcohol breath test.
• Smoking more than 5 cigarettes per day on average within 3 months prior to screening, or refusal to abstain from using any tobacco products during the clinical stay.
• History of surgery within 3 months prior to screening, or planned surgery during the study.
• Blood donation or massive blood loss (>400 mL, excluding physiological blood loss in females) within 3 months prior to the first dose, or donation of 2 therapeutic units of platelets within 1 month.
• Participation and drug administration in any clinical trial within 3 months prior to the first dose.
• Use of any prescription drugs within 14 days prior to dosing.
• Use of any over-the-counter drugs, herbal medicines, or dietary supplements within 7 days prior to dosing.
• Consumption of special diets (e.g., grapefruit and products containing grapefruit ingredients) or strenuous exercise within 48 hours prior to dosing, or other factors affecting drug absorption, distribution, metabolism, and excretion.
• Consumption of any xanthine-rich foods or beverages (e.g., coffee, tea, chocolate, cocoa, milk tea, etc.) within 48 hours prior to dosing.
• Special dietary requirements, inability to comply with the diet and corresponding regulations provided by the center.
• Occurrence of an acute illness during the pre-study screening phase or before study drug administration.
• Other subjects deemed unsuitable for participation by the investigator.